IMMUNOGENETICS (immunology + genetics) — science about patterns of inheritance of antigenic specificity and a role of genetic mechanisms in implementation of immune responses. Relevance And. both in theoretical, and in especially practical plan it is connected with need of the solution of the major problems devoted to genetics of an immune response, genetics of incompatibility of fabrics at changes and to a genetic homeostasis of internal environment of an organism. And. as the science arose at a boundary of two sciences: geneticists (see) and immunology (see) also uses methods in the solution of the tasks facing it genetic analysis (see), molecular biology (see) and immunology.
Historical roots I. consign to the remote past, to observations of different sensitivity of genetically differing individuals of one look in relation to the causative agent of an infection inherent to this look. Long ago breeds of a cattle, resistant and sensitive concerning bacterial and viral infections, pigs and hens were known. Genetically caused distinctions of mice and some other rodents concerning mouse typhus are studied in detail. For people it is undoubtedly shown that monozygotic (identical) twins who are genetic copies of each other have the same infectious disease much more often, than dizygotic (nonidentical) twins. However And. as the science arose not on the basis of observations and comprehension of genetic bases of various sensitivity to infections, and after opening by K. Landshteyner in 1901 of the group factors of blood (And, B,0) which received afterwards the name isoantigens (see. Group-specific substances, Blood groups). Studying of patterns of inheritance of these from antigens also led to formation And. Inheritance from antigens is characterized by either total absence of the phenomenon of domination, or partial domination. In this regard the antigenic phenotype of an organism repeats its genotype.
Studying of isoantigens led to emergence transplant And., the cut is the central problem a problem of interaction of genetically differing somatic cells and the mechanism of this interaction. In turn the central link of this problem is interaction of genetically differing cells of a transplant and the recipient. Achievements in this area also brought And. to comprehension of a role of immune mechanisms in maintenance of a genetic homeostasis of multimillion populations of somatic cells of an organism (F. Vernet, 1964).
In 60 — the 70th years 20 century were established that not only sensitivity of organisms to infections, but also processes of an immunogenesis and antibody response at vaccination, and also intensity of actively arising immunity have genetic bases. At the same time distinctions in efficiency of unambiguous vaccination at different individuals are defined to a large extent heredity (see), than external conditions. Immunization of mice of seven various genotypes of a leitospirama revealed two types of reaction. Mice of a closed line of C57BL develop in 15 — 20 times more of antibodies to leptospira, than a mouse of the SZN line. This sign is inherited as dominant, it is not linked to a floor and determined more than one couple of genes. The dominant mode of inheritance of intensity of reaction is found in relation to many antigens. At the same time animals can be highly (strongly) answering concerning one antigens and low (poorly) answering concerning others. The immune responsiveness of an individual is always specific: in relation to one antigen — one, in relation to another — another. The analysis of genetic determinancy gave the chance to identify the loci controlling an immune response (genes of IR). Their close coupling with a locus of histocompatability is shown; at mice genes of IR are located in the 17th chromosome in the main system of histocompatability H2.
Other mode of inheritance consists that the hybrids of firstgeneration received during the crossing of an individual with a high immune response (on products of antibodies) with the individual relating to the nonreacting line do not give an immune response, i.e. behave as the nonreacting line. Most defiantly this mode of inheritance is shown at transplantation immunology. The proteinaceous or cellular isoantigens which are not causing an immune response in individuals of a certain line do not cause it and in hybrids of this line.
Two modes of inheritance of intensity (force) of reaction on the immunizing agent demonstrate existence at least of two main reasons for genetic conditionality of a weak immune response. One of them is connected with the fact that the immunizing antigenic determinant tozhdestven to certain fabric determinants at animals of this genotype. In this case antigen is not perceived as the stranger and does not include an immunogenesis (i.e. does not cause antibody formation). As hybrids of firstgeneration receive a full range of antigens of each of parents and this antigen is present at their fabrics, inheritance of inability to react to this antigenic determinant is result.
The dominant nature of inheritance of the strong answer is connected with existence of a large number of T or V of cells, immunocompetent in relation to these antigens, in an adenoid tissue of the high-reacting organisms. An opportunity that concerning some antigens the low immune response is connected with hereditarily the caused insufficiency of certain enzymes or fermental systems of the macrophages processing microbic antigens before their utilization by immunocompetent cells is not excluded.
These facts put before modern And. in turn following problems: 1) the differentiated assessment of an immune responsiveness of the person as in sense of specific hereditary defects of T - and V-systems of cells, and in sense of specific antigens; 2) definition of genetic conditionality of force of an immune response on this or that specific antigen before immunization; 3) transfer of genetically low reacting individuals in highly reacting; 4) the principle of individualization of vaccines, according to the Crimea one groups of people are immunized according to one schemes, others — on others.
Transplant And. studies the reasons of incompatibility of fabrics, mechanisms of rejection of genetically alien transplants and a way of overcoming incompatibility. Its main achievements are connected with opening of genetic laws of transplantation. According to these laws, tissue of the donor (skin, etc.), genetically other than tissue of the recipient, stimulates immunological reactions. This genetic difference is that the genome of the donor contains the genes which are absent at the recipient, and not vice versa, i.e. for turning on of the mechanism of immunity the initiating fabrics shall bear signs of genetic allogeneity. So, the skin rag from the individual belonging to any genetically pure line of animals (we will designate a genotype of AA), stimulates immunological reactions and is torn away at change to the recipient belonging to other line (a genotype of B B), but gets accustomed on animals of a genotype of AA. The transplant taken from any of parents successfully gets accustomed on hybrids of AV since they do not bear in themselves elements of genetic allogeneity: hybrids contain a full range of genes of both parent lines. On the contrary, the skin taken from hybrids of AV is torn away at change to the individual belonging to any of parent lines since this skin is the transplant bearing signs of allogeneity (In for AA and A for VV).
Later it was shown that difference even on one gene inevitably provides antigenic allogeneity. The main genetic system of histocompatability of the person received the name HLA. It is established that on the 6th chromosome of the person the genes which are controlling a row immunol, signs and received the name of the main complex of histocompatability (Ministry of Taxes and Tax Collection) are localized. The genes of A, B, C, D determining leukocytic HLA antigens, and the genes controlling a factor of Bf of properdin, a number of components of a complement, immune response genes are its part, etc.
P. which explained surgical failures at changes of fabrics put forward also a problem of overcoming a barrier of incompatibility. And if stimulation of immunity was the main objective of immunology of the first half of 20 century, then there was later a new task — to learn to suppress immunity. Opening in 1953 by P. Medavar and M. Gashek of a phenomenon of unresponsiveness, i.e. tolerance to alien fabrics, defined one of recent trends of researches — search biol, ways of overcoming incompatibility. Search of chemical means of suppression of immunity therefore it was found (or it is synthesized) many chemical immunodepressants — analogs of purines and pyrimidines, alkylating agents, antibiotics (Actinomycinum of D, mitomitsin, puromycin), steroid hormones, etc. was at the same time carried out. However it should be noted that so far all known immunodepressive substances (see) treat the cytostatics which are nonspecific blocking proliferation of cells or synthesis of protein. The oppression of an immune responsiveness caused by them is not specific. The immunogenesis is oppressed concerning all antigens, and the organism is unarmed in the face of any infection. Therefore one of the major tasks in this area is research of the substances and ways providing specific suppression of reaction only to the set antigens.
By 1977 57 leukocytic antigens of the person are described; 47 antigens come to light serol, by methods and are under control of loci And, In, With; 10 antigens are determined by a gene of D and identified so far only by methods with use of cultures of fabrics. Assume that the gene of D is closely linked to immune response genes. The characteristic of human population on leukocytic antigens pursues at least two the aims: selection of the most compatible donors and recipients and allocation of graft-specific antigens in pure form. Width a wedge, uses of organ transplantation and fabrics depends on the successful solution of these tasks.
One individual can differ from another as much as possible on eight antigens of the main HLA system. Selection of the identical donor and the recipient for 4 antigens provides engraftment within a year of 70 — 75% of the replaced kidneys. At difference on one antigen — 60 — 65%, on two — 50 — 55%.
Very close to problems of histocompatibility there is a problem of a role of immunologic mechanisms in processes of maintenance of genetic constancy of multimillion populations of somatic cells of a complete organism. Only the hemopoietic and lymphoid tissues of the person consist not less than of 1012 cells. The fact that the minimum genetic difference is enough for immune recognition of «stranger» gives the chance to build theories of control of genetic constancy of internal environment of an organism. Specific mechanisms of singenny preference and inhibition of the nesingenny breeding cells are already studied. The term «singenny preference» is entered by the Swedish immunogeneticist Helstrem (To. Hellstrom) in 1964. The being of the phenomenon consists that cells and fabrics grow more slowly and breed at their hit in genetically excellent organism even in conditions when this organism is not capable to include immunologic mechanisms of rejection. The phenomenon of an inactivation of nesingenny stem cells is found by R. V. Petrov and L. S. Seslavina in 1967. Studying of a phenomenon showed that live not immune lymphocytes at primary contact with genetically different (nesingenny) cells of the hemopoietic fabrics have ability to inactivate the stem cells which are contained there, i.e. elements on which growth and reproduction of these fabrics depends. Therefore, for any genetically different cell in an organism at once there is very adverse situation. Its own reproductive rate decreases owing to a nesingenny environment, and lymphocytes still in addition actively inhibit its functions.
The described phenomena demonstrate existence of at least two mechanisms playing an essential role in maintenance of a genetic homeostasis of somatic cells during life of an individual; one of them — preferable reproduction genotypic identical cells, the second — active braking of genetically different cells, capable to reproduction. Thanks to these mechanisms (genetically changed) cell which appeared in an organism mutant has very few chances to give posterity or to breed in a little significant amount. It is possible to assume that accumulation in an organism of abnormal cellular clones including cancer, occurs at a combination of at least two conditions: an exit of cells from under the control provided with effect of singenny preference, and disturbance of ability of lymphocytes is active to inhibit reproduction of genetically different cells.
Problems I. have a direct bearing on a number of the major medicobiological problems. The classical immunology developed system of preventive inoculations, danger of mass infectious diseases allowed to eliminate edges. However ensuring protection of an organism against action of the factors bearing alien genetic information (bacteria, viruses, the elementary, foreign proteins and fabrics), is impossible such way. The solution of this problem is possible through a solution of the problem of specific features of an immune response.
Bibliography: Burnett F. M. Cellular immunology, the lane with English, M., 1971, bibliogr.; Petrov R. V. Immunology and immunogenetics, M., 1976, bibliogr.; Efroimson V. P. Immunogenetics, M., 1971.
R. V. Petrov.