sensitization in allergology

From Big Medical Encyclopedia

SENSITIZATION in allergology (fr. sensibilisation from armor. sensibilis sensitive) — immunological the mediated sensitization of an organism to exogenous or endogenous antigens. The term is widely used in scientific and a wedge, practice, however the sense put in it is ambiguous. Sometimes S. define very widely — as the increased reaction of an organism to substances of the antigenic or gaptenny nature. In this case the concept «sensitization» merges with the concept «allergy». But allergy (see) consists not only in sensitization to some antigen (see. Antigens ), but also in implementation of this hypersensitivity in the form of allergic reaction, and sensitization to antigen happens in the beginning and only then if antigen remains in an organism or gets to it again, allergic reaction develops. All this process in the development passes through three stages — immunological, natokhikhmichesky and pathophysiological. It can be divided in time for two periods: the first — preparation (sensitization of an organism to antigen, or a sensitization) and the second — implementation or a possibility of implementation of this state in the form of allergic reaction. Such idea of an allergy corresponds to data a wedge, observations. The person, very often sensibilized to any antigen, is almost healthy until the corresponding allergen, napr, pollen of a plant does not get to an organism at pollinosis (see), medicine at S. to this drug (see. Medicinal allergy ), etc. Pilot studies also confirm this point of view. E.g., for reproduction of an acute anaphylaxis at Guinea pigs (see. Anaphylaxis ) an animal at first enter the so-called sensibilizing dose of antigen and only in 2 — 3 weeks cause shock introduction of the allowing dose of the same antigen. Therefore it would be more correct to limit the concept «sensitization» only to those processes, to-rye occur in an organism from the moment of administration of antigen and come to an end with antibody formation and (or) sensibilized lymphocytes to this antigen. Thereby it is emphasized that sensitization is specific in relation to that antigen, to-ry it causes.

On a way of receiving distinguish active S. and passive (passive transfer). Active S. develops at artificial introduction or natural hit allergen (see) in an organism. Passive S. is observed after introduction to the intact recipient of blood serum or lymphoid cells from actively sensibilized donor. If there is S. of a fruit, then such S. call pre-natal. The page can be monovalent — at sensitization to one allergen and polyvalent — at S. to many allergens. Cross S. name sensitization of a sensibilized organism to other antigens having the general determinants with the allergen which caused Page.

Depending on the chemical nature, physical condition and amount of the allergen which got to an organism, and also from reactivity of an organism its reaction to allergen will turn on various immune mechanisms. This distinction finds expression in features of the formed antibodies (see) — their preferential belonging to this or that class or a subclass immunoglobulins (see) and their credits, and also in formation of sensibilized lymphocytes (see). So, e.g., weak antigens (pollen of plants, house dust, dandruff and hair of animals) cause preferential formation of reagins (see. Antibodies allergic ). (Cells of fabrics, bacteria, disputes of mushrooms, etc.) the organism reacts to corpuscular insoluble allergens most often antibody formation, the mechanisms leading to inclusion tsitotoksichesknkh and (or) to emergence of sensibilized lymphocytes. Soluble allergens (anti-toxic serums, gamma-globulins, products of a lysis of bacteria, etc.), especially in large numbers, cause emergence of the antibodies participating in formation of cell-bound immune complexes and effects of precipitation.

Influence reactivity of an organism (see) on function of immune system is implemented by several ways. First, the immune response on each antigen is determined genetically. From features of functioning of the structural genes controlling synthesis immunoglobulins (see), the class, a subclass, an allotype and an idiotype of the formed antibodies depends. Ig-genes — immune response genes — determine intensity of an immune response by quantity of the formed antibodies and (or) expressivenesses of the allergic reaction of the slowed-down type mediated by sensibilized lymphocytes. So, naira., there are individuals, to-rye answer with excess formation of IgE-antibodies nek-ry weak antigens (pollen of plants, dandruff, etc.). The specific mechanism of excess formation of IgE-antibodies is connected, in particular, with insufficient activity of the corresponding T-kletok-supressorov. Secondly, the immune response is influenced by a condition of barrier functions of skin and mucous membranes, a cut defines a possibility of receipt in an organism of many exogenous allergens. Nair., deficit of secretory IgA promotes penetration through mucous membranes of allergen that leads to formation of reagins. Thirdly, a condition of regulatory systems, influencing intercellular interactions in the course of an immune response, circulation of cells etc., exerts the modulating impact on character of an immune response. Formation of sensibilized lymphocytes, a type of antibodies, their caption and by that feature of allergic reaction depends on these factors.

All this combined gave the grounds for allocation of the following four types C., from to-rykh the first three are connected with features of the formed antibodies, and the fourth — with formation of sensibilized lymphocytes.

Page at reaginic type of an allergy (a synonym: atopic type, the IgE-mediated type, anaphylactic type of an allergy, at hypersensitivity of immediate type) is defined by antibody formation, the reagins which received the name. They belong hl. obr. to IgE and to a lesser extent to IgG4. Therefore the term «sensitization» of the IgE-mediated type though is widely used, but is not rather exact. The formed reagins are fixed generally on mast cells (see) and basophiles and by that create a condition of a sensitization. The page of reaginic type plays the leading role in development of group of atopic diseases (see. Atopy ), napr, an atopic form of bronchial asthma, pollinoses, etc.

S. at cytotoxic type of an allergy became a subject of attention of researchers since 1898 when for the first time in an experiment introduction of erythrocytes of an animal one look to an organism of animal other look received hemolysins. The significant contribution to development of the doctrine about cytotoxins (see) domestic scientists brought. In 1901. I. I. Mechnikov created the doctrine about cellular kernels (cytotoxins), E. S. London formulated the signs distinguishing cytotoxins from the chemical substances having toxic effect on cells; A. A. Bogomolets in 1908 received suprarenotsitotoksichesky serum, and in 1925 under its management antireticular was received tsitotoksichssky serum (see), edges found application in to lay down. to practice. In all these researches cytotoxic antibodies on antigens of homologous or heterological cells were received. At people the mechanism of an allergy of cytotoxic type can turn on at hit in an organism of isoantigens, napr, at hemotransfusion, at a hemolitic disease of newborns. In the latter case mother, negative on Rh-Hr antigen (see. Rhesus factor ), at the time of delivery or less often during pregnancy at damages of a placenta it is sensibilized by erythrocytes of a Rh-positive fruit that leads to formation at it of anti-Rh antibodies, to-rye hl belong. obr. to IgG and freely pass through a placenta. It was also established that cytotoxic antibodies can be formed also to cells of own fabrics in those cases if cells receive autoallergenny properties. The reasons of acquisition by cells of autoallergenny properties are very various. The large role in this process is played by action on cells various hpm. substances, most often the medicines getting to an organism and capable to change an antigenic structure of cellular membranes at the expense of conformational changes of molecules of antigens, damages of a cellular membrane and emergence of the covert (repressed) antigenic determinants, formations of complexes of allergens with a cellular membrane, in to-rykh medicinal or other chemical substance plays a role of hapten. The lizosvmny enzymes of neutrophils which are emitted at phagocytosis and also bacterial enzymes, viruses can have similar effect on a cell. In all these cases of an antibody hl belong. obr. to IgG or IgM. Mechanisms of implementation cytotoxic' actions are various. In one cases it is connected with activation complement (see) so-called komplementooposredovanny cytotoxicity. In other cases so-called antitelozavisimy cell-mediated cytotoxicity joins. At the same time antibodies are fixed on target cells. Through the Fc-end of the molecule they contact Fc-receptors of various cells (K-cells, monocytes, neutrophils). These cells also carry out cytotoxic action. Turning on of this or that mechanism of cytotoxic type of allergies depends on character and properties of the formed antibodies since ability to attach a complement, to connect to Fc-retsepto-rami of various cells is connected with them. So, e.g., IgM, IgG1, IgG3 well fix a complement, at IgG2 this ability is less expressed, an IgG4 and IgE do not fix it in general. The page at cytotoxic type of an allergy plays an essential role in nek-ry cases of a medicinal allergy, in development of a number of autoallergichesky (autoimmune) processes (see. Autoallergichesky diseases ).

The village at an allergy like Artyus (damage by a cell-bound immune complex) is caused by introduction to an organism of large amounts of soluble allergen. It causes antibody formation, to-rye can belong to the different classes of immunoglobulins, however most often they treat immunoglobulins of the classes IgG and IgM. These antibodies call also precipitant for their ability at connection with the corresponding antigen to form in vitro precipitated calcium superphosphate. In a human body constantly there are immune responses with formation of a complex antigen — an antibody (see. Antigen — an antibody reaction ), since any antigens from the outside constantly get to an organism or those are formed in the organism. These reactions are expression protective, or homeostatic, functions of immunity (see) and are not followed by cytotoxic or lytic action. However under certain conditions the computer lek antigen — an antibody can possess the damaging action and promote development of a disease. In such cases say that took S. Kompleks's place antigen — the antibody can show the damaging action under following conditions: the complex shall have a certain size, according to experimental data more than 19S that there corresponds the pier. to the weight (weight) 9•10 5 — 1•10 6  ; it shall be formed about a nek-eye by excess of antigen; permeability of a vascular wall shall be raised since in this case a complex antigen — the antibody can be postponed in fabrics. Usually increase in permeability of a vascular wall is caused by the vasoactive amines which are released from thrombocytes, and for this purpose S. of reaginic type shall join S. at an allergy like Artyus. The page at an allergy like Artyus is the cornerstone serum disease (see), exogenous allergic alveolites (see), etc.

S. at an allergy of the slowed-down type (a synonym hypersensitivity of the slowed-down type) develops in cases when in response to hit in an organism of allergen so-called sensibilized lymphocytes are formed (T-effectors, or T-killers). They treat T-population of lymphocytes (see. Immunocompetent cells ), and their education leads to S.'s development the slowed-down type. Connecting to allergen, these lymphocytes cause allergic reaction of the slowed-down type. The mechanism C. of this kind is the cornerstone of development of many infectious and allergic diseases (see. Infectious allergy ), contact dermatitis (see) etc.

S.'s development is followed by change of reactivity of a row of systems and bodies of an organism and activity of nek-ry fermental systems during a certain term that finds the expression in change of sensitivity to action of various nonspecific factors. So, A. D. A to established increase in excitability baro-and chemoceptors of a carotid sine at sensibilized dogs, and I. A. Huo-dakova found change of kortizolovy type of a steroidogenesis with kortikosteronovy in such animals; in N. D. Beklemishev's laboratory it is established that S.'s development to bacterial antigens in experimental animals is followed by the expressed changes of oxidation-reduction processes. Change of sensitivity of patients with a brucellosis and rheumatism to action of physical factors is revealed. Such change of sensitivity of an organism to action of the most various environmental factors sometimes is named nonspecific S. unlike the specific S. connected with turning on of immune mechanisms in response to this allergen.

For S.'s identification use various methods, to-rye in vivo and in vitro are applied. Treat in the vivo methods skin tests (see). The page at reaginic type of an allergy comes to light all types of skin tests. Development of urtikarny reaction (a blister, sometimes with pseudopodiums, surrounded with a zone of a hyperemia) the first 15 — 20 min. after administration of allergen in skin is characteristic of it. The page at an allergy like Artyus comes to light at intradermal administration of allergen; reaction develops in 4 — 6 hours, the injection site of allergen has an appearance of the center of an inflammation. The page at the slowed-down type of an allergy comes to light intracutaneous and application tests; reaction develops in 24 — 48 hours of S. at reaginic type of an allergy reveal by means of Praus-nitts's reaction — Kyustnera (see. Prausnittsa — Kyustnera reaction ). Various provocative tests (see) it is possible to reveal successfully S. at reaginic type of an allergy and S. at an allergy like Artyus; it is slightly more difficult to reveal the slowed-down type of a sensitization thus. N. D. Beklemishev considers that the fever developing after intravenous administration of bacterial allergen testifies to S., character-. ache for an allergy of the slowed-down type since allergen, connecting to sensibilized lymphocytes, causes release of certain lymphokines, to-rye stimulate formation of endogenous pyrogens.

Are widely used numerous a lab. methods of identification of S. in vitro. From them S. regardless of its type allow to reveal Nek-rye, napr, reaction blastotransformation of lymphocytes (see), the PPN test (see. Leukocytic tests ). By means of others a lab. methods preferential certain type C comes to light. So, e.g., S. at reaginic type of an allergy is diagnosed by means of a radioallergosorbent method (see) and Shultts's reactions — Dale (see. Shulttsa — Dale reaction ), etc.; Page at cytotoxic type of an allergy — by means of Koombs's reaction (see. Koombs reaction ) and Steffen's reactions (see. Steffen reaction ); Page at an allergy like Artyus — various ways of definition of cell-bound immune complexes and pretsipitir at lean antibodies; Pages at an allergy of the slowed-down type determine by method of braking of migration; macrophages (see) or braking of migration of leukocytes, likhmfotoksin by training and other lymphokines. The diagnostic value of these methods is not equivalent. Their use is defined by research problems and the nature of process.

Prevention of a sensitization

the General principles of prevention of S. come down to reduction of receipt in an organism of various allergens and elimination of the conditions promoting Page. Constant improvement of schemes of carrying out inoculations and upgrading of the used drugs, rational restriction of use of heterological anti-toxic serums, especially antitetanic, and their replacement where it is possible, by homologous gamma-globulins, restriction of uncontrolled reception of pharmaceuticals, carrying out sanitation of the centers hron are for this purpose necessary. infections, observance of the rules of hygiene in life limiting receipt in an organism of dust and other allergens, improvement of technological processes for restriction of action for an organism of industrial allergens. Special attention shall be paid to identification of children with the deficit of secretory IgA and other immunodeficiency promoting S.'s development (see. Immunological insufficiency ), and corrective therapy.

See also Desensitization .

Bibliography: Ado A. D. Antigens as extraordinary irritants of a nervous system, M., 1952, bibliogr.; it, General allergology, M., 1978; Beklemishev N. D. Infectious allergy, Alma-Ata, 1968; B e to l e m and-sh e in N. D. and With at x about d about e in and G. S. Allergiya to microbes in clinic and an experiment, M., 1979, bibliogr.; At - shch and I. S N. About elements of biological expediency of allergic reactivity, the Stalemate. fiziol. and ekspery. ter., century 4, page 3, 1979, bibliogr.; P y c to and y B. I. Corticosteroids and allergic processes, M., 1976; Coombs R. R. And. Gell P. G. N of Classification of allergic reactions responsible for clinical hypersensitivity and disease, in book: Clin, aspects immunol., ed. by P. G. H. Gellj a. o., p. 761, Oxford a. o., 1975.

V. I. Pytsky.