IMMUNOLOGY AND IMMUNOLOGICAL PREPARATIONS

Transcription

1 CHAPTER 1 IMMUNOLOGY AND IMMUNOLOGICAL PREPARATIONS 1. INTRODUCTION The science of immunology virtually saw the light of the day through the earnest efforts of Edward Jenner in 1798 who assumed to be true on the basis of reasoning that the value of vaccination as a probable means of protection against the cowpox (vaccinia) ailment. In fact, it was Jenner who first and foremost suggested the protective means of vaccination with non-virulent cowpox against smallpox infection. It is, however, pertinent to mention here that the science of immunology ultimately got its legitimate recognition as a branch of knowledge requiring systematic study and method only in 1881 when the entire universe witnessed an epoch making spate of progress put forward by two eminent scientists Louis Pasteur and Robert Koch. In reality, Pasteur s development of a vaccine for anthrax i.e., an acute infectious disease caused by Bacillus anthracis, using attenuated organisms was enormously hailed by many scientists across the globe. Elie Metchnikoff (1833)*, a noted Russian scientist spotted the pivoted role of phagocytes** in causing immunity in the course of an extensive and intensive research due to infection of the popular waterflea, Daphnia, by a specific fungus. Metchinkoff s observations and findings put forward the wellknown phagocytic theory, which essentially postulated that the prevailing inflammatory responses in the human body were, in fact, the very outcome of numerous on-going cellular reactions instead of the vasculogenic reactions as suggested earlier by Julius Cohnhein. In short, the preliminary as well as the pioneering work of Metchinkoff not only proved adequately but also established the justified role of the cellular substances present in the blood in accomplishing pathogenic microorganisms to a significant extent. Interestingly, Metchinkoff s articulated concept and belief that inflammation produced happen to be a protective rather than a destructive phenomenon. As on date, it has been recognized beyond any reasonable doubt that the phagocytic activity of human WBC designates the primary line of defence against invasion on the body by a host of pathogenic organisms. Virchow and Pfeiffer vehemently opposed Metchinkoff s phagocytic theory based on their claim that the entire process caused solely due * Metchinkoff E., (1893) : Comparative Pathology of Inflammation, Transl FA et. al., Trübner and Co., London. ** A cell e.g. leukocyte or microphage having the ability to ingest and destroy particulate substances, such as : bacteria, protozoa, cells and cell debris. 1

2 2 PHARMACEUTICAL BIOTECHNOLOGY to the action of antibodies, which they ultimately laid as the fundamental foundation of the very understanding of the ensuing immume bacteriolysis. Salient Features of Metchnikoff s Doctrine : The various salient features of Metchnikoff s doctrine are, namely : (a) importance of activated microphage, (b) latest concept that certain diseases are controlled by circulating antibodies, (c) phagocytes (specialized cells) active participation in causing protection against other prevalent diseases, (d) humoral antibodies responsible for the pathogenesis of autoimmune plus other immunogenic ailments, and (e) certain diseases are also produced by cell-mediated reactions. Later on in 1890 Vohn Behring, duly recognized antibodies present in serum to diphtheria toxin. Denys and Leclef (1895) observed that phagocytosis invariably get enhanced by immunization to a substantial extent. Bordet in 1899 observed that the lysis of cells by antibody essentially requires the earnest cooperation of various serum factors that are now collectively known as complement. Landsteiner in 1900, discovered the ABO antigens, a magnificent invention that eventually laid the foundation stone of the science of serology. Richet and Portier (1902) introduced the terminology anaphylaxis i.e., opposite of prophylaxis. In 1903, Almorth Wright based on the clue derived from the humoral theory propounded another theory termed as the theory of opsonization in relation to opsonic activity to phagocytosis. In other words, it explains that antibodies as well as phagocytes are equally important and necessary to cause infectious diseases, and supplement each other in the complete eradication of pathogenic organisms. His remarkable research outputs conferred on him the Noble Prize in Almost after a lapse of 22 long years, Zinsser (1925) put forward a well-defined and explicite contrast between immediate and delayed-type hypersensitivity. Lastly, Heidelberger and Kendall ( ) carried out an elaborated precipitin* studies an antigen-antibody interactions. 2. PRINCIPLES The science of immunology categorically deals with the specific mechanisms by which the living tissues invariably react to the so called foreign biological materials, such as : invading pathogenic microorganisms, so that ultimately either immunity or resistance gets developed in vivo to combat the dreadful diseases in the humans and animals. The credibility as well as the integrity of the defence mechanism system of the host, and in turn its ability to undergo critical and specific reaction(s) thereby counteract the possible invasion by microorganisms seems to be of prime and vital importance for the ultimate survival of the individual. Obviously, the foreign biological materials quite often gain entry into a living body through such barriers as : hair, skin or ruptured spaces. Consequently, the innate immune mechanisms of the body trigers its action to offer adequate protection required spontaneously, which is actually carried out by WBC or leucocytes. It has been duly observed that this particular mechanism is absolutely insufficient to afford full protection in most of the instances commonly encountered ; and, therefore, the body does respond through an immune system. * An antibody formed in the blood serum of an animal owing to the presence of a soluble antigen, usually a protein. When added to a solution of the antigen, it brings about precipitation. The injected protein is known as antigen, and the antibody produced is the precipitin.

3 IMMUNOLOGY AND IMMUNOLOGICAL PREPARATIONS 3 In fact, the entire prevailing immune system is essentially made up of cells and macromolecules that usually give rise to a rather complex network of cellular and molecular interactions so designed to negate the adverse effect caused by microorganisms and parasites. In other words, one may explain this intricate immune response as a mechanism explicitely exhibited either by humans or higher organisms, whereby a very critical as well as specific response is invariably drawn out against the probable invasion of well-defined pathogenic microorganisms and other foreign substances. Besides, it may also be regarded as a specific physiological response which protects human beings against a plethora of dreadful diseases. Interestingly, the ensuing immune response is appreciably signified by memory, specificity and above all the capability to differentiate between self from non-self at the molecular level even. 3. ANTIGENS AND HAPTENS The two terminologies viz., antigens and haptens are intimately associated with immunology ; and, hence one may understand and have a clear concept about them as far as possible Antigens An antigen is either a cell or molecule which will bind with preexiting antibody but will not definitely cause induction of antibody production. Antigen may also be defined as a macromolecular entity that essentially elicits an immune response via the formation of specific antibodies in the body of the host. In a broader perspective the antigen (or immunogen*) is invariably regarded as the afferent branch of the prevailing immune system, as illustrated in Fig. 1.1 below, and is any cell or molecule which would provoke an immune response** very much in an immunologically viable and competent individual. Generally, immunogens (antigens) must fulfil the following two cardinal characteristic features, namely : (a) should be larger than 2000 in molecular weight, e.g., protein, glycoprotein and carbohydrates, and (b) must be absolutely foreign to the individual into whom they have been introduced appropriately. Fig Immune Mechanism. * Sometimes, the term antigen is used synonymously with immunogen, although this usage is incorrect. ** Production of antibodies and/or sensitization of lymphoid cells.

4 4 PHARMACEUTICAL BIOTECHNOLOGY Example : The most befitting example of an antigen is ones own erythrocytes (WBC). Because, they will not induce antibody formation in oneself but will definitely react with an antibody essentially contained in an improperly matched blood transfusion. It is, however, pertinent to state here that quite often an antigen is a protein, but it could also be a polysaccharide or nucleic acid or any other substance. Importantly, it may also be possible that a foreign substance (e.g., protein)-not necessarily belonging to a pathogenic microorganism, may act as an antigen so that on being injected into a host, it may induce antibody formation. Besides, they may turn out to be antigenic and thereby cause stimulation of antibody production, incase they are intimately and lightly get bound to certain macromolecules, for instance : proteins, carbohydrates and nucleic acids Haptens In usual practice, the relatively smaller, less rigid or rather less complex molecules usually are not immunogenetic in their purest form, but may be made so by simply linking them strategically to either larger or more complex structures. Consequently, the smaller molecules are invariably termed as haptens ; whereas, the larger molecules or cells are known as carriers. Hapten may also be defined as a substance that normally does not act as an antigen or stimulate an immune response but that can be combined with an antigen and, at a later time, initiate a specific antibody response on its own. Furthermore, small molecules (micromolecular), such as : drug substances, that may serve as haptens and can normally be made antigenic by coupling them chemically to a macromolecular substance e.g., protein, polysaccharide, carbohydrate etc. The hapten is obtained from a non-antigenic compound (micromolecule) e.g., morphine, carteolol etc., which is ultimately conjugated*, covalently to a carrier* macromolecule to render it antigenic. Morphine should be first converted to the corresponding 3-o-carboxymethyl derivative prior to carbodiimides (CCD) coupling with albumin to provide a functional coupling moiety in the hapten. Another glaring example is of gastrin (hapten) which is duly coupled to albumin (i.e., proteincarrier) by treatment with carbodiimides (CCD), which couple functional carboxyl, amino, alcohol, phosphate or thiol moieties. Importantly, the hapten-conjugate thus obtained is normally subjected to emulsification in a highly refined mineral oil preparation containing-killed Mycobacterium (Complete Freund s * Conjugate : The combined hapten and carrier. ** Carrier : A protein, polypeptide, or inert matrix that is coupled to the hapten to form an antigen.

5 IMMUNOLOGY AND IMMUNOLOGICAL PREPARATIONS 5 Adjivant*), and subsequently injected intradermally either in healthy rabbits or guinea pigs on several occassions at intervals. Evidently, the serum antibody should have not only high degree of specificity but also a reasonably strong affinity for the prevailing antigens. It has been observed that a relatively large variety of low molecular-weight chemical substances may cater for as allergenic haptens (partial immunogens) and induce allergy after combining covalently with an appropriate protein carrier. On one hand this serves as a vital and important phenomenon specifically in drug allergy ; however, the most widely found environmental allergens. Perhaps the most notable exception in the instance of common allergic contact dermatitis produced by a variety of plants, drugs, clothing additives and other similar substances. Examples : (a) Urshiols : The allergenic constituents i.e., the oleoresin fraction, derivatives of pentadecycatechol or heptadecylcatechol, that are solely responsible for causing contact dermatitis in North America usually belong to the natural order Anacardiaceae, the genus Toxicodendron (Rhus), and quite often include oak, sumac and poison ivy. (b) Several plants which essentially belong to the natural order compositae viz., ragweeds, also responsible for causing contact dermatitis, and the allergens have been duly isolated and characterized as sesquiterpinoid lactones. 4. IMMUNE SYSTEMS Immunology, the generation of an immune response or the defence mechanism exclusively depends upon the interaction of the three most vital components of the immune mechanism, namely : (a) immunogen stimulation ; (b) humoral immune system ; and (c) cellular immune system. Since 1901 and 1984 an enormous and substantial research inputs, were made by various scientists across the globe which have enabled the inhabitants of the world to lead a better and safer quality of life through the evolution of immunotechnology i.e., conglomeration of various immune systems. During the said long period ( ) the wonderful findings of scientists and researchers not only brought them wide recognition through most coveted Noble Prizes but also paved the way towards the introduction of remarkable and most trustworthy remedies for complicated not-so-easy diseases of the present day. It would be worthwhile to make a brief and comprehensive illustration of some of these meaningful contributions in a chronological manner as stated below : Emil von Behring (1901) : Awarded with Noble Prize for his interesting discovery that quite a few diseases are caused due to the expression of toxins, which he demonstrated by inoculating healthy animals with diphtheria tetanus toxins to generate antitoxins. Jules Bordet (1919) : Bagged the Nobel Prize for proving that erythrocytes may be haemolyzed with particular antibody and complement accordingly. His work further demonstrated quite successfully the strategical involvement of certain biological processes taking place in vivo, namely : bacterial agglutination**, neutralization of the precipitin reaction, and complementary mediated immune haemolysis. * [Jules Thomas Freund, Hungarian-born US immunologist ] A mixture of killed microorganisms, usually mycobacteria, in an oil and water emulsion. The material is adiministered to induce antibody formation. Because the oil retards absorption of the mixture, the antibody response is much greater than if the killed microorganisms were administered alone. ** A type of antigen-antibody reaction in which a solid antigen clumps together with a soluble antibody. It requires a cell with antigenic markers close to the surface, available for interaction with the antibody. The term often refers to laboratory tests and to transfusion reactions in which antibodies attach the antigens on RBC of a different blood type.

6 6 PHARMACEUTICAL BIOTECHNOLOGY Karl Landsteiner (1930) : Became the Nobel Laureate for his epoch making findings for a deeper and vivid immunological concepts with regard to the discovery of blood group antigens i.e., A- B-O blood groups, that was eventually used for successful transfusions in humans. Ehrlich s Selection Theory : It is directly associated with antibody production, and it was amply revealed that during the intricate phenomenon of acquiring immunity, the critical substances that are exclusively responsible for the fine specificity of recognition were revealed to be the globular proteins that are strategically located in the γ-fraction of blood serum.subsequently, Landsteiner experimentally demonstrated the aforesaid theory to be false, based on blood transfusions. In other words, Ehrlich failed to substantiate his assumption that traces of each individual kind of antibody are carried out in the organism specifically ; whereas, Landsteiner adequately proved that antibodies may only be generated under the influence of foreign substances, i.e., via an instructive process. Linus Pauling s Instructive Theory (1940s) : Pauling was pioneer in assigning a helical structure to the protein molecules ; and, soon after proposed the instructive theory. He even went a step ahead and postulated a template theory particularly for the synthesis of antibody molecules that could have a relativeily broad range of diversity in shapes. However, at a later stage a renowned immunologist Sir Macfarlane Burnet heavily criticized the template theory on logical grounds. Natural Selection Theory (1955) : Niels Kaj Jerne put forward the natural selection theory for the production of antibody. In fact, his proposed theorization revolves round his logical explanation that the antigen neither serves as a template nor as an enzyme modifier. In other words, the antigen is exclusively a highly selection carrier closely associated with a spontaneously circulating antibody to a system of cells that is capable of reproducing this antibody. It has been duly observed that globulins* are being synthesized in a large variant of different configuration. At this juncture the introduction of an antigen into the blood stream essentially gives rise to the selective attachment onto the surface of the antigen only such globulin molecules that should exhibit a complementary configuration. In short, Niels Kaj Jarne brought back a new lease of life to the Ehrlich s Selection Theory almost after a long gap of six decades. Clonal Selection Theory : Burnet in 1957, put forward clonal selection theory with regard to antibody formation that vehemently offered a positive clue that each cell following an usual contact with an antigen yields a clone** of cells that would be exclusively engaged in the production of antibody of a particular kind. Importantly, Burnet s theory suggests two responses taking place, namely : primary and secondary, of which the latter one seems to be more powerful by virtue of the fact that antigenic memory ultimately gives rise to colossal clonal expansion in an extraordinarily rapid manner in the course of subsequent exposure to antigen. Hence, the said theory has not only been accepted across the globe but also attracted enormous glory, fame and recognition which enabled Burnet to bag the Nobel Prize in 1960 (also shared by Sir Peter Medawar). It is, however, pertinent to mention here that Niel s Kaj Jerne also overwhelmingly was honoured with the Nobel Prize in 1984 i.e., almost after a gap of 24 long years for his ever enlightening and wonderful discovery of the following two aspects in the immunological concepts, namely : * One of a group of simple proteins insoluble in pure water but soluble in neutral solutions of salts of strong acids e.g., serum globulin, fibrinogen, and lactoglobulin. ** A group of organisms or cells produced asexually from one ancestor.

7 IMMUNOLOGY AND IMMUNOLOGICAL PREPARATIONS 7 (a) clonal expansion concept, and (b) evaluation of idiotype* network in regulatory mechanism of immune responses. Rodney R Porter and Gerald M Edelman (1972) : The pioneering discovery made by Porter and Edelman with regard to the elucidation of the structure of antibody molecule, which is extremely vital and important in the elaborated study of antigen-antibody interactions, helped them to be honoured with the most coveted and prestigeous Nobel Prize in Importantly, their findings not only proved but also established the most glaring fact that the four polypeptide chains comprising of each immunoglobulin molecule may be enzytmetically cleaved into three distinct segments, such as : two antibody fragements (Fab) ; and one crystalline fragment (Fc). Wu and Kabat s Observations : In 1970, these researchers adequately demonstrated the presence of specific hypervariable regions strategically located on the antibody molecule. These critical observations, in fact, virtually paved the way towards the rapid and tremendous progress in the field of immunology ; and, therefore, legitimately caused a geometrical development equally stretched over the two most virulant segments of medicine as well as modern biology, for instance : organ and tissue transplantation, vaccinology, and molecular biology. Identification of HLA-Complex : The structure and eventually the specialized role and functions of the human leucocyte antigens (HLA) complex were scientifically revealed by Snell, Dausset and Benacerraf in late seventies earned them the Nobel Prize in Somatic Hybridization : The ever sensational production of immunologically homogeneous monoclonal antibodies was accomplished through a wonderful major historical breakthrough by two immunologists : George Kohler and Ceasar Milstein in the year 1975, which bagged them the Nobel Prize in S. Tonegawa s Immunoglobulin Gene Rearrangement : The evolution of somatic recombination theory logistically suggesting the individual coding in fragments of the ensuing variable and constant regions that are ultimately ressembled to generate an enormous quantum of binding sites ; and, therefore, various binding sites may be adequately obtained due to the different combinations and permutations of relatively lighter and heavier chains. At this material time Tonegawa s remarkable epoch making discovery of the most plausible mechanism of shuffling of several gene segments in the plasma cells (i.e., antibody secreting cells) producing a huge variety of antiody molecules. In short, Tonegawa s spectacular and superb scientific observations on the immunoglobulin gene rearrangement made an appreciable contribution both in the fields of immunology and molecular biology. Tonegawa was rightfully awarded with the prestigious Nobel Prize in the year In a nut-shell, one may interestingly observe and access the tremendous sea-change in the most scientific and logistic progress and development during the period and even after that in the fields of immunology and molecular biology which, of course, have enormously improved upon the quality of life of humans across the globe irrespective of their caste and creed. However, the immune systems may be viewed from the following two aspects critically, such as : (a) Manipulation of immune system, and (b) Types of immunity. * In immunology, the set of antigenic determinants (idiotopes) on an antibody that make that antibody unique. It is associated with the amino acids of immunoglobulin light and heavy chains.

8 8 PHARMACEUTICAL BIOTECHNOLOGY 4.1. Manipulation of Immune Systems The immune system or the immune defence mechanism in an individual person may be subjected to a wide spectrum of articulated well-planned manipulation against a host of dreadful and even fatal infectious diseases, caused by highly dangerous and most pathogenic microorganisms, such as : cholera, polio, chicken-pox, small-pox, diphtheria, measles, whooping cough, Hongkong Flu, anthrax, jaundice, hepatitis A, B and C and the like by immunization squarely and effectively. The underlying principle of immunization is solely based on injecting an individual subject with an appropriate dosage with a sterilized and pre-tested/evaluated preparation of a pathogenic microorganism (disease-causing microorganism) that has been rendered harmless absolutely. It has been duly proved and established beyond any reasonable doubt that immune system predominantly and essentially possess two extremely special characteristic features which not only enable the body in preventing the individual from the dreadful infection but also ensure that he must not suffer from the same infection once again i.e., one normally suffers from certain infectious ailments only once in one s life-time (small-pox, measles etc.,). Interestingly, the said two special characteristic features are, namely : (a) Memory : and (b) adaptibility. More explicitely one may understand that the very first encounter of an infections agent, the body starts to learn whether it is either a foreign entity or a nonself entity : and subsequently gets adapted to fight back the caused infection (MEMORY). But, the same individual on being exposed to the infecting agent, the body in turn exhibits a substantially increased agent, the body in turn exhibits a substantially increased immune response that is actually dependent on the earlier encounter. In the science of immunology these are invariably termed as primary and secondary immune responses. Consequently, as a fundamental characteristic features one may proclaim that the immune system has acquired adequate adaptibility Types of Immunity The various types of immunity that are commonly identified, characterized and studied at length are as stated below : (i) Humoral Immunity (ii) Cell-mediated Immunity, (iii) Innate (or Natural Immunity), (iv) Acquired Immunity, and (v) Non-specific Immunity. These different types of immunities shall now be treated individually in the sections that follows : Humoral Immunity Antibodies are immunoglobulin (I g ) molecules (e.g., serum proteins) and they are usually comprised of several categories designated as I g A, I g D, I g E, I g G, and I g M respectively. However, it is pertinent to state here that each category essentially possesses certain specific characteristic features, such as : size, carbohydrate content, electrophoretic-migration velocity, quantum of antigen-combining sites, immunological response, and immunological objective. Examples : (a) I g M : Almost always enjoys the reputation of being the first class of antibody generated invariably in most humoral responses but normally gets switched over to the corresponding I g A, I g E, or I g G at the very early stage in the immune response.

9 IMMUNOLOGY AND IMMUNOLOGICAL PREPARATIONS 9 (b) I g G : Most versatile important and abundantly available class of antibodies taking part in largest humoral immune reactions. Besides, it happens to cross the placenta thereby providing a newly born baby absolute temporary immunity against whatever immunogens the mother has earlier against I g G. (c) I g A : Antibodies are invariably found in a plethora of such secretions as : tears, saliva and mucous membranes. These are quite frequently termed as our first-line-of-defense mechanism by virtue of the fact that most bacteria, viruses and fungi that eventually gain entry into the body do cross a mucous membrane. (d) I g E : Antibodies are equally important in our body s defense against the parasitic worm infections specifically. Prominently and predominantly several allergic manifestations give rise to the release of histamines e.g., allergy due to pollens, house dust, dust mite, human hair, food allergens etc., which in turn afford the apparent discomforts resulting into extrinsic asthma, hay fever, or hives, or excessive sneezing (during changes of season due to pollens in the air). (e) Antibodies normally serve as surface receptors strategically located on certain immunologically active cells so as to enable them to bind immunogen. Importantly, the different types of cells or entities that are held responsible for contributing immensely to the humoral immunity are as follows : (i) B Lymphocytes (or B Cells), (ii) Immunodominant peptides (IDPs), (iii) Antigen-presenting cell (APC), (iv) T Cell subsets (v) Class II MHC (major histocompatibility complex) proteins. It would be worthwhile to have a closer and detailed description and functionalities of each of the cell or entity cited above in the selections that follows : B Lymphocytes [or B cells] The B lymphocytes or B cells are so named because they were first and foremost found in the Bursa* of Fabricius of birds. It has been observed that in birds the multipotent stem cells actually originate in the bone marrow usually migrate to the bursa, and here they virtually get differentiated into specific antibody synthesizing cells. In fact, antibody molecules are normally generated by the plasma cells which are vividly differentiated from B cells. It has been found that B cells are concentrated in various parts of the body, such as : spleen, mucous-associated lymphoid tissue, and regional lymph nodes, where they actually await contact by the foreign epitopes** which promptly initiate the process of conversion into the plasma cells. Interestingly, the characteristic features of B cells may be enumerated as stated below : 1. B cells possess essentially surface immunoglobulins (si g s) plus a number of receptors. 2. The si g form an integral part of B cells ; and, therefore, act as receptor for antigens. * A padlike sae or cavity found in connective tissue usually in the vicinity of joints. ** Any component of an antigen molecule that functions as an antigen determinant by permitting the attachment certain antibodies. (Syn : Antigenic determinant).

10 10 PHARMACEUTICAL BIOTECHNOLOGY 3. B cells may also have immunoglobulines (I g ) in their cytoplasm. 4. Intially, when B cells are immature, si g molecules which are exhibited specially belong to I g M category that do not cross link with other I g Ms. 5. I g D molecules appear prominently on the surface showing extremely high levels with B cell marching ahead to its developmental pathway. 6. Activation of B cell initiates loss of I g Ds together with other receptors appearing in the membrane that eventually enhance the phenomenon of activation. 7. B cells may undergo activation by the aid of lipopolysaccharide preparations from Gramnegative organisms e.g., E. coli, Salmonlla. Besides, activation may be followed by the appearance of a plethora of surface receptors for I g s, ocystalline fragment (Fc) component of heavy I g chain, and also for Epstein-Barr virus*. 8. Antigen critically trigers selection of an appropriate antibody-producing cell and this selection is exclusively based upon the surface receptors. 9. Receptors which are found to be absolutely specific for an antigenic determinant not only provoke but also interact with B cells to initiate strategic proliferation and generate a clone of blast cells**, most of which are capable of giving rise to the same antibody. 10. A portion of the prevailing blast cells get segregated and pass into the plasma cells (i.e., antibody secreting cells), while others do remain behind in lymphoid tissue in the form of memory cells. 11. B cell is characterized by a genetic composition which enables it to produce only one specificity of antibody ; and this is accomplished via random rearrangment of genes which essentially control and monitor both gross and minute antibody structure. 12. B cells are produced continuously in vivo throughout life since the life-span of a mature B cell is only a few days unless contacted by the immunogen for that it remains specific Immunodominant Peptides (IDPs) It is, however, an universal truth that antibody production invariably takes place through the earnest cooperation and interaction of various types of cells. It has been duly observed that either macrophages*** or other cells having identical lineage encounter predominantly the extracellular foreign immunogen present in the blood or lympth, undergoes phagocytocis, and ultimately meets complete destruction. Importantly, in the course of the phagocytic phenomenon the ensuing macrophase critically identifies and recognizes epitope structures present on the immunogen, and notably protects them in the shape of short peptide chains having amino acid lengths that are usually referred to as immunodominant peptides (IDPs). * A member of the herpes virus family, discovered in It is one of the causes of infections mononucleogis. ** The most popular tool for searching sequence databases is a package called BLAST (basic local alignment sequence tool). *** A monocyte that has left the circulation and settled and matured in a tissue. Macrophages are found in abundance in spleen, lymphnodes, alveoli and tonsils. [Syn : Macrophagus]