ANTIBODIES — the proteins of globulinovy fraction of blood serum of the person and hematothermal animals which are formed in response to introduction to an organism of various antigens (bacteria, viruses, proteinaceous toxins, etc.) and specifically interacting with the antigens which caused their education. Contacting active sites (centers) bacteria or viruses, And. interfere with their reproduction or neutralize the toxicants emitted by them. Existence in blood A. points that the organism entered interaction with antigen against the disease caused by it. In what degree immunity depends from And. and in what degree And. only accompany immunity, decides in relation to a specific disease. Determination of level A. in blood serum allows to judge tension of immunity even when And. do not play a crucial protective role.
Protective action And., contained in immune serums, it is widely used in therapy and prevention of infectious diseases (see. Seroimmunity , Serotherapy ). Reactions of Ampere-second antigens apply (serological tests) in diagnosis of various diseases (see. Serological researches ).
throughout a long time about the chemical nature And. knew a little. It is known that And. after administration of antigen are found in blood serum, a lymph, extracts of fabrics and that they specifically react with the antigen. About existence And. judged on the basis of those visible units which are formed at interaction with antigen (agglutination, precipitation) or on change of properties of antigen (neutralization of toxin, a lysis of a cell), but about with what chemical substrate A. are connected, almost nothing was known.
Thanks to use of methods of ultracentrifuging, an immunoelectrophoresis and mobility of proteins in isoelectric field accessory is proved And. to a class of gamma-globulins, or immunoglobulins.
And. represent normal globulins, preformirovanny in the course of synthesis. The immune globulins received as a result of immunization of various animals by the same antigen and at immunization of the same species of an animal various antigens have unequal properties, just as serum globulins of different types of animals are not identical.
Classes of immunoglobulins
Immunoglobulins are developed by immunocompetent cells of lymphoid bodies, differ among themselves on a pier. to the weight, sedimentation constant, electrophoretic mobility, content of carbohydrates and immunological activity. Distinguish five classes (or types) immunoglobulins:
Immunoglobulins M (IgM): pier. weight apprx. 1 million, have a complicated molecule; the first appear after immunization or an antigen challenge, have pernicious effect on microbes which got to blood, promote their phagocytosis; is weaker, than immunoglobulins G, connect soluble antigens, toxins of a bacterium; immunoglobulins G collapse in an organism by 6 times quicker, than (e.g., at rats half-life of immunoglobulin M is equal to 18 hours, and immunoglobulin to G — 6 days).
Immunoglobulins G (IgG): pier. weight apprx. 160 000, them is considered standard, or classical, And.: easily pass through a placenta; IgM are formed more slowly, than; most effectively connect soluble antigens, especially exotoxins, and also viruses.
Immunoglobulins A (IgA): pier. weight apprx. 160 000 or more, are developed by an adenoid tissue of mucous membranes, degradations of enzymes of cells of an organism interfere and resist to pathogenic action of microbes of intestines, easily get through cellular barriers of an organism, contain in colostrum, saliva, tears, slime of intestines, the sweat separated a nose, in blood are in smaller quantity, easily connect to cells of an organism; IgA arose, apparently, in the course of evolution for protection of mucous membranes against aggression by bacteria and transfers of oroimmunity to posterity.
Immunoglobulins E (IgE): pier. weight apprx. 190 000 (according to R. S. Nezlin, 1972); apparently, them are allergic And. — so-called reagins (see below).
Immunoglobulins D (IgD): pier. weight apprx. 180 000 (according to R. S. Nezlin, 1972); in a crust, time is known of them very little.
The structure of antibodies
the Molecule of immunoglobulin consists of two nonidentical polypeptide subunits — lungs (L — from English light) chains about a pier. weighing 20 000 and two heavy (N — from English heavy) chains about a pier. weighing 60 000. These chains connected by disulfide bridges form the main LH monomer. However in a stand-at-ease such monomers do not meet. The most part of molecules of immunoglobulins consists of dimer (LH) 2 , the others — from polymers (LH) 2n . The main N-trailer amino acids of human gamma-globulin are asparaginic and glutaminic, rabbit — alanine and asparaginic to - that. Malt liquor (R. R. Porter, 1959), influencing immunoglobulins papain, found that they break up to two (I and II) a Fab-fragment and a Fc-fragment (III) with a sedimentation constant 3,5S and a pier. it is powerful apprx. 50 000. The ground mass of carbohydrates is connected with a Fc-fragment. According to the proposal of WHO experts the following nomenclature of fragments of antibodies is established: A Fab-fragment — monovalent, actively connecting to antigen; The Fc-fragment — does not interact with antigen and consists of S-trailer half of heavy chains; The Fd-frag-cop — the site of a heavy chain entering a Fab-fragment. 5S it is offered to designate a fragment of peptic hydrolysis as F(ab) 2 , and a monovalent 3,5S-fragment — Fab.
Specificity of antibodies
One of the major properties A. their specificity is, edges it is expressed that And. more actively and more stoutly interacts with that antigen, the Crimea an organism was stimulated. The complex antigen — an antibody in this case has the largest durability. And. are capable to distinguish minor changes in structure in antigens. During the use of the conjugated antigens consisting of protein and the included simple chemical substance — hapten, formed And. are specific to hapten, protein and a complex protein — hapten. Specificity is caused by chemical structure and the space drawing of anti-determinants And. (active centers, reactive groups), i.e. sites A., to-rymi they connect to determinants of antigen. Number of anti-determinants And. often call them valency. So, the molecule IgM-antibodies can have up to 10 valencies, the molecule IgG-and IgA-antibodies of a dvukhvalentna.
According to Karash (F. Karush, 1962), active centers of IgG consist of 10 — 20 amino-acid remains that makes about 1% of all amino acids of a molecule A., and, on Uinkler's representations (M. N. of Winkler, 1963), active centers consist of 3 — 4 amino-acid remains. Tyrosine, a lysine, tryptophane are found in their structure, etc. Antideterminanta are located, obviously, in aminotrailer half of Fab-fragments. Variable pieces of light and heavy chains participate in formation of an active center, and the last possess the main role. Perhaps, the light chain only partially participates in formation of an active center or stabilizes structure of heavy chains. The most full-fledged anti-determinant is created only by a combination of light and heavy chains. Than more points of coincidence of communication between anti-determinants And. and determinants of antigen, that specificity is higher. Different specificity depends on the sequence of the amino-acid remains in an active center And. Coding of a huge variety And. on their specificity it is not clear. Malt liquor allows three possibilities of specificity.
1. Formation of a stable part of a molecule of immunoglobulin is controlled by one gene, and a variable part — thousands of genes. The synthesized peptide chains connect in a molecule of immunoglobulin under the influence of a special cellular factor. Antigen in this case acts as the factor starting synthesis of antibodies.
2. The molecule of immunoglobulin is coded by stable and changeable genes. During cellular division there is a recombination of changeable genes, as causes a variety them and variability of sites of molecules of globulins.
3. The gene coding a variable part of a molecule of immunoglobulins is damaged by special enzyme. Other enzymes recover damage, but owing to mistakes allow various sequence of nucleotides within this gene. It also caused various sequence of amino acids in a variable part of a molecule of immunoglobulin. There are also other hypotheses, e.g. Burnett (F. M of Burnet, 1971).
Heterogeneity (heterogeneity) And. it is shown on many signs. In response to administration of one antigen are formed And., differing on affinity to antigen, antigenic determinants, a pier. to weight, electrophoretic mobility, N-trailer amino acids. Group And. to various microbes cause cross-reactions to different types and types of salmonellas, shigellas, escherichias, animal protein, polysaccharides. Produced And. are heterogeneous on the specificity of rather homogeneous antigen or one antigenic determinant. Heterogeneity And. it is noted not only against proteinaceous and polisakharidny antigens, but also against complex, including conjugated, antigens and against haptens. Believe that heterogeneity And. is defined by the known microheterogeneity of determinants of antigen. Heterogeneity can be caused by education And. on a complex antigen — an antibody that is observed at repeated immunization, distinction of the cells forming And., and also accessory And. to different classes of immunoglobulins which, as well as other proteins, possess the complex antigenic structure controlled genetically.
Types of antibodies
Vhole antibodies have not less than two active centers and at connection with in vitro antigens cause visible reactions: agglutination, precipitation, fixation of the complement; neutralize toxins, viruses, opsonize bacteria, cause a visual phenomenon of immune sticking, an immobilization, swelling of capsules, loadings of thrombocytes. Reactions proceed in two phases: specific (interaction of an antibody with antigen) and nonspecific (this or that of the above-stated phenomena). It is conventional that various serological tests are caused by one, but not a set And. also depend on a technique of statement. Distinguish thermal full And., reacting with antigen at t ° 37 °, and cold (cryophil), showing effect at t ° lower than 37 °. Are available also And., reacting with antigen at a low temperature, and the visible effect is shown at t ° 37 °; these are two-phase, biothermal And., to the Crimea Donat's hemolysins — Landshteynera are carried. Full A. Aktivnost contain all known classes of immunoglobulins and their specificity are defined by a caption, an avidnost (see. Aviditet ), number of anti-determinants. IgM-antibodies are more active, than IgG-antibodies, in reactions of hemolysis and agglutination.
Monovalent antibodies (not precipitant, blocking, agglyutinoida), as well as full And., are capable to connect to the corresponding antigens, but reaction at the same time is not followed by visible in vitro a phenomenon of precipitation, agglutination, etc.
Incomplete And. are found in the person in 1944 to Rh-Hr antigen, found them at viral, rickettsial and bacterial infections in relation to toxins at various morbid conditions. There is a number of proofs of bivalence incomplete A. Bakterialnye incomplete And. have protective properties: anti-toxic, opsonizing, bacteriological; at the same time incomplete And. are found at a number of autoimmune processes — at diseases of blood, especially hemolitic anemias.
Incomplete hetero - from - and autoantibodies are capable to cause damage of cells, and also to play a part in emergence medicamentous leucio-and thrombocytopenia
Normal (natural) is considered to be And., usually meeting in blood serum of animals and the person in the absence of an explicit infection or immunization. Origin antibacterial normal And. it can be connected, in particular, with an antigen challenge normal microflora of an organism. These views theoretically are also experimentally proved by researches on animals-gnotobiontakh and newborns in usual conditions of dwelling. Question of functions normal And. it is connected directly with specificity of their action. L. A. Zilber (1958) believed that individual resistance to infections and, besides, «immunogene readiness of an organism» are defined by their existence. The role normal is shown And. in bacterial action of blood, in opsonization at phagocytosis. By works of many researchers it was shown that normal And. generally are macroglobulins — IgM. Some researchers found normal antibodies in IgA-and IgG-classes of immunoglobulins. In their structure can be both incomplete, and full And. (normal antibodies to erythrocytes — see. Blood groups ).
Synthesis of antibodies
Synthesis of antibodies proceeds in two phases. The first phase inductive, latent (1 — 4 day), at a cut And. and antiteloobrazuyushchy cells are not found; the second phase — productive (begins after an inductive phase), And. are found in plasmocytes and the liquid flowing from lymphoid bodies. After the first phase of antibodyformation very bystry rate of increase begins And., quite often their contents can double each 8 hours and even quicker. Maximum concentration various And. in blood serum after single immunization is registered for the 5, 7,10 or 15 day; after an injection of the deposited antigens — on 21 — the 30th or 45th day. Further in 1 — 3 or more months credits And. sharply fall. However sometimes low level And. after immunization is registered in blood for a number of years. It is established that primary immunization by a large number of various antigens is followed by emergence of heavy IgM (19S) in the beginning - antibodies, then during short term — IgM and IgG(7S) - antibodies and, at last, one easy 7S-antibodies. Repeated stimulation of a sensibilized organism antigen causes acceleration of formation of both classes A., shortening of a latent phase of antibodyformation, term of synthesis of 19S-antibodies also promotes preferential synthesis of 7S-antibodies. Quite often 19S-antibodies do not appear at all.
The expressed distinctions between an inductive and productive phase of antibodyformation are found at a research of their sensitivity to a number of influences that has basic value for understanding of the nature of specific prevention. E.g., it is known that radiation before immunization detains or completely antibodyformation oppresses. Radiation in a reproductive phase of antibodyformation does not influence contents And. in blood.
Allocation and cleaning of antibodies
For improvement of a method of allocation and cleaning And. immunoadsorbents were offered. A method transfer of soluble antigens in insoluble by accession is the cornerstone of them by means of covalent bonds to an insoluble basis from cellulose, sephadex or other polymer. The method allows to receive highly cleared And. in large numbers. Process of allocation of Ampere-second the help of immunoadsorbents includes three stages:
1) extraction And. from immune serum;
2) washing of an immunoadsorbent from nonspecific proteins;
3) eliminating And. from the washed immunoadsorbent (usually buffered solutions with low pH values). Except this method, also other methods of cleaning are known And. They can be divided into two groups: specific and nonspecific. Dissociation is the cornerstone of the first And. from a complex particle antigen — an antibody (precipitated calcium superphosphate, agglutinate). It is carried out by various substances; the method of enzymatic digestion of antigen or a flokkulyat toxin — antitoxin amylase, trypsin, pepsin is eurysynusic. Also thermal elution at t is used ° 37 — 56 °.
Nonspecific methods of cleaning And. are based on release of gamma-globulins: an electrophoresis in gel, a chromatography on ion-exchange resins, fractionation gel filtering through sefadeksa. The method of sedimentation is widely known for sodium sulfate or ammonium. These methods are applicable in cases of high concentration And. in serum, napr, at hyper immunization.
Gelfiltration through sefadeksa, and also use of ion-exchange resins is allowed to divide And. in size of their molecules.
Use of antibodies
And., especially gamma-globulins, are applied to therapy and prevention of diphtheria, measles, tetanus, gas gangrene, a malignant anthrax, leptospirosis, against stafilokokk, causative agents of rage, flu, etc. Specially prepared and purified diagnostic serums are applied in serological identification of causative agents of infections (see Identification of microbes). It was established, that pneumococci, staphylococcus, salmonellas, bacteriophages, etc., adsorbing corresponding And., · stick to thrombocytes, erythrocytes and other alien particles. This phenomenon is called immune sticking. It was shown that in the mechanism of this phenomenon proteinaceous receptors of thrombocytes and erythrocytes which collapse trypsin, papain and formalin play a role. Reaction of immune sticking depends on temperature. It is considered on sticking of corpuscular antigen or on the hemagglutination caused by soluble antigen at presence And. and complement. Reaction is highly sensitive and can be used as for definition of a complement, and very small (0,005 — 0,01 mkg of nitrogen) quantities And. Immune sticking strengthens phagocytosis by leukocytes.
Modern theories of antibody formation
Distinguish instructive theories of antibodyformation, according to the Crimea antigen directly or indirectly participates in formation of specific immunoglobulins, and the theories assuming education genetically preexisting And. selection theories and the theory of repression — derepressions, the allowing possibility of synthesis by one cell of any of A. Predlozhena also the theories aiming to comprehend processes of the immunological answer at the level of a complete organism taking into account interaction of various cells and the standard ideas of synthesis of protein in an organism belong to all possible antigens or the cells synthesizing these A. K to them.
Theory of a direct matrix of Gaurovittsa-Polinga comes down to the fact that antigen, having arrived in the cells developing And., plays a role of the matrix exerting impact on formation of a molecule of immunoglobulin from peptide chains which synthesis proceeds without participation of antigen. «Intervention» of antigen comes only in the second phase of formation of a proteinaceous molecule — a phase of twisting of peptide chains. Antigen so changes trailer N-ami-nokisloty future antibodies (immunoglobulin or its separate peptide chains) that they become complementary to determinants of antigen and easily take up with it. Formed thus And. it is chipped off from antigen, comes to blood, and the released antigen takes part in formation of new molecules A. This theory caused a number of serious objections. She cannot explain formation of unresponsiveness; the surpassing quantity developed by a cell And. in unit of time on the smaller number of molecules of antigen which is available in it many times over; durations of development And. an organism, the estimated years or all life, in comparison with considerably smaller term of preservation of antigen in cells etc. It is also necessary to consider that the cells of a plasmatic or lymphoid row developing And., do not assimilate antigen though presence of native antigen or its fragments at antitelosinteziruyushchy cells completely cannot be excluded. Recently Gaurovitts (F. Haurowitz, 1965) offered the new concept, on a cut antigen changes not only secondary, but also primary structure of immunoglobulin.
The theory of an indirect matrix of Burnett — Fennera gained fame in 1949. Her authors considered that macromolecules of antigen and most likely its determinant get into kernels of cells of germinal type and cause hereditarily the fixed changes in them which consequence education is And. to this antigen. Analogy between the described process and transduction at bacteria is allowed. The new quality of education of immune globulins acquired by cells is transferred to posterity of cells in uncountable generations. However the question of a role of antigen in the described process was disputable
. This circumstance was an origin of the theory of natural selection Erne (K. Jerne, 1955).
Theory of natural selection Erne. According to this theory antigen is not a matrix for synthesis of antibodies and does not cause genetic changes in cells producers And. Its role comes down to selection available «normal» And., spontaneously arising to various antigens. There is it as if so: antigen, having got to an organism, finds corresponding And., connects to it; the antigen formed a complex — an antibody is absorbed by the cells developing And., and the last receive an incentive to make And. such.
Clonal and selection theory of Burnett (F. Burnet) was further development of the idea Erne about selection, but not antibodies, but the cells making A. Burnett believes that as a result of the general process of differentiation in the embryonal and post-natal periods the set of clones lymphoid or immunological the competent cells capable to react with various antigens or their determinants is formed of mesenchymal cells and to develop antibodies — immunoglobulins. The nature of response of lymphoid cells to antigen in the embryonal and post-natal periods is various. The germ or does not produce globulins at all, or synthesizes them a little. However it is assumed that those its clones of cells which are capable to react with antigenic determinants of own proteins react with them and as a result of this reaction are destroyed. So probably the cells forming anti-And - agglutinins at persons with a blood group And yes anti-In - agglutinins — at persons with a blood group of Century perish. If to an embryo to enter any antigen, then similarly it will destroy the corresponding clone of cells, and the newborn during all subsequent life theoretically will be tolerant to this antigen. Process of destruction of all clones of cells to own proteins of a germ comes to an end by the time of its birth or escaping of egg. Now the newborn had only «», and any «others», got to his organism, he distinguishes. Burnett allows also preservation of «forbidden» clones of the cells capable to react with autoantigens of bodies which in development were isolated from the cells developing And. Recognition of «stranger» is provided with the remained clones of mesenchymal cells on which surface there are corresponding anti-determinants (receptors, cellular And.), complementary to determinants of «someone else's» antigen. The nature of receptors is determined genetically, i.e. coded in chromosomes and is not introduced in a cell together with antigen. Existence of ready receptors inevitably leads to reaction of this clone of cells with this antigen, a consequence a cut now two processes are: formation of specific antibodies — immunoglobulins and reproduction of cells of this clone. Burnett assumes that the mesenchymal cell which received antigenic irritation as a mitosis gives rise to population of daughter cells. If such cell settled in marrow limf, a node, it gives rise to formation of plasmocytes, at sedimentation in lymphatic follicles — to lymphocytes, in marrow — to eosinophils. Daughter cells are inclined to vegetative irreversible mutations. During the calculation on all organism the number of the mutating cells can make per day 100 Ltd companies or 10 million, and, therefore, mutations will provide clones of cells to any antigen. Burnett's theory attracted huge interest of researchers and a large number of test experiments. The most important confirmations of the theory were proofs of presence on predecessors of antibody producers (lymphocytes of a marrowy origin) of antitelopodobny receptors of the immunoglobin nature and existence in antibody producers of the mechanism of an intertsistronny exception concerning antibodies of various specificity.
The theory of repression and derepression is formulated by Silard (L. Szilard) in 1960. According to this theory each cell developing And., can potentially synthesize any And. to any antigen, but this process at it is slowed down by a repressor of the enzyme participating in synthesis of immunoglobulin. In turn formation of a repressor can slow down influence of antigen. Silard considers that education And. it is controlled by the special not doubling genes. The number reaches them 10 000 on each unary (haploid) set of chromosomes.
Lederberg (J. Lederberg) considers that in the genes responsible for synthesis of globulins, there are sites controlling formation of active centers And. Normal function of the called sites is slowed down and therefore there is a synthesis of normal globulins. Under the influence of antigen, and also, perhaps, under the influence of some hormones there is a disinhibition and stimulation of activity of the sites of a gene responsible for formation of active centers And., and the cell begins to synthesize immune globulins.
In opinion H. N. Zhukova-Verezhnikov (1972), evolutionary predecessors And. there were protective enzymes similar appearing at bacteria with the acquired antibiotikorezistentnost. As well as And., enzymes consist from active (in relation to substrate) and passive molecules of parts. Owing to profitability the «one enzyme — one substrate» mechanism was replaced by the mechanism of «uniform molecules with the varying part», i.e. antibodies with variable active centers. Information on antibodyformation is implemented in a zone of «reserve genes», or in «a zone of redundancy» on DNA. Such redundancy, probably, can be localized in nuclear or plasmid DNA, edges stores «evolutionary information..., the playing role of the internal mechanism „roughly“ controlling hereditary variability». This hypothesis contains an instructive component, but is not completely instructive.
P.F. Zdrodovsky assigns to antigen a part of a derepressor of the certain genes controlling synthesis complementary A. Odnovremenno antigen as Zdrodovsky according to the theory allows the Selye the adenohypophysis therefore there is a development somatotropic (STG) and adrenocorticotropic (AKTG) of hormones irritates. STG stimulates plazmotsitarny and antiteloobrazuyushchy reaction of lymphoid bodies, in turn stimulated with antigen, and AKTG, influencing bark of adrenal glands, causes allocation of a cortisone by it. This the last in an immune organism oppresses plazmotsitarny reaction of lymphoid bodies and synthesis by cells And. All these provisions were confirmed experimentally.
Action of system a hypophysis — adrenal glands on products And. can come to light only in previously immunizirovanny organism. This system will organize anamnestic serological tests in response to introduction to an organism of various nonspecific irritants.
Profound studying of cellular changes in process of the immunological answer and accumulation of a large number of the new facts proved situation, according to Krom the immunological answer is carried out only as a result of the cooperated interaction of certain cells. According to it several hypotheses are offered.
1. Theory of cooperation of two cells. Many facts testimonial of the fact that the immunological answer in an organism is carried out in the conditions of interaction of various types of cells are saved up. There are confirmations that macrophages the first assimilate and modify antigen, but in the subsequent «instruct» lymphoid cells about synthesis And. It is at the same time shown that there is a cooperation and between the lymphocytes relating to various subpopulations: between T lymphocytes (timuszavisimy, antngenreaktivny, coming from a thymus) and V-cells (timusnezavisimy, predecessors of antiteloobrazuyushchy cells, marrowy lymphocytes).
2. Theories of cooperation of three cells. According to I. Roitt's views, etc. (1969) antigen is taken and processed by macrophages. Such antigen stimulates the antigenreaktivny lymphocytes which are exposed to transformation in the blastoidny cells providing hypersensitivity of the slowed-down type and turning into long-living cells of immunological memory. These cells enter cooperation with antiteloobrazuyushchy progenitors which are in turn differentiated, proliferating in antibody producers. According to Richter (M. of Richter, 1969), the majority of antigens has weak affinity for antiteloobrazuyushchy cells therefore for development And. the following interaction of processes is necessary: antigen + a macrophage — the processed antigen + an antigenreaktivny cell — the activated antigen + the predecessor of an antiteloobrazuyushchy cell — an antibody. In case of high affinity of antigen process will look so: antigen + the predecessor of antiteloobrazuyushchy cells — antibodies. It is supposed that in the conditions of repeated stimulation by antigen the last directly comes into contact with an antiteloobrazuyushchy cell or a cell of immunological memory. This situation is confirmed by bigger radiation resistance of the repeated immunological answer, than primary that is explained by various stability of the cells participating in the immunological answer. Postulating need of three-cellular cooperation for an antibody response, R. V. Petrov (1969, 1970) considers that synthesis And. will occur only if the stem cell (the predecessor of an antiteloobrazuyushchy cell) at the same time receives from a macrophage the processed antigen, and from an antigenreaktivny cell the inductor of an immunopoez formed after it (an antigenreaktivny cell) of stimulation by antigen. If there is a contact of a stem cell only with the antigen processed by a macrophage, then unresponsiveness is created (see unresponsiveness). If the contact of a stem cell only with an antigenreaktivny cell is available, then there is a synthesis of nonspecific immunoglobulin. It is supposed that these mechanisms are the cornerstone of an inactivation of nesingenny stem cells lymphocytes since the inductor of an immunopoez, getting to an allogenic stem cell, is for it an antimetabolite (singenny — cells with an identical genome, allogenic — cells of the same look, on with other genetic structure).
Allergic antibodies — the specific immunoglobulins which are formed under the influence of allergens at the person and animals. At the same time mean circulating in blood A. at allergic reactions of immediate type. Distinguish three main types allergic And.: skin sensibilizing, or reagins; blocking and hemagglutinating. Biol., chemical and physical. - chemical properties allergic And. the person are peculiar (table.).
These properties differ from properties precipitant, complement-linked markedly And., agglutinins and others, described in immunology.
Reagins it is accepted to designate homological skin sensibilizing And. person. It is the major look allergic And. the person which main property is ability to carry out reaction of passive transfer of hypersensitivity to skin of the healthy recipient (see. Prausnittsa-Kyustnera reaction ). Reagins have a number of the characteristic properties distinguishing them from rather well studied immune And. Many questions concerning properties of reagins and their immunological nature remain, however, unresolved. In particular, the question of homogeneity or heterogeneity of reagins in sense of their belonging to a certain class of immunoglobulins is unresolved.
Blocking And. arise at patients with pollinoses in the course of the specific hyposensibilizing therapy to that antigen which makes desensitization. Properties of this look And. remind properties precipitant And.
Under hemagglutinating And. usually mean And. the blood sera of the person and animals capable to specifically agglutinate the erythrocytes connected to pollen allergen (reaction indirect, or passive, hemagglutinations). Linkng of a surface of an erythrocyte with allergen of pollen is reached by various methods, napr, by means of tannin, formalin, twice diazotized benzidine. The hemagglutinating antibodies manage to be found in the people having hypersensitivity to pollen of plants, both to and after the specific hyposensibilizing therapy. In the course of this therapy there is a transformation of negative reactions in positive or increase in credits of hemagglutination reaction. Hemagglutinating And. have property to be adsorbed quickly enough on the erythrocytes processed by pollen allergen, its especially nek-ry fractions. Immunoadsorbents delete hemagglutinating And. quicker, than reagins. The hemagglutinating activity is connected in a nek-swarm of degree and with skin sensibilizing And., however a role skin sensibilizing And. in hemagglutination, apparently, it is small since there is no correlation between the skin sensibilizing and hemagglutinating A. S of other party, there is a correlation between hemagglutinating and blocking And. as at persons with an allergy to pollen of plants, and at healthy faces, immunizirovanny vegetable pollen. This two look And. have many similar properties. In the course of the specific hyposensibilizing therapy there is an increase in level as that, and other type of A. Gemagglyutiniruyushchiye A. to penicillin are not identical skin sensibilizing And. The main reason for education hemagglutinating And. the penicillin therapy was. Apparently, hemagglutinating And. it is necessary to carry to group of the antibodies called by a number of authors «antibodies mi-witnesses».
In 1962 Mr. of W. Shelley offered the special diagnostic test based on so-called degranulation of basphilic leukocytes of blood of a rabbit under the influence of reaction of allergen with specific A. Odnako character And., who take part in this reaction, and their communication with the circulating reagins are found insufficiently out though patients with a pollinosis have data on correlation of this type of Ampere-second the level of reagins.
Establishment of optimum ratios of allergen and the studied serum is extremely important in the practical relation, especially at researches with types of allergens, data on which do not contain in the corresponding literature yet.
To allergic And. animals it is possible to carry the following types And.: 1) And. at an experimental anaphylaxis; 2) And. at spontaneous allergic diseases of animals; 3) And., Artyus's reactions playing a role at development (like precipitant). At an experimental anaphylaxis as the general, and local, in blood of animals find special types anaphylactic And., having property passively to sensibilize leather of animals of the same look.
It was shown that the anaphylactic sensitization of Guinea pigs allergens of pollen of a herd grass meadow is followed by circulation in blood skin sensibilizing A. Eti skin sensibilizing And. have property to carry out a homological passive sensitization of skin of in vivo. Along with these homological skin sensibilizing And. at the general sensitization of Guinea pigs allergens of pollen of a herd grass meadow in blood circulate And., revealed by reaction of passive hemagglutination about an encore - diazotized benzidine. Skin sensibilizing And., carrying out homologous passive transfer and having positive correlation with an indicator of an anaphylaxis, carry to group of homological anaphylactic antibodies, or gomotsitotropny And. Using the term «anaphylactic antibodies», authors attribute them the leading role in reaction of an anaphylaxis. The researches confirming existence gomotsitotropny began to appear And. to proteinaceous antigens and conjugates at different types of experimental animals. A number of authors allocates three look And., participating in allergic reactions of immediate type. It And., connected with new type of immunoglobulins (IgE) at the person and similar And. at monkeys, dogs, rabbits, rats, mice. Second look And. — antibodies like a Guinea pig, capable to be fixed on mast cells and isological fabrics. They differ in a number of properties, in particular, they more termostabilna. Consider that antibodies like IgG can be also at the person the second type of anaphylactic antibodies. The third look — And., the sensibilizing heterological fabrics belonging, e.g., at Guinea pigs to a class γ 2 . At the person only And. the IgG type have ability to sensibilize skin of a Guinea pig.
At diseases of animals are described allergic And., formed at spontaneous allergic reactions. These And. termolabilna, have the skin sensibilizing properties.
Monovalent antibodies in the medicolegal relation are applied during the definition of antigens of a row of isoserological systems (see. Blood groups ) for establishment of accessory of blood to a certain person in cases of criminal offenses (murder, sexual crimes, transport incidents, infliction of bodily injury, etc.), and also at examination of a doubtful paternity and motherhood. Unlike full And., they do not cause agglutination of erythrocytes in the salt environment. Among them distinguish And. two types. The first of them — an agglyutinoida. These And. are capable to cause pasting of erythrocytes in the proteinaceous or macromolecular environment. Second look And. — kriptagglyutinoida which react in indirect test of Koombs with antigammaglobulinovy serum.
For work with incomplete And. a number of the methods which are subdivided into three basic groups is offered.
1. Methods of conglutination. It is noted that incomplete And. are capable to cause agglutination of erythrocytes in the proteinaceous or macromolecular environment. As such environments use blood serum of the AB group (free of antibodies), bull albumine, a dextran, biogel — especially cleared to gelatin, brought by buffered solution to neutral pH, etc. (see. Conglutination ).
2. Fermental methods. Incomplete And. are capable to cause agglutination of the erythrocytes which are previously subjected to processing by nek-ry enzymes. Apply trypsin, ficin, papain, grain yeast extracts to such processing, protelin, bromeline, etc.
3. Koombs's test with antiglobulinovy serum (see. Koombs reaction ).
Incomplete And., belonging to agglyutinoida, can show the action in all three groups of methods. And., belonging to kriptagglyutinoida, are not capable to agglutinate erythrocytes not only in saline solution, but also in the macromolecular environment, and also to block them in the last. These And. open only in indirect test of Koombs, with the help a cut open not only And., belonging to kriptagglyutinoida, but also And., the being agglyutinoidam.
Burnett F. Cellular immunology, the lane with English, M., 1971; And γ-ρο in both F. Immunokhimiya's c and biosynthesis of antibodies, the lane with English, M., 1969, bibliogr.; Dosse Zh. An immunohematology, the lane with fr., M., 1959; Zdrodovsky P. F. Problems of an infection, immunity and allergy, M., 1969, bibliogr.; Immune marker analysis, under the editorship of JI. A. Zilbera, page 21, M., 1968; Cabot E. and Meyer M. Experimental immunochemistry, the lane with English, M., 1968, bibliogr.; N e z l and R. S. Stroyeniye's N of biosynthesis of antibodies. M, 1972, bibliogr.; N about with with e l of. Antibodies and immunity, the lane with English, M., 1973, bibliogr.; Petrov R. V. Forms of interaction of genetically differing cells of adenoid tissues (three-cellular system of an immunogenesis), Usp. sovr. biol., t. 69, century 2, page 261, 1970; Uteshev B. S. and Babichev V. A. Inhibitors of biosynthesis of antibodies. M, 1974; Efroimson V. P. Immunogenetics, M., 1971, bibliogr.
Allergic And. — Ado A. D. Allergy, Mnogotomn. the management on a stalemate. fiziol., under the editorship of H. N. Sirotinina, t. 1, page 374, M., 1966, bibliogr.; Ado A. D. General allergology, page 127, M., 1970; Polner A. A., Vermont I. E. of T. I. K iserov to a question of the immunological nature of reagins at pollinoses, in book: Probl. allergol., under the editorship of A. D. Ado and A. A. Podkolzin, page 157, M., 1971; Bloch K. J. The anaphylactic antibodies of mammals including man, Progr. Allergy, v. 10, p. 84, 1967, bibliogr.; Ishizaka K. Ishizaka T. The significance of immunoglobulin E in reaginic hypersensitivity, Ann. Allergy, v. 28, p. 189, 1970, bibliogr.; Lichtenstein L. M, Levy D. A. a. Ishizaka K. In vitro reversed anaphylaxis, characteristics of anti-IgE mediated histamine release, Immunology, v. 19, p. 831, 1970; Sehon A. H. Heterogeneity of antibodies in allergic sera, in book: Molec. celL basis of antibody formation, ed. by J. Sterzl, p. 227, Prague, 1965, bibliogr.; Stanworth D. R. Immunochemical mechanisms of immediate-type hypersensitivity reactions, Clin. exp. Immunol., At. 6, p. 1, 1970, bibliogr.
M. V. Zemskov, H. V. Zhuravleva, V. M. Zemskov; A. A. Polner (ave); A. K. Tumanov (court.).