AUTOALLERGICHESKY DISEASES

From Big Medical Encyclopedia

AUTOALLERGICHESKY DISEASES (grech, autos + allergy; synonym: autoimmune, autoagressivny diseases) — group of diseases which main mechanism of development is reaction of autoantibodies and sensibilized lymphocytes with own fabrics. Practically all cells and tissues of the person under certain conditions can be subject to the damaging action of lymphocytes and autoantibodies; therefore clinical symptoms And. are extremely various and can be shown by both organ, and systemic lesions.

Emergence of the doctrine about autoallergies (see) as to the reason of diseases it is connected with a name of I. I. Mechnikov. In 1900 — 1901. I. I. Mechnikov and his pupils experimentally proved a possibility of products of antibodies to proteins of own cells of an organism.

In 1904 Mr. Donat and Landshteyner (J. Donath, K. Landsteiner) found in blood serum of patients with a paroxysmal cold haemoglobinuria of an antibody, specifically directed against own erythrocytes. In 1908 Mr. Vidal, Abrami, Bryule (F. Widal, R. of Abrami, M. of Brule) revealed autohemolysins at patients with the acquired hemolitic anemia.

S. S. Golovin in 1904 suggested about an autoimmune pathogeny of a sympathetic ophthalmia. Especially the doctrine about an autoallergy was widely adopted since 40 — the 50th years 20 century. At many diseases autoallergichesky mechanisms of a pathogeny are installed. It is necessary to differentiate, however, strictly And., where these mechanisms are considered as leaders, and the autoallergichesky syndromes complicating diseases of other genesis. Typical examples of the last are the postinfarction syndrome, symptomatic autoimmune anemia at a lymphoid leukosis, acute dystrophy of a liver at infectious hepatitis, autoallergichesky syndromes at burns and a radial illness.

An etiology

Fabrics and cells of an organism gain autoallergenny (autoantigenny) properties as a result of the damaging influence of various environmental factors. These damages lead to release and hit in the general blood stream of physiologically isolated components of cells and fabrics or to change of antigenic properties of proteinaceous structures (see. Autoallergy , Autoantigens ). The injury, insolation, cooling, an infection bacterial and especially virus as viruses have ability to get into cells and to sharply change structure of intracellular protein can be the damaging exogenous factors. Some medicinal substances, having tropism to certain blood cells, become haptens (see), being a part of autoantigens.

In recent years the theory of the general antigenic determinants of certain strains of microorganisms and tissues of the person received confirmation. Existence of such determinants leads to a sensitization not only in relation to microbes, but also in relation to own fabrics with the subsequent their damage.

The strains of a streptococcus of group A having the general antigens with tissue of heart of the person and also nefritogenny strains of a streptococcus, kolitogenny strains of colibacillus are allocated.

At many A.b. etiological factors remain to a crust, time unknown. And. develop at women more often.

The pathogeny

Can be allocated three ways of development And. The first way — education in an organism of autoallergens (release of the isolated antigens — a colloid of follicles of a thyroid gland, a myelin, antigens of a crystalline lens, testicles; a denaturation of fabrics at a burn, a radial illness, etc.; formation of complex and intermediate antigens). In response to emergence of autoallergens the immunologic mechanisms directed to an inactivation and removal of these autoallergens join. These mechanisms, being protective in the basis, in some cases cause damage of cells and fabrics. Such mechanism is supposed at Hashimoto's thyroiditis, an orchitis, encephalomyelitis.

The second way — defects in control of immunologic mechanisms of protection of an organism — the theory of «a forbidden clone» according to Burnett explains. Normal in relation to antigens of own fabrics there is an unresponsiveness (see. unresponsiveness ) and development of clones of lymphoid cells which could participate in immunological reactions with own fabrics or is slowed down, or these clones of an eliminirovana. At pathology owing to still unknown reasons development of such clone is possible, or such clone appears as a result of vegetative mutation of a lymphocyte. Cells of such clone begin to damage body tissues on the «transplant against the owner» mechanism (see. Incompatibility immunological ). In implementation of such way of development And. attach great value to a genetic factor, considering that thanks to genetic disorders so-called forbidden clones of the immunocompetent cells producing autoantibodies function. As the facts confirming a role of a genetic factor cases of family rheumatism, detection of a rhematoid factor at relatives of patients with a pseudorheumatism, antibodies are given to thyreoglobulin at relatives of patients with an autoimmune thyroiditis, single observations of a system lupus erythematosus and other autoallergichesky diseases at enzygotic twins. However these facts are not enough with confidence to carry And. to group of genetic.

Third way of development And. — activation of immunologic mechanisms against the microflora having the general antigens with antigens of a macroorganism. In the course of adaptation to existence in a macroorganism many microbes had antigens, the general with antigens of the owner. It slows down inclusion of immunologic mechanisms of protection against such microflora since in relation to the antigens in an organism there is an unresponsiveness and such microbic antigens are accepted as the. However owing to some distinctions in a structure of the general antigens nevertheless there is an inclusion of immunologic mechanisms of protection against microflora that at the same time leads also to damage of own fabrics. Assume participation of such mechanism in development of rheumatism in connection with availability of the general antigens at some strains of a streptococcus of group A and in tissue of heart, ulcer colitis in connection with availability of the general antigens in a mucous membrane of a large intestine and at some strains of E. coli, in certain cases an infectious and allergic form of bronchial asthma in connection with availability of the general antigens in tissue of a lung and at microflora, vegetans in respiratory tracts.

Irrespective of a pathogenetic way of development And. damage of fabrics can be caused by four immunologic (allergic) mechanisms. From them three mechanisms himergichesky, i.e. connected with action of autoantibodies, and the fourth — kitergichesky, or cellular (see. Allergy ). The first mechanism of damage is connected with formation of allergic antibodies like reagins which are fixed on a surface of cells and at connection with allergen cause release of vasoactive amines. The last cause disturbance of microcirculation and other damages. The second mechanism — cytotoxic. The formed antibodies connect to the corresponding cells and have cytotoxic and cytolytic effect on them in two ways. The direct way is implemented through activation of all components of a complement. The indirect way includes participation in this process of neutrophils which release disturbing factors. The third mechanism — toxic action of a cell-bound immune complex. antigen + antibody. This complex is fixed in fabrics, especially in walls of blood vessels. Precipitated calcium superphosphate fixes and activates a complement. It leads to accumulation in this fabric of neutrophils which englobe a complex and at the same time emit the hydrolases and other factors causing damage of fabrics. The fourth mechanism — allergic reaction of the slowed-down type. All four mechanisms can take part in damage of fabrics, however at various And. one of them acts preferential. Participation of the first mechanism in development And. slightly. The damaging action of cytotoxic autoantibodies (the second mechanism) is most accurately shown at autoallergichesky diseases of blood, the damaging action of cell-bound immune complexes — at a nodular periarteritis, a system lupus erythematosus; the cellular mechanism — at an autoallergichesky thyroiditis, a sympathetic ophthalmia.

The factor promoting development And., dysfunction of hemadens is. So, e.g., at And. often glucocorticoid insufficiency comes to light.

The pathological anatomy of autoallergichesky (autoimmune) processes and diseases

Morphology of autoimmune processes and diseases is presented by two categories of the changes different in the immunological essence. The first, studied by the general immunomorphology, is connected with strained (or perverted) an immunogenesis and concerns generally immunocompetent system. Changes of the second category belong to area of a private immunomorphology and are presented by morphology of the local immunological reactions which are made in a sensibilized organism, i.e. various · types of a fabric allergy.

Immunomorphological studying of autoimmune processes and diseases is based on obligatory comparison of data morphological and immunological (functional) researches. It means that the morphology of changes in the center of an immune response is estimated in parallel with the help immunological (level of antibodies and antigens at blood, urine, a lymph) and morphological indicators of a condition of immunocompetent system.

For immunomorphological studying of autoimmune processes and diseases use three methods:

1) an immunohistochemical (immunofluorescent) method in its various modifications with use of a combination of the luminescing antibodies or antigens with radioactive labels and the «contrasting» markers and attraction for this purpose quantitative assessment of a specific luminescence (mikroflyuorimetriya);

2) a microscopic method (light, polarizing, a submicroscopy) in combination with histochemical reactions;

3) an immunological method (identification of antigens and antibodies in fabrics and liquids of an organism). The leading place among them is taken by an immunohistochemical method which serves not only for detection of cell-bound immune complexes, but also for their «interpretation» (identification of antigen, an antibody, complement).

The morphology of an intense immunogenesis at autoimmune processes and diseases is quite stereotypic, though depends on features of an immunological situation and duration of an antigen challenge. It is presented by a lympho-reticular hyperplasia and plazmotsitarno-macrophagic transformation with accumulation of cells, rich RNA (immunoblasts, pironinofilny cells, plasmocytes) and polysaccharides (PAS cells, macrophages, etc.), first of all in bodies of immunocompetent system (a hyperplasia limf, nodes, a spleen, etc.) that reflects processes of cellular secretion of immunoglobulins (antibodyformation) and products of recirculating sensibilized lymphocytes. Hyperplastic reactions with accumulation of lympho-reticular elements and plazmotsitarno-macrophagic transformation at autoimmune processes and diseases, as a rule, go beyond an adenoid tissue. They are brightly presented in reticuloendothelial (retikulo-histiocytic) system of a liver, lungs, kidneys, friable connecting fabric and can imitate pictures of an interstitial inflammation and productive vasculites (if to be guided by formal morphological features). Expression of an intense immunogenesis should be considered also quite often found myelosis of internals. Processes of cellular proliferation, plazmotsitarno-macrophagic transformation and a myeloid metaplasia are followed by the sharp disturbances of fabric exchange which are coming to the end in some cases with development of a fabric disproteinoz (accumulation PAS-put-telnogo material in limf, nodes, an amyloidosis of a spleen, kidneys etc.).

The morphology of local damage in connection with immunological reaction is defined at autoimmune processes and diseases as the nature of antigen (cross reacting, autologous), duration of its circulation in blood, and quality of a cell-bound immune complex (circulating complement-linked or mestnoobrazovanny at the expense of structural antigen of fabric). At the same time the circulating complement-linked cell-bound immune complexes are capable to cause usually a giperergichesky (immune) inflammation as an immediate allergy, and mestnoobrazuyushchiyesya the cell-bound immune complexes containing fabric antigen lead to development of changes as the slowed-down allergy more often (see. Allergy ). However it is only extreme morphological expressions of local immunological reactions. It is proved that at the autoimmune processes and diseases induced by antigen with formation of the complement-linked cell-bound immune complexes circulating in blood, the inflammatory vascular and fabric changes which are coming to the end with a fibrinoid necrosis develop in connection with gistopatogenny action of these complexes that finds confirmation at an immunofluorescent research of biopsies. At the same time specifics of the developing immune destructions considerably depend on chemical structure and size of a cell-bound immune complex. E.g., histologic and histochemical features of lupoid changes (gematoksilinovy little bodies, a karyorrhexis, lixiviation of kernels, a sharp pyroninophilia, etc.) are connected first of all with feature of the cell-bound immune complex circulating at a lupus containing decomposition products of cellular kernels, nucleoproteids (antigen) and at G-globulins (antinuclear antibodies). Specifics of morphological changes at a pseudorheumatism are also defined by feature of an autologous cell-bound immune complex and the place of its education. It is established that plasmocytes of synovial membranes at a pseudorheumatism produce abnormal autoantigenny γ G-globulins that leads to emergence of antibodies to this globulin (γ Μ-immunoglobulins)))))))))), to formation of a rhematoid factor, sedimentation of a complement-linked krupnomolekulyarny cell-bound immune complex and development of inflammatory and necrotic changes. Development of the amyloidosis which is often found at a pseudorheumatism is connected with the paraprotein macromolecular nature of a cell-bound immune complex.

At the true autoimmune diseases (Hashimoto's disease, an idiopathic addisonova a disease, encephalopathy, a polyneuritis, a multiple sclerosis, an aspermatogeniya, etc.) induced by organ-specific autologous antigen cellular fabric reactions prevail. The morphology of hypersensitivity of the slowed-down type in the form of lympho-histiocytic and macrophagic reaction becomes in these cases dominating (a lymphocytic thyroiditis as morphological expression of a disease of Hashimoto). Hron, the abacterial Glomerulonephritis having morphology of hymenoid or hymenoid and proliferative (mezangialno-hymenoid) can be also considered as autoimmune as in development its important role is played by structural antigen of a basal membrane of the glomerular filter. At various autoimmune processes and diseases combinations of morphology of an allergy both the immediate, and slowed-down type are frequent.

Classification

Because many problems of an etiology and pathogeny And. are still insufficiently studied, their standard classification does not exist. As the worker V. I. Ioffe (1963) classification can be used, in a cut an attempt to divide everything is made And. on character of autoantigens and mechanisms of allergic (immunological) process and to show extent of participation of autoallergichesky process in development of a disease.

The main lack of this classification is the statement of the mechanism of autoallergichesky processes, indistinct and incomplete for modern level of knowledge. On this classification the first group is made by true autoimmune diseases. Here the diseases caused by disturbance of physiological isolation of antigens in relation to the Crimea in an organism are included there is no unresponsiveness. The role of autoantibodies which, as a rule, manage to be revealed in serum of patients is unknown since fabric changes have the nature of allergic reaction of the slowed-down type. With the known share of probability it is possible to carry the following diseases to this group: sympathetic ophthalmia (see), an autoallergichesky thyroiditis of Hashimoto (see. Hashimoto disease ), demyelinating processes — encephalomyelitis (see), multiple sclerosis (see), some forms polyneuritis (see), orchitis (see), idiopathic to an addisonov disease (see).

Treat the second group acquired hemolitic anemia (see), a Werlhof's disease (see. Werlhof's disease ) and collagenic diseases (see). Antigens at these diseases have no organ specificity. The pathogeny is connected with disturbance of homeostatic control of immunologic mechanisms. It is undoubted that not all And., included in this group, have disturbance of a homeostasis of an immunogenesis in the basis. So, e.g., the group of kollagenoz includes a number of nosological forms, apparently, with various mechanism and various extent of disturbance of homeostatic mechanisms of an immunogenesis. Its leading role at system is most evidential to a lupus erythematosus (see).

To the third group A. belong glomerulonephritis (see), hepatitis (see), agranulocytosis (see). Here diseases at which the autoantigennost of fabrics is got due to the damaging action of external factors (microbes, viruses, drugs) with formation of complex and intermediate autoallergens are included. It is also possible to carry to this group rheumatism (see) and vaccinal encephalomyelitis (see).

Broader classification of A. D. Ado (1970) includes not only And., but also autoallergichesky reactions (tab). Ideas of character of autoallergens (autoantigens) participating in autoallergichesky process and of the most common features of its pathogeny are the basis for this classification. On a pathogeny all autoallergichesky reactions are divided into two groups: 1) true, caused by the autoantibodies and sensibilized lymphocytes which are actively formed in an organism; 2) false, caused by introduction to an organism of ready antibodies.




All four mechanisms stated above participate in immunologic mechanisms of damage of fabrics. On character of autoallergens true allergic diseases and reactions are divided on primary and secondary.

Diagnosis

Clinical expression of tension of an immunogenesis is increase limf, nodes and a spleen. In addition to typical for everyone And. clinical signs, the great value for diagnosis is attached to identification of autoantibodies in serum of the patient. The last can be revealed by various, defined for each disease tests. At autoallergichesky hemolitic anemias apply direct and indirect tests of Koombs (see. Koombs reaction ). Apply to identification of antifabric autoantibodies reaction of binding complement (see), a precipitation test in gel on Oukhterlonya (see. Precipitation ), reaction of passive hemagglutination on Boydena (see. Boydena reaction ). At some And;. in serum the special proteins, apparently, concerning autoantibodies, e.g. a rhematoid factor at a pseudorheumatism, a lupoid factor at a system lupus erythematosus come to light. The result of action of antinuclear antibodies at the last disease should be considered formation of lupoid (LE) cells. In diagnosis the hypergammaglobulinemia has approximate value. Quite often, especially in diagnosis of kollagenoz, the analysis of material of a biopsy of fabrics is applied.

At many And. it is possible to receive positive skin allergic reaction of the slowed-down type on corresponding fabric gomoantigen.

However in clinical practice this method was not widely used yet.

Forecast

the Most common feature of the majority And. their heavy progressing current leading to irreversible dysfunctions of appropriate authority or system is. The exception is made by some medicinal gemopatiya having the favorable forecast in the absence of repeated contacts with the corresponding drugs. Introduction to therapy And. corticosteroids considerably prolonged life of many patients.

The principles of treatment

Practically at all And. it is necessary to resort to treatment by corticosteroid hormones which affect as the main mechanism of a course of a disease, suppressing products of autoantibodies, and on secondary changes thanks to antiinflammatory action and substitution of a lack of endogenous corticosteroids. Schemes of treatment are various for each disease. As a rule, prolonged treatment in a combination to the means reducing a possibility of development of side reactions is necessary. Favorable results are achieved, in particular, at the combined treatment by corticosteroids in combination with derivatives of quinoline (delagil, Resochinum, etc.).

At establishment of the diagnosis of medicinal gemopatiya the termination of contact with antigen (hapten) is necessary. At idiopathic forms of hemolitic anemia and thrombocytopenia in some cases the splenectomy is shown.

In recent years the question of treatment is studied And. cytostatic drugs (Novembichinum, tiotef, etc.) and immunodepressants of type 6 of Mercaptopurinum.

Prevention

Due to the ambiguity of many questions of an etiology and a pathogeny And. there are no absolutely effective measures of their prevention yet. It is presumably possible to speak about preventive value of restriction of excessive influences of antigenic irritants, such as vaccination, medicinal therapy, hemotransfusion, especially during the periods of the most labile reactivity of an organism.

Also fight against household and operational injuries, rational treatment hron, the systemic and focal infections, restriction of insolation, the prevention of overcooling matters. For prevention And. careful assessment of reactivity of an organism at the choice of the moment of planned operative measures is especially important, balneo-and physical therapy.


Bibliography: Ado A. D. General allergology, M., 1970; Dygin B. P. Autoimmune diseases in clinic of internal diseases, L., 1970; The Immunopathology in clinic and an experiment and a problem of autoantibodies, under the editorship of P. Misher and K. O. Forlender, lane with it., M., 1963; Ioffe V. I. An immunopathology — a problem of experimental and clinical medicine, Vestn. USSR Academy of Medical Sciences, No. 11, page 3, 1963; To r ayp L. Clinical immunology and an allergy, the lane with English, M., 1966; Lyampert I. M. Etiology, immunology and immunopathology of rheumatism, M., 1972; Modern problems of immunology and an immunopathology, under the editorship of A.A. Smorodintseva and other. L., 1970; Strukov A. I. and Begla-r I am A. P N. Pathological anatomy and pathogeny of collagenic diseases, M., 1963; To the Container ev E. M, etc. Collagenoses, M., 1965; Bendixen G. Classification of hypersensitivity in relation to clinical disease, Ann. intern. Med., v. 64, p. 668, 1966, bibliogr.

Pathological anatomy of autoimmune processes and diseases — Will return F. M. Cellular immunology, the lane with English, M., 1971; The Guide to immunology, under the editorship of O. E. Vyazov and Sh. of X. Hodzhayeva, page 43, etc., M., 1973; Serov V. V. izubzhitsky Yu. N. Principles and possibilities of morphological studying of immunopathological processes, Arkh. patol., t. 33, No. 9, page 3, 1971, bibliogr.; Steffen C. Allgemeine und experimentelle Immunologie und Immunpathologie, Stuttgart, 1968.


H. V. Adrianova, V. I. Pytsky; V. V. Serov (stalemate. An.).

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