COMPLEMENT (Latin complementum addition) — polymolecular system of serum proteins, one of the most important factors of natural immunity. Functions in blood of the person, hematocryal and hematothermal animals. Contains in a lymph and intercellular lymphs. Being included cell-bound immune complexes, To. carries out a lysis sensibilized antibodies of cellular antigens, causes reaction immune sticking (see), participates in opsonization of bacteria, viruses and corpuscular antigens, accelerating their phagocytosis, participates in development of an inflammation.
To. it was for the first time described under the name «alexin» at the end of 19 century as the nonspecific thermolabile factor defining bactericidal properties of fresh blood serum (G. Bukhner, 1889). The term «complement» is entered by P. Ehrlich (1900) who considered that the bactericidal factor supplements cytolytic action of antibodies.
Not less than 18 proteins making system K are known. Their number includes 9 components K., 8 of which are individual proteins, and one represents a complex: 4 proteins of system of properdin, 1 inhibitor of enzyme and 2 enzymes of the inactivator.
According to the nomenclature accepted by WHO, system K. it is designated by a symbol With, its individual components — figures (C1, C2... C9), fragments of components K. — lowercase letters (e.g., SZA). Existence of euzymatic activity in a fragment is noted line over its symbol, and existence of the center of linkng with a membrane of cells — an asterisk about its symbol [Austin (To. F. Austen) et al., 1968].
Components K. circulate in blood in the form of predecessors, without connecting to free antibodies or antigens. Two are described biol, the mechanism of activation (binding) of system K. — classical and so-called alternative, or properdinovy [H. J. Muller-Eberhard, 1975; W. Vogt, 1974].
The classical mechanism of activation To. it is carried out with participation IgG-and the IgM-antibodies which are a part of cell-bound immune complexes, or nonspecific aggregated immunoglobulins of these classes. At connection with antigens or as a result of nonspecific aggregation in molecules of the specified immunoglobulins the centers connecting C1 — the first component of system K form. (A. Ya. Kulberg, 1975). Fixed on C1 immunoglobulin initiates a reaction chain which other components of system K consistently enter.
C1 represents the complex of three subcomponents (C1q, C1rr and C1s) which is formed in the presence of calcium ions; C1q — kollagenopodobny protein about a pier. it is powerful (weighing) 400 000, consisting of six not covalently connected identical subunits. Each subunit supports the distinguishing center for linkng with a molecule of immunoglobulin. Accession of C1q to immunoglobulin is followed by intramolecular reorganization of C1q and activation of the related Clr proferment operating on C1s-proesteraza. The formed C1s-esterase (C1s) influences the second (C2) and fourth (C4) which are in a liquid phase components K.
Molecule C4 (pier. weight 208 000) it is constructed of three peptide chains — an alpha, a beta and scale, connected by disulfide bridges. C1s chips off S4a peptide, a pier from an alpha chain. weight to-rogo 8000, and in the remained C4b-fragment of a molecule arises the center of linkng with a cell membrane, sensibilized antibodies. At impact of C1s on C2, a pier. weight to-rogo 117 000, two fragments — C2b are formed (a pier. weight 37 000) and S2a (pier. weight 80 000). In the last the center of linkng with C4b forms. The C42 complex formed on a cellular membrane is capable to split SZ; therefore it is called SZ-convertase.
Molecule SZ (pier. weight 180 000) it is constructed of two peptide chains — an alpha and a beta. As a result of eliminating of C3 convertase from an alpha chain of SZA peptide about a pier. weighing 9000 in the SZB-fragment of a molecule the center of linkng with a cell membrane is formed and on a membrane C423 complex with peptidazny activity concerning C5 (C5 convertase) forms.
After proteolytic splitting of C5 assembly of membranoatakuyushchy unit from so-called trailer components of system K begins. The molecule C5 is constructed similarly SZ of two peptide chains and and r, a pier. which weight respectively 110 000 and 70 000. C5 convertase chips off from an alpha chain S5a peptide about a pier. weighing 16 500. Formed S5b-fragment has ability to occlude consistently on one molecule C6 and C7. The C567 complex occludes one molecule C8 and six molecules C9. At the time of education the C5 complex — 9 attacks a cell membrane, causing its destruction. Cytolytic activity of a complex is defined by C8 and considerably C9 amplifies.
Along with cytolytic components at activation of system K. the SZA active peptides and S5a, called anaphylatoxins are formed physiologically; they cause allocation of a histamine mast cells. reduction of smooth muscles also increase permeability of vessels, and also serve as chemotactic factors for polimorfonuklearny cells. The directed migration of polimorfonuklearny cells in the place of activation To. causes also trimolecular C567 complex [P. Ward, 1975]. One more biologically active peptide arising at activation of system K., SZB is. At linkng with a cellular membrane it acquires the second stable connecting center concerning the receptors located on a surface of a number of cells (macrophages, thrombocytes, erythrocytes). This process called immune sticking strengthens phagocytosis loaded To. cells and corpuscular particles [S. Ruddy, 1974].
To. takes part also in the mechanism of nonspecific resistance to infections. In this case system K. it is activated without participation of antibodies by the polysaccharides or lipopolisakharida which are a part of cell walls of bacteria, yeast, plants or the aggregated IgA. Binding To. occurs on an alternative way, since SZ, passing stages of activation of C1, C4 and C2. It is shown that take part in formation of SZ-and C5 convertases of an alternative way protein of serum properdin, the SZ-activator of convertase and a number of his predecessors. At activation To. on an alternative way, as well as on classical, the cytolytic C5 complex — 9, and also physiologically the SZA active peptides and S5a is formed. Possibly, this mechanism is the cornerstone of nonspecific elimination from an organism of viruses and the changed erythrocytes [L. Pillemer, 1954, 1955].
All specified functions of reaction products of components K. are directed to destruction and the fastest removal from an organism inf. or alien agents. They define value of system K. as protective factor of an organism.
In addition to protective function, system K. can promote damage of own body tissues at a number of diseases with an autoimmune component (a glomerulonephritis, a system lupus erythematosus, arteritis, myocarditis, an endocarditis). In this case activation of system K. it is carried out as the antibodies directed against fabrics, and the soluble or fixed in fabrics cell-bound immune complexes. The formed C423 and C5 complexes — 9 components K. are fixed at the same time both on sensibilized, and on not sensibilized by antibodies cells, causing destruction of their membranes. The important role in autoimmune process belongs also SZA-and S5a-peptidam and C567 complex [N. R. Cooper, 1974; L. G. Hunsicker, 1974; Mac-Klaski (R. Ms of Cluskey), 1975].
About contents To. judge most often by its hemolitic activity concerning erythrocytes of a ram, sensibilized rabbit hemolysin. A caption To. express in 100 or 50% hemolitic units (Sn100ili CH50), i.e. the minimum quantity To., a cut at the chosen reference conditions of experience respectively 100 or 50% of optimum sensibilized erythrocytes lyse. Contents To. it can be estimated also on its cytolytic action in system lymphocytes — anti-lymphocytic serum [Terasaki (R. by I. Terasaki), 1964]. To., not having lytic activity, e.g. To. horses, a bull, a mouse, it can be defined in an agglutination test loaded To. sensibilized erythrocytes with protein of bull serum — conglutinin (see. Conglutination ).
Individual components K. titrate in the hemolitic test, using for this purpose special reagents which represent the drugs of fresh serum of a Guinea pig deprived only of a titrable component, and other components containing much. As substrates for titration also corresponding intermediate products of hemolysis can be used. Broad use was found immunochemical, by methods of titration with use of antiserums to pure components K.
Content To. in serums of animal different types, according to hemolitic titration, strongly varies. Its highest caption reaching 200 CH50 on 1 ml is defined at Guinea pigs. B1 of ml of serum of the person contains on average 70, and a rabbit 20 CH50 [R. Audran, 1959, 1960]. However credits To. in the hemolitic test not always correspond to its true contents. So, To. some types do not lyse sensibilized mutton erythrocytes though contacts them. Hemolitic activity To. different types it is not identical during the testing in various hemolitic systems [Boyd (W. Page of Boyd), 1969].
Biol, properties K. different types substantially are defined by contents in them individual components. Specific differences are especially expressed on the maintenance of C2 and C4. These components completely are absent or contain in very low credits in serums of a horse, bull, mouse, To. which have no lytic activity. High content of C1 is characteristic of serums of all types. Maintenance of components K. in serum of the person it is defined in weight units.
Individual fluctuations of level and structure To. at healthy aged people of 8 — 35 years are insignificant and do not depend on a blood group and a Rhesus factor. Usually at women contains 10% less To., than at men, and at newborn and pregnant women its contents is reduced on average by 30% [J. Gumbreitier et al., 1960, 1961]. The tendency to increase in level K is noted. aged between 35 and 60 years.
Content To. in serums of patients depends on the nature of a disease. At the majority of acute infections of a purulent etiology, and also at staphylococcal bacteremia during an initial stage increase in credits of K. Predpolagayut is observed that it is connected with activation of cells of reticuloendothelial system, in particular the macrophages synthesizing C2, C4, C5. During elimination of antigens with participation of antibodies credits To. norms at recovery decrease and reach. At a number of the diseases affecting cells of a parenchyma of a liver, napr, cirrhosis, hepatitis, hron, cholecystitis, synthesis of SZ-, S6-, S9-and C1 inhibitor is broken that leads to decrease in the general level K. As a rule, level K. decreases at allergic conditions, autoimmune diseases and diseases of cell-bound immune complexes due to binding To. the cell-bound immune complexes circulating in blood and connected in fabrics. Cases of deficit on separate components K are described., followed various patol, states.
System K. it is active in an organism and in svezhevydelenny serums. To. it is inactivated within 2 — 4 days at storage of serums in the refrigerator (t ° 5 °), and as a result of warming up of serums at t ° 56 ° — within 20 min. The inactivation is described To. under the influence of various physical. factors — a sunlight, the ultraviolet radiation, stirring, at action of chemical agents — weak solutions of acids, alkalis, organic solvents, proteolytic enzymes (L. S. Reznikova, 1967). Activity To. the long time remains in lyophilicly dried up serums, at addition to fresh serums of sodium sulfate (5%) and boric to - you (4%), in the serums which are stored at a temperature — 40 ° below.
Ability To. to be included cell-bound immune complexes use for detection of antibodies and antigens (see. Antigen — an antibody reaction , Reaction of binding complement ). However it must be kept in mind that many antiserums and some antigens connect To. nonspecific. The phenomenon this called anticomplementary action is expressed in decrease in hemolitic activity To. It can be caused by impurity in titrable drugs of the aggregated globulins, lipopolisakharid or proteolytic enzymes, and also bacterial pollution of drugs (Boyd, 1969). The increased ability of antibodies of some individuals in one look to nonspecific fixing To. is called deviabilitety, and the antibodies having this property — deviabilny.
A research of process of activation To., examination biol, properties of products of activation of components K., level K. normal and at various diseases allows to understand its protective function and its role in damage of fabrics. This knowledge is necessary, in particular, for development of evidence-based methods of the prevention and treatment of the diseases caused by activation of system K.
Definition of credits To. at various diseases in dynamics has practical value since is an indicator immunol, conditions of an organism, efficiency to lay down. actions also has predictive value.
See also Immunity .
Bibliography: Boyd U. Fundamentals of immunology, the lane with English, page 346, M., 1969; The Inflammation, immunity and hypersensitivity, under the editorship of G. 3. Moveta, the lane with English, page 422, M., 1975, bibliogr.; Kulberg A. Ya. Immunoglobulins as biological regulators, page 106, M., 1975, bibliogr.; Cabot. an imeyer M, Experimental immunochemistry, the lane with English, page 140, M., 1968, bibliogr.; P e z N and to the island and L. S. A complement and its value in immunological reactions, M., 1967, bibliogr.; A u s t e n K. F. a. o. Nomenclature of complement, Bull. Wld Hlth Org., v. 39, p. 935, 1968; Col ten H. R. Biosynthesis of complement, Advanc. Immunol., v. 22, p. 67, 1976, bibliogr.; Comprehensive immunology, ed. by N. K. Day a. R. A. Good, v. 2, N. Y., 1977; Muller-Eberhard H. J. Complement, Ann Rev. Biochem., v. 44, p. 697, 1975, bibliogr.; Yogt W. Activation, activities and pharmacologically active products of complement, Pharmacol. Rev., v. 26, p. 125, 1974, bibliogr.
I. A. Tarkhanova.