v s<0' KENELM Hf DIGBY, /// M.B., B.S. ; F.R.C.S, Ho Tung Professor of Clinical Stirgery and Professor of Anatomy at the University of Hong Kong ; Honorary Visiting Surgeon to the Government Civil Hospital, Hong Kong. LONDON HENRY FROWDE HODDER & STOUGHTON Oxford University Press 20, Warwick Square, E.C.4. 1919 t QR 181- b5f PRINTED IN GREAT BRITAIN BY KlNC. AND JaRRETT, LIMITED. HOI^LAND STREET, BLACKFRIARS, LONDON, S.E. 1. Ji CONTENTS, PAGE Chapter I. — Introduction ' ... 1 Chaptkr II.— Historical 3 Chapter III.— Previous Theories as to the Function of the Tonsils and of the Appendix 6 Cjiapter IV. — General Question of Immunity 12 Chapter V. — Healthily Acquired Immunity 13 Chapter VI. — Alimentary Immunity 17 Chapter VII.- Distribution of the Subepithelial Lymphatic Glands in Man 19 Chapter VIII. — Comparative Anatomy of the Subepithelial Lymphatic Glands ... • 27 Chapter IX.— Structure of the Subepithelial Lymphatic Glands 46 Chapter X. — The Rabbit's Appendix ... 51 Chapter XI. — Life History of the Subepithelial Lymphatic Glands ... 56 Chapter XII.— Presence of Bacteria in the Subepithelial Lymphatic Glands 60 Chapter XIII. — Mode of Ingestion of Bacteria by the Subepithelial Lymphatic Glands 67 Chapter XIV. — Pathology of the Subepithelial Lymphatic Glands 73 Chapter XV. — Acute Inflammations of the Subepithelial Lymphatic Glands 78 Chapter XVI. — Simple Enlargement or Hyperplasia of the Subepithelial Lymphatic Glands 88 Chapter XVII. — Other Diseases of the Subepithelial Lymphatic Glands 91 Chapter XVIII. — Therapeutic Bearing 93 Chapter XIX. — Some General Considerations 99 Chapter XX. — Resume of the Hypothesis and Summary of the Evidence for and against 103 Bibliography and Index of Names Ill Subject Index tf? ff 117 vii. LIST OF ILLUSTRATIONS. Fig. page 1. Bacteria in wall of healthy rabbit's appendix ... frontispiece 2. Micro-section of vermiform appendix with obliterated lumen 8 3. Diagram showing the circumpharyngeal ring of lymphoid tissue 21 4. Diagram of the lymphoid tissue near the ileo-caecal junction 23 5. Diagram of the human alimentary canal showing the distribu- tion of the subepithelial lymphatic nodules 24 6. The protuberant and tubular types of the faucial and caecal tonsils 29 7. Micro-section of pigeon's caeca 34 8. The appendix of lagomys pusillus 37 9. The beaver's appendix 37 10. The porcupine's appendix 38 11. The peccary's appendix 39 12. The tapir's appendix 39 13. The phalanger's appendix 40 14. The koala's appendix 41 Jo. The wombat's appendix 42 16. The lemur's appendix 42 17. The slow lemur's appendix 43 18. The orang's appendix ... 43 19. The gibbon's appendix 44 20. The chimpanzee's appendix ... 44 21. The gorilla's 'appendix 45 22. The human appendix ... 45 23. The rabbit's caecum and appendix 52 24. A calyx gland in the rabbit's appendix 55 25. The wall of the rabbit's appendix at birth, at 14 days and at 28 days 58 20. Bacteria in a healthy subepithelial lymph node 61 27. Micrococci in the lymphoid tissue of a iiealthy rabbit's tonsil 62 28. Bacilli in the lymphoid tissue of a healthy rabbit's Peyer's patch 63 29. Bacilli in the lymphoid tissue of a healthy rabbit's appendix 64 30. Bacilli in the lymphoid tissue of a healthy rabbit's appendix 65 31. Micro-section of a Peyer's patch from a rabbit which had soot administered with its food for three weeks ... 71 ¥ CHAPTER I. Introduction. After the doctrine of evolution was formulated the values of the various organs in the body were critically examined, and it came to be suggested that structures sometimes persisted in a race of animals long after they had ceased to perform any useful function or indeed any function at all. The question raised is a wide one and has been hotly discussed ; it is usually conceded as a possibility that a structure, especially if it does not become directly injurious, may persist (in a more or less undeveloped form) even when it has ceased to function for generations. Many organs in the body have at one time been claimed to belong to this group of vestigial structures, but with increasing phy- siological knowledge the list steadily shrinks. Tonsils, Adenoids, and the Vermiform Appendix are still commonly regarded as useless, even dangerous, relics of a past usefulness (Schafer, 1912). But the investigations recorded in the following pages point in quite another direction, and appear to support the view that these structures (together with the Noduli Lymph- atici Solitaii et Aggregati) should be grouped together 1 2 IMMUNITY IN HEALTH into one class of ''Subepithelial Lymphatic Glands"*; that they constitute important antibacterial weapons and share a great and valuable function in the pre- servation of health (Digby, 1911). Evidence wiH be adduced to show that these subepithelial lymphatic glands are not so much local defences to strengthen weak spots as organs for the development of general systemic immunity. These considerations do not involve an attack upon surgery for the removal of some of the organs of the subepithelial lymphatic system. The recognition of their utility does not, of course, imply their inviolability when they unhappily become the base or focus of disease. The eye is useful, yet at times it may be necessary to sacrifice even a partially functioning eye for the general health of its owner. * Doubts may arise as to the propriety of using the word " glands " in this connection. The word *' organs " might indeed be substi- tuted. But " glands " has long been employed for other lymphoid collections and is retained in the B.N. A. terminology. It, therefore, seems well to write " Lymphatic Glands " and to describe these as falling into two classes: — 1. Interstitial, e.g. : — Axillary, Bronchial, Cervical, Aortic, etc. 2. SubepitheliaU e-g- : — Solitary nodules. Aggregated nodules. Vermiform process, Faucial tonsil, etc. CHAPTER II. Historical. The history of the Subepithelial Lymphatic Glands is a history of neglect. The very existence of some of these structures was unknown to early anatomy. The tonsils must have been seen by the first physician who inspected a patient's throat : but of the vermiform appendix the earliest record seems to have been in 1524, by Berenger Carpi (Kelynack), while it was not till 1677 that Peyer described the agminated follicles in the intestines, and it was as late as 1724 when Santorini was the first to describe the pharyngeal tonsil. The part played by the subepithelial lymphatic glands in disease was a comparatively late discovery in Medicine, though it is probable that inflammation of the tonsils was recognised early. According to Kely- nack, a case of perforation of the appendix was described in 1759 by Mestivier, but the frequency with which the appendix is the starting point of abdominal suppuration has only been realised within the last thirty years. *'That enteric fever was an entity marked by intestinal lesion was realised in the early part of the Nineteenth Century" (Dreschfield, 1896). The harmful effects of enlargement of the pharyngeal tonsil were pointed out by Meyer, of Copenhagen, in 1868. It was still later before analogies began to be drawn between the various members of the Subepithelial Lymphatic Group. In 1876 Watney described the 3 4 IMMUNITY IN HEALTH lymphatic structure of the vermiform appendix and drew a comparison with the tonsil. Analogies between the tonsils and the vermiform appendix have since been noted by other observers. Ransohoff in 1890 pointed out that both were liable to recurrent inflammatory attacks ; Bland-Sutton added in 1891 that in each of the structures the inflammatory attacks were particu- larly comm6n in early life. Kelynack in 1893 observed '* that the calculi frequently met with in the tonsils are, as far as their inorganic constituents are concerned, practically identical with concretions of the vermiform appendix." Murchison in 1866 described ulceration of the appendix as accompanying ulceration of Peyer's patches in one case of typhoid fever, and many similar cases have been related since. In 1890 Dr. Armand Ruffer showed the presence of micro-organisms undergoing phagocytic destruction in tonsils, Peyer's patches, and vermiform appendix in various animals. (The penetration of Peyer's patches by micro-organisms had been shown five years pre- viously by Ribbert and Bizozzero.) As to their function, it has hardly ever been conceded that the subepithelial glands are of net utility. Darwin in 1874 wrote that the appendix was "useless." Treves in 1885 spoke of "its very slight physiological import- ance," and in 1890 had hardened himself to write it down a^ "useless and functionless." Macewen in 1904 was almost the first to suggest that there might well be a function. Keetley was sufficiently imbued with the idea of a value for the appendix to propose his operation of transplanting the appendix into the abdo- minal wall instead of appendicectomy in certain cases, and Edred Corner (1912) and Keith (1912) have each written favourably of the activities of the appendix, whilst Mackenzie (1912) has taken up the defence of the tonsils. i HISTORICAL 5 Various theories as to the use of the tonsils have been propounded and will be dealt with immediately. But, except for the extravagant idea that they were associa- ted with sexual function (as taught by Chassaignac, according to Mackenzie) the functions proposed have been subsidiary and trivial for the most part. That appendix and tonsils in some w^ay protected the body against alimentary poisons must have oc- curred to a number of thinkers. Adami concedes the likelihood of this. A similar idea has been elaborated by the present writer in several papers in 1911, 1912 and 1913. McCulloch (1913) claims to have anticipated some of these views in 1907. CHAPTER III. Previous Theories as to the Function of the Tonsils and of the Appendix. It is worth while to put aside for a moment the views to be advanced in this book and to consider the previous hypotheses. These hypotheses may be tabulated thus : — (1) That the tonsils and appendix are ontogenetic or phylogenetic remnants. Darwin (1874) strongly urged that the vermiform appendix was a vestigial organ, a dangerous and useless relic, which unfortun- ately had not yet been eliminated by the process of natural selection. The idea has always received a large measure of support and demands careful examin- ation. A structure is said to be vestigial when it ceases to perform any service useful to the individual. It repre- sents some structure the homologue of which has been of value at some period in ancestral history and which itself may be useful to the individual at some stage of development. Two instances may usefully be given. The actions of the small intrinsic and extrinsic muscles of the pinna of the ear are practically negligible. In some remote progenitor of man they were probably as helpful in picking up and locating noises as they are in the horse to-day. Meckel's diverticulum — of inconstant occurrence in the adult — is another vestige, representing perhaps a primitive intestinal arrange- 6 PREVIOUS THEORIES 7 ment and one which has a direct nutritive function during a part of embryonic life. True vestigial struc- tures are not numerous. An organ of no value becomes a direct encumbrance and will tend to hinder its owner in the struggle to perpetuate its kind. Still the muscles of the auricle and Meckel's diverticulum must be admitted as examples. Is the vermiform appendix such another ? In favour of so regarding it, several observations are made. It varies greatly in size, in position and in the mode of its junction with the caecum. These points however are of little weight : the spleen is more variable in size, all other mesenterial organs vary as much or more in position : whilst in connection with the third point it must be remembered that slight arrests of development are liable to occur even in the most important parts of the body. It is said that the blood supply is poor and hence the occasional gangrene of acute appendicitis. But the intense congestion seen in catarrhal appendicitis com- pletely negatives such a view. In fact the gangrene which may occur is the result of the virulence of the infecting organisms and the absence of collateral cir- culation rather than of the meagreness of blood supply. It is said that retrogression is evidenced by. Its being smaller than other part's of the caecum. Actually, though its lumen is smaller its walls are much thicker and more complex in structure. But the two most important witnesses to be interro- gated are Comparative Anatomy and Embryology and their evidence will be taken later (Chapters VIII. and XI.). Suffice it here to say that the tonsil is homologous with a mass of lymphoid tissue in the internal cleft recess of some of the earliest vertebrates, and that the appen- dix is homologous with the lymphoid mass at the apex of the primitive form of caecum, and that in man they show a more highly developed structure than in most 8 IMMUNITY IN HEALTH mammals and one that only attains its full form late in development. The vermiform appendix and the tonsils therefore neither represent a persistent foetal structure as does Meckel's diverticulum, nor do they exhibit the atro- phied condition of the muscle of the external ear. More- over, unlike these relics, they are so often the point of serious disease that they could hardly be expected to Fig. 2. Microscopical section of a human vermiform appendix Avith com- plete obliteration of the lumen, showing large thick-walled blood vessels, fat-spaces and fibrous tissue in place of the mucous membrane and lumen. The tunica serosa and the two muscle coats are not specially abnormal in appearance. (From a camera lucida drawing.) survive if their presence had no counterbalancing ad- vantages. Treves, in his classic Hunterian Lectures of 1885, stated that he never found congenital absence of the human appendix,^ but in three out of one * The Morphological Museum of Columbia University contains two apparently genuine specimens of congenital absence of the human vermiform appendix (see Huntington). But the condition is extremely rare. PREVIOUS THEORIES 9 hundred cases examined, he noted that the lumen was obhterated. There is excellent reason to-day for saying that occlusion of the appendix is the result of old in- flammation. This is seen in the microscopical section of an obliterated appendix. (Fig. 2.) Treves then wrote, "Such specimens may be of interest in connec- tion with the question as to whether the appendix has a function or is functionless," seeming to suggest that these cases argued against the possession of any useful function. As a matter of fact, they point the other way. In a large workshop you may find three per cent, of the men with stiffened or amputated fingers, but it would be the reverse of the truth to infer that fingers were therefore useless. (2) I'hnt the tonsils and appendix secrete a lubricat- ing mucus which facilitates deglutition in the one case and the passage of fxces in the other. This is hardly worthy of serious consideration, for a knowledge of their histology shows that the appendix in man could produce relatively little mucus, and the human tonsil practically none. (3) That the tonsils and appendix form some of the colourless corpuscles in the blood. This is undoubtedly true, though probably only an incomplete expression of their activities. (4) That the tonsils and appendix produce internal secretions. What these internal secretions might be has never been clearly defined, though Savini in 1914 brought forward evidence of an appendicular hormone having an excito-motor influence on the large intestine and some evidence of glycolytic action by the tonsils has been adduced (Farmachidis & Vatterone, 1913). Perhaps we are to regard the lymphocytes in some sense as an internal secretion. But a suggestion in this connection is made subsequently (end of Chapter V.). 10 IMMUNITY IN HEALTH (5) That the lyrnphoid tissues of the tonsils and appendix represent harriers protecting weak spots against bacterial invasion. These regions are often ex- posed to bacterial assault ; moreover, chronic bacterial attacks in any part of the body lead tt) the accumula- tion of lymphocytes and even the production of lymphoid tissue. But the epithelium which is usually a sufficient protection elsewhere also lines these regions. Nor do sore throat's seem more common after complete enucleation of the tonsils. Doubtless the full develop- ment of these subepithelial lymphatic glands in the individual is stimulated by bacteria, but the perpetua- tion of the lymph nodes in the race is probably the result of other functions of greater utility. (6) That the tonsils and appendix are purely mis- chievous ^ acting as "portals of entry^^ and chronic focuses of disease. In pathological circumstances they do so act (Gouget, 1912), as indeed do other parts of the body in diseased states. But this does not disprove any useful function under physiological conditions. (7) That the tonsils and appendix produce lympho- cytes, which pass into the lumen of the alimentary tract and there keep down the numbers and restrain the activities of the bacteria. Lymphocytes containing ingested bacteria may be found in the mucus on the surface of the tonsils, in the saliva and in the lumen of the appendix. It is most likely also that the body in some way, and to a certain extent, can control bac- terial activity in the alimentary canal. Yet when one considers the very small number of lymphocytes and the myriads of bacteria, the conception is no longer plausible. (8) That distension of the appendix initiates peri- stalsis in the large ifitestine. To quote Adami and McCrae (1914), '* The fluid contents of the ileum pour into the caecum, and there and in the ascending PREVIOUS THEORIES 11 colon undergo inspissation prior to their discharge per anum. In other words the caecum and ascending colon have physiologically to undergo great variation in the volume of their contents. It would be to the detriment of their functions were they to be acutely susceptible to pressure changes, were they to undergo peristalsis and void their contents immediately they became filled from the ileum. We must regard them thus, as in the normal state distinctly irresponsive to pressure effects. It is the appendix we hold that is the hydrostatic agent initialling peristalsis in the large gut. In it we have a narrow tube, with no such pronounced variations in calibre, so situated that the weight of the column of forming faeces is communicated to it, and we presume that when this weight reaches a certain point, the dis- tending force acting upon its walls, originates muscular contractions which spread directly into the caecum and so initiate the forward movement of their contents. Such a view explains the tendency to constipation in the bed-ridden, in whom the gravitational effect of the contents of the ascending colon can have little effect; it explains the normal tendency to empty the bowels, either shortly after rising and assuming the erect posi- tion or after the first meal when stimulating peristalsis of the small bowel has driven extra contents into the caecum and so increased the load, it explains the con- stipation that tollows some interval removals of the appendix." This view takes no account of the lymphoid tissue in the wall of the appendix, of the presence of the ap- pendix in many four-footed animals, nor of the import- ance of the ileo-caecal sphincter in initiating peristalsis of the large bowel. Moreover the usual experience is that appendicectbmy tends to relieve rather than to cause constipation. CHAPTER IV. General Question of Immunity. Warfare is a necessary condition of existence. The striif^gle is not only between different animals of like size but also between the largest of animals and the smallest of microscopic bacteria. The weapons of defence in the two instances are, however, different : teeth, horns and claws for the one foe ; antiseptic secre- tions and phagocytic cells for the other. The anti-bacterial weapons are produced for the most part in certain restricted areas of the body and distributed throughout the blood stream. The chief anti-bacterial factories are the spleen* (Luckhardt and Beckt, 1911), the marrow and the lymphatic glands. These three are normally concerned in the destruction of waste products (poisons arising within the body), the first two concerned with purifying the blood, the third with purifying the lymph. * When bacteria and their toxins (poisons introduced from outside the body) appear on the scene it is natural that their removal should fall to these same organs, which react by a great excess production of anti-toxins, bacteriolysins and specially equipped leucocytes which pour into the blood stream to the general pro- tection of the body. * And other haemo-lvniph glands. 12 CHAPTER V. Healthily Acquired Immunity. It is an arresting fact in medicine that some degree of immunity may be acquired by mere contact with cases of an infectious disease without an obvious attack. This may be called healthily acquired immunity.* Thus, the protection of those who have never contracted the disease and yet seem immune in spite of exposure to infection is high where the disease has been rampant previously. Conversely, in "virgin soil," i.e., a com- munity not previously exposed to infection, the ravages have been widespread and excessive, and very few persons have escaped. Quite recently there was an instance of this on the island of St. Kilda, in the Outer Hebrides (Hall, 1913). On the arrival of the fortnightly boat from the mainland an epidemic of influenza broke out and all the inhabitants with the exception of six elderly persons were struck down within a few days. There are many similar experiences in epidemiological records (see articles in Encyclopsedia Britannica) the rapid and terrible spread of " Russian " influenza in 1890; the introduction of measles into the Faroe Islands in 1846 (three-quarters of the population being attacked within six months) ; and the similar epidemic in Fiji in * Immunity may be inherent; or it may be acquired, either by arti- iicial or by natural means. Immunity may be acquired naturally either in a healthy physiological way (where the patient does not exhibit the disease), or in a pathological way (where the patient suffers from the complaint). 13 14 IMMUNITY IN HEALTH 1875 (when 27 per cent, of the inhabitants succumbed in the space of three montlis) ;* and the spread of phthisis amongst the South African Kaffirs. Indeed, it is a general rule that the first epidemic of any disease in a community is the most virulent, each successive outbreak conferring certain immunity even on those not apparently attacked by the disease.! It has also been recorded by Arctic explorers that after a prolonged healthy sojourn in isolation, the return to civilisation was marked by exceptionally severe colds. It may be recalled, in this connection, that immunity against coryza is of short duration. When there is an outbreak of scarlatina in a family or school, some members will escape the illness though freely exposed to infection. Such children may have experienced a slightly increased redness of the tonsils, but nothing which can fairly be called scarlatina. This subject has been investigated of late years by bacterio- logical methods, and it has been found that many of these ''contact" cases, who have never suffered from an attack of the infectious disease, carry the virulent organisms in their throat's and alimentary canals with apparent impunity. These persons form one class of the so-called "healthy carriers" of infectious diseases which constitute such a difficult problem for the Medical Officer of Health to solve. These immune carriers often outnumber the cases of disease ; in epi- * Butler gives an account of the epidemics of measles in Fiji and the Faroe Islands, and refers to similar outbreaks in "virgin soil " on tlie banks of the Amazon, among the natives of Astoria, among the North American Indians, among tlie Hottentots, and among the natives of Tasmania. t It is only fair to point out that some of the extra virulence of an epidemic in a " virgin " community may be due to the early picking out of those individuals below the general average of resistance. Later when the most susceptible individuals have suffered from the disease the epidemic becomes less violent. It is, however, unlikely that this factor alone is responsible for the dying down of epidemics. HEALTHILY ACQUIRED IMMUNITY 15 demic cerebro-spinal meningitis they may be ten times as numerous (Ledingham, 1912). So that of every eleven persons whose throats are reached by the menin- gococcus ten are enabled to resist any general invasion of their bodies. In what way have they become im- mune ? At first one might imagine that they had all suffered from very mild infections of the blood stream. But when their blood has, at times, been examined, no agglutinins have been found such as are present in the blood stream of convalescents. One is tempted, then, to look elsewhere, and reasons will be given for saying that i7n7nunity has been acquired through the agency of the subepithelial lymphatic glands, often, perhaps, without any invasion of the blood stream at all. It is perhaps the general view of bacteriologists that the immunity acquired against an infectious disease by contacts who have not obviously suffered from the ill- ness is due, nevertheless, to an invasion of the blood stream by the causal organism. There is evidence that this is sometimes the case. But whether the infecting organisms reach the blood or not, there is, in the light of evidence adduced in subsequent sections, good reason for supposing that the infecting organisms are first drawn into the subepithelial lymphatic glands. Anti- bacterial substances and specially provided lympho- cytes are formed in the subepithelial lymphatic glands and pass into the blood stream. It is true that the lymphocytes do not provide the chief reaction to all acute infections. Nor is it usually considered likely that the lymphocytes are transformed later into poly- morphonuclear leucocytes.* Yet the ingestion of bacteria in enormous numbers by the subepithelial * Some observers, however, have considered that the natural fate of Ivmphocytes is conversion into polynuclear leucocytes (see Gruner, 1913). IG IMMUNITY IN HEALTH lymphatic glands must surely confer some measure of protection. And, perhaps, some of the ingested and consequently attenuated organisms pass via the sub- epithelial and interstitial lymphatic glands into the blood stream and so to those other manufactories of anti-bacterial weapons, namely — the red marrow and the spleen. CHAPTER VI. Alimentary Immunity, And it is proposed to argue that not only have these glands a prophylactic tendency against infectious disease such as scarlatina, measles, variola, diphtheria, whooping cough, influenza, acute anterior poliomye- litis, epidemic cerebro-spinal meningitis, rheumatic fever and typhoid fever ; but also that to these glands man owes his protection against most of the bacteria in his alimentary canal. The high degree of tolerance that man displays towards the teeming denizens of his intestines has often been noted as a remarkable fact. Streptococci, pneurhococci and diphtheroid bacilli are almost constantly present in the throat ; coli bacilli swarm in the intestines ; one half of the w^eight of the faeces is contributed by the bodies of micro-organisms (Starling, 1912). All these, it will be here alleged are rendered impotent for evil at least partly because the body is forewarned and forearmed by its outpost forts of lymphoid tissue. Of course, the living epithelium of the alimentary tract is in itself a formidable barrier. But when that is passed the body is still capable of disposing of considerable numbers of intestinal bac- teria, unless it is hindered by mechanical or chemical irritation. Many a surgeon has marvelled at the bac- tericidal powers of the peritoneum in cases of wounded 17 • 18 IMMUNITY IN HEALTH intestines if only the gross pieces of faecal material have been removed. And many a physician must have wondered at the comparative harmlessness of coli bacillaemia as evidenced by even extreme degrees of coli bacilluria. * It may be noted, too, that the alimentary tract alone i^ exposed to the bovine type of tubercle bacilli, and that the incidence of bovine infection diminishes with increasing age. CHAPTER VII. Distribution of the Subepithelial Lymphatic Glands IN Man. It will be in order to commence an account of the subepithelial lymphatic glands by describing their an- atomy. They are nearly all distributed along the course of the alimentary canal,* situated directly be- neath the epithelium, but often in some " backwater " or diverticulum and lying especially in those sections, namely, throat, ileum, and caecum where bacteria •' most do congregate." The following is a list of the subepithelial lymphatic glands in the human body, given in the order in which they are met with in passing along the alimentary tract from mouth to anus. Faucial tonsils. Each faucial tonsil projects medially into the isthmus faucium between the anterior pillar (arcus glossopalatinus) in front and the posterior pillar (arcus pharyngopalatinus) behind. The embedded por- tion includes the great bulk of the gland and is en- * Lymph nodes occur along the larger air passages in the normal mannnalian lung especially at the points of division of the bronchial tubes. Hut for the most part they lie outside the muscidar layer and often outside the cartilages (Miller, lf)ll). A nodule may, however, at one point reach directly to the ciliated columnar epithelium as is sliown in the figure of a beautiful preparation by Klein, 187.3. fivrnph nodules also occur sparingly in the laryji^. (Hands, analogous to lymphoid follicles, and called by Henle " trachoma " glands are found in the conjunctiva, and, according to Strohmeyer, are chiefly situated near the medial palpebral commissure. They were first des- cribed by Brush in his description of Peyer's patches of the small intestine as identical structures existing in the under eyelid of the ox (Gray, 1916). These trachoma elands would be better known as " conjunctival " subepithelial lymphatic nodules. 19 20 IMMUNITY IN HEALTH closed in a connective tissue capsule. Laterally it rests upon the superior constlrictor of the pharynx. The greater portion of the free surface tends to bulge in- wards, but at the upper part is a small depression thinly surrounded by lymphoid tissue (Hett). This used, wrongly, to be known as the swpratonsillar fossa but should be called the tonsillar recess.^ From the free surface some ten to twenty crypts or lacunae pass into the tonsil and reach almost to the capsule (Foster, 1912). During deglutition the two faucial tonsils are squeezed towards the middle line thus coming into in- timate contact with the saliva, the mucus or the bolus of food.t The lingual tonsil includes the small masses of lym- phoid tissue at the posterior part of the dorsal surface of the tongue. This part also is pressed into close con- tact with any swallowed material. The crypts are said to be lined with columnar epithelium, partly ciliated and partly goblet cells (Browne), but the sections I have seen showed stratified epithelium only. (See also Sobotta.) The nasopharyngeal tonsil hangs in thick folds from the roof and posterior wall of the nasopharynx. A specially deep cleft separates the right and left halves of the organ. The epithelium covering it is ciliated columnar or stratified in type. Mucus from the nasal * It is possible that we should homologise the tonsiUar sinus in man running forwards deep to the plica triangularis and not the supratonsillar fossa with the tubular part of the tonsil in such animals as the rabbit. (See Chapter VIII.) t Dr. Griffith thus expresses it :— "Bacteriology teaches that germs of pneumonia, influenza, diptheria, tuberculosis and mild and virulent pus are constant inliabitants in our mouths, and are found thickest on, in and about the tonsils. Due to the fact that in every swallowing action the toncils are extruded between the flattened pillars of the pharynx, these organs act their function by screening over the crypts the organisms swept by in the food mass and strain the salivary stream of hosts of microbes as cobbles clean a brook." DISTRIBUTION 21 fossae which trickles or is sniffed backwards comes in contact with its surface, or is brushed on to it from the superior aspect of the soft palate when that is raised. The posterior wall of the oropharyncc presents dis- FiG. 3. Diagram showing the Circumpharyngeal King of I^yniphoid Tissue (Waldeyer's Ring). N. Naso-Pharyngeal Tonsil. F.F. Faucial Tonsils. L. Lingual Tonsil. Crete lymphoid patches, which may however be re- garded as outlying portions of the nasopnaryngeai tonsil. Some lymphoid tissue is said to occur about the lower end of the tuba audit iva. Lymphoid tissue only occurs very sparsely in the oesophagus (Sobotta). 22 IMMUNITY IN HEALTH The pyloric division of the stomach presents a num- ber of solitary lymphatic nodules which become more numerous as the pyloric sphincter is approached and which continue into the proximal part of the duo- denum. A special patch it is said often exists near the entrance to the common bile duct. The noduli lymphatici aggregati {Peyer^s patches) et solitarii of the small intestine occur in the jejunum but are more frequent in the ileum especially towards its lower end. The lymphatic nodules when single are termed solitary and are irregularly dispersed, but when collected together they form oval patches (^ to Ij inches long) with their long axes in the axis of the bowel and invariably situated on the side of the intestine remote from its mesentery. It is said that from twenty to forty-five of these patches may be found (Quain, 1912). The last one is situated a short distance from the ileocaecal valve. They are not always easy to see with the unaided eye. When inflamed or active they may be more obvious from the peritoneal than from the mucous aspect. The vermiform process (vermiform appendix) is a blind tube one to six inches in length. Grayer has recorded one over twelve inches long (Lockwood, in AUbutt's System of Medicine). Its walls are thick, and as much as half the thickness may be due to the lymphoid tissue beneath the mucous membrane. The lumen is small and contains a little material which is similar to the contents of the caecum. The appendix opens into the left side of the caecum about one centi- metre below the ileocaecal valve, but that it represents the original apex of the caecum is shown by the con- tinuance to it of the taeniae coli. A moment's considera- tion will show that the lymphoid tissue in the appendix is situated on the side of the large bowel remote from DISTRIBUTION 23 its original mesentery and therefore sttictly homologous with the Peyer's patches (Fig. 4). The vermiform appendix is able either to fill itself from, or empty itself into, the caecum. I'he noduli lymphatici solitarii oj the large intestine are scattered throughout from the caecum to the rec- tum. A large patch is said to occur at the junction of the rectum and anal canal. Fig. 4. J3iagram of Lymphoid Tissue near the Ileo-Ca?cal Junction, iUus- trating- the serial homology of the lymphoid tisue in the vermiform piocess (appendix) ^vith that of the noduli lymphatici aggregati (Peyer's patches). The most significant fact in connection with the dis- tribution of these subepithelial lymphatic glands is that they are found wherever bacterial activities are great- est. There are certain frontiers of the body which are weak spots from the point of view of bacterial invasion. The dry skin with its dense layers is usually a sufficient Pig. 5. Diagram of tlie Human Alimentary Canal. The shading marks those parts where bacteria flourish most abundantly. The crosses mdicate roughly the positions of the subepithelial lymphatic nodules DISTRIBUTION 25 barrier for the external surface of the mammal ; the nasal filtering of the inspired air and the ciliary action in the air passages sterilise the inspired air and protect the lungs : but the alimentary tract is only lined by a mucous membrane which is thin, delicate, moist, ab- sorbing and in continuous contact at many points with hordes of hostile bacteria. The alimentary lining is clearly the anxious frontier, at some points being weaker than at others. At the fauces come first the fresh organisms in food and drink and also from the dusty or spray-laden atmosphere, and here they colon- ise and multiply. The oesophagus is safer^ as material does not remain in contact with its walls. In the stomach the acid secretions of the cardiac portion numbs or destroys the bacteria, though the activity is less pronounced towards the pylorus. The alkaline contents of the small intestine are readily decomposable and swarm with micro-organisms. In the lower half of the duodenum and upper part of the jejunum the bac- teria are still not very active but towards the lower end of the ileum the longer incubation causes increase in their numbers and activity. Here the frontier is greatly threatened. The caecum with it's very infective fluid contents is in like case, but the walls of the colon and rectum are less menaced, for the inspissation of the fseces does not favour bacterial activity. It is in these dangerous localities — the fauces, the ileum and the caecum— that the subepithelial lymphoid tissue is developed (Fig. 5). Though widely scattered, this tissue is not insignificant in amount. If the human faucial, naso-pharyngeal and lingual tonsils, the soli- tary and the aggregated lymphatic nodules, and the vermiform appendix were massed together, they would form an organ of some bulk. It should be noted, however, that the subepithelial lymphoid tissue does not form a complete covering for t>r» IMMUNITY IN HEALTH the weak places. Such a disposition would, indeed, interfere with the absorption of food. The frontier is defended, not by a wall, but by a chain of forts which draw the attack. There are two apparent exceptions to the rule that the subepithelial lymphoid tissue occurs wherever bac- teria are most abundant. The fore parts of the nasal fossae strain off most of the inspired bacteria, yet there is no tlonsil in the front of the nose. In health, how- ever, the bacteria do not multiply in the nasal mucus. Moreover lymphoid tissue being so prone to enlarge would frequently block the air way, as indeed adenoid tissue often does even in the much wider nasopharynx. The point is referred to in a subsequent Chapter (XVI.). Similarly, the mouth, which always contains patho- genic organisms and is extremely liable to septic in- fections (for example, decayed teeth) is devoid of lym- phoid tissue. But it must be remembered that the buccal cavity is lined by thick stratified epithelium and not by a delicate columnar layer. And, of course, the faucial tonsils are immediately adjacent. It may be noted before closing this section that the thymus appears originally as subepithelial lymphatic tissue about the third internal cleft recesses and is thus serially homologous with the faucial tonsils. It soon, however, migrates, losing its connection with the pharynx, though epithelial remnants in it persist as " Hassal's concentric corpuscles." CHAPTER VIII. Comparative Anatomy of the Subepithelial Lymphatic Glands. It is not easy to obtain accurate data on this branch of the subject. Sohtary and aggregated lymphatic nodules vary much in size and visibility according to their activity and the age of the individual. It is often impossible to distinguish human Peyer's patches with the unaided eye. . Microscopical assistance is necessary : yet very little histological investigation has been imdertaken. The following imperfect account of the comparative anatomy of these glands has been drawn largely from the facts recorded by Berry (1895 and 1901), Hunting- ton (1903), Stapley (1911) and Seccombe Hett and Butterfield (1910 and 1913), which have in some in- stances been confirmed by the present author. The three main groups — namely the iaucial, the ileal and the csecal — are represented in most if not all the higher animals. Each group must be considered in turn. The Faucial Group is arranged round the fore part of what represents the primitive pharynx. In the walls of the fish's pharynx, which is highly developed sub- serving gill respiration, wandering amcebocytes can be seen, and " thymus glands " have been described in the dorsal diverticula of all the gill slits. 27 28 IMMUNITY IN HEALTH However I have not found any clear evidence that definite lymphatic glands — whether interstitial or sub- epithelial— ever occur except in birds and niammals.* Anyhow it is in Ihe internal cleft recesses and the corre- sponding parts of the roof and floor of the embryonic pharynx that the faucial group of lymphoid collections develops, at least in mammals. The faucial tonsils usually retain more or less evi- dence of their origin from the second internal cleft recess. Mammalian tonsils t may be roughly divided into two classes : the first, where the principal feature is a protuberant mass of lymphoid tissue partly pro- jecting into the throat ; the second where the principal feature is a blind tube or recess lined by lymphoid tissue and running backwards to open into the throat. (Fig. 6.) But the distinction is one of degree rather than of kind ; for in the projecting tonsils some depres- sion is usually found in the upper part, whilst in the tubular tonsils the lower lip of the orifice is thickened with lymphoid tissue and pouting. Projecting tonsils occur in the following animals : — Man (Homo Sapiens), Gorilla (Gorilla Savagei), Gibbon (Hylohates), Hippopotamus (Hippopotamus Aniphibius), Dog (Canis Fajniliaris), Hairy armadillo (Dasypus Villosus), Mouflon (Ovis Miisman). Tubular tonsils occur in the following animals : — Grivet Monkey (Cercopitheciis Griseo-viridis), * " Specimens of the intestinal canal of both the Skate and the Common Frog have been examined, but did not show any evidences of lymphoid tissue,'' (Berry, 1901.) t Mr. Hett found that no tonsil was to be found in a few mam- mals— the Rat, the Beaver, the Porcupine and the Bat, but he showed that the great majority of mammals possessed tonsils. Diagram showing A, of Faucial Tonsil; and of Caecal Tonsil. Fig. 6. the Protuberant, and B, the Tubular types 0, the Protuberant, and D, the Tubular types 30 IMMUNITY IN HEALTR Cat (Felis Domestica), Leopard (Felis Pardus), Cow (Bos Taurus), Rabbit (Lepus Cuniculus), Civet (Viverra Civetta), Tasmanian Devil (Dasyurus Sp.), Opossum (Didelphys Carnivora). Many intermediate forms are to be found in other animals. The nasopharyngeal tonsil has been traced in mam- mals, birds, and even reptiles, according to St. Clair Thompson, quoting Alagna (1902). In man the lymphoid tissue principally hangs from the roof and posterior wall as already described. This is not the case in all animals. In the sheep family the surface of the hinder part of the septum nasi is ridged and nodulated by the presence of masses of lymphoid tissue constituting the septal nasopharyngeal tonsil. Excellent specimens, presented by H. Seccombe Hett, Esq., illustrating some of the above points, may be seen in the museum of the Royal College of Surgeons, London. The Ileal Group of lymphatic tissues is probably of widespread occurrence. Huntington (1903), however, states that both aggregated and solitary follicles only occur together in mammals, and that solitary follicles alone only occur in birds. The aggregated patches, as in man, occupy the side of the bowel remote from the line of attachment of the mesentery. Stapley (1911) states that in pigs a continuous elongated patch six feet' in length is to be found. In the rabbit a specially large collection of lymphoid tissue is found stretching for an inch or so immediately above the ileo-caecal valve. It sometimes nearly encircles the bowel at the extreme end of the ileum. Immediately beyond the ileo-caecal sphincter is another patch of about the same COMPARATIVE ANATOMY 81 area with its long axis disposed at right angles to the ileal patch. (Fig. 23.) A terminal branch of the ileo- caecal artery marks the ileo-csecal junction on the ex- terior and sends twigs to both patches. The lymphoid tissue massed in the csecum however usually occurs at its apex and is present in very many different species. And the form in which it presents itself seems to be associated with the animal's diet rather than with the position of the species in the zoological scale. The caecum is the proximal part of the large intestine. Its walls secrete no . digestive juices and one of its chief functions seems to be that it provides a recep- tacle in which digestion by bacterial action can be carried on. The normal alimentary juice of higher animals can break up all food substances with one exception — namely cellulose. The body can deal satis- factorily with protein, carbohydrate and fat without bacterial assistance so long as these foodstuffs are not enclosed in cellulose envelopes. In cows and other herbivora, known as ruminants, bacterial decomposition of the cellulose takes place while the food is incubated in the pouch or first stomach. Then the food is chewed once more and swallowed, finally, a second time. In rodents such as the rabbit the bacterial decomposition of the cellulose takes place in a truly enormous caecum provided with a number of spiral folds increasing the area for ab- sorption. In carnivorous animals the proximal part of the large intestine is of small size. Thus in the same class of animals one may find varying degrees of caecal development correlated to some extent with the diet of the particular species. Furthermore, it may be added, analogous modifications 32 IMMUNITY IN HEALTH appear in genera so widely separated that quite inde- pendent though similar origins must be assumed. The different types of junction of the small and large intestines. Type A. — The junction of the large and small intes- tines may be hardly apparent, or may be indicated only by a change of calibre, an external constriction or an internal valve. Most fishes. Most amphibians, Most reptiles, A few birds, e.g., the Parrot, Some carnivorous marsupials, e.g., the Tasmanian Devil (Dasyurus Viverinus or Sarcophilus Satan- icus), Some edentata, e.g., the Three-toed Sloth (Bradypus Tridactylus), The Laughing Jackass of Australia (Dacelo), Most Whales, Bears, Bats, Weasels. Type B. — In addition to demarcation of the junction, the proximal part of the large intestine is dilated, chiefly by a bulging of the antimesenterial border, to form a single pouch or caecum. This single caecum is of small size in : — • A few fishes, e.g., the Dogfish (Scyllium Canicula), Some reptiles, e.g., the Indian Python, A very few birds, e.g., the Heron, Some monotremes, e.g., the Platypus (Orintho- rhynchus), Many carnivorous mammals, e.g., Cat (Felis Domes- tica), and Dog (Canis Familiaris), Man. The single caecum tends to be larger in ; — COxMPARATIVE ANATOMY 33 Most herbivorous mammals, e.g., Sheep, Horse, Elephant, Some prhnates, e.g., the White-handed Gibbon (Hylohates Lar), and the Orang-outang {Shnia Satyrus), The single caecTum is relatively largest of all in the rodents, e.g., the Rabbit (Lepus Cuniculus), Tyj)e C. — In addition to demarcation of the junction, the proximal part of the large intestine presents bi- lateral ca?ca.* These are present in a few mammals : — Some xlrmadillos, e.g., Dasypus Sexcintus and Clainydophorus, The Little Anteater (Cyclothurus Didactylus). The Manatee (Manatus A'inericanus) presents a bifid c«cum. The bilateral type of csecum is almost constant in birds. The Heron is an exception. They are however very small indeed in the Wedge-tailed Eagle (Aquila Aitdax) and the Lyre Bird (Menura Victoria), Gener- ally speaking the caeca are short in carnivorous birds, for example, the Crow (Corvus Corone), and much longer in herbivorous ones. Long caeca occur in : — The Ostrich (Struthio), The Pheasant (Phasianus). The Duck (Anas), The Goose (Anser), The Swan (Cygnus), The Peafowl (Pavo), The Bustard (Otis), and others. The proximal part of the large intestine nearly always contains subepithelial lymphoid tissue at any rate in birds and mammals. Thus it is foundt in the bilateral * A curious animal, the Hyrax, shows both a juxta-ileocaecal caecum and also a pair of more distant caeca. But this is quite exceptional. t I have sectioned the rectal gland of the Do2:fish and the pyloric ca'ca of other fishes. These, however, do not exhibit lymphoid tissue. c 34 IMMUNITY IN HEALTH caeca of birds (Fig, 7) and m the single caecum of such animals as possess one.* Fig. 7. Microscopical section of the small intestine and the two caeca of a pigeon, showing masses of lymphoid tissue in the caeca. The smaller ligure shows the line of section. C.C. Caeca. S.J. Small intestine. L.I. Large intestine. The lymphoid character of the pigeon's caeca is also depicted in plates illustrating Dr. Berry's paper (1901). Considering the case of lymphoid tissue in the single csecum one finds, here also, that the different types presented are associated rather with dietetic habits than with phylogenetic position. Class A, — The simplest type consists of a mass of lymphoid tissue at the apex of the caecum slightly * Berry sectioned the caecal apex in 32 animals and found lymphoid tissue at or near the caecal apex in all warm blooded animals w ith only one or two exceptions. I COMPARATIVE ANATOMY 35 bulging internally into the lumen. This may be called the caecal tonsil and is characteristically present in the slightly developed caeca of carnivora. It is seen in : — The Dog (Canis Familiaris), The Cat (Felis Domestica), The Lion (Felis Leo), and others. Clasfi B. — The development of the lymphoid appen- dix is a further elaboration. The apical portion of the caecum tapers gradually or, in its highest modifications, is of uniformly small bore being sharply demarcated from the rest of the caecum. It' is interesting to observe that the lymphoid tissues in the fauces and in the caecum each present themselves, dt one time as a bulging mass, at. another time, as a blind tube. (Fig. 6.) The vermiform appendix is of far more widespread occurrence than is generally recognised.* It attains its maximum size and complexity in the rodents, which also exhibit the highest development of the caecum. A well-developed vermiform appendix (or to avoid disputes as to terminology, a caecal apex with reduced" lumen but with lymphoid tissue in its walls) is to be found in the following species : — Most rodents, e.g., Rabbit (Lepus Cuniculus), Fig. 23; Hare; Lagomys PusilluSf't Fig. 8; Beaver (Cas- tor Fiber), Fig. 9 ; Canadian Porcupine (Ery- thrizon Dorsatus), Fig. 10. * At the Royal Society of Medicine in 1916 the following mis-siate- ment : "No mammals other than man have a caecal appendix except apes " occurred in a paper read before the Pathological Section. t This animal possesses two adenoid vermiform appendages, one close to the ileum and the other at the apex of the caecum. Some rodents present two lymphoid areas in the caecum, one immediately beyond the ileo-caecal sphincter, the other at the apex of the caecum. Anparently in this animal both areas have become converted into blind tubes. 36 IMMUNITY IN HEALTH A few ungulates, e.g., Peccary (Dicotyles), Fig. 11; Tapir (Tapirus Americayius), Fig. 12. Same marsupials, e.g., Vulpine Phalanger (Tricho- sums Vulpinus), Fig. 13 ; Koala* {Phascolarctus Cinereus), Fig. 14 ; Wombat (Phascolymis Wom- bat), Fig. 15. ^ Most lemurs, e.g.. Lemur Macaco (Figs. 16 and 17). All the anthropoid apes, Orang (Fig. 18) ; Gibbon (Fig. 19); Chimpanzee (Fig. 20); Gorilla (Fig. 21). Man (Fig. 22). A less well developed appendix also occurs in many other animals, such as the Puma, the Civet, and the Ichneumon. * It must be admitted that the presence of lymphoid tissue has not been demonstrated in every instance in this Hst so far as I am aware. That the apex of the caecum contains lymphoid tissue in its walls in almost all mammals has however been shown by Berry. Stapley, on the contrary, declares that the koala's ca?cum (in which term he includes the appendix) contains no lymphoid tissue. He also failed to find lymphoid tissue in two out of three wombats' appen- dices which were sectioned. He does not, however, mention vhethcr the wombats were old or young, and in this connection the atroph\ of lymphoid tissue after puberty and its fibrosis following inflamma- tion must be borne in mind It should perhaps be added that Staplev's general conclusions as to the form and nature of the appendix are quite opposed to those supported here. i COMPARATIVE ANATOMY 37 Fig. 8. C^:cAL Apex with Small Lumen. Lagomys Pusillus, a rodent (after Pallos, reproduced by Huntington.) I. Ileum. C. Caecum. A. Appendix. E. Extra appendix. I /. Ileum. C. Caecum. A. Appendix. Fig. 9. C^CAL Apex with Small Lumen. Castor Fiber, the Beaver (after Huntington). BS IMMUNITY IN HEALTH Fig. 10. C^.CAL Apex with Small Lumen. Erythizon Dorsatus, the Canadian Porcupine (after Huntington), /. Ileum. C. Caecum. * A. Appendix. COMPARATIVE ANATOMY 3d I. Ileum. C. Ca3cum. A. Appendix. Fig. 11. CiiCAL Apex with Small Lumen. Dicotyles Torquatiis, the Collared Peccary (after Huntington). Fig. 12. C/ECAL Apex with Small Lumen. Tapirus Americanus, the American Tapir (after Huntington). /. Ileum. C. Caecum. A. Appendix. 40 IMMUNITY IN HEALTH Fig. 13. C^CAL Apkx with Small Lumen. Inchosurus Vulpinus, the Vulpine Phalanger (after Huntington). /. Ileum. C. Caecum. A. Appendix. COMPARATIVE ANATOMY 41 Fig. 14. CiECAL Apkx with Small Lumkn. Pliascolarctos Cinereus, the Koala (after Huntington). I. Ileum. C. Caecum. A. Appendix. 4> IMMUNITY IN HEALTH Fig. 15. CtXAL Apex with Small Lumkn. IMiascoloinys Wombat (after Hiinting^ioii). /. Jleiim. <'. Caecum. A. Appendix Fig. 16. ('.TiCAL Apia with Small LuiMkn. Lemur Macaco, the Lemur (after Iluntiu.utou). COMPARATIVE ANATOMY 43 I. Ileum. C. CaEcuni. A. Appendix. Fig. it. C.TXAT. Apkx with Small Lumkn. N vcticebiis Tardigradus, the Slow Lemur (after Huntington). 1. Ileum. C. Caecun A. Appendix. Fkj. 18. (Vi'.CAL Ari:x with Small I.umkn. Simia Satyrus, the Orang (after Huntington). u IMMUNITY IN HEALTH Fig. 19. C^CAL Apkx with Small I.umen. Hylobates Hoolock, the Hoolock Gibbon (after Huntington), I. Ileum. C. Ca^'cum. A. Appendix. Fig. 20. C^CAL Apex avith Small Lumkn. Troglodytes Niger, the Chimpanzee (after Huntington). I. Ileum. C. Caecum. A. Appendix. COMPARATIVE ANATOMY 45 Fig. 21. C/ECAL Apex with Small Lumen. Gorilla Savagei, the Gorilla (after Huntington). I. Ileum. C. Caecum, A. Appendix. /. Ileum. C. Caecum. A . Appendix. Fig. 22. CiECAL Apex with Small Lumkn Homo Sapiens, Man. CHAPTER ]X. Structure of the Subepithelial Lymphatic Glands. All lymphatic glands, whether interstitial or sub- epithelial are composed of a number of similar units. Each unit is best called a lymph nodule, but has also been termed a " lymph-follicle " or '' germ-centre." The lymph nodules are the bricks of which the lymph- atic workshops are built. The lymph nodules may roughly be said to average the size of a pin's head each. Each lymph nodule consists of a mesh-work of reti- form tissue amongst which are densely crowded two types of cells. First type. — In the centre of the nodule are found large cells with abundant cytoplasm. The nuclei do riot usually stain darkly. In ordinary haematoxylin- eosin sections the centre of the nodule is much paler than the periphery. These larger clear cells may also be found sparsely in other parts of the nodule. Flem- ming in 1885 described numerous kario-kinetic figures in the nuclei of these large cells and hence he named the nodules germ-centres. These cells possess highly- developed phagocytic powers and may at times be seen to contain soot-particles, bacteria, and even other cells. ~ Second type. — Each cell is small in size with scanty cytoplasm and a round darkly-staining nucleus. It exactly resembles the small lymphocyte found in the blood stream. These cells are far the more numerous, 46 STRUCTURE 47 they occupy the whole of the periphery of the nodule. They appear to be very densely crowded together and this is the more obvious on account of their darkly staining predominant nuclei. The cytoplasm does not stain well with eosin. Whatever the small lymphocytes may be in the blood, they are undoubtedly phagocytic in the subepithelial lymphatic glands as will be shown subsequently. These two classes of cells have been termed macro- phages and microphages (Ruffer), or endothelial cells and lymphocytes. But I prefer to call them large and small glandular lymphocytes. Glandular lymphocyte is a somewhat clumsy name, but although probably the large and small glandular lymphocytes in the glands become the large and small lymphocytes in the blood, it seems incautious to assume it too dogmatically in the nomenclature. The large glandular lymphocytes are, probably, en- dothelial in nature. They have been said to line the reticular meshwork and to correspond with the endo- thelial wall of a lymphatic vessel. It is generally assumed, following Flemming, that, as mitotic figures are frequently visible, the large glandular lymphocytes by division give rise to the small glandular lympho- cytes. The large lymphocytes can reproduce them- selves as large lymphocytes, however, as is seen in Hodgkin's disease (Lymphadenoma). Perhaps the large glandular lymphocyte divides to form either small or large glandular lymphocytes according to its imme- diate environment. Some have described the small glandular lymphocyte as growing into a large glandular lymphocyte, but I think this very improbable. A few of the large glandular lymphocytes escape from the nodules and eventually enter the blood where they form some, at least, of the infrequent large lymphocytes there found. i8 IMMUNITY IN HEALTH As has been said above the small glandular lympho- cytes are probably derived from the large ones in the lymphatic glands. The great majority pass via the efferent lymphatic channels (and perhaps also directly) into the blood where as small lymphocytes they con- stitute twenty per cent, of the total white corpuscles or 1,400 per cubic mm.* Both small and large glandular lymphocytes func- tion principally as scavengers, being provoked to activ- ity by slightly different stimuli, t The large glandular lymphocytes may join together to form giant cells. Sometimes one large lymphocyte engulfs other cells and various debris and attains to a very great size. It may ultimately die leaving an inert pigmented mass in the gland. Lymphoid structures do not everywhere show con- struction of such definite unit elements as is recorded above. Thus in the medulla of an interstitial lymph- atic gland the small and large glandular lymphocytes are mingled indiscriminately. The lymph nodules every- where become less distinct in very old animals (Baum and Halle, 1908). Clearly marked lymph nodules Tnake up the cortex of every interstitial lymphatic gland. They are also placed eccentrically at intervals along the arterioles of the principal haemo-lymph gland, the spleen. Lymph nodules are present singly or in groups in all the siTbepithelial lymphatic glands. After considering this unit-material or element of lymphatic glands, it remains to consider the manner in which these elements are combined to form the different lymphatic organs. * The researches of Goodall and Gulland seem to show that many lymphocytes are also formed in the bone marrow. t It is most remarkable that the glandular lymphocytes are both motile and phaf^ocytic. The small lympliocytes in the blood are usually described as non-motile and non-phagocytic. STRUCTURE 49 In the interstitial lymphatic glands the lymphoid nodules are arranged peripherally beneath the capsule and they are the first to receive the entering lymph. But the subepithelial lymphatic glands are distin- guished by the absence of afferent lymphatic vessels. (According to Lenart, Henke and others, quoted by Pybus, 1915, injections of carmine into the nasal or oral submucosa eventually find their way into the tonsils on both sides. But it is quite possible that escape of the injection material on to the surface might enter the tonsil that way (see Chapter XIII.). An- atomically, anyhow, afferent lymphatic vessels have never been demonstated.) Here the lymphatic nodules lie against the epithelium of the alimentary canal super- ficial even to the muscularis mucosae. So close to the epithelium do they lie that the lymphoid and the epi- thelial cells are commonly mingled. There is a con- tinuous passage of small glandular lymphocytes from the lymphoid nodule through the epithelium into the lumen of the alimentary canal and back again (see further). The solitary lymph gland consists of a single such nodule only. The nodule is drained by an efferent basal lymphatic vessel which leads eventually to a mesen- teric or other interstitial lymphatic gland. A Peyer's patch represents an aggregation of from ten to sixty (Sobotta) lymphoid nodules. Each nodule has one aspect close to the epithelial surface which is here uncovered by villi. The human vermiform appen- dix, according to the late Mr. Lockwood's estimate, may be lined by as many as 150 to 200 lymphoid nodules. In the case of the nasopharyngeal and faucial tonsils the epithelial surface is much folded, thus permitting a great collection of lymph nodules in a small space yet with each nodule abutting the surface epithelium. 50 IMMUNITY IN HEALTH. Thus are produced the tonsillar crypts and the adenoid fissures. The irregularity of surface probably also favours the stagnation of mucus and the growth of cultures of micro-organisms, and it helps to prevent the emigrated lymphocytes (see pp. 68 and 69) being swept away from the surface. The subepithelial glands develop beneath different kinds of epithelium. The intestinal glands are lined by columnar cells, the faucial tonsils have a covering of stratified epithelium and the nasopharyngeal collec- tions underlie a layer of ciliated columnar cells, or stratified epithelium in parts. It may be characterised generally of the larger sub- epithelial glands that — (1) they have a terminal blood supply. Thus Peyer's patches and the appendix are anti-mesenterial ; (2) they have a large surface area ; (3) whether by folding of the surface or by situation along a diverticulum, they are so arranged as to en- courage stagnation of adjacent alimentary contents. CHAPTER X. The Rabbit's Appendix. Undoubtedly the largest and most highly specialised subepithelial lymphatic gland occurs not in man but in the rabbit. The rabbit's vermiform appendix is the particular example taken but the proximal and distal ileo-csecal patches, though smaller in bulk, present a similar complexity of structure. (Fig. 23.) The rabbit's vermiform (i.e. of similar even cylin- drical shape to a worm) appendix measures several inches in length and J in. to |^ in. in transverse section. The wall of this tube feels quite thick. From the peritoneal aspect it is often possible to see with the naked eye the independent lymphoid nodules (really the deeper layer of these) of about the size of a pin's head. Occasionally each nodule is outlined by a just perceptible row of black dots. On the mucous aspect can be seen the orifices of the calyx-like glands. When a transverse section is examined under a low power it is seen that, whereas in man the lymphoid layer rarely forms as much as one-half of the mural thickness, in the rabbit the lymphoid coat constitutes up to nine-tenths, of the total thickness and the mus- cular coats have come to appear relatively as a very narrow band in the section. (Fig. 24.) The lumen of the appendix is filled with bacteria most of which are gram-positive and of unusually large size. Particles of partially digested vegetable food can be distinguished. Glandular lymphocytes are often to be seen in the lumen. These can easily be shown to contain ingested bacteria. 51 IMMUNITY IN HEALTH Fig. 23. Diagram of the cagcum and appendix in a rabbit. The patches of lymphoid tissue at the ileo-caecal junction are also shown. The small figure in the centre shows the lymphoid tissue from the peritoneal aspect as it occasionally appears to the naked eye. In the specimen fiom which this diagram was taken only the caecal part of the ileo- caecal lymphoid tissue showed this appearance. The mucous membrane of the vermiform appendix of the rabbit is lined by columnar epithelium. Many goblet cells are to be seen. At regular intervals the cokimnar epithelium dips down to form a narrow stem and then spreads out dome-wise to form the deeper calyx-like portion of the gland, up into which projects THE RABBIT'S APPENDIX 53 a rounded portion of one of the superficial layer of lymphoid nodules. The projecting portion of the lym- phoid nodule also is covered by the columnar epi- thelium of the calyx-gland, but so many small glandular lymphocytes may be seen amidst the columnar cells that in some places this layer may almost appear to be wanting. Many of the glandular lymphocytes are crowded with bacteria. The superficial lymphoid nodules which project into the calyx-glands contain principally small glandular lymphocytes. Many of these evince their phagocytic ability by the number of ingested bacteria they display. Beneath the superficial lies a deeper layer of lym- phoid nodules. These nodules are much larger in size. Small and large glandular lymphocytes occur and in addition giant cells, the last two kinds being especially crammed with bacteria and carbon particles. Situated basally, near to the periphery of each deeper nodule, may be seen irregular masses which do not take any stains. These are brownish in colour and contain darker particles. These probably represent the indi- gestible debris from the omnivorous phagocytic activity, either lying in an efferent lymphatic space or deposited more permanently in some interstices of the gland. I have often traced intermediate appearances between the giant-cell and these inert masses. Some- times these masses are so large as to be visible t'o the naked eye, presenting those dotted rings on the serous aspect to which allusion has already been made.* It is perhaps not unfair to compare the superficial layer of lymphoid nodules of the rabbit's appendix with the cortex of an interstitial lymphatic gland ; and the deep layer of nodules with the medulla of an inter- stitial lymphatic gland. * Similar patches of pigment have been described by Professor Shattock (1916) in the human appendix. Fig. 24. Diagram of a Calyx Gland in the Rabbit's Appendix. 1. Lumen of appendix. 2. Neck of calyx crypt. 3. Calyx crypt. 4. Superficial lymphoid nodule. f). Deep lymphoid nodule. ' 6. Muscular layer. 7. Serous lining. A. Undigested vegetable food. B. Emigrated glandular lymphocyte. C. Bacteria. D. Mucus exuding from a goblet cell. E. Columnar epithelium. F. Glandular lymphocyte passing through the epithelium. G. Glandular lymphocyte with ingested bacteria. H. Small glandular lymphocyte. /. Large glandular lymphocyte. J. Mass of dead cells, bacteria and carbon particles. (D (0 '0 ® o ^ o o « 9 ® 0 '0 Fig. 24, CHAPTER XI Life History of the Subepithelial Lymphatic Glands. The records of comparative anatomy show that the subepithelial lymphatic glands occur almost if not quite exclusively in the two highest classes of animals — birds and mammals. It is in accordance with this fact that we find these structures appearing late in human em- bryological history. Follicles of lymphoid tissue do not appear in the tonsil till the last month of foetal life, though the epithelial crypts are represented as early as the fourth month (Keith, 1913). Berry, ir. 1901, stated that the lymphoid tissue in the ca^cal region of mam- mals was almost entirely a post-jiatal development and that it attained its maximum growth at the end of the first week. To confirm this observation I examined the appen- dices of three young rabbits similar in size and appear- ance, and from the same litter. One was killed within an hour or two of birth, the second on the fourteenth, and the third on the twenty-eighth day after birth. Sections of the three appendices were taken and stained in precisely the same way and were drawn with the same camera lucida, eye-piece and objective, and are represented in Fig. 25. It will be seen that the lymphoid tissue can hardly be discerned in the newly- born rabbit, but that its development is very rapid in the first few weeks after birth. When we remember 50 LIFE HISTORY 57 the sterile alimentary contents of the embryo in utero, and the early development of micro-organisms when food (even, as in this series, the maternal milk) is first taken by the mouth, it would almost seem that it re- quired the stimulus of bacteria in the alimentary canal to provoke the development' of the tissue. With regard to the structural form of man's vermi- form appendix we find the same agreement between ontogeny and phylogeny. In the animal series occur types of the globular caecum, the caecum with tapering apex and the caecum with its apex modified into a cylindrical tube of narrow bore sharply demarcated from the rest of the caecum. The human embryonic caecum passes successively through just these stages, first a uniform caecum, then a tapering apex, and lastly, towards the end of fcetal life, a vermiform appendage. The asymmetrical position of the adult's appendix is due to a post-natal development of the lateral wall of the rest of the caecum which occurs in early childhood (Keith, 1913). Though hardly represented during fcetal life, it is during the early years of childhood that the subepi- thelial lymphoid tissue attains its maximum develop- ment. At this period all the lymphatic glands are relatively large and apparently active. In this con- nection it may be recalled that a lymphocytosis is more readily provoked in early life than in the adult, and that the lymphocytes form an unusually large pro- portion of the white cells in the blood of young children. It may be pointed out that the time of greatest activity of the subepithelial lymphatic glands corre- sponds with the period during which the individual is securing immunity against the exanthemata and other infections and it seems that we must correlate those two phenomena — the acquirement of immunity with Fig. 25. Three sections of the wall of the appendix of tliree rabbits from the same litter, (From camera liicida drawings.) Section A was from one killed at birth. wSection B was from one killed on the 14th day after birth. Section C was from one killed on the 28th day after birth. LIFE HISTORY 59 the activity and hyperplasia of the subepithehal lym- phatic glands. At or about the time of puberty a diminution in the size of these glands takes place, and in later years, when presumably a high degree of immunity has been attained, they have usually undergone a partial atrophy. In extreme old age the constituent lymph nodules have greatly diminished in size and number and the subepithelial lymphatic glands are quite in- conspicuous. Doubtless many of the lymphatic nodules have undergone inflamniation followed by absorption or fibosis but a true process of atrophy seems to be mainly responsible. CHAPTER XII. Presence of Bacteria in the Subepithelial Lymphatic Glands. At a time when I was engaged in throat and ear work amongst out-patients, the way in w^hich tonsils and adenoids appeared to attract bacterial infections suggested to me the hypothesis that these organs by inviting a local infection possibly protected the body as a whole by conferring a general immunity, much as the vesicles in vaccination by the doctor strengthen the patient to resist small-pox. In 1911 and 1912, I ad- duced various pieces of evidence in support of such a contention. But if such a hypothesis were correct, it would seem probable that bacteria might be continually entering the subepithelial glands, though a local in- flammatory reaction might not ensue unless the organisms possessed a high degree of pathogenicity. These considerations led to attempts to demonstrate bacteria in the subepithelial lymphatic glands of appar- ently healthy animals. The appendices of rabbits were chiefly studied, but the tonsils of cats, rabbits, and other animals, and also freshly-removed human tonsils and adenoids were examined. The demonstration of bacteria in tissues is not always an easy matter, but in the case of the rabbit's appendix I was surprised at the ease with which enormous numbers of bacteria could be found in the lymph nodules within the wall 60 PRESENCE OF BACTERIA 61 of the appendix of a healthy rabbit (1913). Though I have examined the appendices in over a score of rabbits, some in England and some in China, and I have never failed to find these crowds of bacilli. (Figs. 1, 26, 29 and 30.) f 1^ Fig. 26. Two portions of subepithelial lymph nodes in a healthy rabbit's appendix showing ingested bacilli. (From a camera liicida drawing; eosin-Gram stain; 1/12 in. objective.) I was not then aware of previous work on the sub- ject, but on tracing the literature subsequently, I found that as far back as 1890 Dr. Armand Ruffer had described and beautifully illustrated the presence of 62 IMMUNITY IN HEALTH bacteria and of soot particles in the lymph nodules of the wall of the alimentary canal. He successfully demonstrated bacteria in the appendix, tonsils and Peyer's patches of the rablDit, and the Peyer's patches and tonsils of the dog, and the Peyer's patches of the guinea-pig. Dr. Ruffer in his paper referred to similar observations five years earlier by two independent Fig. 2T. From a photograph of micrococci in the lymphoid tissue of a healthy rabbit's tonsil. (Eosin-Gram stain; 1/12 in. objective.) observers, Ribbert and Bizozzero, but I have been un- able to trace the references he gives. In spite of the high standard of Dr. Ruffer 's histological demonstra- tions the piece of knowledge appears to have fallen into the background. In my own experiments the rabbits were killed very quickly by fracture of the cervical spine, chloroform, PRESENCE OF BACTERIA 63 coal gas, or prussic acid. The abdomen was immediately incised, and the appendix plunged in absolute alcohol or in 10 per cent, formalin in normal saline. Thus there could be no ques- tion of a post-mortem penetration of the tissues by the bacilli. I first found the bacilli in the lymph tissues by overstaining with cold carbol-fuchsin for From a photograph of bacilli in the lymphoid tissue of a healthy rabbit's Peyer's patch. (Eosin-Gram stain; 1/12 in. objective.) twenty-four hours and then decolourising with oil of cloves a varying number of hours — examining the sec- tion from time to time. But I soon found a better way which had also been used by Buffer and his pre- decessors. The bacteria in the rabbit's caecum are for the most part large in size and strongly Gram-positive. They are, possibly, anaerobic, for Dr. Macfarlane was unable to cultivate them for me on aerobic media when 64 IMMUNITY IN HEALTH the attempt was made on one occasion. I suspect these bacteria may be associated with the cellulose-spUtting process which must proceed on a large scale in the rabbit's intestine. A good way in the rabbit therefore is to stain the tissues fairly deeply with eosin and then stain by Gram's method (taking care not to over- decolourise) and mount in xylol balsam. Pappen- FiG. 29. From a photograph of bacilli in the lymphoid tissue of a healthy rabbit's appendix. (Carbol-fuchsin decolourised in clove oil; 1/12 in. objective.) heimer's pyronin and methyl green and Powell-White's eosin and totuidin blue may be used, but have not proved so satisfactory in my hands. Dr. Ruffer em- ployed alum-carmine and Gram's method and was thus able to demonstrate clearly the nuclei as well as the bacteria in the glandular lymphocytes. It is because the bacteria in the rabbit's intestine PRESENCE OF BACTERIA 65 are strongly Gram positive and also have the unmis- takable shape of bacilli, that their presence in the alimentary lymphoid tissues can be so conclusively proved. When we come to the demonstration of dis- solving cocci in the tonsils of man and animals or Gram negative bacilli in the human appendix the matter is less certain, and I have only occasionally been able Fig. 30. From a photograph of bacilli in the lymphoid tissue of a healthy rabbit's appendix, (Eosin-Gram stain; 1/12 in. objective.) to satisfy myself of their presence. But the demon- stration might be easier to an expert in histology. Dr. Buffer figured them conclusively in the dog's tonsil. Hays says " on microscopic examination numerous bac- teria can often be seen in the parenchyme " [of human tonsils]. In the wall of the rabbit's appendix, most, if not all, the bacilli are intracellular being contained in the small 66 IMMUNITY IN HEALTH glandular lymphocytes in the superficial layer of lym- phatic nodules and especially in the larger glandular lymphocytes in the centres of the deep layer of lym- phatic nodules. There may be from one up to a score or more of bacilli in a single cell. They lie apparently within the cytoplasm, outside the nucleus. Some of the bacilli are poorly or irregularly stained, appearing as faint ghosts with perhaps one or two dark spots in their length. A number of the lymphocytes contain no bacteria. I have sometimes seen intracellular bacteria in the efferent lymphatic vessels of the tonsils and other sub- epithelial lymphatic glands in various animals, and Butterfield (1913) describes the " perivascular lymph- atics " of human tonsils as often " filled with micro- organisms." CHAPTER XIII. Mode of Ingestion of Bacteria by the Sub- epithelial Lymphatic Glands. It has already been pointed out that the subepithelial differ from all other varieties of lymphatic glands by the total absence of afferent lymphatic channels. In the ordinary interstitial lymphatic glands the definite nodules of lymphoid tissue lie beneath the capsule and receive the entering lymph. In a subepithelial lymph- atic gland these same nodules are directly beneath the epithelium, upon which they encroach. Instead of receiving lymph from the tissues these nodules welcome bacteria and possibly toxins from the adjacent lumen of the alimentary canal. The passage of toxins would be easy to understand. All the nourishment of the body has to pass through the intestinal mucous mem- brane. The passage of bacteria through healthy epithelium fits in less readily with our general con- ceptions, but that bacteria similar to those in the ali- mentary lumen do occur in immense numbers in the subepithelial lymph nodes has been conclusively shown in the preceding chapter. But I have repeatedly ex- amined sections of the alimentary wall without finding bacteria save in the subepithelial lymphatic glands. Attention has been drawn to the fact that the posi- tion and structure of many of the subepithelial glands 67 68 IMMUNITY IN HEALTH are such as to encourage stagnation of the alimentary contents, and stagnation in its turn will tend to the multiplication of bacteria and their toxins. In the lumen of the alimentary canal then are found man}^ millions of bacteria; on the other side of the epithelium in the lymphoid tissue are to be seen fewer millions of similar bacteria. The question arises by what means these bacteria have been translated across the epithelium. What is the mode of ingestion of these bacteria by the subepithelial lymphatic glands ? Four possibilities readily occur to one. These hypo- thetical processes may be termed : — 1. Chemiotaxis. 2. Physiotaxis. 3. Bacterial motility. 4. Phago taxis. 1. Chemiotaxis, — It is known that phagocytes ap- proach bacteria. If the phagocyte is enmeshed in retiform tissue the bacteria might conceivably be attracted to the phagocyte by chemical means. 2. Physiotaxis. — Alterations of surface tension might determine the passage of bacteria between the epithelial cells. 3. Bacterial Motility. — The powers of locomotion possessed by many bacteria might lead them through the epithelial wall into the lymphoid tissue. This per- haps would be the view of those who regard the subepithelial lymphatic glands simply as weak spots poorly able to resist bacterial assault. 4. Phai^o taxis. — It is common physiological know- ledge that lymphocytes leave the subepithelial lymphatic glands, passing between the epithelial cells into the lumen of the alimentary canal and there engulf bacteria. Ruffer, in 1890, examined the mucus from the surface of human tonsils in four normal persons, and in each case met with "many leucocytes r MODE OF INGESTION 69 full of microbes" therein. Similar observations have frequently been made both before and after that time. It has also been repeatedly noticed that in sections of the epithelium over lymphoid collections small glandu- lar lymphocytes are to be seen between the epithelial cells. It will be seen in Fig, 1 that such glandular lymphocytes may contain bacteria. This is frequently the case. May not glandular lymphocytes wander to the surface, surround bacteria, and return with their prey to the retiform tissue ? To this process I would apply the term phagotaxis. A strong piece of evidence in favour of this theory is to be found in the fact that almost all (if not quite all) the bacteria seen in the epithelial layer lie within glandular lymphocytes. I have only seen small glandular lymphocytes in the epithelium, yet large glandular lymphocytes also contain bacteria. Possibly there is a transference of bacteria, or, as Ruffer described, the large glandular lymphocytes may engulf small glandular lymphocytes with their contained bacteria. I have seen many dead glandular lymphocytes in sections. By this theory glandular lymphocytes found astray in the alimentary lumen would be looked upon as the few which had failed to wander back into the lymphoid tissue. The hypothesis of phagot^-xis also derives strong support from the evidence in favour of the ingestion of inert particles by the subepithelial lymphatic glands. For besides bacteria these glands may be seen to con- tain brownish or blackish granules of apparently inert matter. These granules are probably carbon particles for the most part. They were so described by Ruffer, who pointed out that they were a much more prominent feature in the dog's tonsil than in the rabbit's, a fact he associated with the mouth breathing habit of the dog. Sometimes these granules are sharply angular. 70 IMMUNITY IN HEALTH rendering it unlikely that they are any body pigment. Shattock (1916) in specimens of human appendices showing pigmentation, suggested that the pigmentation sometimes seen in the lymph follicles was altered blood pigment absorbed from the alimentary canal, but the reasons given above seem to favour the view that they are largely carbon particles. It would be interesting to know w^hether the subepithelial lymph glands of workers in sooty atmospheres show an unusual amount of pigmentation . To elucidate the matter a rabbit was fed for three weeks on food containing a large proportion of carbon. Lamp black was mixed with all its food in sufficient proportions to completely blacken it. The rabbit wasted, probably because it ate less of its unnatural- looking food. It was killed with choloroform and the tonsils, Peyer's patches and appendix examined after staining with eosin. The Peyer's patches showed a far greater proportion of brownish-black masses (Fig. 31) than did the Peyer's patches in several other rabbits in the laboratory whose tissues were examined at the same time. Too much value should not be attached to this observation. It was a single experiment, and the amounts of brown pigment seen in other rabbits' Peyer's patches varies considerably. It was not satis- factorily proved that the pigment was carbon. On a subsequent occasion three young rabbits were etherised and in each case the end of the appendix was brought through an abdominal incision and the wound closed. The end of the appendix was then snipped off with scissors and an emulsion of carmine in normal saline syringed into the lumen of the appendix, the end of which was then ligatured. The three rabbits were killed with chloroform respectively 7, 21, and 42 hours after the operation, and paraffin sections prepared. Each showed carmine in the lumen of the appendix. MODE OF INGESTION tl In the rabbit killed after seven hours an unusual number of lymphocytes containing minute dark granules could be observed in the epithelium and even in the lymph follicles. But it could not be conclusively Fig. 31. Microscopical section of a Feyer's patch from a rabbit which had had soot administered with its food for three weeks. Stained with eosin only. (From a camera lucida drawing; 1/12 in. objective.) The section shows glandular lymphocytes and masses of ingested soot. stated that they were carmine particles. The appen- dices of the rabbits killed after 21 and 42 hours pre- sented normal appearances. 1^2 IMMUNITY IN HEALTH Spencer (1897) states, without quoting his authority : — ''Carmine whiqh has been mixed with the food of the animal passes out through the intact wall of the intestines, especially by the way of the solitary the agminated follicles." Bond (1917 and 1918) has described an exactly similar process to phagotaxis on the granulating surface of wounds, which he terms the "return immigration of leucocytes." It is noteworthy that the small glandular lympho- cytes indistinguishable morphologically from the lym- phocytes of the blood are definitely motile and phat^ocytic. I CHAPTER XIV. Pathology of the Subepithelial Lymphatic Glands. In the preceding sections attention has been directed upon- the Physiology of these Glands. In this and some of the following pages the behaviour of these glands in connection with disease will be studied to see how far it support's the main thesis of this book. The grouping together of these glands derives great support from the similarity of the diseases to which they are liable. These diseases may be classified under three headings : — 1. Inflammation. (Chapter XV.). 2. Simple enlargement. (Chapter XVI.). 3. Other diseases. (Chapter XVII.). A separate section will be accorded to an account of each of these. In addition, those morbid states in which infection passes through the subepithelial lymphatic glands, gaining an entry to the general system without obvious injury to the doors it has forced, must be dealt with (Chapter XVII.). A few general points bearing upon the connection between infectious diseases and the subepithelial lymphatic glands may be dealt with at once. Attention has already been drawn (Chapter XI.) to the period of greatest activity of these glands coinciding with the period of childhood when the exanthemata and other infectious diseases are most common. It is also to be observed that the subepithelial lymphatic glands are hyperactive or show definite inflamrnatory changes in 73 74 IMMUNITY IN HEALTH the following complaints : — scarlatina, diphtheria, acute anterior poliomyelitis, rheumatic fever, measles (Ger- man measles rarely), typhoid fever, infantile enteritis and pertussis. Flexner and Clark, and also Land- sfeiner, Levaditi and Pastra have shown that the tonsils from fatal cases of acute anterior poliomy- elitis contain the virus, and Trethowan describes a painful enlargement of the tonsils as a frequent early sign of the disease. These signs of activity are most developed in the initial stages of these diseases. Cer- tainly the subepithelial lymphatic glands bear the brunt of the attack in faucial and intestinal infections. The lesions of scarlatina, typhoid fever and appendi- citis illustrate this statement. Although the subepi- thelial lymphatic glands seem almost to invite disease, they yet seem better able to overcome it. Thus diphtheria — a localised infection — is less serious when limited to the tonsils than when it occurs elsewhere (Jacobi, quoted by Mackenzie). The absence of the subepithelial lymphatic reaction usually signifies a very virulent type of infection or a lowered resistance, and presages a fulminating and often fatal attack. Dr. Palmer relates a typical case of a lad of 14j years of age struck down by malignant scarlet fever. "The throat was normal. There was no glandu- lar enlargement." Death occurred thirty hours after the patient felt ill enough to consult a doctor, or three days after the earliest feeling of malaise. The diagno- sis seems fairly reliable — the patient had not had scarlet fever previously ; the onset was marked by vomiting and an unusually dusky scarlet fever rash appeared on the second day ; a neighbour who had been with him developed scarlet fever of a mild character a few days later; a post-mortem examination helped to exclude the possibility of other disease being present. The subepithelial glands concerned enlarge as a I PATHOLOGY 75 result of repeated infectious diseases such as pertussis, measles, scarlatina and coryza, and also tend to hyper- trophy in insanitary and unhealthy conditions, whether of the patient's general surroundings, or locally of the nose and throat (Chapter XVI.). A swollen condition of the Peyer's patches occurs in cases of obstruction of the small intestine. A limited septic infection may lead to a limited enlargement of the adjacent subepithelial lympathic gland. The following case illustrates this point. H. W., age 18, an engine cleaner, had had left otorrhoea " as long as he can remember." He thought it followed scarlet fever. The left tonsil was very much enlarged, while the right tonsil was about normal in size. I have on several other occasions seen this unilateral tonsillar enlargement follow an otorrhoea on the same side. General increase of lymphatic structures, particularly of the subepithelial variety, signifies prolonged bac- terial assaults, and may be accompanied by a toxin- weakened heart — the so-called status lymphaticus. It may also be observed that a lymphocytosis is characteristic of pertussis, measles, variola, mumps, infantile gastro-enteritis, some cases of tuberculosis, malaria, rickets, and syphilis, and even typhoid fever (Gulland and Goodall). Increase in the number of leucocytes, charactjerised by a relative gain in the lymphocytes and eosinophils, usually develops during the reactionary fever following the injection of tuber- culin (Da Costa). Of course, the interstitial lymphatic glands and possibly the marrow share with the sub- epithelial lymphatic glands in the production of lympho- cytes, but when it is borne in mind that in many of these diseases some of the subepithelial glands show activity, it is reasonable to suppose that they play no yc IMMUNITY IN HEALTH small part in the production of the lymphocytosis, surely a defensive reaction. In connection with the greater activity of the lymphatic tissues in children, it is worth while repeating that a lymphocytosis is more easily provoked in early life, and that the lymphocytes form a constantly higher proportion of the leucocytes in children than they do in the adult. Further, it has already been shown (Chapter V.) that during scarlatinal epidemics a person may apparently secure immunity by a very mild tonsilitis, which is un- accompanied by rash, malaise or other signs of general injury, and that a similar immunity may be obtained in epidemic cerebro-spinal meningitis. A great pro- portion of those exposed to infection show the virus on their nasopharyngeal tonsils (which are liable to show some congestion), yet remain free from the disease and have indeed developed an enormously high opsonic index against the causal micro-organism. Similarly, immune " carriers," who have never clini- cally suffered from the diseases, yet convey the organ- isms of typhoid and cerebro-spinal fever and of diphtheria, cholera and dysentery (Ledingham and Ark Wright). In France, Courmont and Rochaix have produced immunity against typhoid fever both in human beings and animals by the introduction of dead bacilli into the large intestine. Agglutinins have resulted in the blood stream. It seems likely that the dead organisms pass through the epithelium into the subjacent lymph nodes of the solitary follicles or the appendix — just as living organisms do — and that the immunity is pro- duced in that manner. Finally attention may again be drawn to the patho- genic organisms normally inhabiting the alimentary canal. It would be difficult to understand how pneumo- cocci, Klebs-Loffler Bacilli, and the hosts of pyogenic PATHOLOGY 77 and other pathogenic bacteria could exist harmlessly next to the tissues unless the body possessed some method of more or less neutralising the effects of always possible invasions. It is noteworthy that it is not only in man that the subepithelial lymphatic glands are liable to disease. As might be expected, this side of the question has hardly been explored, but Hett has observed tonsils "like a child's unhealthy tonsils" in one Rhesus monkey and in one young gorilla ; actinomycosis in a Kan- garoo's tonsil ; a large cyst in a hyena's tonsil ; tuber- culous disease in several monkeys' tonsils, whilst Mr. Stapley, in a personal letter to me, has written : — "I have never seen an inflamed appendix in a wom- bat, but I have seen several wombats that have died from perforation of a Peyer's patch that was within an inch of the ileo-csecal valve." CHAPTER XV. Acute Inflammations of the Subepithelial Lymphatic Glands. All the subepithelial lymphatic glands share a common liability to attacks of acute inflammation. The evidence marshalled below shows that the initial lesion in almost all cases is inflammation commencing in one of the lymphatic nodules and not, at first, an ulceration of the mucus membrane. A lymphadenitis is the starting point of appendicitis as well as of ton- silitis, of pyloric ulcer as well as of the ulcers of enteric fever. In the case of tonsilitis the mucous membrane is red- dened and the whole organ swollen. Each crypt becomes choked with glandular lymphcocytes and sometimes polymorphonuclear cells and bacteria, which may over- flow to appear on the surface as a projecting white spot. If ulceration occurs it comes later. Peptic ulcers occur for the most part in the adjacent parts of the stomach and duodenum, just where the greater number of lymph nodules are found. The acid gastric juice doubtless accelerates ulceration which has once started, but the commencement of the whole pro- cess is probably an inflammation of the subepithelial lymphatic nodules, going on to suppuration with break- ing down of the overlying epithelium. Landsdown and Williamson have advanced evidence in this direction. 78 ACUTE INFLAMMATIONS 79 Payer's patches become inflamed and swollen with- out ulceration in many cases of enteritis. Even in typhoid fever ulceration is by no means an essential part of the disease. Eustace Smith (1909) writes : " In children there is less tendency to ulceration of the in- testine than at a later period of life. In many cases even when the fever has lasted its full period, Peyer's patches are seen as soft, non-ulcerated swellings," and Dreschfeld states : " In a few cases the lesions of enteric fever have been found with the exception of intestinal ulcers ; the Peyer's patches in these cases presented swelling and congestion only. Death in the cases re- ported had occurred at a date (after the 21st day), when the ulceration ought to have been well marked." Else- where, he says : " In a section [of Peyer's patches in early typhoid fever] stained with aniline dyes for the de ■ tection of micro-organisms, large numbers of typhoid bacilli are seen, most numerously in the centre of the follicle, where the nuclei appear less stained." Appendicitis has been ascribed to many factors, some highly fanciful, others perhaps acting as predisposing causes. The first part of the claim that the appendix is vestigial and therefore prone to inflammation, has already been refuted. So far from the appendix being the shrinking caecum of a vegetarian turning carni- vorous, we find it best developed in association with a huge caecum in the purely herbivorous rodents. Chronic constipation seems to predispose to the disease, whether owing to generally lessened resistance of the body, to altered bacteriological content of the caecum, or to in- terference with the mobility or circulation of the appen- dix by peritoneal adhesions about the large bowel. The wavy contortion of the vermiform process has been said to lead to congestion and consequent lowering of the local resistance of the mucous membrane. Certain it is that the free border of the meso-appendix is so short 80 IMMUNITY IN HEALTH that no normal appendix can be completely straight- ened in situ. However, it is not the vessels in its mesentery, but it is the appendix itself which is bent and bent to a far less extent than are many other por- tions of the alimentary tract. The vermiform process has, however, a terminal blood supply with no collateral circulation ; that is, its vessels do not freely anastomose with vessels of adjacent adoral and adanal gut, as is the case with the rest of the alimentary canal. There is theoretical ground, then, for suspecting that the absence of a free collateral circulation predisposes the vermiform process to attacks of congestion, and so perhaps to bacterial invasion. Foreign bodies have been recorded in a small but sufficient percentage of cases to give rise to the belief that they encourage appendicitis.* Just as fig seeds have been found in the lacunae of diseased tonsils (Pybus, 1915). Yet in neither case can one suppose that foreign bodies are the usual cause of disease in these structures. Bruising of the walls might well follow the attempts of the vermi- form appendix to rid itself of the foreign body, and bruising would certainly favour bacterial invasion. Yet, it must not be forgotten that previous ulceration of the appendix is liable to be followed by a stricture, and an appendix with a stricture may act as a trap for foreign bodies. It is highly probable that the faecal concretions found in many cases of appendicitis follow previous stricture of the lumen. Caecal contents * The followinji: foreign bodies in diseased appendices have been recorded : — game-shot, pins, bristles, hairs, round worms, thread worms, cherry stones, grape stones, date stones, orange pips, and fragments of nutshells. It must however be remembered that concretions have very often been mistaken for fruit stones. Treves, in 1896, in remarking that he. personally, had never foimd a genuine foreign body in the appen- dix, drew attention to the wonderful way in which appendicular con' pretions mjmicked certain seeds and fruit-stones. ACUTE INFLAMMATIONS 81 enter the appendix,"'^ and owing to the stenosis of the lumen the fluid parts escape more easily, and the hardish residue is kneaded into a concretion in which lime salts may be deposited. Eventually, the concre- tion may lead to ulceration and an acute attack. Ad- hesions of the actual vermiform process and cicatrisa- tion of the meso-appendix leading to real kinking, tend to a recurrence of the inflammation, but are themselves the result and not the cause of the initial attack. A traumatic causation must be admitted in a few cases. Either direct violence, as from a blow, or in- direct violence, as from a strain, such as has been met with in bowling at cricket, has on rare occasions been succeeded by an attack of appendicitis. Often the in- jury merely lights up old trouble by breaking down adhesions. The histories of the vast majority of appendicitis cases leave us, however, in doubt a§ to the actual exciting cause. I remember once being shown an appendix (removed at operation from a very early case) which showed an intramural abscess. Kelly, in his standard work, figures a specimen of acute catarrhal appendicitis show- ing numerous minute ulcers, each corresponding to a lymph follicle.! An appendix, the seat of early catarrh, may show enlargement of the lymph-follicles without any appearnce of ulceration. I have sections of most acute early appendicitis which fail to show under the microscope any lesion of the mucous membrane, though numbers of polymorphonuclear leucocytes were visible * Some have erroneously supposed that the vermiform process contains mucus only. If this organ be examined after death it will •be found that the mucus is always stained with stercobilin, and that the lumen often contains one or more boluses of faecal material, the colour and bulk of which may even be visible through the intact wall. t " Plate I., Fig. 1. — Acute appendicitis with superficial ulceration .... with the hand-lens the ulcers are found to occupy the centre of a system of Lieberkuhn's crypts and correspond to the normal position of lymph nodes." f 82 IMMUNITY IN HEALTH throughout all the coats. All these observations support the view that appendicitis commences as a lymphaden- itis, and we are led to the supposition that the exciting cause of the first attack in most cases is the presence of some virulent bacterial strain. Perhaps some variety of streptococcus is most often responsible,. because in the most fulminating types of the disease the early peri- toneal exudate yields a growth of virulent streptococci. Of course, as in all intestinal cases, these organisms are soon overgrown by the prevalent bacillus coli communis. Perhaps the infecting organism is more likely to occur in meat, if there is really any truth in the belief that appendicitis is less frequent amongst the more vege- tarian Chinese and Japanese than amongst the more meat-eating Europeans.* Certainly, one would im- agine that micro-organisms flourishing in dead animal tissues would be more attune^ to living in animal tissues than would most bacteria which might be present in vegetable fibres. It is noteworthy here to recall that appendicitis may occur early in typhoid fever. Anyone with a wide ex- perience of abdominal cases has seen the child who develops rose spots and a tender spleen, after removal of an obviously inflamed appendix. McKillop (1912) recorded such a case in a girl of 19. The tip of the appendix was congested and swollen, and contained a fa3cal concretion. Undoubted symptoms of typhoid fever declared themselves after appendicectomy. * I am not satisfied on this point. I have seen cases of appendicitis amongst Soutliern Chinese snbsisting largely on rice, and liave often noticed in the dissecting room adlierent appendices in Chinese coolies on a principally vegetarian diet. Perhaps one reason for the relative infrequence of severe appendicitis amongst the Chinese may be the method of treatment. The native practitioners in China are very averse to the indiscriminate use of purgatives for all abdominal pains. Treves, in 1902, pointed out what is indeed the usual experience, that Europeans living in the Tropics are more liable to appendicitis than in Europe. The risk of having to eat decomposing or diseased meat is much greater, of course, in tropical countries. ACUTE INFLAMMATIONS 88 The rarer occurrence of tuberculosis and actinimy- cosis also perhaps indicates that the micro-organisms of these diseases may be the causal factor in excep- tional instances.* The ulcers in dysenteric colitis appear to start at the solitary follicles (Dalafield and Prudden). One may even speculate that the rare disease — mesosig- moiditis — may commence in the solitary follicles of the pelvic colon. Without wishing to see subepithelial lymphadenitis in all diseases, one may yet assert that it is the pro- bable commencement of sore throats, peptic ulcers, typhoid fever and appendicitis. The interesting fact has often been noticed that more than one set of subepithelial lymphatic glands may be contemporaneously affected. Thus, tonsilitis will be occasionally accompanied or shortly followed by appen- dicitis (Pybus, 1915). One may imagine that the causal micro-organism is capable of multiplying in these cases in the differing environments of throat and caecum. In certain specific fevers — e.g., scarlatina, all the sub- epithelial lymphatic glands may be seen inflamed at a post-mortem examination (Eustace Smith). All such cases may be rather clumsily described under the name of poly-suhepithelial lymphadenitis. This initial lymphadenitis may, of course, undergo * Tlie morbid anatomy of appendicitis may be summarised as follows : — The gross changes in the early stages are increased vascularity, thickening, hardening and unusual lacerability. Later, ulceration, gangrene and perforation may be found, and calculi, adhesions and irregularities of calibre may succeed. The microscopic appearances include : — ^ • (1) The presence of polymorphonuclear leucocytes in all the ooats. (2) The presence of e.vtra-cellnlar bacteria in the lymph nodes. (This is of little practical value owing to the difficulty of staining gram-negative bacteria in tissues.) (8) Necrosis of lymph nodules. (4) Destruction of the epithelium . (5) Later, fibrosis. 84 IMMUNITY IN HEALTH resolution, and the patient completely recover. Some- times, however, although the parts afterwards are normal in appearance to the naked eye, some injury to the lymph follicle remains, rendering it unduly prone to further attacks of appendicitis. I have repeatedly seen an appendix removed in the fourth or fifth attack of inflammation, or in a quiescent period between un- doubted attacks of appendicitis, which showed no ad- hesions, stenosis, nor obvious sign of previous inflam- mation. Probably, in such cases, the permanent injury consists of some microscopical lesion to the lymph folli- cles. That one attack of appendicitis predisposes to another is surely true. And the same can be said of inflammations of the tonsil. Theoretically, this might be due to a prolonged lowered resistance of the patient or to the continued presence of virulent organisms in the alimentary canal, but since most of the cases of recurrence of these diseases can be shown to be due to the cicatricial effects of previous attacks, it is likely that the fewer cases of recurrence where no such cica- tricial effects are seen with the naked eye are also due to permanent but microscopic lesions. In view of the constant ingestion of bacteria by the subepithelial lymphatic glands, there is no need to assume any primary lesion of the epithelium. Small glandular lymphocytes return from the lumen of the alimentary canal, laden with some exceptionally viru- lent bacteria. The small glandular lymphocytes die, and the toxins of the bacteria repel the efforts of the large glandular lymphocytes to engulf and destroy the smaller cells and the bacteria together. The bacteria then com- mence to multiply extracellulary ; the arterioles of the gland dilate and polymorphonuclear cells migrate to the scene of the conflict. Should resolution not occur, the initial lymphadenitis ACUTE INFLAMMATIONS 85 proceeds to suppuration, and a submucous abscess forms. This soon bursts through the thin overlying mucous membrane, and an ulcer results. The process is multiple, and numerous fine ulcerating points can be seen at this stage. When the protecting epithelium is destroyed the attacks of the initial virus are strength- ened by the irritating juices of the alimentary canal (salvia, hydrochloric acid, or tryptic ferments, as the case may be), and other ^inds of bacteria, so that a chemically-irritated wound with a mixed infection ensues. This stage of multiple fine ulcers can be seen in the vermiform process and in the aggregated lymph nodules. In the tonsils minute ulcers, corresponding to the lymph follicles, are not visible, as they occupy the sides of the crypts. The ulcers soon extend and coalesce, and extensive areas of denuded epithelium can be seen at such a stage in inflammation of any of the subepithelial lymphatic glands. With the appendix' and the Peyer's patches the poisons may be so deadly as to produce localised patches of gangrene, involving the whole thickness of the in- testinal wall. The deepening of the ulceration may lead to abscess formation beyond the organ — always a serious condi- tion. With the faucial tonsil a quinsy or peritonsillar abscess may be set up ; with the pharyngeal tonsil a retropharyngeal abscess ; with the lingual tonsil deep submaxillary suppuration (Ludwig's Angina) ; with the solitary lymphatic nodules of stomach and duodenum, with the aggregated lymphatic nodules of the' ileum and with the vermiform process, various forms and degrees of peritoneal suppuration. With the solitary lymphatic nodules of stomach and duodenum, and with the aggregated lymphatic nodules 86 IMMUNITY IN HEALTH 1. of the ileum, the deepening of the ulcers may breach the wall of an artery and lead to severe and even fatal haemorrhage. If recovery takes place after suppuration has oc- curred, some degree of cicatrisation remains. Much — rarely even perhaps all^ — the lymphoid tissue of the in- flamed organ may be destroyed. The epithelium may be extensively removed. This may cause a localised stenosis of the tonsillar crypt or of the vermiform pro- cess, thus predisposing to the inspissation of retained material and concretion formation (in vermiform ap- pendix and faucial tonsil) or to cystic dilatation beyond (mucocele of appendix, cyst of faucial tonsil, and per- haps Thornwaldt's cystic adenoids), or to subsequent suppuration under pressure beyond the block. The crypts and the appendicular lumen may indeed be completely blotted out after repeated inflammation of the tonsil and the appendix respectively. Inflammation of the intestinal lymphatic structures may be followed by peritoneal adhesions. In the case uf the vermiform process such adhesions may interfere with the blood supply of the organ. Similarly cica- trices in the meso-appendix, consequent upon lymphangitis or lymphadenitis (for the meso-appendix contains one or more lymphatic glands) may cause sharp kinking of the appendix, interfering with the blood supply or the free passage of material along its lumen. Such ~ strictures and adhesions undoubtedly predis- pose to further attacks of inflammation, though the presence of the latter probably lessen the risks to life of such subsequent attacks. Birmingham writes (Shennan, 1912) that " partial occlusion (of the vermiform appendix) is present' in 25 per cent, of all cases (of post-mortem examinations of adults), and in more than half those sixty years old. ACUTE INFLAMMATIONS 87 whereas it is unknown in the child." These figures show the surprising frequency of inflammation of this structure. The tendency to early recurrence of inflammation after a sufliciently severe initial attack is most strongly marked in the case of the vermiform process, but is also frequently noticeable with the lymphoid tissues of the throat. Indeed, the more complex the structure of the subepithelial lymphatic glands the more surely does it exhibit this tendency. Apart from persistence of the original virus in all its intensity, the tendency to recurrence is probably due in general to undue stag- nation from cicatricial contraction. This section cannot be closed without a serious con- sideration of the question of hsematogenous infection. Inflammation of the appendix has been experimentally induced in a few cases by the injection subcutaneously of certain bacteria. It has been suggested that the subepithelial lymphatic glands therefore become infected from the blood stream and not through the overlying epithelium. Perhaps the best clinical evidence in favour of haema- togenous infection is the ulceration of the tonsils in secondary syphilis. In this stage of syphilis the organism is undoubtedly circulating in the blood stream. One may add that other lymphoid tissue is often excited by general infections of the blood stream. Neither the experimental nor the clinical evidence are conclusive, however, for it must be borne in mind that possibly in subcutaneous inoculations, and cer- tainly in secondary syphilis, the micro-organisms pass out in large quantities in the secretions into the alimen- tary canal, and may thence be ingested by the sub- epithelial lymphatic glands, and in them may then give rise to morbid processes. CHAPTER XVI. Simple Enlargement or Hyperplasia of the Subepithelial Lymphatic Glands. Chronic enlargement is an extremely common affec- tion of the Subepithelial Lymphatic Glands, especially in the first two decades of life. All these lymphoid structures are liable to it — tonsils, adenoids, Peyer's patches and vermiform appendix alike. The faucial tonsils can be observed directly. The vast majority of town-dwelling children in England probably have en- largement of their tonsils for some period during child- hood. During one year 57,809 Lancashire school children were medically examined. Of these 2,591 (over 4 per cent.) were Jreported as suffering from enlarged tonsils. The distinction between a normal and an enlarged tonsil is, of course, quite an arbitrary one. When the tongue is forcibly depressed with a spatula the tonsils in any child bulge medial- wards. Nevertheless, there can be little doubt that in a considerable percentage of children the faucial tonsils are sufficiently enlarged to project considerably beyond the pillars of the fauces in the absence of retch- ing and during quiet respiration. Enlargement of the nasopharyngeal tonsil usually accompanies that of the faucial tonsil. The frequency of these affections varies very much in different coun- tries. They are uncommon in South China. ''The Hebrew race is specially predisposed to this hyper- plasia ; climate is also a predisposing factor. Osier is 88 HYPERPLASIA 89 of the opinion that there are more mouth breathers to the acre in England than in any other country, while Massei, in Naples, reports that he has seen only five cases during the past fifteen years in which adenoidec- tomy was indicated." (Crowe, Watkins and Rotholtz.) Enlargement of the lymphoid tissues of the Peyer's patches is often observed at autopsies in children. It is not easy to speak of enlargement of the lymphoid tissues in the wall of the appendix, as there is no standard by which to reckon. Histologically, this overgrowth manifests itself usually as a hyperplasia of the lymph nodules. It is well known that lymph nodules are capable of increas- ing in number as well as in size. The majority of tonsils and adenoids removed during childhood show this structure. In the smaller pro- portion— and these often at a later age — the enlarge- ment is due to the presence of fibrous tissue, probably the result of inflammation of pre-existing hyperplasia.* * This hyperplasia is probably a protective reaction to the insanitary condition of nose, mouth or throat. It certainly follows suppurative processes in middle-ear and nose. The hyperplasia is often initiated by the specific fevers. In the unusual condition known as keratosis pharyngis, the solitary nodules in the oropharynx are chronically enlarged, and are marked on the surface by white patches of adherent bacterial growth. The only harmful results of the hyperplasia are mechanical. They are most marked in the pharynx, the walls of which are fixed and unyielding. The en- larged organs encroach upon and reduce the lumen, thus interfering with the functions of respiration, de- glutition and speech. The nasopharyngeal tonsil may * Messrs. Hett and Butterfielrl (1913) would probably disagree with these statements. 90 IMMUNITY IN HEALTH so fill the nasopharynx as to set up mouth-breathing with all its serious sequelae. The faucial tonsils, if very much enlarged, may then impede even the mouth respiration, and cause chronic deficient oxygenation. Swelling of the lymphoid tissue about the orifice of the tuba auditiva is said to block this tube, leading to re- traction of the membrane of the tympanic cavity, pent- up secretions, and middle-ear suppuration, with result- ing deafness. ' Barnard believed that the common variety of intus- susception in infants, which starts in the lower few inches of the ileum, results from an enlargement of the last Peyer's patch (which is especially prone to hyper- trophy) bulging into the ileum and being seized upon by peristaltic movements. It is just credible that localised hyperplasia of lymph nodules in the vermiform appendix may lead to func- tional blockage of the tube, the stagnation of contents and the formation of calculi. General increase of lymphatic structures signifies prolonged bacterial assaults, and may be accompanied by a toxin-weakened heart in the condition known as status lymphaticus. (See Chapter XIV.). CHAPTER XVII. Other Diseases of the Subepithelial Lymphatic Glands. The subepithelial lymphatic glands may share with other lymphoid tissues in certain obscure infections, namely splenomedallary leuchaemia, lymphatic leuchsemia, and lymphadenoma (Hodgkin's disease). In the latter disease it is the large glandular lympho- cytes which multiply so rapidly at certain stages. The lymphoid tissue of the faucial tonsil is also liable to lymphosarcoma ; that is, a large round-celled sarcoma which spreads to the adjacent lymphatic glands. Malig- nant disease of the epithelial covering of the lymph nodes is also to be met with in stratified epithelioma of the tonsil, and the not very malignant carcinoma of the vermiform appendix. None of these diseases, however, appear to have any bearing on the main thesis of this book. Of more import is the insidious passage of tubercle bacilli through the subepithelial lymph glands to the adjacent interstitial lymphatic glands. This condition is of very frequent occurrence, the upper cervical glands draining the faucial tonsil becoming tuberculous, whilst that organ remains healthy. Cervical glands are more liable to tuberculous disease than, for instance, are inguinal glands, and the disease commonly begins in the upper deep cervical glands which drain the tonsil. 91 92 IMMUNITY IN HEALTH So, too, tabes mesenterica may be unaccompanied by obvious disease of the Peyer's patches. Caseating ileo- colic glands may exist with a normal vermiform appendix. It would seem as if the subepithelial lymphatic glands had an especially high resistance to the tubercle bacillus, but that occasionally a lymphocyte loaded with tubercle bacilli would pass to the nearest intersti- tial gland and there be overcome by its contained bacilli, and a tuberculous focus thus be set up. Or possibly the ingested but undigested tubercle bacilli live so slowly that their relatively inert forms have been transferred to adjacent interstitial glands before their effects begin to be produced. It is as a rule only when the general resistance has been greatly lowered, as in the last stages of phthisis, that tuberculous ulcers on the tonsil are found, though tuberculous disease is found in a certain proportion of enlarged tonsils that have been excised. CHAPTER XVIII. Therapeutic Bearing. A GENERAL acceptance of the theory of the immunising function of the subepithelial lymphatic glands would probably have the following two effects: — (1) It would lead to a more conservative surgery of the subepithelial lymphatic glands. (2) It might stimulate further attempts at securing Immunity by the administration of bacterial cultures by the mouth. With regard to the practical bearing on surgery, it may be declared at the outset- that the excision of the tonsils and appendix can never be abandoned. There has, however, at times been a tendency to remove the faucial tonsils solely because the nasopharyngeal tonsil (adenoids) is being curetted, or to remove the appendix as a routine measure in any laparotomy for other cause. The ruthless advocates of the indiscriminate ''massa- cre" of subepitheHal lymphatic glands would urge with perfect truth that no satisfactory proof has ever been presented showing disability following removal. But the question has never been scientifically studied. What is required is to take many thousands of healthy chil- dren living under similar conditions, in half of whom the healthy tonsils had been enucleated and the ade- noids completely cut off within the first two or three years of life, and then to compare the susceptibility ■93 ^i IMMUNITY IN HEALTH of the two groups to infectious diseases during the remaining years of childhood. The statistical and scientific difficulties would be immense, but until some such investigation has been made, one must conclude that the question of disabilities following removal is quite unproven either way. Isolated cases of infective diseases following tonsilectomy have been recorded. Their occurrence may well have been accidental, but it must not be assumed too readily that removal of the tonsils and adenoids lessens the incidence of infec- tious disease. Indeed, the converse may be the case. A very careful investigation of the after histories of cases submitted to this operation at the Johns Hopkins Hospital has been recorded by Crowe, Watkins and Rotholtz. "During the past four years," they say, ''we have seen eight cases with a history of frequent attacks of tonsilitis preceding, but never with anything but local symptoms." After partial removal of the tonsils "all went well until the next coryza, following which the joint symptoms appeared for the first time." The authors attribute this to cicatricial tissue from the first operation narrowing the crypts as "the joint symptoms gradually disappeared and the temperature returned to normal" after complete removal of the tonsils. But in another part of their paper they write : "Organisms probably pas< through the mucous mem- brane of the nose, nasopharynx and pharynx more frequently than is generally supposed. We have on several occasions seen, in patients whose tonsils and adenoids had been thoroughly removed, an enlarge- ment of the glands of the neck, a return of arthritic symptoms, repeated attacks of rheumatic fever, and especially frequently a recurrence of chorea after a mild coryza or pharyngitis." Quite recently Zahorsky published a valuable paper on the late result's of the removal of the tonsils and THERAPEUTIC BEARING d5 adenoid vegetations. 150 children aged 8 to 12 were under clinical observation in private practice from six months to five years after the operation, and the follow- ing defects were observed : — Deficient nasal respiration ... ... 38 cases. Acute otitis media ... ... ... 21 ,, Bronchitis ... ... ... ... 49 ,, Bronchiolitis ... ... ... ... 22 ,, Pneumonia ... ... ... ... 15 ,, (9 of which occurred during the winter following the operation.) Rheumatic fever ... ... ... 11 cases. Endocarditis ... ... ... ... 7 ,, Chorea ... ... ... ... 6 ,, Diphtheria ... ... ... ... 3 ,, Enlarged cervical glands ... ... 15 ,, Zahorsky concludes : — '' The clinical impression that tonsilectomy increases the tendency to bronchial and pulmonary infection is corroborated by these figures, although they are not conclusive, as no figures are available as to the usual incidence of acute broncho- pneumonia in children. That an attack of acute ton- silitis renders the child temporarily immune to a variety of dangerous infections seems probable. . . . My ob- servation shows that the child beginning his school life without the tonsils is in greater danger of acute diseases than one who still has his tonsils." It may here be emphasised that it would be difficult to show statistically that the loss of a finger was dis- advantageous ; yet we can see the mechanism of digital efficiency so clearly that we can have no doubt as to . the reality of the disadvantage. Granted the mechanism and utility of the subepithelial lymphatic glands, ad- vocated in these pages, we can have little doubt as to the disadvantages entailed by their loss. However, the body has such lar^e powers of com- 06 IMMUNITY IN HEALTH X^ensation that local losses cah usually be made good. It is probable that adjacent subepithelial lymphatic glands hypertrophy and largely replace the organs removed. Another consideration which may serve to stay the surgeon's hand in absence of definite call for operation is the fact that the subepithelial lymphatic glands lie close to an alimentary canal swarming with pathogenic organisms. Any removal involves cutting into this region as well as dividing healthy tissues'. With the vermiform ap- pendix technical skill has so well met the difficulty that the risk in removing a normal or quiescent appen- dix should be little, if any, greater than the risk of exploratory laparotomy. But removal of tonsils and adenoids can make no pretence to being an aseptic operation, and septic complications are far commoner than is generally admitted. The following is a list of complications directly the result of the operation for removing these structures ; — Sapraemia with pyrexia for a week or more. Suppurating cervical glands. Retropharyhgeal abscess. Suppurative otitis media. Septicoemic abscess (e.g., abscess of rib). Endocarditis. Primary, reactionary, and secondary haemorrhage. Syncope, sometimes fatal, during anaesthesia. Bronchitis and pneumonia. Some cases "of scarlatina, of diphtheria and of rheu- matic fever have been recorded. In view of the bacteriology of the fauces, the wonder is that septic complications are not more serious than they are. Perhaps the explanation is that the resulting wounds are freely open ones. Dr. Mackenzie (1912) has written eloquently against THERAPEUTIC BEARING 97 the removal of tonsils and adenoids in the absence of definite indications. Mindful both of tlheir probable physiological value and also of the distinct, though not often serious, risks of the operations for their removal, one may restrict the indications for operation in a table as follows* : — Operation. Indications, (1) Partial Excision of the faucial Chronic interference with swallow- tonsils, ing or with speaking. (2) Enucleation of faucial tonsils. Where there is good reason to suspect the tonsil of containing a chronic focus of infection ; for example, in some cases with re- peated attacks of septic sore throats with tonsillar or periton- sillar abscesses, or where there are concretions in the tonsils. (3) Erasion of nasopharyngeal (A) Chronic obstruction to nasal tonsil. breathing. (B) Deafness, accompanied by a very large mass in the naso- pharynx with retraction of the membrane which does not yield to repeated politzerisation. The nasopharyngeal tonsil must be of very great size to be responsible for blocking the tuba auditiva. Ob- struction of the tuba auditiva is more usually due to inflammation of the mucous membrane and swelling of the lymphoid tissue about its orifice. That removal of the latter can be accomplished by the blind use of curette or finger is to my mind more than doubtful. (4) Appendicectomy. A probable diagnosis of appendi- citis. The indication given here is very vague. Probably no one goes through life without an inflammation of * This table, for convenience, omits malignant disease, which is a rare but perfectly legitimate indication for the removal when prac- ticable of any of the subepithelial lymphatic glands which may be affected. G 98 IMMUNITY IN HEALTH the appendix. But experience has shown that when this inflammation has proceeded to such a degree that the symptoms and signs point definitely to appendicitis, appendicectomy without delay gives distinctly the best results. A mild catarrhal appendicitis, giving rise to an attack of abdominal pain, at first general, but after a few hours localised in the right iliac fossa, with slight rise of temperature, some nausea or even vomit- ing, a tendency to constipation, and tenderness or rigidity with diniinished reflexes in the right iliac region, demands immediate excision of the appendix as, of course, do severer forms of the disease with complications. The routine removal of the tonsils in cases of tubercu- lous disease in the glands of the neck, has been advo- cated on the grounds that the tonsils act as "portals of entry" to the tlibercle bacilli. It is probable that the tonsils have so acted in such cases, but to remove them in all cases of tuberculous cervical glands is to be on a par with the wealthy merchant who returned home to find that malefactors had broken into his house through the front door and damaged his property. * 'Remove the door," cried the angry merchant. The oral or rectal administration of bacterial cultures has sometimes been attempted with some degree of success. Some immunity to typhoid fever and to tuber- culosis has thus been attained. The difficulties that may be apprehended are the destruction of the dead bacilli by alimentary juices, and the considerable dilution of the fluid in which they are suspended, so that but few ever reach the surface of the subepithelial lymphatic glands. On the other hand the administra- tion of too virulent a strain might yield such a violent reaction as to open the way for a mixed infection and an acute inflammation. Perhaps these difficulties will some day be overcome. CHAPTER XIX. Some General Considerations. It is well to avoid teleological explanations in Science. It is, strictly speaking, incorrect to ask why, does an animal possess a particular organ. One may however call attention to homologies and analogies, and one may describe the action of the organ. One may consider the advantages or disadvantages to the individual or the race, examine how the structure arises in the individual and how it comes to be perpetuated in the race. One may even speculate as to what amphimixial chance its occurrence in the species was originally due. In other words, while taking care to avoid the specious, gap-jumping half-truths and errors of tele- ology, it is legitimate to indicate the anatomical, functional, embryological and biological significance of any structure. It is with the biological significance of the subepi- thelial lymphatic glands that this section is concerned. The disadvantage of these glands in the body is their proneness to more or less successful bacterial assaults. Besides becoming the site of a local disease they may become the portals of entry of general disease. Some- times, while the glands do not succumb they are pro- voked to such hyperplasia as to cause mechanical disabilities such as nasal obstruction. The advantage of these glands is — so it is maintained 99 100 IMMUNITY IN HEALTH here — that they are constantly sampling adjacent bacteria and immunising the body against their in- vasion. Considering that they are constantly engulfing bacteria, it is seen how relatively infrequent is their defeat. An occasional attack of tonsilitis or appendi- citis indeed may well be a cheap ransom to pay for immunity from general infections of far greater fre- quency and severity. That the balance of the action of these subepithelial lymphatic glands is advantageous is indicated by their occurrence in the height of their development in the later, more developed and more successful types of animals. The simple forms of subepithelial lymphatic glands merely underlie the epithelium ; in the more complex types some kind of cul-de-sac arrangement is seen, for instance the blind lumen of the vermiform process or the lacunae of the tonsils. The stagnation which results may perhaps favour bacterial growth in close vicinity to the lymph nodules and in some cases the cul-de-sac arrangement may lead to some control over the ex- posure to this growth. Thus the vermiform process may be likened to a test-tube which is filled at intervals with samples of the caecal brew and which can be emptied by the contractions of its own musculature and washed by the mucus of its own secretion. The cul-de-sac arrangement has this weakness that stenosis or blockage of the lumen of the cul-de-sac which may follow one attack of inflammation, will pre- dispose t'o a recurrence of the trouble. Where the subepithelial lymphatic gland is sur- rounded outside by a strong protecting capsule (as for instance the faucial tonsil tying in its fibro-muscular bed), if suppuration occurs its spread is limited. But hyperplasia from excessive work causes an enlargement towards the alimentary lumen and mechanical ill- SOME GENERAL CONSIDERATIONS 101 effects may follow. Conversely, where the subepithelial lymphatic gland is feebly enclosed (as for instance the vermiform process with only the sero-musgular coat between the lymph nodules and the free peritoneal space) suppuration may become very widespread and serious. On the other hand enlargement will not en- croach upon the alimentary lumen or cause harm in any mechanical way. It does, however, seem unfor- tunate that the appendicular artery is an '' end artery." Elsewhere the arteries to the intestines with their dangerous contents anastomose freely with one another up to the margin of the gut. But the artery of the appendix has no collaterals with the ileal or caecal arteries. The arrangement in the rabbit is better. Here the artery supplying the appendix also sends twigs to the adjacent lower end of the ileum. As the ileum receives in addition its own independent blood supply, an anastomosis is formed on the ileum between the ileal and appendicular arteries. A word may be said as to the beneficial position of the noduli lymphatici aggregati which are disposed longitudinally on the antimesenterial side of the gut. Any cicatricial contraction, which might follow an attack of inflammation, will not diminish the alimen- tary lumen nor tend to cut off the blood supply to any part of the circumference of the gut. As to the origin of the subepithelial lymphatic glands it is easy to conceive the attraction of lymphocytes to the submucosa as a result of its occasional invasion by bacteria. The occurrence of lymphocyte-producing centres in this region would be of advantage tending to .the persistence of this variety in the species. The ingestion of bacteria consequent upon lymphoid tissue in the submucosa would enhance the natural powers of resistance and would be a further advantage to its possessor. 102 IMMUNITY IN HEALTH That the subepithehal lymphatic glands are a risk to their owners from the effects of acute attacks of in- flammation can hardly be doubted. If their possession involved no counterbalancing benefits, all variations in the direction of their suppression would have a strong bias in their favour in the struggle for existence and these organs would tend to disappear in the race. In the words of Professor Keith (1912), '' We know from their fossil remains that the great anthropoids are of extreme geological antiquity. Were their appendices (identical in structure with the human appendix) in- jurious or vestigial structures there has been ample time to accomplish their complete suppression." Moreover, any organ that ceases to be of value de- generates. This principle of degeneration is perhaps imperfectly realised. It has probably nothing to do with disuse. " Disuse Inheritance " has long been abandoned as an untenable view. Nevertheless, an organ, the lack of utility of which removes it from the sphere of natural selection, be- comes the sport of variation and chance. Its constancy diminishes with every variation which arises, and the accurate inter-relationship of its parts falls in the average member of ensuing generations. So it is that the eyes of species that have lived for countless gener- ations in the dark have ceased to see. CHAPTER XX. Resume of the Hypothesis and Summary of the Evidence For and Against. The hypothesis is that the subepitheUal collections of lymphoid tissue play an important function in im- munising the body against pathogenic bacteria in proximity to the tissues. These organs secure this general immunity by ingesting the bactieria upon or near the surface of the covering epithelium. The mechanism of ingestion may be called phagotaxis — the lymphocytes leaving the gland-tissue wander to the surfa?ce of the epithelium or beyond into the lumen, engulf bacteria and return with them into the paren- chyme of the gland where the bacteria are slowly over- come or sometimes passed on to a further relay of lymphatic glands for destruction or even via the blood to the spleen and bone marrow. Bacteria are being constantly invited into places which are nearly always impregnable. The bacteria are not only overcome, but a great number of lymphocytes capable from experience — if one may fancifully so put it — of dealing with that kind of bacterium are scattered through the blood stream ready to resist invasion elsewhere. The sub- epithelial lymphatic glands are not only breeding grounds* but also training schools for lymphocytes. The opsonic index against the micro-organisms is in- * The researches of Goodall, GuUand and Paton appear to show that very many of the lymphocytes in the blood are formed in the bone marrow. The whole question of the origin of the white cells in the blood is not yet settled. It is usually assumed that the lympho- cytes do not develop into polymorphonuclear cells, but that the former arise in lymph glands, haemolymph glands and marrow, whilst the latter are formed in the red bone marrow only. 103 104 IMMUNITY IN HEALTH creased : bacteriolysins and antitoxins are produced in large quantities. The subepithelial lymphatic glands confer upon their owners some immunity against the alien myriads of bacteria. They are the immunising stations, or, if you like, the auto-vaccination organs of the body. The line of argument leading to this hypothesis can in brief be indicated thus. The subepithelial lymphatic glands have appeared, reached a high stage of develop- ment and persisted throughout the two highest classes of animals — namely birds and mammals. And this in spite of the apparent anomaly of their great liability to serious infectious disease. They must have a com- pensating function of great value. The continuous in- gestion of bacteria by the subepithelial lympiiatic glands considered together with our knowledge of healthily acquired immunity to infectious disease sug- gests the hypothesis of their auto-vaccinating function. The chief points in favour of the hypothesis may be summarised below : — Biological : — (1) The subepithelial lymphatic glands are only pre- sent in the two latest, highest and most successful classes of animals — namely birds and mammals. They occur without exception throughout these two classes, including phyla of considerable antiquity in a geological scale. Organs of no value become suppressed over long periods of time (Chapter XIX.). As the subepithelial glands are often the seat of disease, their suppression would have been accomplished long ago, had they not some compensating functions of great value. (2) With regard to the mammalian caecum, lymphoid tissue is almost universally present. Sometimes this forms a protuberant mass at the apex. Quite frequently and in many widely different phyla the lumen of the SUMMARY 105 -caecal apex is small. The lymphoid tissue then thickens the wall of this tubular mechanism. The maximum amount of lymphoid tissue is associated with the tubular type and occurs in rodents where the caecum is of immense size and serves for the bacterial decomposi- tion of cellulose. Anatomical : — (1) Position of the subepithelial glands. The lymph nodules are placed directly beneath the epithelium. They are superficial even to the fibres of the muscularis mucosae. (2) Structure of the subepithelial glands. Where the follicles are crowded together the overlying epithelium is folded into pits and recesses so that each lymph nodule subtends the surface. This is well seen in the nasopharyngeal and the faucial tonsils. There are no afferent lymphatic vessels. (3) Distribution of the subepithelial glands. They do not underlie the skin which is thick, resistant, and comparatively free from pyogenic organisms on the surface, but they are found in the throat and along the alimentary tract, where the mucous membrane is thin, permitting of absorption. Moreover they occur exactly at those points where the micro-organisms flourish. The circumpharyngeal ring meets the bacteria entering with the food (and with the inspired air in the case of mouth-breathers). The Peyer's patches, the appendix, and the solitary follicles are placed around the excellent incubating media in the ileum, caecum, and ascending •colon, precisely those parts which are swarming with organisms. The stomach, on the other hand, protected from bacterial growth in its contents by the acid nature of its secretion, is almost free from lymphatic tissue, €xcept towards the pylorus. The whole anatomical arrangement of the subepi- thelial lymphatic glands is such as to bring them into 106 IMMUNITY IN HEALTH close connection with the chief collections of bacteria lying outside of, but adjacent to, the tissues. Physiological : — (1) The subepithelial lymphatic glands in health are continually ingesting bacteria in enormous numbers. By all we know of the production of artificial immunity this ingestion of bacteria must enhance the general powers of the organism against these bacteria. (2) Mere exposure to cases of infectious diseases often serves to confer immunity even in those who do not contract the complaint. (3) The subepithelial lymphatic glands are largest and most active in young children at a period when individuals are acquiring immunity to the various com- mon infections. In old age all lymphatic structures tend to atrophy. Clinical : — (1) The subepithelial glands bear the brunt of the attack in faucial and intestinal infections. Scarlet fever, typhoid fever, and appendicitis are sound exam- ples. In infantile enteritis the Peyer's patches are swollen and infected. As a rule, the tissue which is most seriously attacked provides the greatest number of antibodies. For instance, the power of brain emul- sions to neutralise tetanus toxin has been satisfactorily proved. (Ehrlich, 1906.) (2) The subepithelial glands hypertrophy as a result of repeated infectious diseases. Whooping-cough, scarlet fever, measles, and " colds " (especially if asso- ciated w^ith deficient exercise or unhygienic surround- ings) lead to enlargement of tonsils and adenoids. (3) It is often observed during scarlatinal epidemics that a person may apparently secure immunity by a very mild tonsilitis which is unaccompanied by rash, malaise, or other signs of general injury. (4) In fulminating infections, where septicaemia is SUMMARY 107 early and fatal, the lymphatic reaction is poorly de- veloped. Pathological : — (1) The initial lesion of such diseases as sore throat, typhoid fever and appendicitis is a lymphadenitis. (2) An increase in the number of the glandular lymphocytes in the subepithelial lymphatic glands accompanies most infections of them. (3) The lymphocytes of the blood are formed in part, at least in lymphatic glands. In faucial and intestinal infections these cells are increased in number in the blood. A lymphocytosis accompanies polymorphonu- clear leucocytosis in some pyogenic inflammations, and occurs alone, or predominantly, in Malta fever, measles, variola, infantile gastro-enteritis, some cases of typhoid fever, diphtheria, pertussis, rickets and syphilis. The almost constant presence of lymphocytes about an in- fected area seems to indicate that these cells play an antibacterial part. What is the evidence against this hypothesis and what criticisms may fairly be levelled at it ? Perhaps want of direct evidence is the weakest point in the case presented. The following series of experiments would be almost conclusive. The appendix in the rabbit can be detached from the caecum and sutured so that it opens on the skin. A loop of jejunum (devoid of Peyer's patch) can similarly be isolated and made to open at one end on the surface. Various types of pathogenic bacteria could be introduced into these sinuses, and careful observation made as to : — (1) Whether a stronger dose could be introduced into the appendicular than into the jejunal sinus with- out harmful effects. 108 IMMUNITY IN HEALTH (2) Whether a higher degree of immunity could be produced more rapidly by injection into the appendi- cular than into the jejunal sinus. Until such investigations can be made -the hypothesis can only be tentatively accepted. On the other hand the ingestion of bacteria by the subepithelial lymphatic glands is a firmly established fact, and it is hardly possible for this wholesale ingestion to proceed con- tinuously without enhancing the natural powers of resistance. Another line of opposition may be taken by pointing out that these subepithelial lymphatic glands can be obliterated without apparent harm resulting. Tonsils, adenoids and vermiform appendix have been removed in countless instances and few, if any, ill effects have been discerned. (See pages 94, 95 and 96, however.) These same glands are often so destroyed by suppuration or fibrosis that the lymphoid tissue eventually becomes practically non-existent. And all the subepithelial lymphoid tissue diminishes in quantity after puberty. Further the various collections of subepithelial lym- phoid tissue are absent in a few of the higher and most of the lower types of animals. To all of which it may be replied that an animal can still live when one eye is removed, some animals exist without eyes at all, many successful people's eyesight is defective ; yet we cannot say that the eye has no useful function. BIBLIOGRAPHY BIBLIOGRAPHY AND INDEX OF NAMES Name Reference Page Adami .... "Principles of Pathology," 446 ... . 5 Adami & McCrae . "Test Book of Pathology," 836 ... . 10, 11 Al^AGNA, 1902 . . Arch. Ital. Di Laryngol, XXII., 157 . . 30 Barnard .... "Contributions to Abdominal Surgery" . 90 Baum & Hai,i,e, Anatom. Anzeig., XXXII. (quoted by 1908 .... Schafer, "Microscopic Anatomy," 1912) 48 Berry, 1895 . . Journal of Pathol, and Bacteriol., III., 160 1901 . . Journal of Anat. and Physiol., :K.XXY., 83 27,28,34 36, 56 Birmingham 86 Bizozzero 4, 62 Bland-Sutton, 1891 lyans. Clin. Soc, XXIV., 122 Lancet, I., 547 1908 Clin. Journal, XXXII., 177 4 Bond, 1918 . . . "The Return Immigration of I^euco- cytes," Brit. Med. Journ., II., 277. (See also further references given there). . 72 Browne 20 Butler, 1913 . . Proc. Roy. Soc. Med., Epidemiol. Sect., 120 14 BUTTERFIELD 27, 66, 89 Carpi, Berenger 3 Chassaignac 5 Corner, 1913 . . "The Function of the Appendix and the origin of Appendicitis." Brit. Med. Journ., I., 325 4 Courmont & RocHAix, 1911 . Sem. Med., XXXI., 152 and 236 ... 76 Crowe, Watkins "Relations of Tonsillar and Naso-Pharyn- & RoTHOLTZ, 1917 geal Infections to General Systemic Disorders," Bull. Johns Hopkins Hosp., XXVIIL, 1 94 Da Costa . . "Clinical Haematology" 75 Darwin, 1874 . . "Descent of Man," 2nd Edition, 21 . . 4, 6 Delapield & Prudden .. . . "Pathology" 88 111 112 BIBLIOGRAPHY Name DiGBY, 1911 . 1912 . 1913 . 1913 . 1917 . DrESCHFELD, 1896 Ehrwch, 1906 . Farmachidis & Vatterone, 1913 Flexner & CXark 1911 . . . FtEMMING, 1885 Foster, 1912 . Goodali, & Paton, 1905 . . . GOUGET, 1912 . . Gray, 1916 . . Grauer .... Griffith . . . Gruner, 1913 . . GOODAI.1., GUI^IvAND & Paton, 1904 . GULI^AND & GoODAIvL, 1914 . Hall, 1913 . . . Hassal .... Hays, 1912 . . Reference "Subepithelial Lymphatic Glands," Guy's Hospital Gaz., XXV., 203 .... . "Functions of Tonsils and Appendix," Lancet, I., 150 Lancet, I., 1731 "Subepithelial Ivymphatic Glands," Universal Medical Record, HI., 109 . . China Medical Journal "Enteric Fever" in Allbutt's "System of Medicine" "Studies on Immunity," Section XXXI. Rif. Med., XXIX., 987 Joiirn. Amer. Med. Assn., LVII., 1685 . Arch. F. Mikr. Anat., XXIV "Surgical Removal of Tonsils," Amer. Journ. of Surg., XXVI., 150 . . . . Journ. of Physiol., XXXIII., 20 ... . La Presse Mddicale, 813 "Human Anatomy" "Biology of the Blood Cells" Journ. of Physiol., XXX., 1 . Henke Henle HeTT, 1913 Hett & Butter- field, 1910 . . Huntington, 1903 "The Blood" Guy's Hospital Gaz., XXVII., 347 .. . "Care of Nose and Throat in Children," American Journ. of Obstet., lyXVI., 877 "Anatomy and Comparative Anatomy of the Palatine Tonsil and its Role in the Economy of Man," Brit. Med. Journ., II.. 743 Journ. of Anat. and Physiol., XLIV., 35 "Anatomy of the Peritoneum and Abdo- minal Cavity" Page 2, S 5 3, 79 106 74 46, 47 20 103 10 19 20 20 15 48, 103 75 13 26 65 49 19 20, 27, 30 77, 89 27, 89 27, 90, 37 38, 39, 40 41, 42, 43 44,45 BIBLIOGRAPHY 118 Name Jacobi . . KRKTI.KY, 1909 . 1907 1909 1909 Kkith, 1912 1913 Kei,i.y, 1905 . iClXYNACK. 1893 . Ki^KiN, 1873 L/ANDSDOWN & WII.I.IAMSON . . IvANDSTEINER, Levaditi & •PaSTIA, 1911 . . Lenart .... Ledincham & Arkwright, 1912 lyUCKHARDT & BECHX, 1911 . . LOCKWOOD . . . MCCULI^OCH, 1913 . Macewen, 1904 . macfari.ane Mackenzie, 1912 Reference Annals of Surgery, Iv., 203 and 1342 Lancet, I., 1761 Lancet, I., 1 Proc. Roy. Soc. Med., Suri^ical Section, 67 "Functional Nature of Caecum and Appen- dix," Brit. Med. Joiirn... II., 1599 . . "Human Embr3'ology and Morphology" "Vermiform Appendix" "Pathology of the Vermiform Appendix" "Anatomy of the Lymphatic System" . . Page 74 Brit. Jourri of Surg., II., 306 Sent. Mfrf., XXXI., 296 "The Carrier Problem in Infectious Diseases" Anier. Journ. of Physiol., XXVIII. , 257 . "Allbutt's System of Medicine" , . . Lancet, I., 1827. (See also further refer- ences given there) Brit. Med. Journ., II., 873 MCKILI.OP, 1912 "Massacre of the Tonsil," Maryland Med. Journ., LV., 138 Annals of Otol., Rhinol. and Laryngol., XXI., 416 Australas. Med. Gaz., XXL, 496 Lancet, II., 37 MassEI . . . Mestivier . . Meyer, 1870 . Miller, 1911 . Murchison, 1866 OSLER .... Paemer, 1912 . Med. Chi. Trans., hUl., 191 Anat. Record^ v., 118 Trans. Path. Soc, XVIL, 117 'A Case of Malignant Scarlet Fever,' Lancet, IL, 758 Peyer . . Pybus, 1915 Hunterian Lectures on "Some Infections of the Tonsils," Lancet, I., 1009, 1065 . 4, 102 56, 57 81 3,4 19 78 74 49 76 12 22, 49 5 4 63 4, 5, 74, 96 82 89 3 3 19 4 74 3 49, 80, 83 114 BIBLIOGRAPHY Nafne Reference QUAIN, 1912 . . "Anatomy" RiBBERT ^ Ransohoff, 1890 . Trans. Amer. Surg. Assoc, VIII., 151 . RuFFER, 1890 . . "On the Phagocytes of the Alimentary Canal," Quart. Jotim. of Microscopic Sci., XXX., 481 4 62, 63, Savini, 1914 Santorini, 1724 . "Observ. Anatomicae Venetiis" .... SCHAFER, 1912 . . Presidential Address, British Association, Lancet, II., 675 SoBOTTA .... "Histology" ShaTTOCK, 1916 . "Mechanical Causation of Appendicitis," Brit. Med. Journ., I., 690 Proc. Roy. Soc. Med., Path. Section, 23 Shennan, 1912 . "Post Mortems and Morbid Anatomy" . Smith, Kustace, 1909 ..... "Diseases of Children" Spencer, 1897 . . "Pathology of the Ivymphadenoid Struc- tures," Lancet, I., 722 StapIvEY, 1911 . . "Morphology of the Vermiform Appen- dix," Proc. Roy. Soc. Victoria, 23 N.S., Pt. 11, Art. XXVIII ■ . STARI.ING, 1912 . "Principles of Human Physiology" . . Trethowan, 1912 "Acute Anterior Poliomyelitis," Lancet, II., 938 .....'. Treves, 1885 . . Hunterian Ivectures, Brit. Med. Journ., I., 527 1890 . . . "Surgical Treatment of Typhlitis" . . 1896 . . . "Surgery of the Peritoneum," Brit. Med. Journ., II., 1305 1902 . . . "Inflammation of tfie Vermiform Appen- dix," Lancet, I., 1815 Watney Zahorsky, 1919 Interstate Med. Journ., XXVI., 67 . . Page 22 4, 62 4 ,47, 65, ,61 69 9 3 1 20, 49 53, 70 86 79, 83 72 27,' 36, 30 77 17 74 4,8, 9 4 80 82 3 94, 95' INDEX SUBJECT INDEX Abscess formation — deep sul)maxillary, 85 intraninral, 81 peritoneal, 85, loi peritonsillar, 85, 97 retropliar3^ngeal, 85 of rib, 96 submucous, 85 Actinomycosis — in a kangaroo's tonsil, 77 of the vermiform appendix, 83 Acute anterior poliomyelitis — healthily acquired immunity against, 17 subenithelial glands involved in, 74 Adenoids — cystic disease of, 86 eiffects of removal of, 94, 95, 96, 108 enlargement of, 88, 89 {See also Tonsil, nasopharyn- geal.) Adhesions, 79, 81, 84 Afferent lymphatic vessels, ab- sence of, in subepithelial lymphatic glands, 49, 67, 105 Agglutinins — absence of, in some inmmne carriers. 15 in artificial immunity to typhoid fever by rectal injection, 76 Alimentary immunity, 17 Amazons, epidemic of measles among, 14 Amphibians, junction of small and large intestines in, 32 Anas, bilateral cseca in, 33 Anatomical evidence, 105 Anser, bilateral caeca in, 33 Anthropoid apes, 35, 102 Antibodies, greatest number pro- vided by tissue most seri- ously attacked, 106 Antitoxins — excess production of, 12, 104 production of in subepithelial lymphatic glands, 15 Appendicectomy (see appendix, excision of.) Appendicitis — absence of collateral circulation as cause of, 80, loi actinomycosis as cause of, 83 adhesions as cause of, 81, 84 causes of, 79, 80, 81, 82, 83 Chinese, in, 83 chronic constipation as cause of, 79 diagnosis of, 97, 98 discovery of, 3 earliest recorded case of perfora- tion of, 3 in Europeans living in the tropics, 82 foreign bodies as cause of, 80 intramural abscess in, 81 Japanese, in, 82 kinking as cause of, 81 lymphadenitis as starting point of, 82, 107 morbid anatomy of, 83 mucous cyst as result of, S6 multiple ulcers corresponding to lymphoid nodules in, 85 obliteration of lumen as result of, 8, 9, 86 partial occlusion as result of, 86 peritoneal abscess with, 85, loi polymorphonuclear leucocytes "in, 81, 83 purgatives as cause of, 82 ransom for immunity, as, 100 recurrent attacks, 86, 87, 100 streptococci as cause of, 82 stricture as result of, 80 symptoms of, q8 terminal blood supply as cause of, 80, lOI trauma as cause of, 81 tubercle bacilli as cause of, 83 118 INDEX Appendicitis (cont.) — typhoid fever, in, 82 ulceration absent in, 81 vegetarianism and, 82 " vestigial " character as cause of, 6, 79 wavy contortion as cause of, 79 Appendix vermiformis — absence of collateral circulation, 7 alleged uselessness of, i, 7 alleged vestigial character of, 7 bacteria in ral)bit's, 51, €0 to 66 blockage of lumen due to local- ised lymphoid hyperplasia, 90 blood supply of, loi carcinoma of, 91 chronic focus of disease, as, 10 comparative anatomy of, 35 to 45 congenital absence of, 8 contents of, 23, 81 development of, form of, in man, 57 discovery of, 3 distribution of, in animals, 35 to 45 effects of removal of, 108 embrvologv of, 7, 56 excision of, 97 homologies of structure with that of an 'interstitial lym- phatic gland. 53 inflammation of {see Appen- dicitis.) lymphoid tissue of, 22 malignant disease of, 97 musculature of, 100 obliteration of lumen of, 9 permitting passage of tubercle bacilli, 92 portal of entry of disease, as, 10 position in man, 22 rabbit's, 51 to 5^^ recognition of disease of, 3 secretion of, 9 serial homoloev of, with Peyer's patches, 23 significance of frequent disease of, 9 small lumen of, 7 structure of, in man, 22, 105 thick wall of, 7 trpnsplpntation of, 4 Appendix vermiformis (cont.) — variability in its connection with the caecum, 7 variability in position, 7 variability in size, 7 Arctic explorers, colds among, 14 Armadillos, bilateral caeca in, 33 Astoria, epidemic of measles in, ^4 Atrophy of Ivmphoid tissue, 36, 59 Auricle, muscles of, 6, 7 Auto-vaccination organs, 104 B. B.N. A. terminology, 2 BacilM in rabbit's caecum, 63 Bacteria — presence of in Ivmphoid tissue of cat's tonsil, 60 presence of in lymphoid tissue of dog's Fever's patch, 62 presence of in Ivmphoid tissue of dog's tonsil, 62 presence of in lymphoid tissue- of guinea-pig's Peyer's patch, 62 presence of in Ivmphoid tissue of human adenoids. 60 presence of in lymphoid tissue of human appendix. 65 presence of in lymphoid tissue of human tonsil, 60, 65 presence of in lymphoid tissue of rabbit's appendix, 60, 61, 64, 65 _ presence of in IVmphoid tissue of rabbit's Peyer's patch, 62, 63 presence of in lymohoid tissue of rabbit's tonsil, 60, 62 presence of in subepithelial Ivmphatic glands, 60 to 66 Bacterial moti'ity. 68 Bactpriolys'ns, excess production of, 12, 104 Bats- absence of faucial toTisils i". 28 junction of laree and small in- testines in, 32 Bears, junction of large and small intestines in, 32 INDEX 119 Beaver — absence of faucial tonsils in, 28 hmphoid appendix in, 35, 37 Biological evidence, 104 Birds- bilateral caeca in, 33 junction of large and small in- testines in, 32, 33 lymphoid tissue in, 33, 34, 56, 104 lymphoid tissue in bilateral cseca of, 33, 34 nasopharyngeal tonsil in, 30 single caecum in, 32 Blood infections in immune car- riers, 15 Bone marrow (see Marrow.) Bos Taurus, tubular tonsils in, 30 Bradypus tridactylus, junction of large and small intestines in,' 32 Brain emulsions neutralise tetanus toxins. 106 Bronchial subepithelial lymphatic glands, 19 Bronchitis, 95 Bronchiolitis, 95 Broncho-pneumonia, 95 Bustard, bilateral cseca in, 33 Cascal tonsil, 29, 35 Caecum — bifid caecum, 33 bilateral caeca, 33 distribution of, in animals, 32, 33 •form of lymphoid tissue in, associated with diet, 34 function of, 31 Ivmplioln tissue at apex, 34 lymphoid tissue near ileo-caecal junction, 30, 31, 52 post-natal development of lym- phoid tissue in, 56 single ctecum, 32 Calculi in tonsil (see also Con- cretion) , 4 Calyx gland, 53, 54, 55 Canadian porcupine, lymphoid appendix in, 35, 38 Canis familiaris — csecal tonsil in, 35 caecum in, 32 projecting tonsils in, 28 unusual amount of carbon par- ticles in subepithelial lym- phatic glands of, 69 Carbon particles, ingestion of by subepithelial lymphatic glands, 69, 70 Carcinoma of vermiform appen- dix, 91 Cardiac disease following tonsil- lectomy, 94, 95, 96 Carmine — injections into oral and nasal mucosa, 49 mixed with food, 70, 71, 72 Carnivora — caecal tonsil in, 35 caecum in, 31, 32 Carriers in infectious disease, 14, 15. 76 Castor fiber — absence of faucial tonsils in, 28 lymphoid appendix in, 3s, 37 Cat— ctGcal tonsil in, 35 tubular tonsils in, 30 Cellulose digestion — in rodents, 31 in ruminants, 31 Cellulose-splitting bacilM, 64 Cercopithecus griseo-viridis, tubu- lar tonsils in, 28 Cerebro-spinal meningitis — healthily acquired immunity against, 17 immune carriers during epi- demics, 15, 76 Cervical lymphatic glands — enlargement of, in tonsillectom- ised children, 95 septic disease of, 97 tuberculous disease of, 91, 92 Chemiotaxis, 68 Chimpanzee, lymplioid appendix in, 36, 44 Chinese, appendicitis am.ong, 82 Cholera carriers, 76 Chorea in tonsillectomised chi'- dren, 95 Chronic constipation, 79 Circumpharyngeal ring of lymph- oid tissue, 21 120 INDEX Civet— slightly developed appendix in, tubular tonsils in, 30 Clamydophorus, bilateral caeca in, 33 Colds, chronic enlargement of ton- sils and adenoids after, 75, 106 Coli bacillaemia, 18 Coli bacilli, 17 Coli bacilluria, 18 Colic subepithelial lymphoid tissue, 23 Colourless corpuscles, 9 Compensating function, 104 Concretions {see also Calculi) — in appendix, 4, 80, 81 in tonsil, 97 Conjunctival subepithelial lymph- atic glands, 19 Contact cases in infectious disease, 14 Corvus corone, bilateral caeca in, 33 Coryza — short duration of immunity in convalescents, 14 subepithelial Ivmphatic glands enlarged after, 7c;, 106 Cow- cellulose digestion in, 31 tubular tonsils in, 30 Criticisms of hypothesis, 107 Crow, bilateral cncca in. 33 Crypts of tonsil (see also Lacunae) — chot^ed with lymphocvtes and bacteria in acute inflamma- tion, 78 foreign bodies in, 80 obliteration of, 86 Cyclothurus didactylus — bilateral caeca in, 33 Cygnus, bilateral caeca in, 33 Cysts— in human adenoids, 86 in human appendix. 86 in human tonsils. 86 in hyena's tonsil, 77 Dacelo, i unction of large and small intestines in, 32 Dasypus sexcintus, bilateral caeca in, 33 Dasypus villosus, projecting ton- sils in, 28 Dasyurus — junction of large and small in- testines in, 32 tubular tonsils in, 30 Deafness — due to swelling of lymphoid tissue at pharyngeal end .of tuba auditiva, 97 as indication for erasion of the nasopharvngeal tonsil, 97 Degeneration, principle of, 102 Deglutition, interference with, due to enlarged tonsils, 89, 07 Dicotyles, Ivmphoid appendix in, 36, 39 Didelphys carnivora, tubular ton- sils in, 30 Diphtheria — carriers in, 76 following removal of tonsils and adenoids, 95 healthilv acquired immunity against, 17 less serious if limited to the tonsil, 74 occasional lymphocytosis in, 107 presence of organisms in throat 17 subepithelial lymphatic glands involved in, 74 Diphtheroid bacilli present in throat, 17 Diseases of subepithelial lymph- atic glands, 73 to 92, 106, 107 Dog- caecal tonsil in, 35 caecum in, 32 projecting tonsils in, 28 unusual amount of carbon par- ticles in subepithelial lym- phatic glands in, 69 Dogfish, caecum in, 32 Duck, l)ilateral caeca in, 33 Duodenal subepithelial lymphoid tissue, 22 Dysenterj'— carriers in, 76 commences in solitary follicles 83 INDEX 121 r;dentatfl. iimction of large and small intestine in, 32 Kffercnt lymphatic vessels, bac- teria in, 66 niepliaiit, can-uni in, 33 Hndocarditis, after removal of ton- sils and adenoids, 95 Fiulotbelial cells of lymphoid tissue, 47 Hiiteric fever (see also Typhoid fever), lymphocytosis in, 107 F:nucIeation of faucial tonsils, in- dications for, 97 lipithelioma of tonsil, 91 r-rasion of nasopharynj^eal tonsil, indications for, 97 Erythrizon dorsatus, lymphoid appendix in, 35, 38 Europeans livinjJ in the tropics, appendicitis among, 82 Evolution and the subepithelial lymphatic glands, i, 104 Exanthemata, 73 Excision of adenoids — indications for, 97 a septic operation, 96 Excision of appendix, indications for, 97, 98 Excisions of faucial tonsils, indi- cations for, 97 Eyes, comparison with subepithe- lial Ivmphatic glands as to disabilitv from absence or defect of, 108 Faeces, half weight of formed by bacteria, 17 Faroe Island, epidemic of measles in, 13 Faucial tonsil (sec Tonsil, faucial.) Felis doniestica — cax'al tonsil in, 35 tubular tonsils in, 30 'Felis Leo, ca?cal tonsil in, 35 Felis Pardus, tubular tonsils in, 30 Fibrosis of lymphoid tissue, 36, 59 Fiji, epidemic of measles in, 13. 14 Fingers, injuries and disease of no proof of uselessness, 9 Fishes — caecum in, 32 junction of small and large in- testines in, 32 pyloric caeca of, 33 rectal glands of, 33 wandering amocbocytes in gills of, 27 Foreign bodies — in tonsillar crypts, 80 in vermifortn appendix, 80 Fulminating infections, 74 G. Gangrene — of Peyer's patch, 85 of vermiform appendix, 85 Germ centre, 46 German measles, subepithelial Ivmphatic glands involved in, 74 Giant cells in lymphoid tissue, 48. 53 Gibbon — lymphoid appendix in, 36, 44 projecting tonsils in, 28 Glandular lymphocytes — large, 47, 48, 53, 66, 69. 84 small, 47, 48, 51, 53. 65, 69, 72, 78, 84 Goose, bilateral caeca in, 33 Gorilla— lymphoid appendix in, 36, 43 projecting tonsils in, 28 tuberculous tonsils in, 77 unhealthy tonsils in, 77 Grivet monkey, tubular tonsils in, 28 H. HaematoiJpnous infection of sub- epithelial lymphatic glands, 87 Haemolymph glands, 12 Haemorrhage — from ulceration of solitarv folli- cles of stomach duodenum and ileum. S6 primary, reactionary and secon- dary after removal of tonsils and adenoids, 96 122 INDEX Hairy armadillo, projecting ton- sils, 28 Hare, lymphoid appendix in, 35 Hassal's concentric corpuscles, 26 Healthily acquired immunity, 13, 104 Healthy carriers, 14 Heart— anccsthetic svncope during re- moval of tonsils and aden- oids, 96 disease of, following partial tonsillectomy, 94, 95 endocarditis, following removal of tonsils and adenoids, 94, 95 toxin-weakened in status lymph- aticus, 75 Herbivora, caecum in, 31 Heron, caecum in, 32 Hippopotamus, projecting tonsils in, 28 Hodj?kin's disease, 47, 91 Homo Sapi«?ns — Ivmpboid appendix in, 36, 45 projecting tonsils in, 28 Horse, caecum in, 33 Hottentots, epidemic of measles among, 14 Hyena, cyst in tonsil of, 77 Hyfobates Lar. — caecum in, 33 projecting tonsil in, 28 Hyoerplasia — of subepithelial glands, 88, 89 causes of, 89 results of, 89, 90 Hypertrophy — of sub'^pithelial lymphatic elands after partial removpl, 96 as result of repeated infectious diseases. 106 Hypoth*>sis of the immunisint? function of the subppith«'ii! lymphatic inlands, 103 criticisms of, T07, to8 evidence for, 104, 10=;. to6. T07 further experimentpl evidence required, 107, to8 Hyrax, caeca in, 33 Ileal subepithelial lymphatic glands, 22 in birds, 30 in mammals, 30 in the pig, 30 in the rabbit, 30 Ileo-caecal junction {see Junction of large and small intes- tines.) Ileo-caecal lymphoid patches in the rabbit- distal, 30, 52 proximal, 30, 52 Immunising organs, 15, 100 Immunising stations, 104 Immunity- acquired^ artificially, 13 by introduction into large- intestine, 76, 98 bv oral administration, 93, '98 naturally. 13 healthily or physiologically, pathologically, 13 inherent. 13 Indian python, caecum in, 32 Infantile enteritis, 74, 75, 107 Infectious diseases, 73, 75 Influenza — epidf^mics of, 13. 14 healthily acquired immunity against, 17 presence of organisms of in throat, 17 Ingestion by subepithelial lym- phatic glands — of carmine particles, 70, 71, 72 of dead bacilli, 76 of live bacilli. 68, 106, 108 of soot particles, 54, 69 Inguinal lymphatic glands, tuber- culous disease of, 91 Interstitial lymphatic glands, 2, 16 arrangen'ent in medulla of, 48 nodules in cortex of, 49 Intussusception due to enlarge- ment of last Peyer's patch, 90 J. Ichneumon, slicrhtlv developed ap- pendix in, 36 Japanese, appendicitis among, 82 Jejunal subepithelial lymphoid tissue, 22 INDEX 123 Joint attacks following partial ton- sillectomy, 94, 95 Junction of small and large in- testine, tliree types of, 32, 33 K. Kangaroo, actinomycosis of tonsil of, 77 Keratosis Pharyngis, 89 Kinking of Vermiform Appendix. 79. 86 Klebs-Loffler baci?li {sec also Diphtheria) , 76 Koala, appendix in, 36, 41 Lacunae of Tonsil {see also Crypts of Tonsil) , 20, 100 fig seeds in, 80 stagnation in, 50, 87, 100 ulcers of, 85 Lagomys Pusillus, lymphoid ap- pendices in, 35, 37 Lamp Black mixed with rabbit's food, 70, 71 Large Intestine, subepithelial lym- phoid tissue in, 2^, Laryngeal subepithelial lymphatic glands. 19 Laughing Jackass, junction of large and small intestines in, 32 Lemurs, lymphoid appendix in, 36, 42, "43 Lemur Macaco, lymphoid appen- dix in, 36, 42 Leopard, tubular tonsils in, 30 Lepus cuniculus {see also Rab- bit)— cfecum in, 33 lymphoid appendix in, 35 tubular tonsils in, 30 Leucocytes, excess production of, 12 Leucocytosis, in pyogenic infec- tions, 107 Lingual tonsil, 20 Lion, crccal tonsil in, 33 Little anteater, bilateral caeca in, 33 Ludwig's angina, 85 Lymph nodule, 46 distribution of, 48, 49 less distinct in old age, 48 Lymphadenitis, the starting point Of" appendicitis. 78, 82, 107 dysenteric ulcens, 83 mesosigmoiditis, 83 pyloric ulcer, 78 tonsilitis, 78, 107 typhoid ulcers, 78, 79, 107 Lymphadenoma, 47, 91 Lymphatic glands — active in early life, 57 as antibacterial factories, 12 classification of, 7 interstitial, 2, 16 only present in birds and mam- mals, 28, 104 subepithelial, 2 unit of structure of, 46 Lymphatic leuchaemia, 91 Lymphatic vessels — afferent, 49, 67, 105 efferent, 49, 66 perivascular, 66 Lymphocytes- accumulation as results of chronic bacterial attacks, 10, roi, 107 antibacterial action of, 107 breeding ground for", 103 emigrated, so, 68, 69 excess production of, 103 formed in h^mphatic glands, 48, 107 in epithelium overlying lym- phoid tissue, 49, 53, 54, 55, 69, 71 large, 47 large glandular, 47, 48, S3, 66, 6q, 84 not the chief reaction to infec- tious disease, 15 on surface of tonsils with con- tained bacteria, to, ^4, 35. "68 passage into lumen of alimentary canal, 10, 54, q.s, 68 probably do not become poly- morphonuclears. IS. T03 proportion in the blood, 48, 57 small, 48 small glandular. 47, 48, 51, 53, ,. _ 6q, 69, 72, 78. 84 training schools for, 103 Lymphocytosis — characteristic of various di- seases, 75, 107 124 INDEX Lymphocytosis (cont.) — readily provoked in early life, 57. 76 constantly present in the first years, 57 following tuberculin infections, 75 Lymphosarcoma of tonsil, 91 Lyre bird, bilateral caeca in, 33 M. Macrophage, 47 Malignant scarlet fever, 74 Mammals — caecum in, 32, 33 faucial tonsils in, 28 lymphoid tissue in, 28, 56, 104 h'mphoid tissue in caecum of, 34 to 45 nasopharyngeal tonsil in, 30 occurrence of faucial tonsils in, 28, 30 protuberant type of faucial ton- sil, 28, 2g tubular type of faucial tonsil, 28, 29 Man — caecum in, 32 distribution of subepithelial lymphatic glands in, 19 to 26 lymphoid appendix in, 36, 45 projecting tonsils in, 28 Manatus Americanus, bifid ca2cum in, 33 Manatee, bifid caecum in, 33 Marrow — as antibacterial factory, 12, 16, 103 as source of Ivmphocvtes, 48, 103 as source of polymorphonuclear cells, 103 Marsupials, junction of large and small intestines in, 32 Measles- epidemics of, 13, 14 healthily acquired inmiunity against, 17 lympiiocytosis in, 75, 107 subepithelial glands chronically enlarged after, 75, 106 subepithelial glands involved in. 74 Meckers diverticulum, 6, 7, 8 Membrana tympani, retraction of, 97 Menura victoriae, bilateral c£eca in, 33 Mesenteric lymphatic glands, 49 tuberculous disease of, 92 Meso-appendix, 79, 86 Meso-sigmoiditis, 83 Microphage, 47 Middle ear, svippurative pro- cesses of 90, 95 Mitotic figures, in lymph no- dules, 47 Mode of ingestion of bacteria, 67 Monkeys, tuberculous tonsils in, 77 Monotremes, caecum in, 32 Morbid anatomy of appendicitis, 33 Moudon, projecting tonsils in, 28 Mouth breathing, 90 Mucocele of vermiform appendix, 86 Muscularis mucosae, 49, 105 Musculature of vermiform appen- dix, function of. 100 N. Nasal obstruction, 95 Nasopharyngeal tonsil {sec tonsil, nasojiharyngeal) Noduli lymphatici aggregati {sec also Peyer's patches) — advantage of longitudinal dis- position, lOI discovery of, 3 position of, 22 recognition of disease of, 3 structure of, 22 NoduU lymphatici solitarii — of duodenum, 22, 78 of large intestine, 23, 103 of small intestine, 22, 105 of stomach. 22, 78 structure of, 49 North American Indians, epi- demic of measles among, 14 Nose, suppurative processes of, 89 INDEX 1^5 o. Obstruction of the small intes- tine, enlargement of Peyer's patclies in, 75 Oesophageal subepithelial lym- phoid tissue, 21 Opossum, tubular tonsils in, 30 Opsonic index, 76, 103 Oral administration of bacterial cultures, 98 Orang Outang — CcGcum in, 33 lymphoid appendix in, 36, 43 Ornithorhynchus, ctecum in, 32 Oro-pharyngeal subepithelial lym- phoid tissue, 21 Keratosis pharyngis of, 89 Ostrich, bilateral caeca in, 33 Otis, bilateral caeca in, 33 Ovis musman, projecting tonsils in, 28 Parrot, junction of large and small intestines in, 32 Passage of bacilli through sub- epithefial to interstitial lymphatic glands, 91 in case of Peyer's patches, 92 in case of tonsils, 91 in case of vermiform appendix, 92 Pathogenic bacteria, harmless presence of, in alimentary canal, 17 Pathological evidence, 107 Pathology of the subepithelial lym- phatic glands, 73 to 92 Pavo, bilateral caeca in, 33 Peafowl, l)ilateral creca in, 33 Peccary, lymphoid appendix in, 36, 39 Peptic ulcers, 78 Perforation in appendicitis, 85 Peritoneal abscess, 85, loi Peritoneum, bactericidal powers of, 17 Peritonsillar abscess, 85, 97 Perivascular lymphatics, micro- organisms in, 66 Pertussis {see also Whooping cough) — Pertussis (cont.) — lymphocytosis in, 75 subepithelial lymphatic glands chronically enlarged after, 75 subepithelial lymphatic glands involved in, 74 Peyer's patches {see also Noduli Lymphatici Aggregati) — discovery of, 3 enlargement of, 90 in infantile enteritis, 107 perforation of, in wombats, 77 peritoneal abscess with, 85 permitting passage of tubercle bacilli, 92 position of, 22, 105 recognition of disease of, 3 structure of, 22, 49 in typhoid fever, 106 uncovered by villi, 49 Phagocytic power of glandular lymphocytes, 51, 53 Phagotaxis, 68, 103 Phascolarctus cinereus, lymphoid appendix in, 36, 41 Phascolymis wombat, lymphoid appendix in, 36, 42 Phasianus, bilateral caeca in, 33 Pheasant, bilateral caeca in, 33 , Physiological evidence, 106 Physiology of subepithelial lym- phatic glands, 73 Physiotaxis, 68 Pigmented masses in subepithelial lynlphatic glands, 48, 51, 53 Pinna, extrinsic and intrinsic muscles of, 6, 7, 8 Platypus, caecum in, 32 Plica triangularis, 20 Pneumococci, presence in throat, 17, 76 Pneumonia in tonsillectomised children, 95 Polymorphonuclear leucocytes, 95 in acute appendicitis, 81, 83 Poly-subepithelial lymphadenitis, 83 Porcupine, absence of faucial ton- sils in, 28 Portals of entry of disease, tonsils and appendix as, 10, 74, 99 Post-mortem penetration of tissues by bacilli, 63 Primates, caecum in, 33 126 INDEX Principle of degeneration, 102 Processus i»erniiformis {see Appen- dix Vermiforniis) Pyogenic bacteria, harmless pre- sence of in alimentary canal, 76 Pyloric caeca of fisiies, absence of lymphoid tissue in, '33 Pyloric subepithelial lymphoid tissue, 22 Pyloric ulcer, lymphadenitis the starting point of, 78 Pyrexia, following removal of ton- sils and adenoids, 96 Puma, blightly developed appen- dix in, 36 Purgatives, use of, and appendi- citis, 82 Quinsy, 85 R. Kabbit {see also Ivcpus Cuniculus) caecum ni, 33 calyx glands of, 53, 54, 55 collateral circulation to appen- dix of, lOI lymphoid appendix in, 35, 51, 52, 53, 54, 55 post-natal development of Ij^m- phoid tissue in, 56 tubular tonsils in, 30 Ransom for immunity, 100 Rat, absence of faucial tonsils in, 28 Recurrent attacks of inflammation of the subepithelial lym- phatic glands, 84, 86, 87, 100 Rectal administration of bacterial cultures, 76, 98 Rectal gland of the dogfish, ab- sence of hnnphoid tissue in, 33 Removal of tonsils and adenoids, complications and sequelae of, 94, 95, 96 Reptiles — caecum in, 32 junction of large and small in- testines in, 32 Reptiles {cont.)-^ nasopharyngeal tonsil in, 30 Retiform tissue, 46 Retraction of membrana tympani, 97 Retropharyngeal abscess, 85 Return immigration of leucocytes, 72 Rhesus monkey, unhealthy tonsils in, 77 Rheumatic fever — following partial tonsillectom}', 94 following removal of tonsils and adenoids, 95 healthily acquired immunity against, 17 subepithelial lymphatic glands involved in, 74 Rib, abscess of, after removal of tonsils and adenoids, 96 Rickets, lymphocytosis in, 75, 107 Rodents— caicum in, 33 lymphoid appendix in, 35, 51 Ruminants, cellulose digestion in, 31 Sapraemia following removal of tonsils and adenoids, 96 Sarcoma of tonsil, 91 Sarcophilus satanicus, 32 Scarlatina — following removal of tonsils and adenoids, 96 healthily acquired immunity against, 14, 17, 76, 106 malignant, a case of, 74 polvsubepithelial Ivmphadenitis 'in, 83 subepithelial h mphatic glands : bear brunt of attack in, 74, 106 chronically enlarged after, 75, T06 inflamed in, 76,- 83 Scyllium canicula, caecum in, 32 Septal nasopharyngeal tonsil in the sheep family, 30 Septicaemia in fulminating infec- tions the lymphatic reaction poorly developed. 106 INDEX 127 Septicsemic abscess after removal of tonsils and adenoids, 96 Sexual function, alleged relation cf tonsil to, 5 Sheep — aiecuni in, 33 septal nasopharyngeal tonsil in, 30 Simia satyrus — ctecuni in, 33 lymphoid appendix in, 36, 43 Sniall intestine, subsepithelial lymphoid tissue in, 22 Solitary follicles {see Noduli Lymphatici Solitarii). Soot particles — in glandular lymphocytes, 53, 54} 55> 69 in lymphoid tissue of alimentary canal, 69, 70, 71 Specific fevers, hyperplasia of ton- sils after, 89 Speech, interference with, 90, 97 Spleen — as antibacterial factory, 12, 16, 103 lymph nodules in, 48 Spienomedullary leuchaemia, 91 St. Kilda, epidemic of influenza in, 13 Status lymphaticus, 75, 90 Stenosis of vermiform appendix, S6 Stercobilin, 81 Stomach — lymphoid tissue in, 22, 105 in ruminants, 31 Streptococci — as cause of acute appendicitis, 82 presence in healthy throats, 17 Stricture of vermiform appendix, 86 Struthio, bilateral caeca in, 33 Subepithelial lymphatic glands — absence of in some animals, 104 absence of from mouth, 26 absence of from nasal fossae, 26 absence of from skin, 23, 105 absence of afferent lymphatic vessels, 49, 67, 105 absence of reaction of, in ful- minating infections, 74 active in early life during ac- quirement of immunity, 57, 73, 106 analogous diseases of the dif- ferent ones, 4, 73 appendicular, 22 Subepithelial lymphatic glands {cont.) atrophy in old age, 59, 106 bear brunt of fauciai and in- testinal infections, 73, 106 best developed in highest types of animals, 100, 104 bronchial, 19 characteristics, three general of, 50 circum pharyngeal ring, 21 colic, 23 comparable with a chain of forts rather than with a wall, 26 comparative anatomy of fauciai, ileal and caecal groups, 27 to 45, 104 compensation after removal of, 96 conjunctival, 19 counterbalancing benefits of, 8, 104 disabilities following removal, 94, 95, 96, 108 disadvantages of, 99 discovery of, 3 discovery of ingestion of bacteria by, 4 disease of in other anmials than man, 77 distribution in relation to areas of bacterial activity, 23, 24, 25, 26, 27 duodenal, 22 enlargement of, following re- peated infections, 74 epithelium covering, 50, 105 fauciai, 19 generally, 2 giant cells in, 48 hyperplasia of : causes of, 88, 89 results of, 89, 90, 99 ileal, 22 immunising stations, as, 15, 104 increased number of lympho- cytes in, during infections of, 107 inflammation of, 73, 78 to 87 ingestion of dead bacteria by, /6 ingestion of live bacteria by, 68 jejunal, 22 large intestine, of, 23 laryngeal, 19 life history of, 56 lingual, 20 lymph nodules in, 49 128 INDEX Subepithelial lymphatic glands (cont.) — lymphocytes with engulfed bac- teria on surface of, 68 nasopharyngeal, 20 occurs only in birds and mam- mals, 104 oesophageal, 21 oropharyngeal, 20 organs for acquiring immunity, as, 15, 100 origin of, loi pathology of, 73, 107 physiology of, 73, 106 pigmented masses in, 48, 53 polysubepithelial lymphadenitis, ,*' pyloric, 22 recognition of disease of, 3 recurrent attacks of inflamma- tion of, 4, 86, 87 restrain bacterial activity in the alimentary canal, 10 . results of inflammation of, 85, 86 small intestine of, 22 stagnation of alimentary con- tents in association with, 50, 68, 100 structure of, 49, 105 submucous abscesses of, 85 superficial to muscularis muco- sae, 49, 105 surgery of, 2, 93 " trachoma," 19 Summary of evidence for main hypothesis, 104 to 107 Suppurative middle ear disease after removal of tonsils and adenoids, 95, 96 Suppurating cervical glands after removal of tonsils and adenoids, 96 Supratonsillar fossa, 20 Surgery of the subepithelial lym- phatic glands, 2, 93 Swan, bilateral caeca in, 33 Syphilis— lymphocytosis in, 75, 107 secondary ulceration of tonsils in, 87 Syncope, anaesthetic, during re- moval of tonsils and aden- oids, 96 Tabes mesenterica, 93 Tapir, lymphoid appendix in, 36, 39 Tapirus Americanus, lymphoid ap- pendix in, 36, 39 Tasmanian Devil — junction of large and small in- testines in, 32 tubular tonsils in, 30 Tasmanians, epidemics of measles among, 14 Teleological explanations, 99 Terminal blood supply, 50 Test tube, vermiform appendix as a, ICG Tetanus toxin, neutralised by brain emulsions, 106 Thornwaldt's disease of adenoids, 8*6 Three-toed sloth, junction of large and small intestines in, 32 Thymus — development of, 26 first appears as a subepithelial lymphatic gland, 26 Thymus glands, 27 Tonsil— ctecal, 29, 35 faucial — action during deglutition, 20 advantages of irregular surface of, 49, 50, 100 calculi or concretions in, 4, 97 capsule^f, 100 chronic focuses of disease, 10 compprative anatomj' of, 7, 27, ■2,8, 29, 30 cr37)ts or lacunae, 20, 56 cyst of, 77, 86 development of, 56 diphtlieria limited to, 74 disease of, in other animals than man, 77 embryology of, 7 enlargement of, 88, 89 results of, 89, 90, 100 enucleation of — indications for, 9; for tuberculo'is disease of cervical gla'^U, 98 epithelioma of, 91 , excision of — indications for, 97 sequelae of, 94, 95, 96 fibrosis of, 89 foreign bodies in lacunae of, 80 function of, 4, 5, 6 to 11, 103 INDEX 129 Tonsil (cont.)— history, 3, 4, 5 hyperplasia of, 89 inflammation of — in infectious diseases, 73 as ransom for immunity, 100 recurrent attacks of, 84, 86, 87, 100 unilateral, 75 Lymphadenitis the starting point of inflammations of, 78, 107 _ occurrence in mammalia, 28 permittini? passage of tubercle bacilli, gi " portals of entry " of disease, ;o protuberant and tubular types and their distribution, 28, .29, 30 position of, 19, 20 quinsy, 85, 97 recurrent attacks of inflamma- tion, 84, 86, 87, 100 relations of, 20 sarcoma of, 91 secretion of, 9 stagnation in lacunae of, 5G, 100 structure, 20, 49 tuberculous disease in mon- keys*, 77 ulceration of in secondary syphilis, 87 lingual — deep submaxillary !' abscess with, 85 position of, 20 structure of, 20 nasopharyngeal {see also Aden- oids.)— advantages of irregular sur- face, 50 discovery of, 3 effects of removal of, 94, 95, 96, 108 enlargement of and its results, 89,^90 erasion or» excision of — indicj>*idns for, 97 position'of, 20 recog^iition of disease of, 3 structure of, 20, 49 Tonsillar recess, 20 Tonsillar sinus, 20 Trachonia glands, 19 Trauma as cause of appendicitis, 81 Trichosurus Vulpinus, lymphoid appendix in, 36, 40 Tropics, appendicitis in, 82 Tuba auditiva — lymphoid tissue at lower end, 21 when swollen, as cause of deaf- ness, 97 Tubercle bacilli — indisious passage through sub- epithelial to interstitial glands, 91 presence in alimentary tract, 18 Tuberculin injections, lymphocy- tosis following, 75 Tuberculosis — artificial immunity against, by introduction of dead bacilli into the rectum, 98 bovine type, 18 of cervical lymphatic glands, 91, .98 . ' of ileocolic lymphatic glands, 92 of inguinal lymphatic glands, 91 of tonsils — in man, 92 in monkeys, 77 of vermiform appendix, 83 Typhoid- appendicitis in, 82 artificial immunity against, bv introduction of dead bacilli into the rectum, 76, 98 carriers in, 76 healthily acquired immunity against, 17 lymphadenitis the starting point of ulcers, 78, 107 lymphocytosis in, 75, 107 Peyer's patches bear brunt of in- fection in, 106 subepithelial glands involved in, 74 typhoid bacilli in lymphoid no- dules in, 79 without ulceration, 79 U. Ulceration — in appendicitis, 85 in dvsenteric colitis, 83 peptic. 78, 86 of Peyer's patches, 79, 86 130 INDEX Ulceration (cont,) of tonsils, 78 in secondary syphilis, 87 in tuberculosis, 92 in typhoid fever, 79 Unit of structure of lymphatic glands, 46 Variola — healthily acquired immunity against, 17 lymphocytosis in, 75, 107 Vegetarianism and appendicitis, 82 Vermiform appendix or process (sec Appendix vermiformis) Vestigial structures, i, 6, 7 •'Virgin soil/^ 13 Viverra Civetta, tubular tonsils in, 30 Vulpine Phalanger, lymphoid ap- . pendix in, 36, 40 W. Weasel, junction of large and small intestine in, 82 Wedge-tailed eagle, bilateral caeca in, 33 Whale, junction of large and small intestine in, 32 White-handed Gibbon, caecum in, 33 Whooping cough {sec also Per- tussis)— healthily acquired imnmnity against, 17 leading to enlarged tonsils and adenoids, 106 Wombat — lymphoid appendix in, 36, 42 perforation of last Peyer's patch in, 77 o csi; -J A? n PLEASE DO NOT REMOVE CARDS OR SLIPS FROM THIS POCKET UNIVERSITY OF TORONTO LIBRARY iP. Digby, Kenelffi Hutchinson 181 Inmunity in Health D54 Biological