Introduction

Immediate allergic reactions are IgE-mediated immune reactions that damage one's own tissues. In 1921, Prausnitz and Küstner showed that reagins, factors found in the serum of patients with this form of allergy, are responsible for the development of immediate allergic reactions. Only 45 years later, Ishizaka established that reagins are immunoglobulins of a new, hitherto unknown class, later called IgE. Both IgE themselves and their role in diseases caused by immediate allergic reactions have now been studied quite well. An immediate allergic reaction goes through a number of stages: 1) contact with the antigen; 2) IgE synthesis; 3) fixation of IgE on the surface of mast cells; 4) repeated contact with the same antigen; 5) binding of antigen to IgE on the surface of mast cells; 6) release of mediators from mast cells; 7) the effect of these mediators on organs and tissues.

Pathogenesis of immediate type allergic reactions

A. Antigens. Not all antigens stimulate the production of IgE. For example, polysaccharides do not have this property. Most natural antigens that cause immediate allergic reactions are polar compounds with a molecular weight of 10,000-20,000 and a large number of cross-links. The formation of IgE leads to the ingestion of even a few micrograms of this substance into the body. Based on molecular weight and immunogenicity, antigens are divided into two groups: full antigens and haptens.

• 1. Complete antigens, such as pollen antigens, epidermal and animal serum antigens, and hormone extracts, themselves induce an immune response and IgE synthesis. The basis of a complete antigen is a polypeptide chain. Its areas recognized by B lymphocytes are called antigenic determinants. During processing, the polypeptide chain is split into low-molecular fragments, which combine with HLA class II antigens and, in this form, are transferred to the surface of the macrophage. When fragments of processed antigen are recognized in combination with HLA class II antigens and under the influence of cytokines produced by macrophages, T lymphocytes are activated. Antigenic determinants, as already indicated, are recognized by B lymphocytes, which begin to differentiate and produce IgE under the influence of activated T lymphocytes.
• 2. Haptens are low molecular weight substances that become immunogenic only after the formation of a complex with tissue or serum carrier proteins. Reactions caused by haptens are characteristic of drug allergies. The differences between complete antigens and haptens are important for the diagnosis of allergic diseases. Thus, complete antigens can be determined and used as diagnostic preparations for allergy skin tests. It is almost impossible to determine a hapten and produce a diagnostic drug based on it, with the exception of penicillins. This is due to the fact that low molecular weight substances are metabolized when they enter the body and complexes with the endogenous carrier protein form mainly metabolites.

B. Antibodies. IgE synthesis requires interaction between macrophages, T- and B-lymphocytes. Antigens enter through the mucous membranes of the respiratory tract and gastrointestinal tract, as well as through the skin and interact with macrophages, which process and present it to T-lymphocytes. Under the influence of cytokines released by T lymphocytes, B lymphocytes are activated and turn into plasma cells that synthesize IgE (see. rice. 2.1 ).

• 1. Plasma cells that produce IgE are localized mainly in the lamina propria of the mucous membranes and in the lymphoid tissue of the respiratory tract and gastrointestinal tract. There are few of them in the spleen and lymph nodes. The total level of IgE in serum is determined by the total secretory activity of plasma cells located in different organs.
• 2. IgE binds tightly to receptors for the Fc fragment on the surface of mast cells and remains here for up to 6 weeks. IgG also binds to the surface of mast cells, but they remain associated with receptors for no more than 12-24 hours. The binding of IgE to mast cells leads to the following.

A. Since mast cells with IgE fixed on their surface are located in all tissues, any contact with antigen can lead to general activation of mast cells and an anaphylactic reaction.

b. The binding of IgE to mast cells increases the rate of synthesis of this immunoglobulin. In 2-3 days it is updated by 70-90%.

V. Since IgE does not cross the placenta, passive transfer of sensitization to the fetus is not possible. Another important property of IgE is that, in combination with an antigen, it activates complement along the alternative pathway (see. Ch. 1, p. IV.G.2) with the formation of chemotaxis factors, such as anaphylatoxins C3a, C4a and C5a.

B. Mast cells

• 1. Mast cells are present in all organs and tissues, especially in the loose connective tissue surrounding the blood vessels. IgE binds to mast cell receptors for the Fc fragment of the epsilon chains. IgE directed against different antigens is simultaneously present on the surface of the mast cell. One mast cell can contain from 5,000 to 500,000 IgE molecules. Mast cells from allergic patients carry more IgE molecules than mast cells from healthy people. The number of IgE molecules bound to mast cells depends on the level of IgE in the blood. However, the ability of mast cells to activate does not depend on the number of IgE molecules bound to their surface.
• 2. The ability of mast cells to release histamine under the influence of antigens is expressed differently in different people, the reasons for this difference are unknown. The release of histamine and other inflammatory mediators by mast cells can be prevented by desensitization and drug treatment (see Precautions). Ch. 4, pp. VI--XXIII).
• 3. In immediate allergic reactions, inflammatory mediators are released from activated mast cells. Some of these mediators are contained in granules, others are synthesized during cell activation. Cytokines are also involved in immediate allergic reactions (see. table 2.1 And rice. 1.6 ). Mast cell mediators act on blood vessels and smooth muscles and exhibit chemotactic and enzymatic activity. In addition to inflammatory mediators, oxygen radicals are produced in mast cells, which also play a role in the pathogenesis of allergic reactions.
• 4. Mechanisms of release of mediators. Mast cell activators are divided into IgE-dependent (antigens) and IgE-independent. IgE-independent activators of mast cells include muscle relaxants, opioids, radiocontrast agents, anaphylatoxins (C3a, C4a, C5a), neuropeptides (for example, substance P), ATP, interleukins-1, -3. Mast cells can also be activated by physical factors: cold (cold urticaria), mechanical irritation (urticarial dermographism), sunlight (solar urticaria), heat and exercise (cholinergic urticaria). In IgE-dependent activation, the antigen must bind to at least two IgE molecules on the surface of the mast cell (see Fig. rice. 2.1 ), therefore antigens that carry a single antibody binding site do not activate mast cells. Formation of a complex between the antigen and several IgE molecules on the surface of the mast cell activates membrane-bound enzymes, including phospholipase C, methyltransferases, and adenylate cyclase (see Table 1). rice. 2.2 ). Phospholipase C catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to form inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. Inositol 1,4,5-triphosphate causes the accumulation of calcium inside cells, and 1,2-diacylglycerol in the presence of calcium ions activates protein kinase C. In addition, calcium ions activate phospholipase A 2, under the influence of which arachidonic acid and lysophosphatidylcholine are formed from phosphatidylcholine. When the concentration of 1,2-diacylglycerol increases, lipoprotein lipase is activated, which breaks down 1,2-diacylglycerol to form monoacylglycerol and lysophosphatidylic acid. Monoacylglycerol, 1,2-diacylglycerol, lysophosphatidylcholine and lysophosphatidylic acid promote the fusion of mast cell granules with the cytoplasmic membrane and subsequent degranulation. Substances that inhibit mast cell degranulation include cAMP, EDTA, colchicine And cromolyn. Alpha adrenergic agonists and cGMP, on the contrary, enhance degranulation. Corticosteroids inhibit the degranulation of rat and mouse mast cells and basophils, but do not affect human lung mast cells. Mechanisms of inhibition of degranulation under the influence of corticosteroids and cromolyn have not been fully studied. It is shown that the action cromolyn not mediated by cAMP and cGMP, and the effect of corticosteroids may be due to increased sensitivity of mast cells to beta-agonists.

D. The role of inflammatory mediators in the development of immediate allergic reactions. The study of the mechanisms of action of inflammatory mediators has contributed to a deeper understanding of the pathogenesis of allergic and inflammatory diseases and the development of new methods for their treatment. As already noted, mediators released by mast cells are divided into two groups: granule mediators and mediators synthesized upon activation of mast cells (see. table 2.1 ).

1. Mediators of mast cell granules

A. Histamine. Histamine is formed by decarboxylation of histidine. The content of histamine is especially high in the cells of the gastric mucosa, platelets, mast cells and basophils. The peak effect of histamine is observed 1-2 minutes after its release, the duration of action is up to 10 minutes. Histamine is rapidly inactivated by deamination by histaminase and methylation by N-methyltransferase. The level of histamine in the serum depends mainly on its content in basophils and has no diagnostic value. The level of histamine in the serum can only indicate how much histamine was released immediately before blood sampling. The action of histamine is mediated by H 1 and H 2 receptors. Stimulation of H 1 receptors causes contraction of smooth muscles of the bronchi and gastrointestinal tract, increased vascular permeability, increased secretory activity of the glands of the nasal mucosa, dilation of skin vessels and itching, and stimulation of H 2 receptors causes increased secretion of gastric juice and an increase in its acidity, contraction of smooth muscles esophagus, increased permeability and vasodilation, mucus formation in the respiratory tract and itching. It is possible to prevent a reaction to subcutaneous administration of histamine only with the simultaneous use of H 1 - and H 2 -blockers; blockade of receptors of only one type is ineffective. Histamine plays an important role in regulating the immune response because H2 receptors are present on cytotoxic T lymphocytes and basophils. By binding to H2 receptors of basophils, histamine inhibits the degranulation of these cells. Acting on various organs and tissues, histamine causes the following effects.

• 1) Contraction of bronchial smooth muscles. Under the influence of histamine, the blood vessels of the lungs dilate and their permeability increases, which leads to swelling of the mucous membrane and an even greater narrowing of the lumen of the bronchi.
• 2) Dilation of small and narrowing of large vessels. Histamine increases the permeability of capillaries and venules, so when administered intradermally, hyperemia and a blister occur at the injection site. If vascular changes are systemic in nature, arterial hypotension, urticaria and Quincke's edema are possible. Histamine causes the most pronounced changes (hyperemia, edema and mucus secretion) in the nasal mucosa.
• 3) Stimulation of the secretory activity of the glands of the gastric mucosa and respiratory tract.
• 4) Stimulation of intestinal smooth muscles. This manifests itself as diarrhea and is often observed with anaphylactic reactions and systemic mastocytosis.

b. Enzymes. Using histochemical methods, it was shown that mast cells of the mucous membranes and lungs differ in the proteases contained in the granules. The granules of mast cells of the skin and the lamina propria of the intestinal mucosa contain chymase, and the granules of mast cells of the lungs contain tryptase. The release of proteases from mast cell granules causes: 1) damage to the basal membrane of blood vessels and the release of blood cells into the tissue; 2) increased vascular permeability; 3) destruction of cell debris; 4) activation of growth factors involved in wound healing. Tryptase remains in the blood for quite a long time. It can be found in the serum of patients with systemic mastocytosis and patients who have suffered an anaphylactic reaction. Determination of serum tryptase activity is used in the diagnosis of anaphylactic reactions. Other enzymes released during mast cell degranulation include arylsulfatase, kallikrein, superoxide dismutase, and exoglucosidases.

V. Proteoglycans. Mast cell granules contain heparin and chondroitin sulfates are proteoglycans with a strong negative charge. They bind positively charged histamine molecules and neutral proteases, limiting their diffusion and inactivation after release from the granules.

d. Chemotaxis factors. Degranulation of mast cells leads to the release of chemotaxis factors, which cause directed migration of inflammatory cells - eosinophils, neutrophils, macrophages and lymphocytes. Migration of eosinophils is caused by anaphylactic eosinophil chemotaxis factor and platelet activating factor (see. Ch. 2, p. I.G.2.b) is the most powerful known factor of eosinophil chemotaxis. In patients with atopic diseases, contact with allergens leads to the appearance in the serum of the anaphylactic neutrophil chemotaxis factor (molecular weight about 600). It is believed that this protein is also produced by mast cells. In immediate allergic reactions, other mediators are released from mast cells that cause directed migration of neutrophils, for example, high molecular weight neutrophil chemotaxis factor and leukotriene B4. Neutrophils attracted to the site of inflammation produce free oxygen radicals, which cause tissue damage.

2. Mediators synthesized upon activation of mast cells

A. Metabolism of arachidonic acid. Arachidonic acid is formed from membrane lipids under the action of phospholipase A 2 (see. rice. 2.3 ). There are two main pathways for the metabolism of arachidonic acid - cycloxygenase and lipoxygenase. The cycloxygenase pathway leads to the formation of prostaglandins and thromboxane A2, the lipoxygenase pathway leads to the formation of leukotrienes. In mast cells of the lungs, both prostaglandins and leukotrienes are synthesized, in basophils - only leukotrienes. The main enzyme of the lipoxygenase pathway of arachidonic acid metabolism in basophils and mast cells is 5-lipoxygenase, 12- and 15-lipoxygenase play a lesser role. However, 12- and 15-hydroperoxyeicosotetraenoic acids, which are formed in small quantities, play an important role in inflammation. The biological effects of arachidonic acid metabolites are listed in table 2.2 .

• 1) Prostaglandins. Prostaglandin D2 appears first among those that play a role in immediate allergic reactions and inflammation of the oxidation products of arachidonic acid along the cycloxygenase pathway. It is formed mainly in mast cells and is not synthesized in basophils. The appearance of prostaglandin D 2 in the serum indicates degranulation and the development of the early phase of an immediate allergic reaction. Intradermal administration of prostaglandin D 2 causes vasodilation and increased permeability, which leads to persistent hyperemia and blister formation, as well as the release of leukocytes, lymphocytes and monocytes from the vascular bed. Inhalation of prostaglandin D2 causes bronchospasm, which indicates the important role of this arachidonic acid metabolite in the pathogenesis of anaphylactic reactions and systemic mastocytosis. The synthesis of the remaining products of the cycloxygenase pathway - prostaglandins F 2alpha, E 2, I 2 and thromboxane A 2 - is carried out by enzymes specific to different cell types (see. rice. 2.3 ).
• 2) Leukotrienes. The synthesis of leukotrienes by human mast cells mainly occurs during allergic reactions of the immediate type and begins after the binding of the antigen to IgE fixed on the surface of these cells. The synthesis of leukotrienes is carried out as follows: free arachidonic acid, under the action of 5-lipoxygenase, is converted into leukotriene A 4, from which leukotriene B 4 is then formed. When leukotriene B 4 is conjugated with glutathione, leukotriene C 4 is formed. Subsequently, leukotriene C 4 is converted into leukotriene D 4, from which, in turn, leukotriene E 4 is formed (see. rice. 2.3 ). Leukotriene B 4 is the first stable product of the lipoxygenase pathway of arachidonic acid metabolism. It is produced by mast cells, basophils, neutrophils, lymphocytes and monocytes. It is the main factor in the activation and chemotaxis of leukocytes in immediate allergic reactions. Leukotrienes C 4 , D 4 and E 4 were previously combined under the name “slow reacting substance of anaphylaxis”, since their release leads to a slowly increasing persistent contraction of smooth muscles of the bronchi and gastrointestinal tract. Inhalation of leukotrienes C 4, D 4 and E 4, as well as inhalation of histamine, leads to bronchospasm. However, leukotrienes cause this effect at 1000 times lower concentrations. Unlike histamine, which acts primarily on small bronchi, leukotrienes also act on large bronchi. Leukotrienes C 4 , D 4 and E 4 stimulate contraction of bronchial smooth muscles, mucus secretion and increase vascular permeability. In patients with atopic diseases, these leukotrienes can be found in the nasal mucosa. Leukotriene receptor blockers have been developed and are successfully used for the treatment of bronchial asthma - montelukast And zafirlukast.

b. Platelet activating factor is synthesized in mast cells, neutrophils, monocytes, macrophages, eosinophils and platelets. Basophils do not produce this factor. Platelet activating factor is a powerful stimulator of platelet aggregation. Intradermal administration of this substance leads to the appearance of erythema and blister (histamine causes the same effect at 1000 times higher concentration), eosinophilic and neutrophilic infiltration of the skin. Inhalation of platelet activating factor causes severe bronchospasm, eosinophilic infiltration of the respiratory mucosa and increased bronchial reactivity, which can persist for several weeks after a single inhalation. A number of alkaloids, natural inhibitors of platelet activating factor, have been isolated from the ginkgo tree. Currently, new drugs are being developed based on them. The role of platelet activating factor in the pathogenesis of immediate allergic reactions is also that it stimulates platelet aggregation with subsequent activation of factor XII (Hageman factor). Activated factor XII, in turn, stimulates the formation of kinins, the most important of which is bradykinin (see. Ch. 2, p. I.G.3.b).

3. Other inflammatory mediators

A. Adenosine is released during mast cell degranulation. In patients with exogenous bronchial asthma, after contact with an allergen, the level of adenosine in the serum increases. Three types of adenosine receptors have been described. The binding of adenosine to these receptors results in increased cAMP levels. These receptors can be blocked using methylxanthine derivatives.

b. Bradykinin, a component of the kallikrein-kinin system, is not produced by mast cells. The effects of bradykinin are diverse: it dilates blood vessels and increases their permeability, causes prolonged bronchospasm, irritates pain receptors, stimulates the formation of mucus in the respiratory tract and gastrointestinal tract.

V. Serotonin is also an inflammatory mediator. The role of serotonin in immediate allergic reactions is insignificant. Serotonin is released from platelets during their aggregation and causes short-term bronchospasm.

d. Complement also plays an important role in the pathogenesis of immediate-type allergic reactions. Activation of complement is possible both through the alternative route - IgE complexes with antigen - and through the classical pathway - plasmin (it, in turn, is activated by factor XII). In both cases, as a result of complement activation, anaphylatoxins are formed - C3a, C4a and C5a.

Delayed allergic reactions are reactions that occur only a few hours or even days after exposure to the allergen. The most typical example of this group of allergic manifestations turned out to be tuberculin reactions, therefore sometimes the entire group of delayed-type allergic reactions is called tuberculin-type reactions. Delayed allergies include bacterial allergies, allergic reactions of the contact type (contact dermatitis), autoallergic diseases, transplant rejection reactions, etc.

Bacterial allergy

Delayed bacterial allergies can appear with preventive vaccinations and with certain infectious diseases (tuberculosis, diphtheria, brucellosis, coccal, viral and fungal infections). If an allergen is applied to the scarified skin of a sensitized or infected animal (or injected intradermally), the response begins no earlier than 6 hours later and reaches a maximum after 24-48 hours. At the site of contact with the allergen, hyperemia, thickening and sometimes necrosis of the skin occurs. Necrosis occurs as a result of the death of a significant number of histiocytes and parenchymal cells. When injecting small doses of allergen, there is no necrosis. Histologically, as with all types of delayed-type allergic reactions, bacterial allergies are characterized by mononuclear infiltration (monocytes and large, medium and small lymphocytes). In clinical practice, delayed skin reactions of Pirquet, Mantoux, Burnet, and others are used to determine the degree of sensitization of the body during a particular infection.

Slow allergic reactions can also occur in other organs, for example, in the cornea and bronchi. When a tuberculin aerosol is inhaled into BCG-sensitized guinea pigs, severe shortness of breath occurs, and histologically, infiltration of the lung tissue with polymorphonuclear and mononuclear cells, which are located around the bronchioles, is observed. If tuberculosis bacteria are introduced into the lungs of sensitized animals, a strong cellular reaction occurs with fantastic decay and the formation of cavities (Koch phenomenon).

Contact allergy

Contact allergies (contact dermatitis) are caused by a variety of low-molecular substances (dinitrochlorobenzene, picrylic acid, phenols, etc.), industrial chemicals, paints (Ursol is the active substance of poison ivy), detergents, metals (platinum compounds), cosmetics, etc. Molecular the weight of most of these substances does not exceed 1000, i.e. they are haptens (incomplete antigens). In the skin they combine with proteins, probably through a covalent bond with the free amino and sulfhydryl groups of proteins and acquire allergenic properties. The ability to combine with protein is directly proportional to the allergenic activity of these substances.

The local reaction of a sensitized organism to a contact allergen also appears after about 6 hours and reaches a maximum after 24-48 hours. The reaction develops superficially, mononuclear infiltration of the epidermis and the formation of small cavities containing mononuclear cells in the epidermis occur. Epidermal cells degenerate, the structure of the basement membrane is disrupted and epidermal detachment occurs. Changes in the deep layers of the skin are much weaker than with other types of local reactions of delayed type a.

Autoallergy

Delayed allergic reactions also include a large group of reactions and diseases that occur as a result of damage to cells and tissues by so-called autoallergens, i.e., allergens that arise in the body itself. The nature and mechanism of formation of autoallergens are different.

Some autoallergens are contained in the body in finished form (endoallergens). Some tissues of the body (for example, tissues of the lens, thyroid gland, testes, gray matter of the brain) during phylogenesis turned out to be isolated from the immunogenesis apparatus, due to which they are perceived by immunocompetent cells as foreign. Their antigenic structure turns out to be an irritant for the immunogenesis apparatus and antibodies are produced against them.

Of great importance are secondary or acquired autoallergens, which are formed in the body from its own proteins as a result of the action of any damaging environmental factors (for example, cold, high temperature, ionizing radiation). These autoallergens and the antibodies formed against them play a certain role in the pathogenesis of radiation, burn disease, etc.

When the human or animal body’s own antigenic components are exposed to bacterial allergens, infectious autoallergens are formed. In this case, complex allergens may arise that retain the antigenic properties of the component parts of the complex (human or animal tissue + bacteria) and intermediate allergens with completely new antigenic properties. The formation of intermediate allergens is very clearly visible in some neuroviral infections. The relationship between viruses and the cells they infect is characterized by the fact that the nucleoproteins of the virus, during its reproduction, interact extremely closely with the nucleoproteins of the cell. The virus at a certain stage of its reproduction seems to fuse with the cell. This creates especially favorable conditions for the formation of large-molecular antigenic substances - products of interaction between a virus and a cell, which are intermediate allergens (according to A.D. Ado).

The mechanisms of occurrence of autoallergic diseases are quite complex. Some diseases apparently develop as a result of disruption of the physiological vascular-tissue barrier and the release from tissues of natural or primary autoallergens, to which the body has no immunological tolerance. Such diseases include allergic thyroiditis, orchitis, sympathetic ophthalmia, etc. But for the most part, autoallergic diseases are caused by antigens of the body’s own tissues, altered under the influence of physical, chemical, bacterial and other agents (acquired or secondary autoallergens). For example, autoantibodies against one’s own tissues (cytotoxin-type antibodies) appear in the blood and tissue fluids of animals and humans during radiation sickness. In this case, apparently, water ionization products (active radicals) and other tissue breakdown products lead to denaturation of proteins, turning them into autoallergens. Antibodies are produced against the latter.

Autoallergic lesions are also known, which develop due to the commonality of antigenic determinants of the tissue's own components with those of exoallergens. Common antigenic determinants have been found in the heart muscle and some strains of streptococcus, lung tissue and some saprophytic bacteria living in the bronchi, etc. The immunological reaction caused by an exoallergen, due to cross-antigenic properties, can be directed against its own tissues. In this way, some cases of allergic myocarditis, an infectious form of bronchial asthma, etc. may occur. And, finally, a number of autoimmune diseases are based on dysfunction of lymphoid tissue, the appearance of so-called forbidden clones directed against the body’s own tissues. These types of diseases include systemic lupus erythematosus, acquired hemolytic anemia, etc.

A special group of lesions, similar in mechanism to autoallergic reactions, consists of experimental diseases caused by cytotoxic serums. A typical example of such lesions is nephrotoxic glomerulonephritis. Nephrotoxic serum can be obtained, for example, after repeated subcutaneous injection of crushed rabbit kidney emulsion into guinea pigs. If guinea pig serum containing a sufficient amount of anti-renal cytotoxins is administered to a healthy rabbit, they develop glomerulonephritis (proteinuria and death of animals from uremia). Depending on the dose of antiserum administered, glomerulonephritis appears soon (24-48 hours) after administration of the serum or after 5-11 days. Using the fluorescent antibody method, it was established that, according to these periods, foreign gamma globulin appears in the glomeruli of the kidneys in the early stages, and after 5-7 days autologous gamma globulin appears. The reaction of such antibodies with a foreign protein fixed in the kidneys is the cause of late glomerulonephritis.

Homograft rejection reaction

As is known, true engraftment of transplanted tissue or organ is possible only with autotransplantation or homotransplantation in identical twins. In all other cases, the transplanted tissue or organ is rejected. Transplant rejection is the result of a delayed allergic reaction. Already 7-10 days after tissue transplantation, and especially sharply after graft rejection, a typical delayed reaction to intradermal injection of donor tissue antigens can be obtained. Lymphoid cells play a decisive role in the development of the body's response to the transplant. When tissue is transplanted into an organ with a poorly developed drainage lymphatic system (anterior chamber of the eye, brain), the process of destruction of the transplanted tissue slows down. Lymphocytosis is an early sign of incipient rejection, and the experimental imposition of a thoracic lymphatic duct fistula in the recipient, which allows to some extent reduce the number of lymphocytes in the body, prolongs the life of the homograft.

The mechanism of transplant rejection can be represented as follows: as a result of transplantation of foreign tissue, the recipient's lymphocytes become sensitized (become carriers of transfer factors or cellular antibodies). These immune lymphocytes then migrate into the graft, where they are destroyed and release the antibody, which causes destruction of the transplanted tissue. When immune lymphocytes come into contact with graft cells, intracellular proteases are also released, which cause further metabolic disorder in the graft. Administration of tissue protease inhibitors (for example, s-aminocaproic acid) to the recipient promotes the engraftment of transplanted tissues. Suppression of lymphocyte function by physical (ionizing irradiation of lymph nodes) or chemical (special immunosuppressive agents) effects also prolongs the functioning of transplanted tissues or organs.

Mechanisms of delayed-type allergic reactions

All delayed-type allergic reactions develop according to a general plan: in the initial stage of sensitization (shortly after the introduction of the allergen into the body), a large number of pyroninophilic cells appear in the regional lymph nodes, from which immune (sensitized) lymphocytes are apparently formed. The latter become carriers of antibodies (or the so-called “transfer factor”), enter the blood, partly they circulate in the blood, partly settle in the endothelium of blood capillaries, skin, mucous membranes and other tissues. Upon subsequent contact with the allergen, they cause the formation of the allergen-antibody immune complex and subsequent tissue damage.

The nature of the antibodies involved in the mechanisms of delayed allergy is not fully understood. It is known that passive transfer of delayed allergies to another animal is possible only with the help of cell suspensions. With blood serum, such a transfer is practically impossible; the addition of at least a small amount of cellular elements is required. Among the cells involved in delayed allergy, cells of the lymphoid series seem to be of particular importance. Thus, with the help of lymph node cells and blood lymphocytes, it is possible to passively tolerate increased sensitivity to tuberculin, picryl chloride and other allergens. Contact sensitivity can be transmitted passively with cells of the spleen, thymus, and thoracic lymphatic duct. In people with various forms of insufficiency of the lymphoid apparatus (for example, lymphogranulomatosis), delayed-type allergic reactions do not develop. In experiments, irradiation of animals with X-rays before the onset of lymphopenia causes suppression of tuberculin allergy, contact dermatitis, homograft rejection reaction and other delayed-type allergic reactions. The administration of cortisone to animals in doses that reduce the content of lymphocytes, as well as the removal of regional lymph nodes, suppresses the development of delayed allergies. Thus, it is lymphocytes that are the main carriers and carriers of antibodies in delayed allergies. The presence of such antibodies on lymphocytes is also evidenced by the fact that lymphocytes with delayed allergies are able to fix the allergen on themselves. As a result of the interaction of sensitized cells with the allergen, biologically active substances are released, which can be considered as mediators of delayed-type allergies. The most important of them are the following:

1. Macrophage migration inhibitory factor . It is a protein with a molecular weight of about 4000-6000. It inhibits the movement of macrophages in tissue culture. When administered intradermally to a healthy animal (guinea pig), it causes a delayed allergic reaction. Found in humans and animals.

2. Lymphotoxin - a protein with a molecular weight of 70,000-90,000. Causes destruction or inhibition of growth and proliferation of lymphocytes. Suppresses DNA synthesis. Found in humans and animals

3. blastogenic factor - protein. Causes the transformation of lymphocytes into lymphoblasts; promotes the absorption of thymidine by lymphocytes and activates the division of lymphocytes. Found in humans and animals.

4. In guinea pigs, mice, and rats, other factors were also found as mediators of delayed-type allergic reactions that have not yet been identified in humans, for example,skin reactivity factor causing inflammation of the skin,chemotactic factor and some others, which are also proteins with different molecular weights.

Circulating antibodies may appear in some cases during delayed-type allergic reactions in the tissue fluids of the body. They can be detected using the agar precipitation test or the complement fixation test. However, these antibodies are not responsible for the essence of delayed-type sensitization and do not participate in the process of damage and destruction of tissues of the sensitized organism during autoallergic processes, bacterial allergies, rheumatism, etc. According to their significance for the body, they can be classified as witness antibodies (but classification of antibodies by A. D. Ado).

The influence of the thymus on allergic reactions

The thymus influences the formation of delayed allergies. Early thymectomy in animals causes a decrease in the number of circulating lymphocytes, involution of lymphoid tissue and suppresses the development of delayed allergy to proteins, tuberculin, disrupts the development of transplantation immunity, but has little effect on contact allergy to dinitrochlorobenzene. Insufficiency of thymus function affects primarily the state of the paracortical layer of the lymph nodes, i.e., the layer where, during delayed allergies, pyroninophilic cells are formed from small lymphocytes. With early thymectomy, it is from this area that lymphocytes begin to disappear, which leads to atrophy of the lymphoid tissue.

The effect of thymectomy on delayed allergies is manifested only if the thymus is removed in the early stages of the animal’s life. Thymectomy performed in animals a few days after birth or in adult animals does not affect the engraftment of the homograft.

Allergic reactions of the immediate type are also under the control of the thymus, but the influence of the thymus on these reactions is less pronounced. Early thymectomy does not affect the formation of plasma cells and the synthesis of gamma globulin. Thymectomy is accompanied by inhibition of circulating antibodies not to all, but only to some types of antigens.

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Types of allergic reactions (hypersensitivity reactions). Hypersensitivity of immediate and delayed type. Stages of allergic reactions. Step-by-step mechanism for the development of allergic reactions.

1. 4 types of allergic reactions (hypersensitivity reactions).

Currently, according to the mechanism of development, it is customary to distinguish 4 types of allergic reactions (hypersensitivity). All these types of allergic reactions, as a rule, are rarely found in their pure form; more often they coexist in various combinations or change from one type of reaction to another type.
At the same time, types I, II and III are caused by antibodies, are and belong to immediate hypersensitivity reactions (IHT). Type IV reactions are caused by sensitized T cells and belong to Delayed hypersensitivity reactions (DTH).

Pay attention!!! is a hypersensitivity reaction triggered by immunological mechanisms. Currently, all 4 types of reactions are considered hypersensitivity reactions. However, true allergies mean only those pathological immune reactions that occur through the mechanism of atopy, i.e. according to type I, and reactions of types II, III and IV (cytotoxic, immunocomplex and cellular) types are classified as autoimmune pathology.

1. The first type (I) is atopic, anaphylactic or reagin type - caused by IgE class antibodies. When an allergen interacts with IgE fixed on the surface of mast cells, these cells are activated and the deposited and newly formed allergy mediators are released, followed by the development of an allergic reaction. Examples of such reactions are anaphylactic shock, Quincke's edema, hay fever, bronchial asthma, etc.
2. The second type (II) is cytotoxic. In this type, the body’s own cells become allergens, the membrane of which has acquired the properties of autoallergens. This occurs mainly when they are damaged as a result of exposure to drugs, bacterial enzymes or viruses, as a result of which the cells change and are perceived by the immune system as antigens. In any case, for this type of allergy to occur, antigenic structures must acquire the properties of autoantigens. The cytotoxic type is caused by IgG or IgM, which are directed against Ags located on modified cells of the body’s own tissues. The binding of Ab to Ag on the cell surface leads to the activation of complement, which causes damage and destruction of cells, subsequent phagocytosis and their removal. The process also involves leukocytes and cytotoxic T- lymphocytes. By binding to IgG, they participate in the formation of antibody-dependent cellular cytotoxicity. It is the cytotoxic type that causes the development of autoimmune hemolytic anemia, drug allergies, and autoimmune thyroiditis.
3. The third type (III) is immunocomplex, in which body tissues are damaged by circulating immune complexes involving IgG or IgM, which have a large molecular weight. That. in type III, as well as in type II, reactions are caused by IgG and IgM. But unlike type II, in a type III allergic reaction, antibodies interact with soluble antigens, and not with those located on the surface of cells. The resulting immune complexes circulate in the body for a long time and are fixed in the capillaries of various tissues, where they activate the complement system, causing an influx of leukocytes, the release of histamine, serotonin, lysosomal enzymes that damage the vascular endothelium and tissues in which the immune complex is fixed. This type of reaction is the main one in serum sickness, drug and food allergies, and in some autoallergic diseases (SLE, rheumatoid arthritis, etc.).
4. The fourth (IV) type of reaction is delayed-type hypersensitivity or cell-mediated hypersensitivity. Delayed reactions develop in a sensitized organism 24-48 hours after contact with the allergen. In type IV reactions, the role of antibodies is performed by sensitized T- lymphocytes. Ag, in contact with Ag-specific receptors on T cells, leads to an increase in the number of this population of lymphocytes and their activation with the release of mediators of cellular immunity - inflammatory cytokines. Cytokines cause the accumulation of macrophages and other lymphocytes, involving them in the process of destruction of antigens, resulting in inflammation. Clinically, this is manifested by the development of hyperergic inflammation: a cellular infiltrate is formed, the cellular basis of which is made up of mononuclear cells - lymphocytes and monocytes. The cellular type of reaction underlies the development of viral and bacterial infections (contact dermatitis, tuberculosis, mycoses, syphilis, leprosy, brucellosis), some forms of infectious-allergic bronchial asthma, transplant rejection and antitumor immunity.

Reaction type		Development mechanism		Clinical manifestations
Type I Reagin reactions		Develops as a result of the binding of an allergen to IgE fixed on mast cells, which leads to the release of allergy mediators from the cells, which cause clinical manifestations		Anaphylactic shock, Quincke's edema, atopic bronchial asthma, hay fever, conjunctivitis, urticaria, atopic dermatitis, etc.
Type II Cytotoxic reactions		Caused by IgG or IgM, which are directed against Ag located on the cells of their own tissues. Complement is activated, which causes cytolysis of target cells		Autoimmune hemolytic anemia, thrombocytopenia, autoimmune thyroiditis, drug-induced agranulocytosis, etc.
Type III Immune complex-mediated reactions		Circulating immune complexes with IgG or IgM are fixed to the capillary wall, activate the complement system, tissue infiltration by leukocytes, their activation and production of cytotoxic and inflammatory factors (histamine, lysosomal enzymes, etc.), damaging the vascular endothelium and tissue.		Serum sickness, drug and food allergies, SLE, rheumatoid arthritis, allergic alveolitis, necrotizing vasculitis, etc.
Type IV Cell-mediated reactions		Sensitized T- lymphocytes, in contact with Ag, produce inflammatory cytokines that activate macrophages, monocytes, lymphocytes and damage surrounding tissues, forming a cellular infiltrate.		Contact dermatitis, tuberculosis, mycoses, syphilis, leprosy, brucellosis, transplant rejection reactions and antitumor immunity.

2. Hypersensitivity of immediate and delayed type.

What is the fundamental difference between all these 4 types of allergic reactions?
And the difference is in what type of immunity, humoral or cellular, these reactions are caused. Depending on this they distinguish:

3. Stages of allergic reactions.

In most patients, allergic manifestations are caused by IgE-class antibodies, therefore we will consider the mechanism of allergy development using the example of type I allergic reactions (atopy). There are three stages in their course:

• Immunological stage– includes changes in the immune system that occur upon first contact of the allergen with the body and the formation of corresponding antibodies, i.e. sensitization. If by the time At is formed the allergen is removed from the body, no allergic manifestations occur. If the allergen is re-entered or continues to be in the body, an “allergen-antibody” complex is formed.
• Pathochemical– release of biologically active allergy mediators.
• Pathophysiological– stage of clinical manifestations.

This division into stages is quite arbitrary. However, if you imagine Allergy development process step by step, it will look like this:

1. First contact with an allergen
2. IgE formation
3. Fixation of IgE on the surface of mast cells
4. Sensitization of the body
5. Repeated contact with the same allergen and formation of immune complexes on the mast cell membrane
6. Release of mediators from mast cells
7. The effect of mediators on organs and tissues
8. Allergic reaction.

Thus, the immunological stage includes points 1 - 5, pathochemical - point 6, pathophysiological - points 7 and 8.

4. Step-by-step mechanism for the development of allergic reactions.

1. First contact with an allergen.
2. Ig E formation.
   At this stage of development, allergic reactions resemble a normal immune response, and are also accompanied by the production and accumulation of specific antibodies that can combine only with the allergen that caused their formation.
   But in the case of atopy, it is the formation of IgE in response to the incoming allergen, and in increased quantities in relation to the other 5 classes of immunoglobulins, which is why it is also called Ig-E dependent allergy. IgE is produced locally, mainly in the submucosa of tissues in contact with the external environment: in the respiratory tract, skin, and gastrointestinal tract.
3. Fixation of IgE to the mast cell membrane.
   If all other classes of immunoglobulins, after their formation, circulate freely in the blood, then IgE has the property of immediately attaching to the mast cell membrane. Mast cells are connective tissue immune cells that are found in all tissues in contact with the external environment: tissues of the respiratory tract, gastrointestinal tract, and connective tissues surrounding blood vessels. These cells contain biologically active substances such as histamine, serotonin, etc., and are called mediators of allergic reactions. They have pronounced activity and have a number of effects on tissues and organs, causing allergic symptoms.
4. Sensitization of the body.
   For the development of allergies, one condition is required - preliminary sensitization of the body, i.e. the occurrence of hypersensitivity to foreign substances - allergens. Hypersensitivity to a given substance develops upon first encounter with it.
   The time from the first contact with an allergen to the onset of hypersensitivity to it is called the period of sensitization. It can range from a few days to several months or even years. This is the period during which IgE accumulates in the body, fixed to the membrane of basophils and mast cells.
   A sensitized organism is one that contains a reserve of antibodies or T cells (in the case of HRT) that are sensitized to that particular antigen.
   Sensitization is never accompanied by clinical manifestations of allergy, since only Ab accumulates during this period. Immune complexes Ag + Ab have not yet formed. Not single Abs, but only immune complexes are capable of damaging tissue and causing allergies.
5. Repeated contact with the same allergen and the formation of immune complexes on the mast cell membrane.
   Allergic reactions occur only when the sensitized organism encounters a given allergen again. The allergen binds to ready-made Abs on the surface of mast cells and the formation of immune complexes: allergen + Ab.
6. Release of allergy mediators from mast cells.
   Immune complexes damage the membrane of mast cells, and from them allergy mediators enter the intercellular environment. Tissues rich in mast cells (skin vessels, serous membranes, connective tissue, etc.) are damaged by the released mediators.
   With prolonged exposure to allergens, the immune system uses additional cells to ward off invading antigens. A number of more chemical substances - mediators - are formed, which causes further discomfort for allergy sufferers and increases the severity of symptoms. At the same time, the mechanisms of inactivation of allergy mediators are inhibited.
7. The action of mediators on organs and tissues.
   The action of mediators determines the clinical manifestations of allergies. Systemic effects develop - dilation of blood vessels and increased permeability, mucous secretion, nervous stimulation, smooth muscle spasms.
8. Clinical manifestations of an allergic reaction.
   Depending on the organism, the type of allergens, the route of entry, the place where the allergic process occurs, the effects of one or another allergy mediator, symptoms can be system-wide (classical anaphylaxis) or localized in individual systems of the body (asthma - in the respiratory tract, eczema - in the skin ).
   Itching, runny nose, lacrimation, swelling, shortness of breath, drop in pressure, etc. occur. And the corresponding picture of allergic rhinitis, conjunctivitis, dermatitis, bronchial asthma or anaphylaxis develops.

In contrast to immediate hypersensitivity described above, delayed hypersensitivity is caused by sensitized T cells rather than antibodies. And it destroys those cells of the body on which the immune complex Ag + sensitized T-lymphocyte has been fixed.

Abbreviations in the text.

• Antigens – Ag;
• Antibodies – Ab;
• Antibodies = same as immunoglobulins(At=Ig).
• Delayed hypersensitivity - HRT
• Immediate hypersensitivity - IHT
• Immunoglobulin A - IgA
• Immunoglobulin G - IgG
• Immunoglobulin M - IgM
• Immunoglobulin E - IgE.
• Immunoglobulins- Ig;
• Antigen-antibody reaction – Ag + Ab

Allergy is a disease of our age. It is a fairly young disease. Our ancestors managed, in some magical way, to avoid this disease. They just didn't know about it. Allergic reactions are usually divided into types of allergies: delayed and immediate type.

Immediate allergic reactions

Immediate allergies often cause: rashes, severe itching and swelling. Allergic reactions of the immediate type are characterized by the speed of onset of the reaction after taking medications, food and other contacts with the allergen. In severe cases of the disease, anaphylactic shock may occur, which poses a threat to human life.

Delayed allergic reactions

Delayed type allergies are difficult to diagnose, as they are a chronic phenomenon in which allergens tend to accumulate in the body. In most cases, delayed-type allergic reactions occur against the background of several allergens.

Allergic reactions type 1

An allergic reaction of the first type can manifest itself in the following forms:

• rhinitis;
• conjunctivitis;
• dermatitis;
• rash in the form of hives;
• Quincke's edema;
• bronchial asthma;
• anaphylactic shock.

Allergic reactions type 2

Type 2 allergic reaction is caused by the hypersensitivity of antibodies that attach to parts of tissue that have artificial or natural components. For example: with hemolytic disease of newborns, allergies to medications.

Allergic reactions type 3

The third type includes hypersensitive reactions in some excess of antigen. This is facilitated by immune complex nephritis and serum sickness. During the inflammatory process, deposits occur on the walls of the bloodstream and, as a result, tissue damage occurs, which causes type 3 allergic reactions.

The third type of reaction can also occur against the background of:

• rheumatoid arthritis;
• lupus erythematosus;
• allergic dermatitis;
• immune complex glomerulonephritis;
• exogenous conjunctivitis.

Allergic reactions type 4

Type 4 allergic reactions are characteristic of the following diseases:

• tuberculosis;
• brucellosis;
• infectious-allergic bronchial asthma, etc.

When type 4 allergies develop, the respiratory organs, gastrointestinal tract, and skin are most often affected.

Allergic reaction type 5

There is also a 5th type of allergic reactions, in which antibodies have a stimulating effect on cell function. In fact, specific antibodies are overactive. These diseases include thyrotoxicosis.

Allergy type urticaria

An allergic reaction similar to urticaria, manifests itself in the form of blisters. And at the same time, it can be very difficult to identify the allergen. Most often this appears after taking medications or food.

Allergy type urticaria appears precisely when there are pathological disorders of internal organs, and in particular the patient’s nervous system suffers. This result occurs after exposure to direct sunlight. Solar urticaria occurs.

In severe cases of allergic reactions, after using medications or food, doctors prescribe laxatives: antihistamines, calcium gluconate, calcium chloride, an adrenaline solution is administered, and for external use, a 1% menthol solution, a solution of salicylic acid or calendula is very effective. If it is still not possible to determine the allergen, it is better to prescribe therapeutic fasting under the supervision of a doctor.

Complex treatment methods

To cure allergies, you need to follow these steps:

1. eliminate contact with possible allergens;
2. take necessary medications;
3. reduce the painful sensitivity of your own body to allergens;
4. use folk remedies;

There are known allergens in everyday life. These include fungi, mites in house dust, and the epidermis of dogs and cats. You should exclude woolen items from the patient's room: it is better to put them in a closet. When spring comes, the risk of allergies increases. It is necessary that the patient's windows are closed, as there are many allergens in the air. You need to wear things made from natural fabrics, exclude animals from entering the room, and carry out wet cleaning of the room.

Chapter 5. Delayed allergic reactions

Allergic reactions of the delayed (cellular) type are reactions that occur only a few hours or even days after the resolving effect of a specific allergen. In modern literature, this type of reaction is called “delayed-type hypersensitivity.”

§ 95. General characteristics of delayed allergies

Delayed allergic reactions differ from immediate allergies in the following ways:

1. The response of the sensitized organism to the action of the permissive dose of the allergen occurs after 6-48 hours.
2. Passive transfer of delayed allergies using serum from a sensitized animal is not possible. Consequently, antibodies circulating in the blood - immunoglobulins - are not of great importance in the pathogenesis of delayed allergies.
3. Passive transfer of delayed allergies is possible with a suspension of lymphocytes taken from a sensitized organism. On the surface of these lymphocytes, chemically active determinants (receptors) appear, with the help of which the lymphocyte connects with a specific allergen, i.e., these receptors function like circulating antibodies in immediate allergic reactions.
4. The possibility of passive transmission of delayed allergies in humans is due to the presence in sensitized lymphocytes of the so-called “transfer factor”, first identified by Lawrence (1955). This factor is a substance of peptide nature, having a molecular weight of 700-4000, resistant to the action of trypsin, DNase, RNase. It is neither an antigen (small molecular weight) nor an antibody, since it is not neutralized by antigen.

§ 96. Types of delayed allergies

Delayed allergies include bacterial (tuberculin) allergies, contact dermatitis, transplant rejection reactions, autoallergic reactions and diseases, etc.

Bacterial allergy. This type of reaction was first described in 1890 by Robert Koch in patients with tuberculosis when they were injected subcutaneously with tuberculin. Tuberculin is a filtrate of a broth culture of the tuberculosis bacillus. Persons who do not have tuberculosis give a negative reaction to tuberculin. In patients with tuberculosis, after 6-12 hours, redness appears at the site of tuberculin injection, it increases, swelling and induration appear. After 24-48 hours the reaction reaches its maximum. With a particularly strong reaction, even skin necrosis is possible. When injecting small doses of allergen, there is no necrosis.

The reaction to tuberculin was the first allergic reaction studied in detail, so sometimes all types of delayed-type allergic reactions are called “tuberculin allergy.” Slow allergic reactions can also occur with other infections - diphtheria, scarlet fever, brucellosis, coccal, viral, fungal diseases, with preventive and therapeutic vaccinations, etc.

In the clinic, delayed-type skin allergic reactions are used to determine the degree of sensitization of the body in infectious diseases - the Pirquet and Mantoux reactions in tuberculosis, the Burnet reaction in brucellosis, etc.

Slow allergic reactions in a sensitized organism can occur not only in the skin, but also in other organs and tissues, for example, in the cornea, bronchi, and parenchymal organs.

In experiments, tuberculin allergy is easily obtained in guinea pigs sensitized with the BCG vaccine.

When tuberculin is injected into the skin of such pigs, they develop, like humans, a delayed-type allergic skin reaction. Histologically, the reaction is characterized by inflammation with infiltration of lymphocytes. Giant multinucleated cells, clear cells, and histiocyte derivatives - epithelioid cells are also formed.

When tuberculin is introduced into the blood of a sensitized pig, it develops tuberculin shock.

Contact allergy called a skin reaction (contact dermatitis), which occurs as a result of prolonged contact of various chemicals with the skin.

Contact allergies most often occur to low molecular weight substances of organic and inorganic origin that have the ability to combine with skin proteins: various chemicals (phenols, picrylic acid, dinitrochlorobenzene, etc.). paints (ursol and its derivatives), metals (compounds of platinum, cobalt, nickel), detergents, cosmetics, etc. In the skin they combine with proteins (procollagens) and acquire allergenic properties. The ability to combine with proteins is directly proportional to the allergenic activity of these substances. With contact dermatitis, the inflammatory reaction develops mainly in the superficial layers of the skin - infiltration of the skin with mononuclear leukocytes, degeneration and detachment of the epidermis occurs.

Transplant rejection reactions. As is known, true engraftment of transplanted tissue or organ is possible only with autotransplantation or syngeneic transplantation (isotransplantation) in identical twins and inbred animals. In cases of transplantation of genetically foreign tissue, the transplanted tissue or organ is rejected. Graft rejection is the result of a delayed allergic reaction (see § 98-100).

§ 97. Autoallergy

Delayed allergic reactions include a large group of reactions and diseases that occur as a result of damage to cells and tissues by autoallergens, i.e., allergens that arise in the body itself. This condition is called autoallergy and characterizes the body's ability to react to its own proteins.

Usually the body has a device with the help of which immunological mechanisms distinguish its own proteins from foreign ones. Normally, the body has tolerance (resistance) to its own proteins and body components, that is, antibodies and sensitized lymphocytes are not formed against its own proteins, and therefore its own tissues are not damaged. It is assumed that inhibition of the immune response to one’s own autoantigens is carried out by suppressor T-lymphocytes. A hereditary defect in the functioning of T-suppressors leads to the fact that sensitized lymphocytes damage the tissues of their own host, i.e., an autoallergic reaction occurs. If these processes become sufficiently pronounced, then the autoallergic reaction turns into an autoallergic disease.

Due to the fact that tissues are damaged by their own immune mechanisms, autoallergy is also called autoaggression, and autoallergic diseases are called autoimmune diseases. Sometimes both are called immunopathology. However, the last term is unfortunate and should not be used as a synonym for autoallergy, because immunopathology is a very broad concept and, in addition to autoallergy, it also includes:

• immunodeficiency diseases, i.e. diseases associated either with a loss of the ability to form any immunoglobulins and antibodies associated with these immunoglobulins, or with a loss of the ability to form sensitized lymphocytes;
• immunoproliferative diseases, i.e. diseases associated with excessive formation of any class of immunoglobulins.

Autoallergic diseases include: systemic lupus erythematosus, some types of hemolytic anemia, myasthenia gravis (a pseudoparalytic form of muscle weakness), rheumatoid arthritis, glomerulonephritis, Hashimoto's thyroiditis and a number of other diseases.

Autoallergic syndromes, which are associated with diseases with a non-allergic mechanism of development and complicate them, should be distinguished from autoallergic diseases. These syndromes include: post-infarction syndrome (formation of autoantibodies to the area of ​​the myocardium that died during the infarction, and their damage to healthy areas of the heart muscle), acute liver dystrophy due to infectious hepatitis - Botkin's disease (formation of autoantibodies to liver cells), autoallergic syndromes in burns, radiation illness and some other diseases.

Mechanisms of formation of autoallergens. The main question when studying the mechanisms of autoallergic reactions is the question of the ways of formation of autoallergens. There are at least 3 possible ways of forming autoallergens:

1. Autoallergens are contained in the body as a normal component. They are called natural (primary) autoallergens (A.D. Ado). These include some proteins of normal tissues of the nervous system (the main protein), lens, testicles, thyroid colloid, and retina. Due to the peculiarities of embryogenesis, some proteins of these organs are perceived by immunocompetent cells (lymphocytes) as foreign. However, under normal conditions these proteins are positioned so that they do not come into contact with lymphoid cells. Therefore, the autoallergic process does not develop. Violation of the isolation of these autoallergens can lead to the fact that they come into contact with lymphoid cells, as a result of which autoantibodies and sensitized lymphocytes will begin to form, which will cause damage to the corresponding organ. A hereditary defect in suppressor T lymphocytes is also important.

   This process can be schematically represented using the example of the development of thyroiditis. There are three autoallergens in the thyroid gland - in epithelial cells, in the microsomal fraction and in the colloid of the gland. Normally, in the cell of the follicular epithelium of the thyroid gland, thyroxine is separated from thyroglobulin, after which thyroxine enters the blood capillary. The thyroglobulin itself remains in the follicle and does not enter the circulatory system. When the thyroid gland is damaged (infection, inflammation, trauma), thyroglobulin leaves the thyroid follicle and enters the blood. This leads to stimulation of immune mechanisms and the formation of autoantibodies and sensitized lymphocytes, which cause damage to the thyroid gland and a new entry of thyroglobulin into the blood. So the process of damage to the thyroid gland becomes wave-like and continuous.

   It is believed that the same mechanism underlies the development of sympathetic ophthalmia, when, after an injury to one eye, an inflammatory process develops in the tissues of the other eye. By this mechanism, orchitis can develop - inflammation of one testicle after damage to the other.

2. Autoallergens do not pre-exist in the body, but are formed in it as a result of infectious or non-infectious tissue damage. They are called acquired or secondary autoallergens (A.D. Ado).

   Such autoallergens include, for example, protein denaturation products. It has been established that blood and tissue proteins under various pathological conditions acquire allergenic properties that are foreign to the body of their carrier and become autoallergens. They are found in burn and radiation sickness, dystrophy and necrosis. In all these cases, changes occur to the proteins that make them foreign to the body.

   Autoallergens can form as a result of the combination of drugs and chemicals that enter the body with tissue proteins. In this case, the foreign substance that has entered into a complex with the protein usually plays the role of a hapten.

   Complex autoallergens are formed in the body as a result of the combination of bacterial toxins and other products of infectious origin that have entered the body with tissue proteins. Such complex autoallergens can, for example, be formed by the combination of some components of streptococcus with proteins of myocardial connective tissue, or by the interaction of viruses with tissue cells.

   In all these cases, the essence of autoallergic restructuring is that unusual proteins appear in the body, which are perceived by immunocompetent cells as “not their own”, foreign and therefore stimulate them to produce antibodies and the formation of sensitized T-lymphocytes.

   Burnet's conjecture explains the formation of autoantibodies by derepression in the genome of some immunocompetent cells capable of producing antibodies to their own tissues. As a result, a “forbidden clone” of cells appears that carry antibodies on their surface that are complementary to the antigens of their own undamaged cells.

3. Proteins of some tissues may be autoallergens due to the presence of common antigens with certain bacteria. In the process of adaptation to existence in a macroorganism, many microbes have acquired antigens that are common to the host's antigens. This slowed down the activation of immunological defense mechanisms against such microflora, since there is immunological tolerance in the body towards its own antigens and such microbial antigens were accepted as “one’s own”. However, due to some differences in the structure of common antigens, immunological mechanisms of protection against microflora were activated, which simultaneously led to damage to one’s own tissues. It is assumed that a similar mechanism is involved in the development of rheumatism due to the presence of common antigens in some strains of group A streptococcus and heart tissue; ulcerative colitis due to common antigens in the intestinal mucosa and certain strains of Escherichia coli.

   In the blood serum of patients with an infectious-allergic form of bronchial asthma, antibodies were found that react both with antigens of the bronchial microflora (Neisseria, Klebsiella) and with lung tissue.