The nature of immunity - Part II

Correspondence Address:
M L Kothari
Department of Anatomy, Seth G.S.Medical College, Parel, Bombay-400012
India

Source of Support: None, Conflict of Interest: None

Check

PMID: 1032825

An unorthodox approach to the nature of immunity is presented differentiating it from reactivity. Immunity is a gestalt force, all to the good of an individual, staking the concept of auto-immunity ridiculous and rejectable. Reactivity is a vector force that may protect or persecute; it is basically concerned with restoring the integrity of the human body. The concept of cytologue amplifies the idea of integrity, and allows reactivity to fight a microbe, heal a wound, reject a graft, and gives rise to "auto-immune' disorders, by a concerted Cellulohumorovascular Response.

:: Towards a Definition of Reactivity

breed what is called auto-immunity, (c) one's neurones and muscles immuno­logically may prove more foreign than many a microbe.

There are, then, no self cells, but a selfing process that occurs, in man for example, during the later half of intra­uterine existence and early part, of post­natal life (vide supra) whereby the body decides what it is going to treat as its own. The human embryo, constituting a more-or-less completely formed human individual by about the 10th week of ges­tation, ^[3],[27] is made up of suicytes-its own cells. The process of "immunologic maturation," CARE, or selfing allows the suicytes to be classified into selfed/ CAREd suicytes and unselfed/unCAREd suicytes (neurones, for example). In a chimera, the guest cells are accepted as self, by being selfed. The guest cells, thus constitute, selfed allocytes. Any­thing else-cells, cell products, inanimate material - not belonging to the selfed category (suicytes/allocytes) constitutes not-self, Suicytes/sui-elements that, through injury, mutation, degeneration^α or any other process like binding to a drug or microbial, cease to confirm to the selfed-pattern become deselfed, and turn into actants or "auto-antigens." (The reactocytic hell that a body lets loose on a kidney in SLE is because of the deselfing that the renal tissue undergoes from time to time. Deselfing is the basis of "auto­immunity"). While at terms, the good, bad, and indifferent aspects of reactivity can be acronymically expressed as PAR, CAR, and KAR. Par is ProAuto Reacti­vity, CAR is ContraAuto Reactivity, and KAR is a hybrid term to be read as Kore­monai Aremonai Reactivity. Needless to elaborate, CARD stands for ContraAuto Reactivity Disease, hitherto called auto­immune disease. Severe anaphylactic re­action is an extreme example of CARD, while allergy or hypersensitivity repre­sents it in milder form.

Any reactive process is made up of PAR, CAR and KAR in varying propor­tions: tuberculous meningitis, for exam­ple, is successfully combated by PAR, but it leaves behind a trail of paralyzed ner­ves engulfed in the fibrous tissue gene­rated by the antitubercle PAR. May be, that is the reason why immunity stands for no reactive quarrel, as far as possible. As a wag put it, `in a war it is not impor­tant who is right, but who is left.' The body follows this lesson by insisting that immunity is absence ''avoidance of reacti­vity.

The above principle found its immediate and profound impact in the Listerian et Senimelweissian principles of asepsis and antisepsis which are, apart from immun­ity, the means of avoiding a confronta­tion or a reactive showdown with the mic­robes - a kind of Swiss neutrality, a re­fusal to enter into a potentially dangerous dialogue. The gains have been the tour de force of modern medicine: "Actually. in terms of lives saved, the development of sanitary measures such as antisepsis and sanitary control of food, water, and insect vectors, represents the greatest single lifesaving achievement in medical history.'' ^[56]

Reactivity may now be defined as cel­lulohumorovascular activity comprising focal, local and systemic formation and presence of extraneous specific and non­specific cells and humours that aim penul­timately at restoration of the body's in­tegrity to as near to status quo ante possi­ble, the reactivity response having been excited by disturbances in the cytologue due to the presence of (i) damaged, dead or deselfed suicytes/sui-elements, (ii) any inanimate material (iii) microbes, or (iv) all ocytes/allo-elements, the entire process passing through the phases of re­cognition, reaction, removal of the dis­turbing cells/elements, and restitution to status quo ante with the help of such pro­cesses as replication of missing cells (e.g., epithelial cells, liver cells), vascu­larization, devascularization, and contrac­ture of the matriceal fibrous tissue. Na­ture's masterstroke vis-a-vis reactivity was to ask the ubiquitous fibroblast to provide the fibrous scaffold for any reac­tive focus, so that the inherent contracti­bility of the fibrous tissue would help eventually to reduce the focus to the smallest possible size, on completion of the job.

:: Reactocytes/Reactocompetence

Halliday, ^[25] the author of "Glossary of Immunological terms" defines immunocy­tes as "Cells concerned in immunity, es­pecially antibody-formation". The latter italicized part of the definition betrays the all too common antibody-ism. When it comes to defining immunocompetence, the antibody-obsession is no less: "Im­munocompetent cell: Any cell which can be stimulated by antigen to either form antibodies or give rise to cells which form antibodies". ^[56] If the oversung antibody has proved such a grand illusion as far as immunity goes, why not extend the honour of immunocompetence to a mac­rophage or to an epithelial cell which, with palpable competence, provide posi­tive protection to an individual. Any cell, then, that partakes in offering immunity is an immunocyte/immunocompetent cell. The "immunocyte" in the definitions stat­ed above can be reactocytically under­stood by being designated specific. A specific reactocyte is one which secretes a specific reactin against an actant or can combine directly and specifically with that actant. When such a process occurs in vivo, the background but vital perfor­mance is by the unsung macrophages, complements, reticuloendothelial cells, and so on each of which is a reactologi­cally competent in its own right.

:: PAR, CAR and Vaccination

Vaccination, often called active immun­isation, illustrates very well the funda­mental differences between immunity and reactivity. Firstly, it is wrong to call such a procedure as immunisation for what is gained is not immunity but reac­tivity which may be absent, adequate, in­jurious or fatal. (The fallacy is much greater when injection of ATS or any other serum is called passive immunisa­tion, which could be but a way of killing a person). Small pox vaccination pre­sents a case in point. It may not take. So often, it succeeds in arming the indi­vidual with adequate reactivity against the virus. It may prove a nuisance, since the reaction of the body to the vaccine may lead to "progressive nec­rosis of the skin at the vaccination site and the development of metastatic lesions in other areas of the skin and in the vis­cera". ^[48] H Sometimes, it may lead to "postvaccinial perivenous encephalitis" which is nothing but fatal. ^[53] It should thus become clear that vaccination - no longer to be turned immunisation - is blessed with PAR, fraught with CAR and is basically a process of eliciting in the individual what may be called thwartive reactivity, outlined below.

:: Thwartive Reactivity

Thwartive (from thwart - "to oppose successfully; to prevent from. accomplish­ing a purpose" ^[47] ) reactivity (also called thwartivity) is the ability of an individual to knock a microbe, an allocyte or an allo-element out of action by means of cells and/or humours, specific and/or non­specific on the latter entering the indi­vidual's body past the immunity barrier, this being an active arrestive response by the organism against the intruding ele­ment with which it came in contact ear­lier, accidentally or by design.

The evolution of thwartivity is import­ant both ontogenically and phylogenical­ly-as a phenomenon evolving both hori­zontally (in a herd) and vertically (through generations). For example, in­fection with tubercle bacilli, for the first time, in an individual or a group excites a reaction that may be mild, moderate or severe, silent or symptomatic. This can be called the initial reaction which ser­ves to (a) fight against the intruder, but more importantly, (b) to prime the or­ganism/s to react thwartively-thwartive reaction - against subsequent infections by the mycobacteria. At phylogenic level, the evolution is slightly different. A generation gets infected by tubercle only to succumb to it. The lethal brush with the microbe however does not go wasted, for the subsequent genera ions grow more and more resistant to the bacillus, by ex­hibiting strong thwartive capabilities. It is a little emphasized fact of macromicro­bial. interaction that, without any help from the much-vaunted antibiotics, man­kind in a generation and through gene­rations has emerged victorious against this or that microbe - fantastic feat by Nature at mass "immunization" or vacci­nation, allowing us to generalize that thwartive reactivity is our license to sur­ vive.

The above is best illustrated by a few, justifiably lengthy, quotes from some leading works on microbiology: "In ­observing the progress of tuberculous in­fection, it is important to differentiate between that which occurs following in­fection of a person who has had no pre­vious experience with Mycobacterium tuberculosis and that which occurs in a person who has previously been infected. In the former instance, there develops what we call primary infection or pri­mary disease. In primary infection, one or more mycobacterial cells lodge within an alveolus where they are rapidly phagocytosed, most likely by alveolar macrophages. Because of their resistance to destruction, these virulent mycobac­teria multiply within these macrophages almost as rapidly as they do in an arti­ficial culture medium. However, since the maximum rate of multiplication is still slow, the increase in numbers of vi­rulent tubercle bacilli will be slow. Therefore, the appearance of symptoms or pathologic condition due to the infec­tion may require several weeks. When the number of tubercle bacilli becomes significant, an inflammatory cellular exu­date appears. Therefore, primary tuber­culous infection is characterized by be­ing pneumonic.
"In spite of the cellular reaction, there is little resistance to the multiplication of the tubercle bacilli, and soon after infec­tion, dissemination from this focus oc­curs. This dissemination is primarily by way of the lymphatics, and there is early extensive involvement of The regional (hilar) lymph nodes. At the same time, there is spillover from the lymphatics in­to the bloodstream with a seeding of viru­lent tubercle bacilli in all of the organs and tissues of the body. In a small pro­portion of persons thus affected, this pro­cess advances until widespread tubercu­lous disease, and possibly death, occurs, provided treatment is not given. In the majority of such persons, however, after a period of a few weeks the following dramatic changes are seen. The rate of multiplication markedly decreases, the pneumonic process resolves, and the dis­semination of tubercle bacilli, to other or­gans ceases. The same changes also oc­cur in all other tissues where tubercle bacilli may reside. Resolution of the disease process may proceed to a point such that, in many people so infected, lit­tle or no residue of the infection remains. In some, particularly in infants and chil­dren, all that may remain may be a Ghon complex; that is, a small calcified nodule in the lung and enlarged hilar lymph no­des.

Coincident with the changes described above, two immunologic manifestation ap­pear. First, the affected individual be­comes tuberculin positive. In other words, he shows reactions of delayed hy­persensitivity to certain low molecular weight proteins or polypeptides which are found in the tubercle bacillus. We have already noted that mycobacteria marked­ly promote induction of delayed hyper­sensitivity to other proteins so it is no wonder that they exert the same effect for their own protein constituents. Secondly, the macrophages within which the tubercle bacilli previously were able to multiply so readily now have acquired the ability to markedly inhibit the multi­plication of virulent tubercle bacilli. Therefore, since the tubercle bacilli are now unable to grow within these cells, the disease process is arrested and, with time, many of the virulent cells are des­troyed. In other words, the diseased per­son has now become immunized as a con­sequence of the reaction of his immuno­logic system to the infection. This type of immunity is known as acquired cellu­lar immunity." ^[62] . The foregoing drives home the evolution of thwartivity at in­dividual (ontogenic) and group level. A passage from Dubos ^[15] renders clear the phylogeny of thwartivity: "Precise ob­servations are available concerning the changes in the clinical manifestations of tuberculosis among some Indian tribes of North America. In the first and the second generations to suffer from the tuberculosis epidemic in the Qu'Appelle Valley reservation, extensive glandular involvement was the rule in school-age children. Meningitis, generalized miliary disease, and bone and joint disease were extremely frequent-evidence of inability of the host to localize infection. In 1921, at a time when the generalized epidemic was in the third generation, the disease showed a greater tendency to localize in the lung and to exhibit a chronic course; the mortality was falling, and glandular involvement had dropped to 7 per cent among school children. This latter mani­festation of high susceptibility to tuber­culosis has continued to decline steadily and was seen in less than 1 per cent of children in the 4th generation. In other words, while tuberculosis among the Amerindians exhibited at first a very acute course, different in character front that observed in people who have had contact with the tubercle bacillus for several generations, now it is undergoing a change which makes it resemble the more chronic type of disease commonly seen among Western people under normal conditions." Antia ^[2] makes a comparable observation about mankind's thwartive re­sistance to the much-feared leprosy ba­cillus, the resistance having evolved over generations: "The human being is much less susceptible to leprosy than to tuber­culosis or many other diseases; and even if he should develop the infection, about 80 per cent of the cases are self-healing."

Having presented the concept of thwar­ tivity-the arrestive cellulohumoral res­ponse by an organism against an actant (microbe, toxin, a graft) by which the organism was primed earlier-a few im­portant generalizations on it are in order: (1) If reactivity against a foreign element can be described as a double-edged wea­pon, thwartivity represents the self-pre­serving edge, while combativity (comba­tive reactivity) (see below) represents the self-destructive edge. (2) Apart from providing the faculty of wound healing, the CelluloHumoroVascular Reactive System is basically evolved and geared to provide thwartivity against the micro­bes so as to minimise reactive quarrels and the attendant dangers. Evolutional­ly, it has little to do with either tumor immunity or transplant immunity, either Robert Good or Christiaan Barnard. Im­munity has nothing to do with the fetal engraftment onto a mother. Maternal re­activity is concerned in this process, by being conspicuously kept out through means not yet understood, but sialomucin­coating of fetal trophoblast is the prime suspect. Sialomucin, or whatever the substance be, illustrates the principle ^[36] that in Nature, functional necessity is the mother of structural innovation. (3) Next to immunity, thwartivity represents the second line of defense mediated lar­gely by the mopping macrophages (pha­gocytes) and the inactivating antiba­dies. (4) Resistance is another name for uncompromised immunity and/or good thwartivity, while susceptibility im­plies compromised immunity and/or poor/absent thwartivity. The state of re­sistance/susceptibility, in an individual, is determined by a dynamic balance that could change from hour to hour. (5) All forms of vaccination aim at induction of thwartivity, and often take advantage of cross-reactivity - Jerner successfully ex­ploiting, in 1796, cowpox virus to thwart smallpox is a classic example; ^[14] others are the use of attenuated organisms (BCG) and toxoids. (6) Antimicrobial agents act by preventing/cutting short a reactive quarrel, hence affording thwartivity of a kind. Their extraneous nature and their multiple effects have been responsible for the dangers they pose. (7) Thwartivity may uncommonly be too severe - ana­phylactic (truly, hyperphylactic), prov­ing once more that reactivity is not an unmixed blessing. Generalizations (1) to (4) merit elaboration, as follows.

:: Combative Reactivity

In absence of thwartivity, an organism enters into a regular combat - an eye for an eye, a tooth for a tooth - with the intruding microbe, and the result is not always good for the host. A reperu­sal of the large quotations above would show that both in ontogeny and in phylogeny, until such time that thwartivity de­velops as a force, combativity involves sacrifice of tissues or lives. Viral hepati­tis, thanks to successful combativity and to the enormous regenerative power of liver, can mean a normal liver again, but during the acute quarrel, the host is on a precipice. The victory may sometimes be pyrrhic for the eventual outcome may be cirrhosis. Combative reactivity may pull the host out of tuberculous meningi­tis, but the aftermath may be bilateral oph1halmoplegia from nerves paralyzed by fibrous engulfment. Like in day to day life, a reactive quarrel averted, is a quar­rel won.

A stage in between good thwartivity and combativity (or a combination of the two) is the stage of chronic, but localiz­ed, inflammation or granuloma, where the protracted battle restricts itself to a focus without endangering the life or some vital parts of the organism. Reference to the quote from Dubos, above, will now amp­lify the significance of his statement that, "the disease showed a greater tendency to localize in the lung and to exhibit a chronic course." Most of the chronic granulomas represent this combination of combativity and thwartivity-the former unable to reach a definitive result in fa­vour or against the host, the latter suc­cessful enough to contain the disease to a small area.

:: Resistance versus Susceptibility

Often these terms are used in an ab­stract manner, but this conceptual vacancy can be mitigated in the light of our appreciating the nature of compro­mised immunity and/or nil/impaired thwartivity.

As was pointed out much earlier, a prime immunity mechanism is an intact epithelial cover. A large closed fracture may have an uneventful course but a small compound fracture may not, for the in the latter case, immunity was compro­mised for want of a few epithelial cells. The modern therapy of "immunosuppres­sion" involves the use of almost lethal cytotoxic agents that destroy epithelia from head-to-foot and inside-out., and it is then not surprising that the hitherto most harmless commensals turn into le­thal pathogens. ^[43] The fault lies not with the pathogens but with the compromised immunity barrier. Cosmetics to decdorize the vagina may only lead to resistant vaginitis and candidiasis-a price paid for disturbing the normally operative me­chanism. Lack of asepis and antisepsis, in surgery, is a flagrant violation of the im­munity barrier, an error that many an antibiotic may fail to rectify. The change of normal microbial flora, so common thanks to the modern antibioticism ^{[28],[42],[43]} can mean impaired immunity with re­sultant susceptibility. Resistance, in im­munological terms, then means uncompro­mised immunity mechanisms - of every type and on every front.

The entry of a microbe into a virgin individual or a population is not resisted for want of thwartivity, with the result that a person, group or a generation ap­pears as susceptible to the microbe, the susceptibility being expressed as comba­tive reactivity with the odds often against the host. The susceptibility, however, changes into resistance wish the evolu­tion-individually, groupwise, phylogenically-of good thwartivity. On the other hand thwartivity, natural to an indivi­dual, may be impaired under varied con­ditions. Protein malnutrition may mean poor digestive enzymes right at the level of the scavenging macrophages so that the engulfed tubercle bacilli instead of being digested and eliminated, may multiply un­inhibitedly ^[12] to eventually excite comba­tive foci called clinically and pathologi­cally as active tuberculosis. Hypercorti­cism, resulting from stress ^[33] or by medi­cation, seriously impairs thwartivity, con­verting resistance into susceptibility. ^[28]

The foregoing discussion on resistance/ susceptibility may drive home a point that in an encounter between a microbe and man, the latter may play a more de­cisive role in inviting/avoiding infection. Such eulogistic accounts of man's "suc­cess" against microbe as Paul de Kruif's Microbe Hunters and such anthropocen­tric labelling of microbes as "microassa­sins" ^[50] have fostered the idea, in minds medical and lay, that the microbes are the villain-of-the-piece. In reality, the Homo sapiens may be the greater villain. Such elaboration is pertinent in the pre­sent article for "immunity" from within ^[23] and antibiotics from without ^[50] have been hitherto held as "protecting" man against the microbial "enemy." The truth is prob­ably different as follows.

:: Microbes versus Man

In the heading above, ordinarily Man would have had the pride of place, but biorealistically he can't, for he is too puny in comparison with the Microbes: "Their prevalence is stupendous; it has been cal­culated that by weight they exceed all animal life on earth twenty times. Their numbers are incalculable and beyond comprehension." ^[21] Notwithstanding this awesome microbial dominance, clemency seems to be the rule, cruelty an excep­tion. "By far the most common type of relationship between an infectious agent and the host," Wood ^[58] generalizes, is of the "nondestructive' symbotic or commensal" variety. The human population explosion has had its start as early as 1400 A.D., ^[59] much before Pasteur, Lister or Domagk had offered anything against the "micro-assasins." Man is, what he is, because of-and not despite-the mic­robes.

In interactional terms, the microbial plagues of the past were an outcome of man's alarmist ^[51] combative reaction against a particular microbe, this being man's initial reaction towards any mic­robe. Later, symbiosis prevailed, on the dawning of thwartive wisdom-the prin­ciple that a quarrel avoided was a quar­rel won. This axiom had its most impres­sive application-"the greatest lifesaving achievement in medical history" ^[56] -in the simple practices of sanitation, antisepsis, and asepsis, Man's penchant for entering into a combat with a microbe has been, is, and will be his own undoing.
"The fault dear Brutus, is not in our stars but in ourselves." (Shakespeare). We must now realize that it is not the microbe that is pathogenic, but man's re­action to it that makes it so. Either every microbe is pathogenic, or none is. This has been stated very well in The Biologic and Clinical Basis of Infectious Diseases, published in 1975. In an early chapter, Youmans ^[60] points out that although we have so far regarded "pathogens" as mic­robes possessing some unique disease-pro­ducing power, it must be emphasized that such special pathogenic characteristics of microbes are probably the exception ra­ther than the rule. "It is now recognized that many bacteria not ordinarily regard­ed as pathogens have the capacity to pro­duce infection and disease, and this capa­city will depend more upon host defense mechanisms than upon any special charac­teristics of the microbial cell." ^[60] Man, know thyself, and the limitations of the powers of thy "immunity", and antibio­tics.

Antibiotics generate "immunodefici­ency." ^[46] This they do by interfering with the macromicrobial dialogue, a necessary prelude to the emergence of effective thwartivity in an individual or a group. They also render a person vulnerable to other infections by upsetting the micro­bial flora. The dangers they pose led Raeburn ^[46] to prophesize, in 1972, that "In years to come, the story of antibiotics may rank as Nature's most malicious trick" on man. Hard-core statistical facts more than support the above prognosis: Dubos ^[15] begins his chapter on microbial diseases with a cynical heading-"THE SO-CALLED CONQUEST OF MICRO­BIAL DISEASES," pointing out that des­pite so much blah blab on victory over microbes, paradoxically the percentage of beds occupied by patients suffering from infection is now as high as it was 50 years ago. A recent editorial ^[17] in the BMJ painfully generalizes that the mortality from cerebellar abscesses has risen from 25% in the fifties to 55% in the seventies despite all the antibiotics now available, and that today brain abscesses carry the same mortality as they did in the hand of Macewen in 1893. Paterson ^[42] concedes that antibiotics had, had their day, but the gains have been more than offset by a steady increase in the incidence of infections caused by microbes previously considered much less pathogenic or even non-pathogenic. Youmans too is justifi­ably cynical in attributing the foregoing to "Medical Progress. He concludes that while managing-an intractable infection, what is needed is not the "right"antibiotic, but an understanding and the rectification of the disturbed macromicrobial interrelationship. No antibiotic, extant or on the horizon, could ever compensate for a combative focus that a ventricular shunt or a valve excites by the mere fact of be­ing foreign, nor could it mitigate the cy­totoxic ravage perpetrated by modern im­munosuppressive advances. The unsur­mountable problem of microbial resista­nce to antimicrobials is too self-evident to merit any detailing here.

The handwriting on the "immunologi­cal" wall is clear: Fleming and his fol­lowers have had a past, but Semmelweiss and Lister have a perennial future. The best "immune" response is one that is not needed-as a response or a reaction. Not­withstanding the eulogies by Robert Good-"the dominant figure of modern immunology" ^[49] - so-called "immunity" and "immune-reaction" are poorly trust­worthy in man's battle against microbes. It has been customary to call the latter parasites; the truth is that microbes are the host, and man is but a guest in ' the microbial world. It will be a great day for mankind when "so useless" modern medicine will stop bragging about anti­biotics and antibodies, and come to ecolo­gical terms with the mighty microbes.^[15]

:: Summing Up

Biorealistic appraisal -of the nature of "immunity". renders imperative. the. reali­zation thatt the era of immunologism, Leleism (Immunity as everyone's: fool); and Goodism (Immunity can knock off microbes with one hand, malignant cells with another) should come to an end, the sooner the better. The swelltide of im­munologismic arrogance has bred resear­chosis, papyrosis, and confusion worse confounded from unintelligible double-speak, all climaxed recently by "the scientific scandal of the century," the fa­mous la a ffaire de Summerlin from the prestigious Sloan-Kettering Institute, New York. ^[49] Perusal of Burnet's ^[10] Genes, Dreams and Realities makes it painfully clear that the much-vaunted molecular biology is failing us everywhere to which immunology is no excep­tion. The future of immunologic research is clear-there is no future. The disco­very of "auto-immunity" has added a can­cerous mass of facts, unlikely to make much beneficial sense vis-a-vis man and his maladies.

Immunity and reactivity are gestalt processes that, like most natural proces­ses, permit wider understanding but lit­tle interference. Immunity is the liaison officer between the self of man and the not-self microbes, and sees to it that man keeps afloat in the microbial ocean. Re­activity is far more complex, but its rai­son d'etre is to recognize any disturbance in cytologue, react and reject the distur­ber be it from without or within, and finally to restore things to status quo ante. No wonder, then, that aseptic inflamma­tion, septic inflammation, "auto-immun­ity," wound healing, graft rejection or the rejection of an implanted glass piece, one and all, evoke basically the same Cellulo­HumoroVascular Response.^[65]

 

:: References

1.	Adams J. C : Outline of Fractures - Churchill Livings tone, Edinburgh . London, 1972.
2.	Antia, N. H.: Letter to the editor, Times of India, Bombay, March 28, p. 8, 1976.
3.	Bhatnagar, S. M. and Kothari, M. L.: Essentials of Human Embryology, Kothari Book Depot, Bombay, p. 40, 1969.
4.	Bierens de Haan, B., Eliis, H. and Wilks, M.: The role of infection on wound heal­ing, Surg. Gynec. & Obstet., 138: 693-700. 1974.
5.	Boyd, W.: A Textbook of Pathology. Structure and Function in Disease, Lea and Febiger, Philadelphia, 1970.
6.	Brand, P.: Quoted by Wilson, Dorothy, C. in, Ten Fingers for God, McGraw-Hill, New York, 1965.
7.	Britton, S., Thoren, M. and Sjoberg, H. E.: The immunological hazard of Cu­shing's syndrome. Brit. Med. J., 4: 678­682, 1975.
8.	Burnet, F. M.: Cell Immunology, Mel­bourne Univ. Press, Carlton, 1969.
9.	Burnet, M.: Immunological Surveillance, Pergamon Press, Oxford, 1970.
10.	Burnet, F. M.: Genes Dreams and Real­ities, Medical and Technical Publishing Co., Bucks, 1971.
11.	Calland, G. H.: Iatrogenic problems in end stage renal failure, New Eng, J. Med., 287: 334-336, 1972.
12.	Dannenberg, A. M., Jr.: Macrophages in inflammation and infection, New Eng. J. Med., 293: 489-493, 1975.
13.	De Robertis, E. D. P., Nowinski, W. W. and Salz, F. A.: Differentiation, growth, renewal and senescence of cell populations. In. Cell Biology, W. B. Saunders, Phi­ladelphia, p. 340, 1966.
14.	Dubos, R.: The evolution of medical microbiology. In, Bacterial and Mycotic Infections of Man, Ed. Dubos, R. J. and Hirsch, J. G., Pitman, London, p. 1, 1955.
15.	Dubos, -R.: The evolution of microbial diseases. In, Bacterial and Mycotic In­fections of Man, Ed. Dubos. R. J. and Hirsch, J. G., Pitman, London. p. 20, 1965.
16.	Dubos, R.: Quoted in, Familiar .Medical Quotations, Ed.. Strauss, M.B.,,. Little Brown & Co., Boston, p. _ 241 b.,..1968.
17.	Editorial: Brain- abscess, Brit. Med. J­3: 3: 504-505, 1975.
18.	Florey, E.: An Introduction to General and Comparative Animal Physiology, W.B. Saunders, Philadelphia, p. 228, 1966­
19.	Florey, H. W.: Inflammation, in, Genera. Pathology, Ed. Florey, L., Lloyd-Luke Ltd., London, p. 22, 1970.
20.	Fould, L.: Neoplastic Development. I. Academic Press, London, New York, p 112, 1969.
21.	Glemser, B.: Man Against Cancer, Funk & Wagnalls, New York, 1939.
22.	Good, R. A.: Quoted in, Time, March 19, p. 30, 1973.
23.	Good. R. A.: The dual immunity system: and resistance to infection. Medicine, 52: 405-410, 1573.
24.	Gray, P.: Towering trivia. Book review of The People's Almanac by Wallechinsky, D. and Wallace, L., Doubleday. Time, March 15, p. 54, 1973.
25.	Halliday, W. J.: Glossary of Immunolo­gical Terms, Butterworths, London, 1971.
26.	Halpern, B.: Nature and properties of antibodies. In, Allergy 1974, Eds. Gander­ton, M. A. and Frankland, A. W., Pit­man, London, p. 141, 1975.
27.	Hamilton, W. J. and Mossman, H. W : Hamilton, Bovd and Mossman's Human F-nbryo'ogv, W. Heffer and Sons, Cam­bridge, 1972.
28.	Hirsch, J. G.: Host resistance to infec­tious diseases. In, Bacterial and Mycotic Infections of Man. Ed. Dubos, R. J. and Hirsch, J. G., Pitman, London, p. 170, 1965.
29.	Hughes. Jones, N. C.: Immune Mechan­isms. In. Clinical Physiology, Eds. Camp­belt, Dickinson, and Slater, Blackwell, Ox­ford. p. 2:71, 1963.
30.	Humphrey, J. H. and White, R. G.: Im­munology for Students of Medicine, Blackwell, Oxford, p. 106, 1970.
31.	Illich, I.: Medical Nemesis: The Ex­propriation of Health. Rupa & Co., Bom­bay, 1975.
32.	John Wayne.: Quoted in, The Wit and Wisdom of Hollywood. Ed. Wilk, Max, Book Section, Readers' Digest, November, p. 145, 1972.
33.	Keele, C. A. and Neil. E.: Samson Wright's Applied Physiology, Oxford Univ. Press, London, 1971.
34.	Kothari. M. L. and Mehta, Lopa, A.: Finite lifetime of somatic Cells - A basis of finite lifespan of animals, J. Postgrad. Med., 15: 53-63, 1969.
35.	Kothari, M. L. and Mehta, Lopa, A.: The nature of diabetes mellitus. A point of view. Ind. J. Med. Sci., 24: &31-677, 1970.
36.	Kothari, M. L., M2hta, Lopa, A., Kothari, Jyoti, M. and Kothari Meena, L.: Func­tional significance of the evolution, and the anatomy of the mammalian thoracic duct, Ind. J. Med. Sci., 24: 414-418, 1970.
37.	Kroeker, E. J.: Chronic bronchitis and pulmonary emphysema, Lahey Clin. Found. Bull., 24: 56-55, 1975.
38.	Leblond, C. P.: Classification o`. cell po­pulations on the basis of their prolifera­tive behaviour, Nat. Cancer Inst. Monogr., 14: 119-150, 1564.
39.	Leblond, C. P. and Walker, B. E.: Re­newal of cell populations, Physiol. Rev., ": 255-275, 1965.
40.	Lele, R. D.: Quoted in, Medical Times, Vol. V. No. 6, Bombay, p. 3, 1975.
41.	Malleson, A.: Need Your Doctor Be So Useless? George Allen & Unwin. London, 1973.
42.	Paterson, P. Y.: Introduction to infec­tious diseases. In, The Biologic and Clini­cal Basis of Infectious D:seases, Eds. You­mans, G. P., Paterson, P. Y. and Som­mers, H. M., W. B. Saunders, Philadel­phia, p. 1, 1975.
43.	Paterson, P. Y.: Infection in the com­promised host. In, The Biologic and Clini­cal Basis of Infectious D:seases, Eds. You­mans, G. P., Paterson, P. Y. and Som­mers, H. M., W. B. Saunders, Philadel­phia, P. 701, 1575.
44.	Pickering, G.: High Blood Pressure, Churchill, London, 1963.
45.	Prehn, R. T.: Neoplasia. In, Principles of Pathobiology, Eds. Lavia, M. F. and Hill, R. B., Jr., Oxford Univ. Press, London, p. 191, 1971.
46.	Raeburn, J. A.: Antibiotics and immu­nodeficiency, Lancet, 2: 954-956, 1972.
47.	Random House Dictionary of the English Language: Random House, New York, 1567.
48.	Stewart, F. S.: Bigger's Bacteriology and Immunology for Students of Medicine, Bei'liere Tindall and Cassell, London, p.498, 1968.
49.	Stoler, P.: Skin deep. Book review of The Patchwork Mouse by Hixon, J., An­chor, Doubleday, Time, March 8, p. 53, 1976.
50.	Tainter, M. C.: Medicine's golden age: The triumph of the experimental method, Tran. N. Y. Acad. Sci., 18: 206-227, 1956.
51.	Thomas, L.: The Lives of a Cell, Notes of a Biology Watcher, Viking Press, New York, 1975.
52.	Vonnegut, K., Jr.: Breakfast of Cham­pions, Dell Publishing Co., New York, p. 289, 1574.
53.	Vries, E. D.: Postvaccinial Perivenous Encephalitis, Elsevier Publishing Co., New York, p. 1, 1930.
54.	Watford, R. L.: The role of autoimmune phenomena in the aging process. In, As­pects of Biology of Ageing, Ed. Woll­house, H. W., Cambridge Univ. Press, Cambridge, p. 351, 1967.
55.	Webster's Third New International Dic­tionary o' the English Language Unabridg­ed: G. & C. Merriam Co., Springfield, Vol. I, 1971.
56.	Weiser, R. S., Myrvik, Q. N. and Pear­sall, N. N.: Fundamenntals of Immuno­logy, Lea & Febiger, Philadelphia, 1969.
57.	Wood Jones, F.: Quoted in, Dorland's Illustrated Medical Dictionary, W. B. Saunders, Philadelphia, p. 349, 1957.
58.	Wood, W. S.: Host-agent interactions in infectious diseases. In, Internal Medicine Based on Mechanisms of DL-ease, C. V. Mosby Co., Saint Louis, pp. 86-123, 1963.
59.	Wrigley, E. A.: Population and History, World University Library, London, p. 78, 1939.
60.	Youmans. G. P.: Characteristics of host­bacteria interaction: External defence mechanisms. In, The Biologic and Clini­cal Basis of Infectious Diseases, Eds. You­mans, G. P., Paterson, P. Y. and Som­mers, H. M., W. B. Saunders, Philadel­phia, p. 1975.
61.	Youmans, G. P.: Characteristics of host­bacteria interaction: Internal defense mechanisms. In, The Biologic and Clini­cal Basis of Infecious Diseases, Eds. You­mans, G. P., Paterson, P. Y. and Som­mers, H. M., W. B. Saunders, Philadel­phia, p. 24, 1975.
62.	Youmans, G. P.: Tuberculosis. In, The Biologic and Clinical Basis of Infectious diseases, Eds. Youmans, G. P., Paterson, P. Y. and Sommers, H. M., W. B. Saun­ders, Philadelphia, p. 335, 1975.
63.	Zweifach, B. W., Grant, L. and McClus­key, R. T. Eds.: The Inflammatory Pro­cess, Vol. I, Academic Press, New York, 1974.
64.	Zweifach, B. W., Grant, L. and McClus­key, R. T. Eds.: T}e Inflammatory Pro­cess, Vol. II, Academic Press, New York, 1973.
65.	Zweifach, B. W., Grant, L. and McClus­key, R. T. Eds.: The Inflammatory Pro­crys. Vol. III, Academic Press, New York, 1974.

	Previous article Next article