The nature of immunityML Kothari, Lopa A Mehta
Department of Anatomy, Seth G. S. Medical College, Parel, Bombay-400012., India
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, making 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 give rise to "auto-immune" disorders, by means of a concerted CelluloHumoroVascular Response.
Immunity: Friend or Foe?
As of 1976, medicine knows not what immunity stands for. We extoll its virtues by pontificating that "Man lives in a sea of microorganisms; the immune system is his license to survive."α (Good),  an eulogy that turns counterfeit when Burnet  declares that immune mechanisms are "more basically concerned with the control of tissue integrity and reaction against recognised anomaly it tissues than in defence against micro-organisms and the production of antibody." This Burnetian concept of "immunologic surveillance"  loses credibility on Burner postulating that it is the immunocyte itself that breeds all auto-immune diseases and on Walford  generalizing that all degenerative processes are attributable to immunity. The final coup de grace comes from Prehn  when he ascribes cancerogenesis to immunity.
Our Ignorance Is Our Forte
Our ignorance of the raison d'etre of immunity is our forte: we can twist and turn immunity the way it suits medicine's whims and whams. "Immune Responses Can be Variously Manipulated For Patients' Benefit." Under the aforestated heading printed in bold, Lele  very recently promised: "Our clinical goals are therefore divergent.... Whereas the goal in infectious diseases is to enhance the immune response, the goal in organ transplant is to induce immune tolerance. The goal in cancer therapy is one of terminating unresponsiveness to the tumour antigen, while that in autoimmune disorders is one of re-establishing unresponsiveness to `self' antigens." Immunity seems to be every medical man's fool.
A Wasteland of Words
A major side effect of the above comedy is that immunology, as a science, is a semantic jungle, a wasteland of words, "encumbered by a wretched and baffling vocabulary unmatched by any other science."  The outcome is predictable: "Immunologists speak only to immunologists, and even then it is open to question whether one immunologist knows what another immunologist is talking about."  The fundamental words antigen and antibody are inept and confusing, and immunity still goes abegging for a definition, what to talk of the semantic atrocity autoimmunity which is supposed to connote immunity turning against the host. The rank antibody-ism of immunologists is their exaggerated sense o f humour that is not only confounding but can be quite boring.
A Non-anthropocentric Approach
The essence of immunity is shrouded in anthropocentrically used "military"  terminology-defense, offense, destruction and the like. By all dictionary and textbook definitions, immunity is supposed to be defensive; yet when it lets loose some antibody into the circulation as in rheumatoid disease, it is incriminated as self-destructive or autoclastic.  According to what suits them, immunologists declare immunity as defensive when some antibody against a cancer is detected, and as destructive when lymphocytes are found focally in various "autoimmune" diseases, hence justifying the whipping up of immunity in cancer and the smothering of it in "autoimmune" disorders.
The situation is rendered much clearer, however, if we eschew the defence-destruction-business and look upon immunity as a vector force that turns out to be good, bad or indifferent depending on its strength, direction, and the target it works at. It is a homeostatic/histeostatic mechanism that-like any other mechanism e.g., vasoconstriction or catecholamine release in shock-could work as much for as against the organism.
A Plea for Pluralism
In the current era of immunology, immunity/immunology is supposed to be represented only by the trio of antigen, antibody (cellular or humoral), and antigen-antibody-reaction. But there is far more than meets the immunologist's eye -macrophage, neutrophil, platelets, eosinophils, clotting mechanism, the fibroblasts, the serous membranes and what not. ,,, One and all of these work alone or in concert, with antibody or the lymphocyte if need be, to strive at or ensure histeostasis. A sentence from Kurt Vonnegut  is to the point: "My adrenal gland gave me a shot of adrenaline. . . . It also caused coagulants to pour into my blood stream, so in case I was wounded, my vital juices wouldn't drain away." Intact epithelium over a fractured bone is far greater an immune force than all the antibodies and immunocytes put together. Remove the epithelium, and the open fracture turns infected, osteomyelytic and prone to delayed union.  Blood vessels are indispensable to any immune process -reactive, reparative, or rejective. A wound would not heal unless the blood vessels initialy obliged by proliferating, later by perishing, and the epithelia] cells did not reactively multiply to bridge the gap. Immunity, thus, is a concerted effort of cells, humors, and blood, vessels, which, by mostly reacting to a situation of disturbed histeostasis, comprise CelluloHumoroVascular Reactive System (CHVRS). On a closer scrutiny, one would realise that the greater truth is not immunity but reactivity-reactivity that saves when operative against a wound or Salmonella More Details typhi, but which kills when berserk against a few molecules of benzylpenicillin, or a CNS that has the temerity to share some antigens with a tiny bronchial carcinoma.
Cytologue: A Concept
The human body is an assemblage of 6000 billion cells-2000 times more in number than the present world population, each cell as complete a representative of life as the host individual. (The blue whale weighing 150 tons comprises about 12,000,000 billion cells). These myriad cells hang on to each other without rivets and screws, multiply, migrate, fall off, secrete, and do so many other things that leave us wonderstruck. Each cell carries around itself an individuality, a uniqueness that is unprecedented, unparalleled., and unrepeatable and which is representative of the uniqueness of the host. Lewis Thomas  succinctly describes this cellular/human uniqueness: "Everyone is one in 3 billion (the total human population today) at the moment. . . . Each of us is a self-contained, free standing individual, labelled by specific protein configuration at the surface of cells .... to the extent that a fragment of cell membrane will be recognised and rejected between any conceivable pairs among the 3 billion, excepting identical twins." In a person, then, each cell is an untamable I-specialist, that will only tolerate another cell with which it can see I-to-I.
All the cellular stars in a cytogalaxy called an organism stay put in cohesion and work in unison by conversing with one another through an organism-specific code of communication; they recognise friend-or-foe by using such a code as a password. This "call of cell to cell"-called cytoclesis by Wood Jones  -in an individual is what can be called cytologue. An immediate corollary of such a concept is that any breach or interference in this cytologue would be recognised as threatening the organism's integrity, and the organism, in turn, would react to set things right and see that the head-to-foot gestalt cytologue is reestablished.
The breach in cytologuic wholeness may occur through discontinuity as after injury or infarction, whereas interference may be sensed following (i) desel fing of self-cells (suicytes) and/or self-elements (sui-elements') leading to the so-called auto-immune phenomena, (ii) the presence of foreign cells as after an allograft, (iii) the presence of microbes, and (iv) the presence of a foreign body like the one that Elie Metchnikoff put into the starfish larvae in the Straits of Messina in 1882, a simple experiment that was crowned by a Nobel prize in 1908. The foregoing cytologuic concept accounts for the hitherto ill-understood fact that our body treats injury, infarction, infection, allografting, or foreign body by a prototype cytohumorovascular response generally called inflammation and eulogized by Howard Florey  as "the backbone of pathology."
Evolution of CHVRS
Heterotrophism is another way of saying that life assimilates life, through the digestive lining, a biophenomenon that may have determined the entodermal lining as the prime source of the cells of the "immune" system to oversee that nothing that comes patently as not-self (called "food") manages to get into the organism in the not-self form, nor survive as such within the organism. It is little wonder, then that the bursa of Fabricius (antibody production) and thymus (immunocyte production), the key organs governing "immunity", develop from the entodermal lining.  The equivalent of the bursa of Fabricius in man is GALT -Gut Associated Lymphoid Tissue.  The ubiquitous macrophage/phagocyte originally lined the digestive tract of the coelenterates  and served as the foodpicker for the hydra. That very phagocyte, in man, has not lost its digestive enzymes which can take care of the phagocytosed microbe. Animal life's decision to assimilate life and to sustain upon it without disturbing its own cytologue forced upon it the evolution of the very complex "immune" system off its primitive looking entodermal lining. Let us say a "Hurrah" for Nature's foresight and versatility. Lest it be forgotten, the "immune" system starts operating right at the level of the starfish larva, or the earthworm.
CHVRS and Histeostasis
The CelluloHumoroVascular Response Reactivity (CHVR), usually called immunity/immune response, is designed to recognise cytologuic disturbance, react against the injured/altered (self) or intruding (foreign) elements, remove/reject them, and finally to restore the involved tissue or organ to as near status quo ante as possible. Such a mechanism can be designated histeostatic comparable to the homeostatic mechanism, conceived and popularized by Walter Cannon.
We may understand how the new concept outlined above differs from the traditional idea of immunity. Halpern,  writing on the subject in Allergy '74, presents this traditionality: "The survival of highly developed organisms is dependent on the absolute integrity of `self', in other words the unfailing recognition animate or inanimate aggressors. Only a system capable of detecting the most subtle of molecular differences is in a position to ensure the efficient protection of the organism." Halpern's definition is militaristic; it talks of the need to detect "the most subtle of molecular differences" without telling why should this be such a compelling imperative; further it alludes to "protection" of "the absolute integrity of `self' " without explaining how a minor scratch while shaving, in no way "endangering" the life of the organism, excites the same tissue response as does an infection or a major trauma;  lastly, and most importantly, it is unable to explain the not uncommon paradox of this protector turning into a persecutor, or of the immune system treating its own injured/infarcted tissues_ with the same relentlessness as it treats a foreign body or a graft. The concept of cytologue-and the cytologuic imperative to remain undisturbed-makes it comprehensible that the "aggressors" can arise as much from within as from without.
Immunity/reactivity may be, for an organism good, bad, indifferent, or a mixup of these. That most human beings are able to merrily live out their total lifespan means that the wages of immunity/activity are largely good; the fact that the picture in Goodpasture's syndrome, or SLE, is quite devastating implies that the wages can be bad; the occurrence  of increasing levels of "autoantibodies" (more truly, antiautobodies) with increasing age, without our being able to really incriminate them for pathogenesis, is an example of its indifferent nature. It is interesting to see what makes for this goodness, badness and indifferentness, with the important proviso that immunity and reactivity be treated as separate from now, immunity enjoying its pristine connotation of all good for an individual, and reactivity meaning a force good, bad or indifferent.
Epistemologic, etymologic and eusemantic considerations compel the assertion that immunity ought to mean unalloyed good for an individual. Immunity (L. immunitas; Fr. immunis) implies "freedom or exemption from a charge, duty, obligation, tax, imposition, penalty, or service"  and connotes aristocracy on the part of an organism whereby it does not have to enter into a reactive quarrel with things from without or within. In its real sense, then, immunity is non-reactivity. Whenever CelluloHumoro. Vascular System comes into operation, it becomes reactivity which may be good, bad, or indifferent. Immunity and reactivity are poles apart and should be treated as such. Geniticists, anthropologists, phylologists, endocrinologists and many others who have nothing to do with a bacterium or virus versus the human body and yet are claiming to be working on immunochemistry, immunoassay and the like, had better accepted that they are exploiting the "reactive" faculty of the human body, thus working truly on reactive-chemistry for immunochemistry, genetics of reactivity for immunogenetics, radioreactivity-assay for radioimmunoassay, and the like.
Nature of Immunity
Immunity, mediated by immunity g mechanisms, strives at keeping an organism's cytologue in a gestalt state by preventing the intrusion, into the organism, by members of the microbial ocean that a metazoic organism swims through, during life. The immunity mechanisms comprise a variety of forces, the prime one being the intact epithelial sheet that covers the cutaneous and mucosal areas of the body-all areas that come or could come in contact with the milieu exterieur. This provides, for the organism, a virtually impervious envelope, a close mimicry of which is to be found in serous cavities.
The impervious cytosheet covering all the mesothelial cytosheets lining the the exposed areas  of the body is protected by a number of surface-f orces physical, chemical, humoral, cellular, and, it may appear strange, microbial.
The physical group comprises: (a) the ceaseless exfoliation of all epithelial cells-cutaneous and mucosal, whereby microbes are, as it were, pushed away from the body; (b) the continuous flow of fluids from the secreting surfaces, through the ducts, to the exterior; (c) pH differences: "The skin usually has an acid pH and this tends to inhibit the growth of most disease-producing bacteria . . ."  , such low pH is present in the stomach and in the vagina; (d) the ciliation in the respiratory tract that keeps the flower respiratory tract virtually sterile. 
The chemicals are the ubiquitous lysozyme and such bactericidal substances as the long chain fatty acids in the secretions of the sebaceous glands. The important surface humour is IgA. , Phagocytes-as over the lung alveoli's , -constitute cellular moppers for the microbes. Each epithelial surface has its own indigenous microbial flora  -microbiota-which through metabolic competition and production of germicides such as organic acids prevent infection.
Premunition, called the phenomenon of infection immunity  - is an example of a thief guarding against a fellowthief, a compelling evidence of the beneficial effects of macromicrobial coexistence. "It has long been recognised that the persistence in the body of a given microbial agent is accompanied by a high level of resistance to superinfection. Such a state of resistance was early recognized and designated as infection immunity or premunition. Although emphasized chiefly for its relevance to malaria, tuberculosis, syphilis and relapsing fever, infection immunity is certainly of very general occurrence, but its study has been grossly neglected." 
"One of the remarkable facts about immune mechanisms is that anitbodies (or anticells) are not formed against the body's own tissues; that is, the antibody forming mechanism can differentiate between `self' and 'not-self'. A state of tolerance towards a potential antigen (from within) is acquired during prenatal and early postnatal life."  The state of tolerance is a facet of immunity whereby an individual does not react to his own tissues and elements, and is achieved during prenatal, and early postnatal life through a process of "immunologic maturation"  whereby cells capable of reacting against the body's own cells/elements are eliminated. Acronymically, this could be called CARE- . ContraAuto Reactivity Eliminated, Burnet and Medawar got their Nobel prize for showing that if foreign cells are introduced into an organism prior to CARE, the guest cells are accorded self-status (they are `self ed') by the body through elimination of reactocytes capable of reacting against the guest antigens. This freak - found in natural/artificial chimera-can compel CARE to be rarely read as ContraAllo Reactivity Eliminated. It is interesting that the CARE process works only for cells that are actively dividing (possibly presenting thereby their antigens, to the reactocytes) so that cell-systems that stop dividing very early in development (sensory cells, neurones, muscle cells) are not CAREd or selfed, making them constitute, for the organism, "occult" i antigens (literally meaning hidden notself elements). Throughout life, cellsystems possessing occult antigens are guarded against "immune-invasion" by a .protective barrier, possibly akin to the epithelial barrier found in the thymus.
The Orwellian double-speak of immunology has fostered the present view of a Janus-faced immunity, as bad as it could be good-immunitis divinitas et devilitas. A burden of this article is to divest immunity of this conceptual and semantic diabolism and restore to it its pristine meaning of good, whenever operative. Immunity becomes, then, incapable of doing any harm-a conceptual clarity that does away with such semantic atrocity as auto-immunity and which takes away from the realm of immunity such tissuesores as allergy and hypersensitivity, relegating them to the arena of reactivity. It is immunitas divinitas, the devilitas role being taken by reactivity depending on circumstances.
In the above elaboration of the nature of immunity, no reference has been made to the role of immunity in fighting/preventing autochthonous cancer. Such a view is a direct antithesis of today's raging fashion that immunity protects against cancer. "From the human and medical angles ... without immunological surveillance, cancer would be more frequent and occur at younger age than it does."  Elsewhere, in support of immunological surveillance, Burnet fantasizes a situation where cancer cells from an adult could implant into an abrasion on the skin of an infant, adding that "to prevent such a calamity we believe that nature, to speak teleologically, invented the mechanism of vertebrate immunity." Yet, regardless of the immune surveillance, cancer afflicts humankind unimpeded, forcing Burnet  to recant and declare that the outcome of cancer research including the immunological approach, has been "precisely nil" and that "Nothing of value for either prevention or cure has come from the laboratories."
Both "tumor immunity" and "transplantation immunity" are lab-oratorial or Barnaradian artifacts that have little to do with biologic reality. Oceanic research on the former has proved its worthlessness; the latter is rich with the unending promise of the soon-to-dawn transplant era. A doctor-patient's personal experience  with such adventurism at the renal level is reminiscent of the Spanish Inquisition. Transplant era will not dawn for it has no backing of a preceding night, anywhere near reality.
The only area where the "immunologic surveillance" operates is in attacking and eliminating an individual's deselfed suicytes/sui-elements, but there the surveillance is not immunologic but reactologic as rendered clear by what follows.
The Nature of Reactivity
The etymologic bulldozer capable of demolishing the immunologic Tower of Babel is the word reactivity. It stems from the root react meaning  "to act in return on an agent or influence," or "act reciprocally upon each other," or "to act in opposition, as against some force." The foregoing are pregnant with the anti (= against) emphasis in the two fundamental but ill-conceived immunologic terms antigen and antibody. Let antigen be replaced by the term actant, and conceptual/semantic clarity starts. An actant acts to which an organism/tissue reacts; the faculty j to react is reactivity; the process is reaction mediated by reactocytes and/or reactins (humours/ antibodies), the science is reactology, There is no antigen-antibody reaction but actant-reactant interaction. In such refined context, immunoassay becomes reactoassay, immunochemistry becomes reactochemistry and so on. Reactivity is both non-specific (wound healing) and specific (Rh-reactivization of a negative mother by her Rh-positive fetus).
Specific humoral reactivity-that wondrous faculty of the vertebrate organism to throw a reactinic tat (antibody) for an actant tit (antigen), with nearly unparalleled lock-and-key specificity-has been the be-all and end-all of "immunology" modern and ancient. This very obsession has been immunology's undoing, for it has blindfolded until today the researchers to the facts that (a) such specificity has so often very little to do with an organism's immunity, (b) that an antibody has been proved time and again to be antihost, and (c) that the eureka eureka trumpeted by cancer immunologists on the finding of an anticancer antibody has ended with the realisation that such antibodies in fact protect the cancer against the host's immune system by subversively coating it.
The service rendered by immunology's antibody-ism hinges on the lock-and-key specificity involved. It has helped study of phylongeny by being able to tell, that a baboon is closer to man than a bat. It has facilitated medico-legal investigations, hormonal estimations to the levels of a nanogram, and offered evidence of the interaction an organism has had with an actant (e.g., Widal test). The therapeutic help has been limited. "Passive immunization" has proved hazardous (ATS therapy), save for such areas as snakebite or gas-gangrene. Probably the greatest therapeutic impact of the knowledge of specific actant-reactin interaction, and its avoidance, has been in making blood transfusion a safe affair.