ANTIGENS (grech, anti-against + gennaö to create, make) — any substance which, coming to an organism in the parenteral way, causes the response specific immunological reaction which is shown in formation of specific antibodies. Hit And. in an organism can be followed by emergence of a condition of tolerance to this substance (see unresponsiveness) or sensitization to this And. (see. Allergy ).
Specific And. there can be a certain molecular and homogeneous substance. However antigenic properties of separate substances are shown and if they are a part of complex mixtures and systems. Therefore in clinic of infectious diseases, in laboratory and epidemiological practice the term «antigen» is often used in relation to such complex systems as microbic, vegetable and zooblasts, fabric extracts, biological liquids etc., having at the same time in a look separate contained in these systems A. The term «antigen» is quite often used also for designation of substances which, unlike full And., are not capable to stimulate independently synthesis of antibodies (see) in an organism, but can specifically react with already formed antibodies. In immunology for definition of such substances the special term — haptens is accepted (see).
By the nature And. — high-molecular polymers of a natural origin or synthesized in the artificial way. Properties full And. proteins, polypeptides, polysaccharides, and also probably high-polymeric nucleic acids and complex compounds of these substances possess.
Antigenicity is defined not only features of chemical constitution of substances, but depends also on specific accessory of an immuniziruyemy animal and his genetic constitution (see. Immunogenetics ). The same substance, without being antigenic in relation to animals of one look, causes specific immunological reaction at introduction to individuals of other look. So, polysaccharide a dextran is not And. for rabbits, and at introduction to the person stimulates synthesis of specific antibodies even after a single injection. Moreover, within one look individuals, refractory meet (not developing antibodies) and, on the contrary, highly sensitive to this A.
Antigennost as the biological phenomenon it is relative, and implementation of this property requires penetration of substance into internal environment of an immunocompetent organism sensitive to this substance.
Despite huge number of the facts received during the chemical research A., the immunology did not reach yet such level that it was possible to carry out the full list of those physical. - chemical features of a structure of substances which create a necessary basis for emergence of antigenic properties. Nevertheless some signs distinguishing antigenic substances from not antigenic, e.g., properties full are known And. the substances which are characterized, as a rule, high a pier possess. it is powerful — 10 000 and above.
Functionally active proteins consist of subunits — the polypeptide chains connected with each other in a uniform molecule by disulfide or hydrogen bindings. Dissociation of these bonds in some cases leads to disturbance of antigenic specificity. So, enzyme lactate dehydrogenase (pier. weight 135000) consists of four subunits of two genetically different types. Unlike native enzyme, polypeptide subunits in the dissociated state not only are not capable to induce synthesis of specific antibodies, but also do not react with an antiserum to native enzyme.
Emergence of antigenic ability with increase in molecular weight of substances is characteristic not only of proteins, but also of polysaccharides. The research of various drugs of dextrans with a molecular weight from 10 000 to 200 of 000 showed that stimulation of an antibody response in the person is caused by dextrans, a pier. which weight not lower than 50 000. At the same time it would be incorrect to consider that high molecular weight is obligatory property A. So, sulfonated polystyrene — high-molecular polymer — has no antigenicity. Nucleic acids, despite a high pier. weight, much weaker And., than proteins. Seralbumin and hemoglobin have an identical pier. the weight (about 70 000), however ability to induce antibody formation at hemoglobin it is expressed in much smaller degree, than at albumine.
The explicit exception of stated is made by antigenoaktivny substances which are characterized rather low a pier. it is powerful: glucagon, hormone of a pancreas (pier. weight 3800) and others which antigenic action is shown at immunization with adjuvants (see). Moreover, synthetic polypeptides which molecular weight is equal to 4000 and 1200 can have immune properties.
In addition to the size of a molecule, antigenicity of substance is defined as well by some other its properties. One of necessary properties A., as believe, rigidity of structure of the determinant groups which are its part is. So, gelatin, representing the slaboantigenny protein denatured by heating does not possess the fixed internal structure; a lot of glycine, not having in α-position of side groups that causes a possibility of longitudinal rotation is its part. If to enter the gelatin of chemical group increasing rigidity of its structure (tyrosine, tryptophane, phenylalanine) into a molecule, then it will be transformed in rather strong And. A similar sort data were obtained during the studying of antigenic properties of synthetic polypeptides. To increase rigidity of molecules in polisakharidny And. piranozny or furanozny rings can.
The research of artificial polypeptides allowed to establish a role of some amino acids in manifestation of antigenic properties of substances. During the comparison of polypeptides glyu58-, tir4-, glyu57-, liz38-, ala5-it was shown that alanine as well as tyrosine, increases immunogene properties of polypeptide. Decrease in influence glutaminic to - you on antigenicity of polypeptide after introduction to its structure of a small amount of tyrosine is established.
The question of value of the loaded groups is less clear for manifestation of antigenicity. According to one researchers, NH 3 + - groups are necessary for ensuring antigenic activity of polypeptides. However other researchers consider that at synthetic polypeptides, the free of loaded groups after deamination, ability to induce synthesis of antibodies not only remains, but also amplifies.
Property of antigens is their ability to be exposed in an organism to processes of metabolism. In this regard the substances given about a role of an optical isomerism of amino acids in definition of antigenicity are interesting. As it appeared, the polypeptides constructed of L-amino acids are active stimulators of an antibody response whereas polypeptides from D-amino acids are capable to cause antibody formation only at introduction them in small doses. In high doses D-polypeptides cause tolerance.
Antigenic activity of substances, and in particular their ability to induction of synthesis of antibodies, is most strongly shown if the immuniziruyemy animal belongs to other, than a source of this substance, to a look. It is conventional that antigenicity of proteins of subjects is higher, than the immuniziruyemy animal treats more remote taxonomical group.
Proteins and carbohydrates of blood and internals usually not antigens for an organism, in Krom they are synthesized, and at the same time antigens for other individuals of the same look. This pattern does not extend to so-called zabaryerny bodies, i.e. the bodies separated from a blood-groove by special barriers (a blood-brain barrier, a gemato-testicular barrier, etc.) which proteins normal usually do not come to blood and are And. for own organism. The brain, a crystalline lens, epithelial bodies, a seed plant is among such bodies.
Tolerance (immunological areactivity of an organism to this antigen) to own proteins well speaks from positions of the clonal and selection theory of immunity. One of original positions of this theory claims that «recognition» of own proteins of an organism and tolerance to them are connected with elimination in the embryonal period of development of all clones of the lymphoid cells capable to react against And. this organism. From positions of this theory And. are represented by the substances bearing in themselves signs of alien genetic information. Therefore, in order that substance could show the antigenic properties, it shall differ from And. fabrics of an immuniziruyemy individual. From here follows that antigenicity of substance depends also on its specificity.
By means of a method complex And., i.e. And., into which molecule a certain chemical group is artificially entered, it was established that antigenic specificity complex And. is defined not by all macromolecule in general, but properties of this group — determinant group. At the same time it turned out that specificity And. is defined not only by chemical structure of determinant group, but also situation it in antigen, and also a spatial relationship of atoms in it and their stereoisomerism connected with it.
In natural proteins antigenic specificity is also defined by a small part of its molecule. It is established that against fibroin of silk hydrolysates of silk about a pier can specifically suppress reaction of antibody formation. it is powerful, equal apprx. only 600 — 1000, and the most effective in such suppression are glycylalanine chains of 12 amino acids (a pier. weight 900). From octapeptides it was the most effective gli-/gli3-ala3-/tir-about a pier. it is powerful apprx. 600 which is a body of a specific antigenic determinant. According to other researchers, antigenic specificity of a dextran, synthetic polypeptides (polyalanine, a polylysine), a myoglobin depends on small reactive sites about a pier. weighing within 350 — 990.
Comparison of antigenic properties at proteins with the known sequence of the amino-acid remains allowed to establish that for emergence of new antigenic specificity enough minimum changes in primary structure of proteins. So, antigenic distinctions of insulin at some animals (pigs, cattle, sheep, horses) are caused by substitution of the amino-acid remains in only three sites of a polypeptide chain. Genetic options of molecules of immunoglobulins of the person [Inv (a +) and Inv(a-)] differ among themselves with only one amino-acid rest in the 189th provision of light chains, however it it appears enough that they differed as And.
The analysis of antigenic specificity of synthetic polypeptides showed further that to a large extent their specificity is defined by character of endgroups. However in some cases it was possible to note existence of cross-reactions and between polypeptides which endgroups differed from each other. As it was found out, such cross-reactions were caused by availability of the general amino acids in other provisions. In the subsequent experiences it was established that antibodies can be directed against all polypeptide consisting of five amino acids, in general. Similar results were yielded also by experiences with carbohydrate haptens. The leading influence on specificity of antigen of endgroups was here too revealed, and also shown that antibodies can be directed also against all hapten in general. The biggest group, edges can react with this antibody and, therefore, define specificity of antigen, are, obviously, geksasakharida.
Thus, in natural proteins and polysaccharides antigenic specificity is defined by structure and the sequence of amino acids in a polypeptide chain and monosugars in polysaccharide, especially their trailer amino acids or monosugars.
It is known that secondary and eventually tertiary structure of a proteinaceous molecule is defined by the sequence of amino acids. On the other hand, antigenic specificity of a molecule of protein is defined generally by the groups located on its surface. Therefore it is possible to claim that antigenic specificity of protein depends also from its secondary and, perhaps, tertiary structure. Besides, the stated above results of studying of antigenic properties of a lactate dehydrogenase show that antigenic specificity of the high-molecular proteins consisting of subunits can be defined also by their quarternary structure.
The antigenic determinants which are formed on a surface of a proteinaceous molecule can differ in a form, the sizes, on number and a set of the amino acids entering these determinants. As a result at immunization even pure crystal drug of protein in an organism forms antibodies of different types, heterogeneous on the specificity. The number of antigenic determinants in a molecule (valency of antigen) varies at different proteins depending on the sizes of molecules: from 5 in a molecule of ovalbumin (a pier. weight 40 500) to 40 in a molecule of thyreoglobulin (a pier. weight 650 000). However direct dependence between valency and a pier. it is powerful And. does not exist.
The nature of interaction of antigenic determinants and other part of a molecule in definition of antigenic properties of substance for the present is completely not disclosed. Nevertheless the saved-up facts demonstrate that stimulation of immunological reactions of an organism is carried out by reactive groups of molecules A., defining its specificity, i.e. determinant groups.
Speaking about specificity natural And. first of all mean their specific specificity. Really, for individuals of this look the antigenic specificity not characteristic of individuals who belong to any other type of living beings is inherent. It is not necessary to think, however, that there are some substances which are specially «responsible» for antigenic species specificity. Have such species specificity, obviously, many if not the majority of the substances which are contained in an organism.
Though all types of living beings accurately differ from each other species-specific And., degree of this distinction can be unequal. Closely related types are characterized by existence enough similar species-specific A. Vidam, far remote from each other, are inherent and sharply differing species-specific And. On the basis of the accounting of this phenomenon the independent biological direction — an immunosistematnka, using a method of the antigenic analysis for the solution of complex taxonomical problems and questions of the evolutionary relations of different types of microorganisms, plants and animals grew.
Already at the beginning of our century it was established that groups of various individuals of the same look can differ from each other according to contents And., who received afterwards the name of isoantigens. Isoantigens were revealed in cells of all studied animal species. However rather fully they are studied only at the person. As it appeared, the isoantigenic structure of cells of the person is exclusively difficult. Only in erythrocytes of the person more than 15 systems of the isoantigens including apprx. 100 A were revealed. (see. Blood groups ). Just as practice of hemotransfusion demanded development of the researches which led to the description of an antigenic structure of erythrocytes, the increase in interest of clinical physicians in change of fabrics and bodies which is observed today caused transition to careful studying of antigenic structure of other cells of an organism. It was established that the majority And., causing reaction of the recipient against a transplanted organ, contains in leukocytes. Therefore special attention was paid on studying And., contained in these blood cells. Various researchers described a large number various And. leukocytes. By comparison of all these And. with each other it turned out that the majority them belongs to the uniform system which received the name HL-A. In addition to this system, one more system leukocytic is revealed so far And., genetically independent of the HL-A system — system of group 5. As it was established, all And. both systems, except for, perhaps, antigen 9, are presented by several alleles (see). It was also shown that these And. are present, in addition to leukocytes, at cells of many bodies and tissues of the person that is especially important for selection of donors and recipients at organ transplantation in clinic (see. Incompatibility immunological ).
In addition to the isoantigens characteristic of erythrocytes and for leukocytes, the isoantigens inherent in thrombocytes, lymphocytes, granulocytes, blood serum, etc. were found. Therefore, in addition to the «general» isoantigens, exist, obviously, and organospetsifichesky isoantigens. The question is this, having huge theoretical and practical (at organ transplantation) the importance and at the same time exclusively difficult, in a crust, time it is almost not developed.
Also. By I. Mechnikov it was established that receiving the immune serums directed against cells of certain bodies or fabrics — so-called cytotoxins is possible. This opening formed the basis of the doctrine about antigenic specificity of body (fabric). Existence organospetsifichesky And. it was shown practically in all bodies. Data that in a number of bodies there are two types organospetsifichesky were obtained And., which meet in the bodies of representatives of the same name of different types of living beings, and And., the characterizing bodies only representatives of this look.
Now for most bodies (a liver, a kidney, lens, etc.) hl are investigated. obr. water-soluble organospetsifichesky And., which represent more or less complex systems of proteins. As for organospetsifichesky And., not passing into extracts, about them there are only single sketchy data. In the latest time were found And., the general for a kidney, a liver, spleens, hearts, but absent in blood serum. Some researchers allocate them in new group — interorgan
A. K to group described And. adjoin allocated by nek-ry researchers so-called organoid And., characterizing antigenic specificity of cellular kernels, mitochondrions, ribosomes etc.
In recent years existence is established And., characteristic of the organisms, their bodies or fabrics which are at certain stages of an ontogeny. These And. received the name stadiospetsifichesky And.
For pathology essential value had detection so-called pathological And., the resulting pathological processes. Also others concern them «cancer», «burn», «beam» And., formed in patholologically the changed fabrics. Emergence new is proved And. (transplant, komplementfiksiruyushchy and superficial) in cells of the tumors induced by viruses.
Antigenic specificity of substances of cells and fabrics reflects essential features of their structure, function and a physiological state. Opening of the reasons of antigenic effect of substances, the analysis of their properties, clarification of chemical bases of antigenic specificity of substances — all these questions are one of the main questions of modern immunochemistry. At the same time the research of properties of environmental antigens in a crust, time is not limited to a framework actually of immunochemistry and infectious immunology and serves for the solution of many questions having all-biological value, and, in particular, questions of evolution of an animal and flora.
The analysis of antigenic properties of viruses, bacteria, cells and fabrics of metaphytes showed exclusive complexity of their antigenic structure. Along with And., inherent to groups of individuals or all individuals relating to one look (specific, group And. bacteria, isoantigens), are present at tissues of animals And., widespread it is more or less wide at representatives of other types. Establishment of that fact that to some extent the general was important And., except for heterogeneous And. like Forssman's antigens, reflect genealogical bonds between types at which they occur.
Different body tissues differ on degree of their trans-species similarity And. Blood serum, liver, spleen and some other internals contain preferential Ampere-second strongly expressed specific specificity. On the contrary, And. muscles, seed plants, a brain, a crystalline lens on the specificity differ a little from And. homologous bodies and fabrics at representatives of different types of mammals and even in general at vertebrata. It is explained by similarity of a chemical structure and properties of the corresponding proteins bearing identical function. Obviously, in the course of evolution, at its some stage, exclusively full device of structure of such proteins for performance of the functions having the vital value therefore all subsequent mutations breaking this compliance eliminirovatsya by natural selection was reached. As a rule, such general And. the proteins which are characterized by extremely weak antigenicity (haemo-globins, insulin, a karbomilsintetaza), or proteins of the fabrics anatomically isolated from lymphoid system of an organism (proteins of a crystalline lens) are.
Other reason of existence of the general And. at representatives of different types, especially at types, phylogenetic far remote from each other, antigenic adaptation of types parasites is to And. the owner, reflecting ecological bonds between types.
Some antigens of high-organized animals and, in particular, the person bear protective function in maintenance of genetic constancy of internal environment of an organism. It is established that And. the AB0 systems (see Blood groups) are present not only at fabrics, but also in the form of water-soluble And. in biological liquids and secrets. Explaining possible value. the phenomena of secretion of antigens, P. N. Kosyakov assumed that he AB0 antigens in saliva and in upper parts went. - kish. a path play a protective role, neutralizing the hemagglutinins of an animal or vegetable (lectins) origin which are contained in food. Group And. semen protect men's sex cells from influence of the isoantibodies which are in a female genital tract at the time of fertilization.
In the phenomena of group incompatibility of a maternal organism and a fruit isoantigens (the AB0 systems, etc.) the last, being in amniotic liquid, amnion and chorion, play a protective role, connecting the maternal antibodies getting through a placenta and without «allowing» them to fabrics of a fruit.
In recent years nek-ry researchers the provision on a possible morphogenetic role moves forward And. in an embryogenesis (see. Immunology of an embryogenesis ).
Biological value A. certainly it is not limited to their participation in the phenomena considered above. So, e.g., the question of communication of isoantigens of blood with predisposition of the persons differentiated on these is intensively investigated recently And., to a nek-eye to types of diseases.
See also Autoantigens .
Bibliography: Topical issues of immunology, under the editorship of L. A. Zilber and P. A. Vershilova, page 312, M. 1964, bibliogr.; Boyd U. Fundamentals of immunology, the lane with English, M., 1969, bibliogr.; And γ-ρο in both F. Immunokhimiya's c and biosynthesis of antibodies, the lane with English, M., 1969, bibliogr.; Zilber JI. And. also G. I. Virusologiya and immunology of cancer, M., 1962, bibliogr Is Abelian.; P. N. Immunologiya's jambs of isoantigens and isoantibodies, M., 1965, bibliogr.; Petrov R. V. Immunology of acute radiation injury, M., 1962, bibliogr.; Tumanov A. K. Serumal systems of blood, M., 1968, bibliogr.; Efroimson V. P. Introduction to medical genetics, M., 1968, bibliogr.; Andersson B. Interaction between immunocompetent cells and antigen, Stockholm, 1972, bibliogr.; Immunological tolerance to microbial antigens, ed. by H. Friedman, N. Y., 1971. bibliogr.; Kissme-y e r-N ielsen F. Thorsby E. Human transplantation antigens, Copenhagen, 1970; Strong and weak histocompatibility antigens, Copenhagen, 1970, bibli-ogr.; Surface antigens on nucleated cells, Copenhagen, 1971, bibliogr.
Lake of E. Elms, V. M. Barabanov.