IMMUNOCHEMISTRY (immuno [logiya] + chemistry) — the section of immunology studying chemical bases of immunological processes. Development immunology (see) substantially is defined by achievements in the area I.
Attempts to analyze chemical essence of immune responses were made still at the end of 19 — the beginning of 20 century. At the same time the first data that squirrels or the complexes of protein received in the synthetic way with simple chemical connections can act as antigens were received. During the same period S. Arrhenius and T. Madsen offered a chemical explanation of the mechanism of reaction antigen — an antibody (see. Antigen — an antibody reaction ), P. Ehrlich formulated the humoral theory immunity (see). In 30 — the 50th 20 century thanks to basic researches of K. Landshteyner, Geydelbergera (M. of Heidelberger), J. Mar rack, E. Kabat, R. Porter, etc. laid the foundation modern And.: important data on chemistry of environmental and artificial antigens are obtained, the immunoglobin nature of antibodies is defined and methodical methods of allocation of antibodies in pure form are developed, the main chemical patterns serol, reactions are analyzed. Further researches allowed to study in detail the principles of the structural organization of determinant groups of antigens, to decipher structure of antibodies and to determine the main consistent patterns of their biosynthesis that made possible widely to develop researches in the field of the theory immunol, processes. In turn progress in studying of a chemical structure of antigens defined approaches to designing of synthetic vaccines and creation new immunofarmakol. drugs. The successful solution of the listed tasks became possible thanks to use of a wide arsenal physical. and chemical methods of a research and use of various synthetic connections which are an analog of environmental antigens or their separate determinant groups. The large volume of information on a structure of determinant groups of antigens was saved up at immunization of experimental animals by complexes of protein with the most various on the structure organic compounds. With improvement of the technology of receiving synthetic polypeptides they began to be used widely as models of environmental antigens. With their help it was convincingly shown that antigenic specificity depends as on the sequence of the amino-acid remains in polypeptide chains, and on a way of laying of a polypeptide chain in space. Being guided by these data and these chemical structures of a number of proteins, it was succeeded to synthesize the polypeptides having the same antigenic specificity as natural proteins. On the basis of the polysaccharides of a number of microorganisms given fine structure (hl. obr. bacteria of intestinal group) synthetic analogs of determinant groups of bacterial antigens were received. Use of natural proteins and artificial antigens of the known structure for immunization of genetically homogeneous lines of animals of one look allows to study the features of a genotype causing a possibility of an immune response on certain chemical structures. Thanks to a research of antigens of one chemical structure differing among themselves in molecular weight it is established that high-molecular antigens cause effective antibody formation while low-molecular — a state immunol. tolerances (see. unresponsiveness ), and at certain ways of introduction cause reactions of cellular immunity.
Considerable achievement And. disclosure of submolecular structure was immunoglobulins (see) and philosophy of the structural organization of active centers (anti-determinants) of antibodies (see. Antibodies ). Five main classes and several subclasses of immunoglobulins were allocated and in details investigated, the amino-acid sequence of the polypeptide chains making them is in whole or in part defined and ways of laying of polypeptide chains of immunoglobulins in space are established. On the basis of this yielded and results of a research of immunoglobulins methods of the X-ray crystallographic analysis, a submicroscopy and a spektrofotometriya succeeded to construct reliable model of the molecule IgG and approximate models of immunoglobulins of other classes. The analysis of primary structure of polypeptide chains of immunoglobulins showed that each of chains is coded by two genes. This conclusion having big obshchebiol. value, served as an incentive to broad expansion of researches on genetics of immunoglobulins and the mechanism of their biosynthesis. One of important achievements in this direction was allocation in a high cleaning type of information RNA for each of polypeptide chains of immunoglobulins and reproduction of biosynthesis of polypeptide chains in acellular system. Studying of the nucleotide sequence of information RNA for peptide chains of the immunoglobulins and genes controlling structure of immunoglobulins is begun. Also patterns of assembly of a molecule of immunoglobulin in a plasmocyte were disclosed and the mechanism of its secretion is analyzed by a cell.
Big achievement And. it is also necessary to consider identification and a research of the nature of antigensvyazyvayushchy receptors of lymphocytes. It is established that B-lymphocytes bear immunoglobulins on the surface, and the last are produced by these lymphocytes. An immunochemical research of the receptor device of lymphoid cells — one of the most intensively developing areas I.
Considerable success is achieved in studying of a structure of an anti-determinant and the mechanism of reaction anti-gays — an antibody. It is established that small pieces of polypeptide chains of an antibody participate in formation of an anti-determinant. The site of a molecule of an antibody bearing an anti-determinant managed to be separated from all molecule, having kept its specific structure. Thereby it was shown that active sites of a molecule of an antibody have structural autonomy in relation to other part of a molecule. Use various chemical and physical. methods for a research of structure of an anti-determinant in combination with data on a structure of determinant groups of antigens created premises for reliable chemical interpretation of the principle of a complementarity of antigens and antibodies and understanding of the mechanism of reaction antigen — an antibody. It is established that the active center of an antibody represents a cavity, depth a cut for a number of antibodies does not exceed 1,2 nanometers. By the calculations executed by Kabat, the anti-determinant of antibodies to a dextran is commensurable from the rest of an izomaltogeksoza and is equal on length of 3,4 nanometers and on width of 1,2 nanometers. It is obvious that anti-determinants of antibodies of various specificity are not identical by the sizes and a configuration in the same measure in what determinant groups of antigens differ on a structure, a complex antigen — the antibody is formed at the expense of various noncovalent bonds — electrovalent, hydrogen, hydrophobic. The role of the corresponding bonds is defined by a structure of specific determinant group of antigen (see. Antigen — an antibody reaction ).
Progress in a research of structure and function of antibodies is substantially connected with achievements in the area genetic engineering (see). Realizing the principles of self-assembly of a molecule of protein, it was succeeded not only to reconstruct functionally active molecules of an antibody and their fragments from separate chains and their pieces, but also to create the hybrids which are not existing in the nature. E.g., methods of receiving hybrid molecules of antibodies with anti-determinants, various on specificity, are developed. Such antibodies at which one of anti-determinants is specific to ferritin and another to any fabric or microbic antigen, found broad application for specific contrasting of antigens in a submicroscopy.
Use of immunochemical approaches for assessment of functional properties of antibodies and their complexes with antigen has essential value for establishment of the mechanism biol, the reactions arising in an organism at interaction of antigens and antibodies. In this regard much attention is paid to studying of reaction of binding complement (see. Complement , Reaction of binding complement ), to the mechanism of fixing of cell-bound immune complexes in fabrics, biochemical, to the reactions arising at immediate hypersensitivity. Results of these researches are of great importance for clarification of a pathogeny of many diseases connected with a persistention in an organism of complexes antigen — an antibody.
One of the major directions I. it is connected with studying of molecular mechanisms of an immunogenesis. In addition to the nature and properties of antigensvyazyvayushchy receptors of immunocompetent cells, chemical mechanisms of cooperative interaction of various cells of lymphoid system are investigated, the nature of the factors acting as humoral regulators of an immunogenesis becomes clear. By means of immunochemical methods fractionation of immunocompetent cells, predetermined to synthesis of antibodies of various specificity is carried out.
The increasing value immunochemical methods during the studying of the mechanism immunol gain, tolerances, transplant and atrepsy (see. atrepsy , Immunity transplant ). Various methods of allocation and fractionation of graft-specific and opukholespetsifichesky antigens are developed. Highly sensitive immunochemical methods found application in diagnosis of a number of malignant tumors (primary cancer of a liver, tumors went. - kish. path).
For disclosure of essence of processes of immunity along with chemical mechanisms of artificial immunity chemical bases of natural immunity are investigated: the chemical nature of many mediators of process of an inflammation, including the factors responsible for change of permeability of vessels at various stages of inflammatory process, and chemotactic factors for leukocytes and lymphocytes are deciphered. The last, in particular, can be formed at disintegration of gamma-globulin and represent various splinters of its molecule. Properties of various biologically active factors which are formed at activation of system of a complement are studied. Considerable success is achieved in studying biochemical, mechanisms of process of phagocytosis — power engineering specialists of this process, a role of cyclic mononucleotides, functions of enzymes of lysosomes.
And. enriched immunology with a large number of new methods of a research. Here it is necessary to carry methods of quantitative assessment serol, reactions, highly sensitive methods of definition of antigens and antibodies with use of the equipment of immunoadsorbents and the radio isotope analysis, various methods of preparative division of antigens and antibodies. The number of immunochemical methods continuously grows due to implementation in biology and medicine new physical. and chemical methods of a research. The immunochemical methods which are characterized by high specificity and sensitivity found application in many fields of experimental biology and medicine in which use of the principles of reaction antigen — an antibody is reasonable. Number of immunochemical methods (Immunoelectrophoresis, radioimmunol. methods, radial immunodiffusion) it is used in diagnosis of infectious and internal diseases, and also in forensic medicine.
Bibliography: Immune marker analysis under the editorship of L. A. Zilber, M., 1968; To at l b e r A. Ya. Immunoglobulins as biological regulators, M., 1975, bibliogr.; To EB from E. A. and M e y e r M. M. Experimental immunochemistry, the lane with English, M., 1968; Nezlinr.S. Structure and biosynthesis of antibodies, M., 1972.
A. Ya. Kulberg.