Chapter 3

On the model of experimental anaphylaxis and anaphylactic shock, the main regularities in the development of allergic reactions of the immediate type were revealed, in the development of which three successive stages are distinguished (A. D. Ado): 1) the stage of immune reactions; 2) the stage of pathochemical disorders; 3) the stage of pathophysiological disorders.

§ 88. Stage of immune reactions

The stage of immune reactions is characterized by the accumulation in the body of antibodies specific for this allergen.

The most typical allergic antibodies - reagins (also called "skin-sensitizing antibodies" for their ability to be fixed in the skin) belong to immunoglobulins E. They are easily fixed on cells of various tissues and therefore are called "cytophilic". They are thermolabile - they are destroyed when heated to 56°C. The allergen binds to the antibody predominantly on the cell surface. The reaction proceeds without the participation of complement (Fig. 11.1). This mechanism takes place in atopic human diseases, anaphylactic reactions. In addition to IgE, antibodies belonging to the IgG class are involved in allergic reactions.

Antibodies belonging to the IgG class form complexes with the allergen (Ag + Ab) in biological fluids (blood, lymph, intercellular fluid). If the complex is formed in excess of the antigen, then it is usually deposited in the vascular wall. The resulting Ag + Ab complex can fix the complement on itself. Complement components (C3, etc.) have a pronounced chemotactic effect, i.e., the ability to attract neutrophils. The latter phagocytize the complex and secrete lysosomal enzymes (proteases) that destroy collagen and elastic fibers and increase vascular permeability. Thrombi form inside blood vessels. This type of reaction occurs in the Arthus Phenomenon and serum sickness (see Fig. 11.II).

Another way of cell damage by the immune complex Ag + Ab is possible. In this case, the allergen (for example, an antibiotic) is fixed on the cells (on leukocytes and erythrocytes). Circulating antibodies form a complex with the allergen fixed on the cell surface and damage the cell (see Fig. 11. III). And in this case, the reaction proceeds with the participation of complement. Such a mechanism is possible with manifestations of drug allergies.

§ 89. Stage of pathochemical changes

If a specific allergen re-enters a sensitized (i.e., containing allergic antibodies) organism, then a physicochemical reaction occurs between the antibody and the allergen and a macromolecular immune complex is formed, consisting of the allergen and the antibody. Fixing in the tissues, the immune complex causes a number of metabolic changes. So, the amount of oxygen absorbed by the tissues changes, it first increases, then decreases, proteolytic and lipolytic enzymes are activated, etc., which leads to dysfunction of the corresponding cells. For example, a consequence of damage to connective tissue mast cells, blood leukocytes (especially basophils) is the release of histamine, serotonin and some other biologically active substances, allergy mediators.

§ 90. Mediators of allergic reactions

• Histamine. In humans and animals, histamine is found in mast cells of the connective tissue, blood basophils, to a lesser extent in neutrophilic leukocytes, in smooth and transverse striated muscles, liver cells, epithelium of the gastrointestinal tract, etc.

  The participation of histamine in the mechanism of allergy is expressed in the fact that it causes spasm of smooth muscles (for example, bronchioles, uterus, intestines, etc.) and increases the permeability of blood capillaries, causing edema, urticaria, petechiae, etc. In addition, histamine increases the hydrophilicity of loose fibers connective tissue, contributing to the binding of water in the tissues and the occurrence of extensive edema such as Quincke's edema.

  Histamine is involved in the mechanisms of such allergic reactions in humans as itching, urticaria, short-term hypotension. Hypotensive reactions such as collapses (or shock) are also due to the participation of kinins (bradykinin), and persistent bronchospasm (with bronchial asthma) is due to the action of a slowly reacting substance (MRSA) on the bronchial tree.

• Slow reacting allergy substance (MRSA) is an unsaturated fatty acid containing sulfur with a molecular weight of 300-500 daltons. MRSA is formed in mast cells under the influence of allergen exposure. It is destroyed by the enzyme arylphosphatase, which is formed in eosinophils. This substance causes a slow contraction of smooth muscle organs, as opposed to the rapid contraction due to histamine. MRSA causes spasm of human bronchioles, its activity is not suppressed by antihistamines and proteolytic enzymes.
• Serotonin (5-hydroxytryptamine). Information about the participation of serotonin in allergic reactions is rather contradictory. In animal experiments, it has been found to cause bronchospasm in guinea pigs, cats, and rats. In rats and mice, serotonin is released from mast cells under the influence of egg white, dextran, and some other substances. There is a sharp swelling of the muzzle, paws, testicles - an anaphylactoid reaction.

  In human allergic reactions, serotonin is not essential.

• The chemotaxis factor for eosinophils is a peptide with a molecular weight of 500, released from the lungs, smooth muscle organs, mast cells under the influence of an allergen and IgE antibodies in immediate allergic reactions. The release of this factor; occurs simultaneously and in parallel with the release of histamine and the slow-reacting substance (MRSA) of allergy.
• Bradykinin is a polypeptide consisting of 9 amino acids. Participation of bradykinin in the pathogenesis of allergic reactions is determined by the fact that it expands blood capillaries, increases their permeability, lowers the tone of arterioles and lowers blood pressure.
• Acetylcholine - participates in the mechanism of allergic reactions mainly in those organs and tissues where cholinergic processes are directly involved in normal (physiological) processes (for example, in synapses of the autonomic and central nervous systems, in the nerves of the heart, intestines, etc.). In the process of sensitization, the activity of tissue and blood cholinesterase changes, and with the permissive introduction of the allergen, the release of acetylcholine from the tissues increases.
• Prostaglandins E 1 , E 2 - are involved in the mechanisms of allergic reactions - bronchospasm, mast cell lysis, release of mediators.

§ 91. Mechanisms for the release of mediators of allergy of the immediate type

The release of mediators from the cell during allergies is a complex energy-dependent process. Different mediators are released in different parts of the cell. A slowly reacting substance is released from the phospholipids of cell membranes. Histamine, serotonin, heparin and eosinophil chemotaxis factor - from mast cell granules. Acetylcholine is released from the vesicles of the synaptic structures of nerve cells.

Attachment of the allergen to immunoglobulin E on the surface of mast cells first causes an excitatory effect, the end result of which is the release of the mediators of the allergic reaction contained in the mast cell granules. The release of mediators by mast cells is a complex energy-consuming process in the presence of calcium ions.

The amount of released mediators strongly depends on the content of cyclic-3, 5 "-monophosphate (cAMP) in mast cells. An increase in the content of cAMP in mast cells inhibits their release of histamine. The morphological reflection of histamine release is mast cell degranulation (Fig. 12).

Acetylcholine also causes the release of histamine, but this process is not accompanied by changes in cAMP metabolism.

Prostaglandin E activates adenylcyclase, causes the accumulation of cAMP and inhibits the release of histamine from cells.

§ 92. Stage of pathophysiological changes

The pathophysiological stage of allergic reactions is the final expression of those immune and pathochemical processes that took place after the introduction of a specific allergen into the sensitized organism. It consists of the reaction of allergen-damaged cells, tissues, organs and the body as a whole.

Allergic damage to individual cells has been well studied on the example of blood cells (erythrocytes, leukocytes, platelets), connective tissue (histocytes, mast cells, etc.). Damage extends to nerve, smooth muscle cells, heart muscle, etc.

The response of each of the damaged cells is determined by its physiological characteristics. Thus, processes of excitation and inhibition occur in the nerve cell, contracture in the myofibrils of smooth muscles, exudation and emigration increase in the capillaries, granular leukocytes (basophils, etc.) and mast cells swell and throw out their granules - cell degranulation occurs.

Allergic damage to tissues and organs occurs as a result of damage to the cells that make up this tissue, on the one hand, and as a result of a violation of the nervous and humoral regulation of the functions of these organs, on the other. For example, contracture of the smooth muscles of the small bronchi gives bronchospasm and a decrease in the lumen of the airways. However, a change in the excitability of the respiratory center and sensitive nerve endings is also involved in the complex mechanism of the disorder of the act of breathing in bronchial asthma and the occurrence of expiratory dyspnea. There is an intense secretion of mucus that clogs the lumen of the bronchioles, the expansion of the capillaries braiding the alveoli, and the increase in the permeability of the walls of the capillaries.

Introduction

Immediate allergic reactions are IgE-mediated immune responses that cause damage to 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. Now both IgE themselves and their role in diseases caused by immediate allergic reactions are well studied. An allergic reaction of an immediate type goes through a series of stages: 1) contact with an antigen; 2) IgE synthesis; 3) fixation of IgE on the surface of mast cells; 4) repeated contact with the same antigen; 5) antigen binding 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.

The pathogenesis of immediate 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 such a substance. According to molecular weight and immunogenicity, antigens are divided into two groups: complete antigens and haptens.

• 1. Complete antigens, for example, antigens of pollen, epidermis and animal serum, hormone extracts, themselves induce an immune response and IgE synthesis. The basis of a complete antigen is a polypeptide chain. Its parts recognized by B-lymphocytes are called antigenic determinants. During processing, the polypeptide chain is cleaved into low molecular weight fragments, which are combined with HLA class II antigens and, in this form, are transferred to the surface of the macrophage. When fragments of the processed antigen are recognized in combination with HLA class II antigens and under the action of cytokines produced by macrophages, T-lymphocytes are activated. Antigenic determinants, as already mentioned, are recognized by B-lymphocytes, which begin to differentiate and produce IgE under the action of activated T-lymphocytes.
• 2. Gaptens 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 total antigens and haptens are important in the diagnosis of allergic diseases. Thus, total antigens can be determined and used as diagnostic preparations for skin allergy tests. It is practically impossible to determine the hapten and make a diagnostic preparation on its basis, 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 endogenous carrier protein form mainly metabolites.

B. Antibodies. Synthesis of IgE 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 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 strongly to receptors for the Fc fragment on the surface of mast cells and persists here for up to 6 weeks. IgG also binds to the surface of mast cells, but they remain bound to receptors for no more than 12–24 hours. 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 an antigen can lead to a general activation of mast cells and an anaphylactic reaction.

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

v. Since IgE does not cross the placenta, passive transfer to the fetus of sensitization is not possible. Another important property of IgE is that, in combination with an antigen, it activates complement through an alternative pathway (see Fig. 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 vessels. IgE binds to mast cell receptors for the Fc fragment of epsilon chains. On the surface of the mast cell simultaneously present IgE directed against different antigens. One mast cell can contain from 5,000 to 500,000 IgE molecules. The mast cells of allergic patients carry more IgE molecules than the mast cells of healthy ones. The number of IgE molecules associated with 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 action 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 section 4.4). ch. 4, pp. VI--XXIII).
• 3. In case of 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-type allergic reactions (see. tab. 2.1 and rice. 1.6 ). Mast cell mediators act on blood vessels and smooth muscles, exhibit chemotactic and enzymatic activity. In addition to inflammatory mediators, oxygen radicals are formed in mast cells, which also play a role in the pathogenesis of allergic reactions.
• 4. Mechanisms for the release of mediators. Mast cell activators are divided into IgE-dependent (antigens) and IgE-independent. IgE-independent mast cell activators include muscle relaxants, opioids, radiopaque agents, anaphylatoxins (C3a, C4a, C5a), neuropeptides (eg, substance P), ATP, interleukins-1, -3. Mast cells can also be activated under the influence of 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 ), so antigens that carry a single antibody binding site do not activate mast cells. The formation of a complex between an antigen and several IgE molecules on the mast cell surface activates membrane-bound enzymes, including phospholipase C, methyltransferases, and adenylate cyclase. rice. 2.2 ). Phospholipase C catalyzes the hydrolysis of phosphatidylinositol-4,5-diphosphate to form inositol-1,4,5-triphosphate and 1,2-diacylglycerol. Inositol-1,4,5-triphosphate causes the accumulation of calcium inside the 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 action of which arachidonic acid and lysophosphatidylcholine are formed from phosphatidylcholine. With an increase in the concentration of 1,2-diacylglycerol, lipoprotein lipase is activated, which cleaves 1,2-diacylglycerol to form monoacylglycerol and lysophosphatidic acid. Monoacylglycerol, 1,2-diacylglycerol, lysophosphatidylcholine and lysophosphatidyl 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-agonists and cGMP, on the contrary, increase 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 action of corticosteroids and cromolyn not fully explored. It is shown that the action cromolyn is not mediated by cAMP and cGMP, and the effect of corticosteroids may be due to an increase in the 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 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: mediators of granules and mediators synthesized upon activation of mast cells (see Fig. tab. 2.1 ).

1. Mast cell granule mediators

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 of histamine action 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 serum depends mainly on its content in basophils and has no diagnostic value. By the level of histamine in the serum, one can only judge 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 the smooth muscles of the bronchi and gastrointestinal tract, increased vascular permeability, increased secretory activity of the glands of the nasal mucosa, vasodilation of the skin 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 s / c 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 the regulation of the immune response because H 2 receptors are present on cytotoxic T lymphocytes and basophils. By binding to the H 2 receptors of basophils, histamine inhibits the degranulation of these cells. Acting on different organs and tissues, histamine causes the following effects.

• 1) Contraction of the smooth muscles of the bronchi. Under the action of histamine, the vessels of the lungs expand and their permeability increases, which leads to mucosal edema and an even greater narrowing of the bronchial lumen.
• 2) Expansion of small and narrowing of large vessels. Histamine increases the permeability of capillaries and venules, therefore, when administered intradermally, hyperemia and a blister occur at the injection site. If vascular changes are systemic, arterial hypotension, urticaria and Quincke's edema are possible. The most pronounced changes (hyperemia, edema and secretion of mucus) histamine causes in the nasal mucosa.
• 3) Stimulation of the secretory activity of the glands of the mucous membrane of the stomach and respiratory tract.
• 4) Stimulation of the smooth muscles of the intestine. This is manifested by diarrhea and is often observed in 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 basement membrane of blood vessels and the release of blood cells into tissues; 2) increased vascular permeability; 3) destruction of cell fragments; 4) activation of growth factors involved in wound healing. Tryptase remains in the blood for a long time. It can be found in the serum of patients with systemic mastocytosis and patients who have had an anaphylactic reaction. Determination of serum tryptase activity is used in the diagnosis of anaphylactic reactions. During degranulation of mast cells, other enzymes are also released - 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 and neutral protease molecules, limiting their diffusion and inactivation after release from the granules.

d. Chemotaxis factors. Degranulation of mast cells leads to the release of chemotaxis factors that cause directed migration of inflammatory cells - eosinophils, neutrophils, macrophages and lymphocytes. The migration of eosinophils is caused by anaphylactic eosinophil chemotaxis factor and platelet activating factor (see. ch. 2, P. I.D.2.b) is the most powerful known eosinophil chemotaxis factor. In patients with atopic diseases, contact with allergens leads to the appearance in the serum of anaphylactic neutrophil chemotaxis factor (molecular weight of about 600). It is assumed that this protein is also produced by mast cells. Immediate-type allergic reactions also release other mediators from mast cells that cause targeted migration of neutrophils, such as high molecular weight neutrophil chemotaxis factor and leukotriene B4. Neutrophils attracted to the site of inflammation produce oxygen free radicals that cause tissue damage.

2. Mediators synthesized upon activation of mast cells

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

• 1) Prostaglandins. Prostaglandin D 2 appears first among those playing a role in immediate allergic reactions and inflammation of the products of oxidation of arachidonic acid along the cyclooxygenase pathway. It is formed mainly in mast cells and is not synthesized in basophils. The appearance of prostaglandin D 2 in serum indicates degranulation and the development of an early phase of an allergic reaction of an immediate type. Intradermal administration of prostaglandin D 2 causes vasodilation and an increase in their permeability, which leads to persistent hyperemia and blistering, as well as to the release of leukocytes, lymphocytes and monocytes from the vascular bed. Inhalation of prostaglandin D 2 causes bronchospasm, which indicates the important role of this metabolite of arachidonic acid in the pathogenesis of anaphylactic reactions and systemic mastocytosis. The synthesis of other products of the cyclooxygenase pathway - prostaglandins F 2alpha, E 2, I 2 and thromboxane A 2 - is carried out by enzymes specific for 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 is converted by 5-lipoxygenase 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. This is the main factor in the activation and chemotaxis of leukocytes in allergic reactions of the immediate type. Leukotrienes C 4 , D 4 , and E 4 were formerly lumped together under the name "slow-reacting anaphylactic substance" because their release leads to slowly progressive, sustained contraction of bronchial and gastrointestinal smooth muscle. 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 concentration. Unlike histamine, which acts predominantly on the small bronchi, leukotrienes also act on the 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. Developed and successfully used for the treatment of bronchial asthma blockers of leukotriene receptors -- 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 wheal (histamine causes the same effect in 1000 times greater concentration), eosinophilic and neutrophilic infiltration of the skin. Inhalation of platelet activating factor causes severe bronchospasm, eosinophilic infiltration of the respiratory mucosa, and an increase in bronchial reactivity, which may 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 on their basis. The role of platelet activating factor in the pathogenesis of immediate-type allergic reactions also lies in the fact 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.D.3.b).

3. Other inflammatory mediators

a. Adenosine is released when mast cells degranulate. In patients with exogenous bronchial asthma after contact with the allergen, the level of adenosine in the serum increases. Three types of adenosine receptors have been described. Binding of adenosine to these receptors leads to an increase in cAMP levels. These receptors can be blocked with 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, and stimulates the formation of mucus in the respiratory tract and gastrointestinal tract.

v. Serotonin is also an inflammatory mediator. The role of serotonin in allergic reactions of the immediate type 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 allergic reactions. Complement activation is possible both by the alternative - by complexes of IgE with the antigen, - and by the classical way - by 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.

Allergic reactions manifest themselves with different symptoms, and can affect both one or several systems of the human body.

The variety of forms of allergy is explained by the type of hypersensitivity and the characteristics of allergens.

Currently, there are 4 types of allergic reactions, each of which has its own mechanism of development, and is manifested by certain clinical manifestations.

The human immune system and allergies, what is the connection?

The human immune system performs one of the most important functions - it ensures the cellular and macromolecular constancy of the body, protecting it at any time of life from everything alien.

The organs of the immune system also destroy atypical cells that have appeared in the body as a result of various pathological processes.

The human immune system is complex and consists of:

• Individual organs - the spleen and thymus;
• Islands of lymphoid tissue located in different parts of the body. Lymph nodes, intestinal nodes, lymphoid ring of the pharynx consist of lymphoid tissue;
• Blood cells - lymphocytes and special protein molecules - antibodies.

Each link of immunity does its job. Some organs and cells recognize antigens, others remember their structure, others contribute to the production of antibodies necessary to neutralize foreign structures.

Physiologically, any antigen in the body during the first penetration into the body leads to the fact that the immune system remembers its structure, analyzes it, remembers and produces antibodies that are stored in the blood plasma for a long time.

The next time the antigen arrives, the pre-accumulated antibodies quickly neutralize it, which prevents the development of diseases.

In addition to antibodies, T-lymphocytes take part in the body's immune response; they secrete enzymes endowed with antigen-destroying properties.

An allergic reaction occurs according to the type of immune system response to antigens, but such a reaction goes through a pathological path of development.

The human body is almost constantly affected by hundreds of different substances. They enter through the respiratory and digestive systems, some penetrate the skin.

Most of these substances are not perceived by the immune system, that is, there is refractoriness to them from birth.

An allergy is said to be a hypersensitivity to one or more substances. This causes the immune system to start the allergic response cycle.

An exact answer about the causes of changes in immunity, that is, about the causes of allergies, has not yet been received. An increase in the number of sensitized people has been noted in recent decades.

Allergists attribute this fact to the fact that modern man very often encounters new irritants for him, most of which are obtained artificially.

Synthetic materials, dyes, cosmetics and perfumes, medicines and dietary supplements, preservatives, various flavor enhancers - all these are structures alien to the immune system, for which a huge amount of antigens is produced.

Many scientists attribute the development of allergies to the fact that the human body is subjected to overload.

Antigenic saturation of the organs of the immune system, congenital features in the structure of some body systems, chronic pathologies and infectious diseases, stress and helminthiases are provocateurs of a malfunction in the immune system, which can become the main cause of allergies.

The above mechanism for the development of allergies applies only to exoallergens, that is, external stimuli. But there are also endoallergens, that is, they are produced inside the body.

In humans, a number of structures do not naturally interact with the immune system, this ensures their normal functioning. An example is the lens of the eye.

But with an infectious lesion or injury, the natural isolation of the lens is disrupted, the immune system perceives the new object as foreign and begins to react to it by producing antibodies. This gives impetus to the development of certain diseases.

Endoallergens are often produced when the structure of normal tissue changes at the cellular level due to frostbite, burns, radiation or infection. The pathologically altered structure becomes alien to the immune system, which leads to the launch of an allergy.

All allergic reactions have a single mechanism of development, consisting of several stages:

• IMMUNOLOGICAL STAGE. It is characterized by the first penetration of the antigen into the body, in response to this, the immune system begins to produce antibodies. This process is called sensitization. Antibodies are formed after a certain period of time, during which antigens can already leave the body, which is why an allergic reaction most often does not develop at the first contact of a person with an allergen. But it inevitably arises during subsequent penetrations of antigens. Antibodies begin to attack antigens, which leads to the formation of antigen-antibody complexes.


• PATHOCHEMICAL STAGE. Antigen-antibody complexes begin to act on the so-called mast cells, damaging their membrane. Mast cells contain granules, which are a depot for inflammatory mediators in an inactive stage. These include bradykinin, histamine, serotonin and a number of others. Damage to mast cells leads to the activation of inflammatory mediators, which, due to this, enter the general circulation.
• PATHOPHYSIOLOGICAL STAGE - the result of the influence of inflammatory mediators on tissues and organs. Allergy symptoms develop - capillaries expand, a rash forms on the body, a large amount of mucus and gastric secretions form, swelling and bronchospasm appear.

Between the immunological and pathochemical stages, the time interval can consist of both minutes and hours, as well as months and years.

The pathochemical stage can develop very quickly. In this case, all manifestations of allergies occur abruptly.

Classification of allergic reactions by type (according to Gell and Coombs)

In medicine, the division of allergic reactions into 4 types is used. Between themselves, they differ in the mechanism of development and the clinical picture.

A similar classification was developed by Coombs, Gell in 1964.

Allocate:

1. The first type is anaphylactic or reaginic reactions;
2. The second type is cytolytic reactions;
3. The third type is immunocomplex reactions;
4. The fourth type is cell-mediated reactions.

Each type of allergic reactions has its own mechanism of development and certain clinical manifestations. Different types of allergies occur both in pure form and combined with each other in any way.

Allergic reaction type 1

The first type of allergic reaction occurs when antibodies from groups E (IgE) and G (IgG) interact with antigens.

The resulting complexes settle on the membranes of mast cells and basophils, which in turn leads to the release of biologically active substances - inflammatory mediators.

Their effect on the body causes clinical manifestations of allergies.

The time of occurrence of anaphylactic reactions of the first type takes several minutes or several hours after the allergen enters the body.

The main components of a type 1 hypersensitivity reaction are allergens (antigens), reagins, basophils, and mast cells.

Each of these components performs its function in the occurrence of allergic reactions.

Allergens.

In most cases, microparticles of plants, proteins, products, animal saliva protein, medicines, spores of various types of fungi and a number of other organic substances act as provocateurs for the occurrence of anaphylactic reactions.

Ongoing research has not yet allowed to fully find out what physical and chemical properties affect the allergenicity of a particular substance.

But it has been precisely established that almost all allergens coincide with antigens in 4 characteristics, these are:

• Antigenicity;
• Specificity;
• Immunogenicity;
• Valence.

The study of the most famous allergens made it possible to understand that they all represent a multi-antigenic system with several allergenic components.

So in the pollen of flowering ragweed, 3 types of components were found:

• Fraction without allergenic properties, but with the possibility of activating the production of antibodies from the IgE class;
• Fraction with allergenic characteristics and the function of activating IgE antibodies;
• Fraction without the properties of inducing antibody formation and without reacting to the products of immune reactions.

Some allergens, such as egg white, sera foreign to the body, are the strongest antigens, and some are weak.

The antigenicity and immunogenicity of a substance do not affect the degree of its allergenicity.

It is believed that the allergenicity of any irritant is determined by several factors, these are:

• The physico-chemical origin of the allergen, that is, is it a protein, polysaccharide or molecular weight.
• The amount of irritant affecting the body (dose).
• Where the allergen enters the body.
• sensitivity to catabolism.
• Adjuvant, that is, enhancing the immune response, properties.
• Constitutional characteristics of the organism.
• Immunoreactivity of the body and the physiological ability of the processes of immunoregulation.

It has been established that atopic diseases are inherited. In persons prone to atopy, a high rate of IgE class antibodies circulating in the blood was detected and the number of eosinophils was increased.

The antibodies responsible for type 1 hypersensitivity belong to the IgE and IgG4 classes.

Reagins have a classical structure, represented by two similar polypeptide light chains and two similar heavy chains. The chains are linked to each other by disulfide bridges.

The level of IgE in healthy people in serum does not exceed 0.4 mg / l. With the development of allergies, their level increases significantly.

IgE antibodies are highly cytophilic to basophils and mast cells.

The half-life and subsequent elimination of IgE from the body is 2-3 days, if they bind to basophils and mast cells, then this period reaches several weeks.

Basophils and mast cells.

Basophils are 0.5% -1.0% of all white cells circulating in the blood. Basophils are characterized by the presence of a large number of electron-dense granules containing biologically active substances.

Mast cells are the structural unit of almost all organs and tissues.

The highest concentration of mast cells is found in the skin, mucous membranes of the digestive and respiratory tracts, and around the blood and lymph vessels.

In the cytoplasm of these cells are granules with biologically active substances.

Basophils and mast cells are activated when an antibody-antigen complex occurs. Which in turn leads to the release of inflammatory mediators responsible for all the symptoms of allergic reactions.

Mediators of allergic reactions.

All mediators released from mast cells are divided into primary and secondary.

Primary ones are formed even before degranulation and they are in granules. The most significant of them in the development of allergies are histamine, chemotaxins of neutrophils and eosinophils, serotonin, proteases, heparin.

Secondary mediators begin to form after the cells are subjected to antigenic activation.

Secondary mediators include:

• Leukotrienes;
• Platelet activating factor;
• Prostaglandins;
• Bradykinins;
• Cytokines.

The concentration of secondary and primary inflammatory mediators in the anatomical zones and tissues is not the same.

Each of the mediators performs its function in the development of allergic reactions:

• Histamine and serotonin increase the permeability of the vascular walls, contract smooth muscles.
• Neutrophil and eosinophil chemotaxins stimulate each other's production.
• Proteases activate the production of mucus in the bronchial tree, causing degradation of the basement membrane in the blood vessels.
• Platelet activating factor leads to aggregation and degranulation of platelets, increase the contraction of the smooth muscles of lung tissue.
• Prostaglandins increase the contractility of the muscles of the lungs, cause platelet adhesion and vasodilation.
• Leukotrienes and bradykinins increase the permeability of the walls of blood vessels and contraction of the muscles of the lungs. These effects last much longer than those caused by histamine and serotonin.
• Cytokines are involved in the occurrence of systemic anaphylaxis, cause symptoms that occur during inflammation. A number of cytokines support inflammation occurring at the local level.

Anaphylactic (reaginic) hypersensitivity reactions cause the development of a fairly large group of allergies, these are:

• Atopic bronchial asthma;
• Hives;
• allergic rhinitis;
• Pollinosis;
• Anaphylactic shock;
• Eczema;
• food allergy.

The first type of allergic reactions is more typical for children.

The second type of allergic reactions

Cytotoxic reactions develop during the interaction of IgM or IgG with an antigen that is located on the cell membrane.

This causes the activation of the complement system, that is, the body's immune response. Which in turn leads to damage to the membranes of unaltered cells, this causes their destruction - lysis.

Cytological reactions are typical for:

• Drug allergies occurring in the form of thrombocytopenia, leukocytopenia, hemolytic anemia.
• Hemolytic disease of the newborn;
• Hemotransfusion reactions according to the type of allergy;
• autoimmune thyroiditis;
• Nephrotoxic nephritis.

Diagnosis of reactions of the second type is based on the detection in the blood serum of cytotoxic antibodies belonging to the class IgM and IgG1-3.

The third type of allergic reactions

Immunocomplex reactions are caused by immune complexes (IC) formed during the interaction of an antigen (AG) with specific antibodies (AT).

The formation of immune complexes leads to their capture by phagocytes and to the elimination of the antigen.

This usually occurs with large immune complexes that are formed when there is an excess of AT relative to AG.

Immune complexes with small sizes, formed at an elevated level of AH, are phagocytosed weakly and lead to immunopathological processes.

Excess antigen occurs in chronic infections, after prolonged contact with external antigens, if the body is subjected to constant autoimmunization.

The severity of the reaction caused by immune complexes depends on the amount of these complexes and their level of deposition in the tissues.

Immune complexes can be deposited in the walls of blood vessels, in the basement membrane of the glomeruli of the kidney, in the synovial bag of the articular surfaces, in the brain.

A type 3 hypersensitivity reaction causes inflammation and degenerative-dystrophic changes in the tissue affected by immune complexes.

The most common diseases caused by the third type of allergic reaction:

• Rheumatoid arthritis;
• Glomerulonephritis;
• Allergic alveolitis;
• Multiform exudative erythema;
• Certain types of drug allergies. Most often, the culprits of this type of hypersensitivity are sulfonamides and penicillin.

Immunocomplex reactions accompany the development of meningitis, malaria, hepatitis, and helminthiasis.

Type 3 hypersensitivity reactions go through several stages of their development.

After the precipitation of immune complexes, the complement system is bound and activated.

The result of this process is the formation of certain anaphylatoxins, which in turn cause degranulation of mast cells with the release of inflammatory mediators.

Histamines and other biologically active substances increase the permeability of the vascular walls and promote the release of polymorphonuclear leukocytes from the bloodstream into the tissue.

Under the influence of anaphylatoxins, neutrophils are concentrated at the site of precipitation of immune complexes.

The interaction of neutrophils and immune complexes leads to the activation of the latter and to the exo-secretion of polycationic proteins, lysosomal enzymes, and superoxide radicals.

All these elements lead to local tissue damage and stimulate the inflammatory response.

MAA, the membrane attack complex, which is formed upon activation of the complement system, also takes part in cell destruction and tissue degradation.

The whole cycle of development of allergic reactions of the third type leads to functional and structural disorders in tissues and organs.

The fourth type of allergic reactions

Cell-mediated reactions occur in response to exposure to intracellular bacteria, viruses, fungi, protozoa, tissue antigens, and a number of chemicals and drugs.

Drugs and chemicals cause the fourth type of allergic reaction, usually during antigenic modification of macromolecules and cells of the body, they eventually acquire new antigenic properties and become targets and inducers of allergic reactions.

Normally, cell-mediated reactions are an important protective property of the body that protects a person from the negative effects of protozoa and microbes in cells.

Antibody protection does not act on these pathogenic organisms, since it does not have the property of penetrating into cells.

The increase in metabolic and phagocytic activity that occurs during type 4 reactions in most cases leads to the destruction of microbes that are the cause of such an immune system response.

In those situations when the mechanism of neutralizing pathogenic forms becomes unproductive and the pathogen continues to be in the cells and acts as a constant antigenic stimulus, delayed-type hypersensitivity reactions become chronic.

The main components of a type 4 allergic reaction are T-lymphocytes and macrophages.

The penetration of a chemical substance into the skin and other organs leads to its combination with the protein structures of the skin and to the formation of macromolecules endowed with the properties of an allergen.

Subsequently, allergens are absorbed by macrophages, T-lymphocytes are activated, and their differentiation and proliferation occur.

Repeated exposure of sensitized T-lymphocytes to the same allergen causes their activation and stimulates the production of cytokines and chemokines.

Under their influence, macrophages are concentrated where the allergen is located, and their functional ability and metabolic activity are stimulated.

Macrophages begin to produce and release oxygen radicals, lytic enzymes, nitric oxide and a number of other biologically active substances into the surrounding tissue.

All these elements have a negative effect on tissues and organs, causing inflammation and a local degenerative-destructive process.

Allergic reactions related to type 4 begin to manifest clinically approximately 48-72 hours after the ingestion of the allergen.

During this period, T-lymphocytes are activated, macrophages accumulate in the place of accumulation of allergens, the allergens themselves are activated and tissue toxic elements are produced.

Cell-mediated reactions determine the development of diseases such as:

• contact dermatitis;
• Allergic conjunctivitis;
• Infectious-allergic rhinitis and bronchial asthma;
• Brucellosis;
• Tuberculosis;
• Leprosy.

This type of hypersensitivity also occurs when the transplant is rejected during organ transplantation.

IMPORTANT TO KNOW: What is allergic asthma and how to treat this disease.

What is delayed and immediate allergy?

It is customary to subdivide allergies and depending on how long it took for its development:

• Allergic reactions of the immediate type are characterized by the development of symptoms almost immediately after contact with the allergen.
• The delayed type of allergy is characterized by the appearance of symptoms not earlier than a day after contact with the irritant.

The division of allergies into these two types is, first of all, necessary for the formulation of an effective treatment regimen.

Allergy of the immediate type.

These reactions differ in that antibodies predominantly circulate in liquid biological media of the body. An allergy occurs a few minutes after repeated exposure to an allergenic substance.

After repeated contact, antigen-antibody complexes are formed in the body.

The immediate type of allergy is manifested in the first, second and partially third types of allergic reactions related to the Gell and Coombs classification.

Allergic reactions of the immediate type go through all stages of development, that is, immunological, pathochemical and pathophysical. They are distinguished by a quick transition to each other.

From the moment of contact with the irritant to the appearance of the first symptoms, it takes from 15 minutes to two to three hours. Sometimes this time takes only a few seconds.

An immediate type of allergy is most often caused by:

• medicines;
• plant pollen;
• food products;
• synthetic materials;
• Means of household chemicals;
• Animal saliva protein.

Immediate-type allergies include:

• Anaphylactic shock;
• Rhinoconjunctivitis;
• An attack of bronchial asthma;
• Urticaria;
• food allergies;
• Quincke's edema.

Conditions such as anaphylactic shock and Quincke's edema require the use of medications in the first minutes of their development.

Use antihistamines, in severe cases, hormones and anti-shock therapy.

Allergic reactions of the delayed type.

Delayed type hypersensitivity is characteristic of type 4 allergic reactions.

It develops, as a rule, two to three days after the allergen enters the body.

Antibodies do not take part in the formation of the reaction. Antigens attack sensitized lymphocytes that have already formed in the body during the first penetration of the antigen.

All inflammatory processes are caused by active substances secreted by lymphocytes.

As a result, the phagocytic reaction is activated, monocyte and macrophage chemotaxis occurs, the movement of macrophages is inhibited, and leukocytes accumulate in the area of ​​inflammation.

All this leads to a pronounced inflammatory reaction with the subsequent formation of granulomas.

Delayed allergies are often caused by:

• Fungal spores;
• Various bacteria;
• Conditionally pathogenic organisms - staphylococci and streptococci, pathogens of toxoplasmosis, tuberculosis and brucellosis;
• Serum vaccines;
• Near substances with simple chemical compounds;
• Chronic inflammatory pathologies.

For typical allergic reactions of a delayed type, a specific treatment is selected.

Some diseases are treated with drugs designed to stop systemic connective tissue pathologies. Immunosuppressants are also used.

There are several differences between immediate-type allergies and delayed-type hypersensitivity reactions:

• Immediate ones begin to appear 15-20 minutes after contact of the irritant with the sensitized tissue, delayed not earlier than a day.
• With immediate allergic reactions, antibodies circulate in the blood, with delayed ones they are not.
• In reactions with an immediate type of development, the transfer of hypersensitivity to a healthy organism along with the blood serum of an already sick person is not excluded. With a delayed type of response, the transfer of hypersensitivity is also possible, but it occurs during the transfer of leukocytes, cells of lymphoid organs and exudate cells.
• In delayed-type reactions, the toxic effect of the allergen on the tissue structure occurs, which is not typical for immediate-type reactions.

The main place in the diagnosis of allergization of the body is occupied by the clinical picture of the manifestations of the disease, an allergic history and immunodiagnostic studies.

A classified allergist selects a treatment based on an assessment of all the data. Other narrow specialists are also involved in the treatment of patients with delayed-type reactions.

Conclusion

The division of allergic reactions into types allows you to choose the right tactics for treating patients. It is possible to accurately determine the type of reaction only after conducting appropriate blood tests.

Delaying the establishment of an accurate diagnosis is not worth it, since timely therapy can prevent the transition of easily occurring allergies to more severe ones.

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Delayed-type allergic reactions develop over time and do not carry the same danger as immediate-type reactions. The latter appear within a few minutes after exposure to the allergen. They cause serious harm to the body and, if left untreated, can be fatal.

Causes of the development of allergic reactions of the immediate type

An allergy develops when the body comes into contact with any substance to which there is hypersensitivity. For humans, this substance is not dangerous, but the immune system, for inexplicable reasons, thinks otherwise. The most common allergens are:

• dust particles;
• some medicines;
• plant pollen and mold fungi;
• highly allergenic foods (sesame, nuts, seafood, honey, citrus fruits, cereals, milk, beans, eggs);
• poison of bees and wasps (with a bite);
• animal hair;
• artificial fabrics;
• household chemical products.

The pathogenesis of the development of an allergy of the immediate type

When the allergen first enters the body, sensitization develops. For unknown reasons, the immune system concludes that this substance is dangerous. In this case, antibodies are produced that gradually destroy the incoming substance. When the allergen enters the body again, the immune system is already familiar with it. Now he immediately puts into play the antibodies developed earlier, thereby causing an allergy.

An allergic reaction of the immediate type develops within 15-20 minutes after the intake of the allergen. It takes place in the body in three stages, going sequentially one after another:

1. immunological reaction. The incoming antigen interacts with the antibody. This is immunoglobulin E, which is attached to mast cells. In the granules of the cytoplasm of mast cells are mediators of allergic reactions of the immediate type: histamines, serotonins, bradykinins and other substances.
2. pathochemical reaction. It is characterized by the release of allergy mediators from mast cell granules.
3. pathophysiological response. Mediators of an immediate allergic reaction act on body tissues, causing an acute inflammatory response.

What are immediate allergic reactions?

Depending on which organ or tissue the allergen has entered, various reactions develop. Immediate type allergies include urticaria, angioedema, atopic bronchial asthma, allergic vasomotor rhinitis, anaphylactic shock.

Hives

Acute urticaria is characterized by the sudden onset of an itchy, blistering rash. The elements have a regular rounded shape and can merge with each other, forming elongated blisters. Urticaria is localized on the limbs and trunk, in some cases - on the mucous membrane of the oral cavity and larynx. Usually, elements appear at the site of exposure to the allergen, for example, on the arm, near a bee sting.

The rash lasts for several hours, after which it disappears without a trace. In severe cases, urticaria can last for several days and be accompanied by general malaise and fever.

Quincke's edema

Quincke's edema is a giant urticaria, which is characterized by a sharp swelling of the subcutaneous fat and mucous membranes. Pathology can affect any part of the body: face, mouth, intestines, urinary system and brain. One of the most dangerous manifestations is laryngeal edema. It also swells the lips, cheeks and eyelids. Quincke's edema, affecting the larynx, leads to difficulty in breathing up to complete asphyxia.

This type of immediate allergic reaction usually develops in response to medicinal substances or the venom of bees and wasps.

Atopic bronchial asthma

Atopic bronchial asthma is manifested by sudden bronchospasm. Difficulty breathing, paroxysmal cough, wheezing, viscous sputum, cyanosis of the skin and mucous membranes occur. The cause of the pathology is often the inhalation of allergens: dust, pollen, animal hair. This variant of an immediate allergic reaction develops in patients with bronchial asthma or in persons with a hereditary predisposition to this disease.

Allergic vasomotor rhinitis

Pathology, similar to atopic bronchial asthma, develops when allergens are inhaled. Vasomotor rhinitis, like all allergic reactions of the immediate type, begins against the background of complete well-being. The patient develops itching in the nose, frequent sneezing, abundant secretion of rare mucus from the nose. At the same time, the eyes are affected. There is lacrimation, itching and photophobia. In severe cases, an attack of bronchospasm joins.

Anaphylactic shock

Anaphylactic shock is the most severe form of allergy. Its symptoms develop at lightning speed, and without emergency care, the patient dies. Usually the cause of development is the introduction of drugs: penicillin, novocaine and some other substances. In young children with hypersensitivity, anaphylactic shock may occur after eating highly allergenic foods (seafood, eggs, citrus fruits).

The reaction develops 15-30 minutes after the allergen enters the body. It is noted that the sooner anaphylactic shock occurs, the worse the prognosis for the patient's life. The first manifestations of pathology are severe weakness, tinnitus, numbness of the limbs, a tingling sensation in the chest, face, soles and palms. The person turns pale and breaks out in a cold sweat. Blood pressure drops sharply, the pulse quickens, there is a tingling behind the sternum and a feeling of fear of death.

In addition to the above symptoms, anaphylactic shock may be accompanied by any other allergic manifestations: rashes, rhinorrhea, lacrimation, bronchospasm, Quincke's edema.

Emergency care for immediate type allergies

First of all, with the development of an allergic reaction of an immediate type, it is necessary to stop contact with the allergen. To eliminate hives and vasomotor rhinitis, it is usually enough to take an antihistamine. The patient needs to ensure complete rest, apply a compress with ice to the site of the rash. More severe manifestations of an allergy of the immediate type require the introduction of glucocorticoids. When they develop, you should call an ambulance. Then provide an influx of fresh air, create a calm atmosphere, give the patient warm tea or compote to drink.

Emergency care for anaphylactic shock is the introduction of hormonal agents and the normalization of pressure. To facilitate breathing, it is necessary to lay the patient on pillows. If respiratory and circulatory arrest is recorded, then cardiopulmonary resuscitation is performed. In a hospital or ambulance, tracheal intubation with oxygen is performed.

Performing cardiopulmonary resuscitation

Cardiopulmonary resuscitation includes chest compressions and mouth-to-mouth artificial respiration. It is necessary to carry out resuscitation in the absence of consciousness, breathing and pulse in the patient. Before the procedure, you should check the patency of the respiratory tract, remove vomit and other foreign bodies.

Cardiopulmonary resuscitation begins with chest compressions. You should fold your hands into the castle and press on the middle of the sternum. In this case, the pressure is carried out not only by the hands, but also by the entire upper body, otherwise there will be no effect. 2 pressures are performed per second.

For artificial respiration, you need to close the patient's nose, throw back his head and blow air strongly into his mouth. To ensure your own safety, you should put a napkin or handkerchief on the lips of the victim. One CPR session includes 30 chest compressions and 2 mouth-to-mouth breaths. The procedure is carried out until signs of breathing and cardiac activity appear.

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Allergic reaction of immediate type

They tend to develop rapidly. An allergic reaction of an immediate type manifests itself after a short time interval (from half an hour to several hours) after repeated contact with the allergen. Among them are:

• First or anaphylactic type. It is realized in the form of anaphylactic shock.

This is an extremely dangerous acute condition. Most often it develops against the background of intravenous or intramuscular administration of drugs.

Less common with other routes of penetration of the allergen into the body. As a result of hemodynamic disorders, circulatory failure and oxygen starvation in the organs and tissues of the body develop.

Clinical symptoms are caused by a contraction of smooth muscles, an increase in the permeability of the walls of the vascular bed, disturbances in the endocrine system and blood clotting parameters.

Cardiovascular insufficiency develops. The pressure in the bloodstream drops sharply. On the part of the bronchopulmonary system, spasm, hypersecretion of mucus and pronounced edema of the respiratory tract are observed. Sharply growing in the larynx, it can lead to the death of the patient as a result of asphyxia.

Due to the release of their cells of an excess amount of heparin, complications develop due to a decrease in blood clotting, and with the development of DIC, there is a threat of numerous thromboses.

1. It can also manifest itself in the form of various forms of a rash on the skin.
2. Pollinosis.
3. Atopic bronchial asthma.
4. Angioedema.
5. allergic rhinitis.

• The second or cytotoxic type.

It is the basis of the following changes in the blood formula, as a result of drug allergies:

1. decrease in the number of leukocytes and platelets of immune origin;
2. development of hemolytic anemia.

• Third or.

The main pathogenetic mechanism of such conditions as serum sickness and allergic vasculitis.

Delayed allergic reaction

It appears after a certain time. From the moment of contact with the allergen, it takes up to two days before the onset of signs of allergy.

• Type four or delayed hypersensitivity.

This type causes contact dermatitis, an allergic component in bronchial asthma.

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

§ 95. General characteristics of delayed allergies

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

1. The response of a sensitized organism to the action of a resolving dose of an allergen occurs after 6-48 hours.
2. Passive transfer of a delayed allergy with the help of the serum of a sensitized animal fails. Therefore, antibodies circulating in the blood - immunoglobulins - are of little importance in the pathogenesis of delayed allergies.
3. Passive transfer of a delayed allergy is possible with a suspension of lymphocytes taken from a sensitized organism. Chemically active determinants (receptors) appear on the surface of these lymphocytes, with the help of which the lymphocyte connects to a specific allergen, i.e., these receptors function like circulating antibodies in immediate allergic reactions.
4. The possibility of passive transmission of delayed allergy 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 because it is not neutralized by the antigen.

§ 96. Types of delayed allergies

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

bacterial allergy. For the first time this type of response was described in 1890 by Robert Koch in tuberculosis patients with subcutaneous injection of tuberculin. Tuberculin is a filtrate of the broth culture of the tubercle bacillus. Persons who do not suffer from tuberculosis give a negative reaction to tuberculin. In patients with tuberculosis, after 6-12 hours, redness appears at the injection site of tuberculin, it increases, swelling and induration appear. After 24-48 hours, the reaction reaches a maximum. With a particularly strong reaction, even skin necrosis is possible. With the injection of small doses of the allergen, necrosis is absent.

The reaction to tuberculin was the first allergic reaction to be 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 Burne reaction in brucellosis, etc.

Delayed 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 the experiment, tuberculin allergy is easily obtained in guinea pigs sensitized with the BCG vaccine.

With the introduction of tuberculin into the skin of such pigs, they develop, like in humans, a delayed-type skin allergic reaction. Histologically, the reaction is characterized as inflammation with lymphocyte infiltration. Giant multinucleated cells, light cells, derivatives of histiocytes - epithelioid cells are also formed.

When tuberculin is injected 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 allergy often occurs to low-molecular substances of organic and inorganic origin, which 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 - skin infiltration with mononuclear leukocytes, degeneration and detachment of the epidermis occurs.

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

§ 97. Autoallergy

Delayed-type allergic reactions include a large group of reactions and diseases resulting from damage to cells and tissues by autoallergens, i.e., allergens that have arisen 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 by which immunological mechanisms distinguish self from foreign proteins. Normally, the body has tolerance (resistance) to its own proteins and body components, i.e., antibodies and sensitized lymphocytes are not formed against its own proteins, therefore, its own tissues are not damaged. It is assumed that inhibition of the immune response to self-antigens is realized by suppressor T-lymphocytes. A hereditary defect in the work 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. Both are sometimes referred to as immunopathology. However, the latter term is unsuccessful 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 (pseudoparalytic form of muscle weakness), rheumatoid arthritis, glomerulonephritis, Hashimoto's thyroiditis and a number of other diseases.

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

Mechanisms of formation of autoallergens. The main issue in the study of the mechanisms of autoallergic reactions is the question of the ways of formation of autoallergens. There are at least 3 ways of formation of autoallergens:

1. Autoallergens are contained in the body as its normal component. They are called natural (primary) autoallergens (A. D. Ado). These include some proteins of normal tissues of the nervous system (basic protein), lens, testicles, colloid of the thyroid gland, retina. Some proteins of these organs, due to the peculiarities of embryogenesis, are perceived by immunocompetent cells (lymphocytes) as foreign. However, under normal conditions, these proteins are located 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, resulting in the formation of autoantibodies and sensitized lymphocytes, which will cause damage to the corresponding organ. The hereditary defect of suppressor T-lymphocytes is also important.

   This process can be schematically represented by 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 cleaved from thyroglobulin, after which thyroxine enters the blood capillary. 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 bloodstream. This leads to the 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 undulating 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. According to this mechanism, orchitis can develop - inflammation of one testicle after damage to the other.

2. Autoallergens do not preexist 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 self-allergens include, for example, products of protein denaturation. It has been established that blood and tissue proteins in various pathological conditions acquire allergenic properties that are alien to the body of their carrier and become autoallergens. They are found in burn and radiation sickness, in dystrophy and necrosis. In all these cases, changes occur with proteins that make them foreign to the body.

   Autoallergens can be formed as a result of the combination of drugs and chemicals that have entered the body with tissue proteins. In this case, a foreign substance that has entered into a complex with a 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 combining some components of streptococcus with proteins of the connective tissue of the myocardium, 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", alien and therefore stimulate them to produce antibodies and form sensitized T-lymphocytes.

   Burnet's hypothesis 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, carrying on their surface antibodies complementary to the antigens of their own intact cells.

3. Proteins of some tissues can be self-allergenic due to the fact that they have common antigens with certain bacteria. In the process of adapting to existence in a macroorganism, many microbes have developed antigens that are common with those of the host. This hindered 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 “their own”. However, due to some differences in the structure of common antigens, immunological mechanisms of protection against microflora were switched on, which simultaneously led to damage to their 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 tissues; ulcerative colitis due to common antigens in the intestinal mucosa and some 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 tissues.

Continuation: Chapter 6

A delayed-type allergy makes itself felt after a few hours and a day.

When an irritant influences the body, various negative changes occur. They can be expressed directly when the allergen enters, and also be detected after some time. Changes that are delayed are called delayed-type allergic reactions. They may appear in a few hours or days.

What influences the reaction

Delayed-type allergic reactions begin with a sensitization process

Delayed allergy occurs in the same way as other reactions. When an irritant enters the body, a process of sensitization occurs. This causes the development of sensitivity of the immune system to foreign substances. Lymph nodes begin to produce pyroninophilic cells. They become "material" for the creation of immune lymphocytes that carry antibodies. As a result of this process, antibodies appear both in the blood and in other tissues, mucous membranes, and body systems.
If re-penetration of the irritant occurs, then the antibodies respond to the allergens, which leads to tissue damage.
How the antibodies that cause delayed-type allergic reactions are formed is not yet fully known. But the fact has been revealed that it is possible to transfer a delayed allergy only with the use of a cell suspension. This mechanism was developed by scientists as a result of an experiment on animals.
If blood serum is used, then it is impossible to transfer antibodies. This is due to the fact that it is necessary to add a certain number of elements of other cells. Lymphocytes play a special role in the formation of consequences.

Characteristics

Delayed-type reactions differ from immediate manifestations in characteristic features.

If signs of damage occur, from the moment the allergen enters the human body until symptoms are detected, it takes from 1 to 2 days.

If you conduct a blood test to identify the allergen, then in the case of delayed manifestations of allergy, antibodies are not detected.

The mechanism of transferring an allergic reaction to a healthy person can only occur when using leukocytes, lymphatic cells and exudate cells. If blood serum is used, the transfer of immediate manifestations will be carried out.

With delayed reactions, sensitized leukocytes can feel the cytotoxic and lytic effects of the stimulus.

In the event of a delayed reaction to tissues, an allergen of a toxic nature is exposed.

The mechanism of the reaction

The process of occurrence of a delayed-type reaction consists of three stages:

immunological;

pathochemical;

pathophysiological.

At the first stage, the thymus-dependent immune system is activated. Strengthening of cellular immune defense occurs with insufficient work of humoral mechanisms:

when the antigen is inside the cell;

when converting cells into antigens.

In this case, the antigens are:

• protozoa;

  mushrooms with spores.

Allergic reactions of a delayed type can occur upon tactile contact with an allergen.

The same mechanism is activated when creating a complex allergen characteristic of contact dermatitis (due to drug, chemical and household irritation).
At the pathochemical stage, the mechanism for the formation of lymphokines, macromolecular substances produced by the interaction of T and B lymphocytes with stimuli, is activated. Lymphokines can be formed depending on:

genotypic features of lymphocytes;

type of antigens;

antigen concentrations.

Lymphokines that affect the formation of a delayed-type reaction can be in the form of:

a factor that inhibits the migration of macrophages;

interleukins;

chemotactic factors;

lymphotoxins;

interferons;

transfer factors.

Also, an allergic reaction is caused by lysosomal enzymes, activation of the kallikrein-kinin system.
At the pathophysiological stage, the mechanism of damage can be expressed in the form of three reactions.

During the direct cytotoxic action of sensitized T-lymphocytes, the allergen is recognized by the lymphocyte, and they come into contact with each other. At the stage of a lethal blow, the damage mechanism is activated. The defeat occurs at the third stage of target cell lysis, when its membranes disintegrate, mitochondria swell.

Under the action of T-lymphocytes through lymphotoxin, only those cells that caused its occurrence or triggered the mechanism of its production are damaged. In this case, the cell membrane begins to collapse.

When lysosomal enzymes are released during phagocytosis, tissue structures are damaged. The mechanism of enzyme formation begins in macrophages.

The main distinguishing feature of delayed-type reactions is the inflammatory process. It is formed in various organs, which leads to the occurrence of diseases of the body systems.

Inflammation with the formation of granulomas can be caused by exposure to:

bacteria;

fungal spores;

pathogenic and conditionally pathogenic microorganisms;

substances with a simple chemical composition;

• inflammatory processes.

Types of delayed reactions

There are a fairly large number of delayed-type reactions. The main common occurrences are:

bacterial allergy;

contact allergy;

autoallergy;

homograft rejection reaction.

bacterial allergy

A delayed bacterial lesion is often detected with the introduction of various vaccines, as well as diseases of an infectious nature. These include:

In the event of sensitization and the introduction of an allergen, the reaction occurs no earlier than 7 hours after the irritant enters the body. A person may experience redness, the skin may thicken. In some cases, necrosis appears.
If a histological examination is performed, then bacterial allergy is characterized by mononuclear infiltration.
In medicine, delayed-action reactions are widely used in the determination of various diseases (Pirquet, Mantoux, Burne reactions). In addition to the skin, the symptoms are evaluated on the cornea of ​​​​the eye, the bronchi.

contact allergy

With contact allergies, manifested in the form of dermatitis, the effect on the body occurs with the help of low molecular weight substances:

dinitrochlorobenzene;

picrylic acid;

There is also the influence of ursola, platinum compounds, components of cosmetics. When they enter the body, these incomplete antigens combine with proteins and cause an allergic reaction. The better the substance combines with the protein, the more allergenic it is.
The most pronounced symptoms occur after 2 days. The reaction is expressed as a mononuclear infiltration of the epidermis. As a result of tissue degeneration, structural disturbance, epidermis exfoliation occurs. This is how the allergy is formed.

Autoallergy

Delayed allergens can cause serious damage

Sometimes allergens are formed directly in the body. They affect cells and tissues, causing severe damage.
Endoallergens - one of the types of autoallergens, are present in the body of every person. When separating some tissues from the apparatus of immunogenesis, immunocompetent cells perceive these tissues as foreign. Therefore, they affect the process of producing antibodies.
In some cases, autoallergens are purchased. This is due to damage to proteins by external factors (cold, high temperature).
If a person's own antigens combine with bacterial allergens, then the formation of infectious autoallergens is detected.

Homograft rejection

When transplanting tissues, complete tissue engraftment can be observed when:

autotransplantation;

homotransplantation in identical twins.

In other situations, rejection of tissues and organs occurs. This process is caused by a reaction of an allergic type of delayed action. 1–2 weeks after transplantation or tissue rejection, the body responds to the introduction of donor tissue antigens under the skin.
The reaction mechanism is determined by lymphoid cells. If tissue transplantation was carried out in an organ with a weak lymphatic system, then the tissue is destroyed more slowly. When lymphocytosis occurs, we can talk about the beginning rejection.
When a foreign tissue is transplanted, the recipient's lymphocytes become sensitized. Soon they pass into the transplanted organ. Their destruction occurs, the release of antibodies, violation of the integrity of the transplanted tissue.
Reactions of the delayed type can be expressed in the form of various signs. They require increased diagnosis and careful treatment, as they become the causes of serious diseases.

Allergy(Greek allos - another and ergon - action) - increased sensitivity of the body to various substances, associated with a change in its reactivity. The term was proposed by the Austrian pediatricians Pirke and Schick (S. Pirquet, V. Schick, 1906) to explain the phenomena of serum sickness observed by them in children with infectious diseases.

The hypersensitivity of the organism in case of Allergy is specific, that is, it increases to that antigen (or other factor) with which: there has already been contact and which caused a state of sensitization. The clinical manifestations of this hypersensitivity are usually referred to as allergic reactions. Allergic reactions that occur in humans or animals upon initial contact with allergens are called non-specific. One of the options for nonspecific allergies is paraallergy. A paraallergy is an allergic reaction caused by some allergen in the body, sensitized by another allergen (eg, a positive skin reaction to tuberculin in a child after vaccination with smallpox). A valuable contribution to the doctrine of infectious paraallergic was made by the work of P. F. Zdrodovsky. An example of such a paraallergy is the phenomenon of a generalized allergic reaction to Vibrio cholerae endotoxin (see Sanarelli-Zdrodovsky phenomenon). The resumption of a specific allergic reaction after the introduction of a nonspecific stimulus is called metallurgy (for example, the resumption of the tuberculin reaction in a patient with tuberculosis after the introduction of a typhoid vaccine).

Classification of allergic reactions

Allergic reactions are divided into two large groups: immediate reactions and delayed reactions. The concept of allergic reactions of immediate and delayed types first arose as a result of clinical observations: Pirke (1906) distinguished between immediate (accelerated) and delayed (extended) forms of serum sickness, Zinsser (N. Zinsser, 1921) - fast anaphylactic and slow (tuberculin) forms skin allergic reactions.

Reactions of immediate type Cook (R. A. Cooke, 1947) called skin and systemic allergic reactions (respiratory, digestive and other systems) that occur 15-20 minutes after exposure to a specific allergen on a patient. Such reactions are a skin blister, bronchospasm, a disorder of the gastrointestinal tract, and more. Reactions of immediate type include: anaphylactic shock (see), Overy's phenomenon (see. Skin anaphylaxis), allergic urticaria (see), serum sickness (see), non-infectious allergic forms of bronchial asthma (see), hay fever ( see Pollinosis), angioedema (see Quincke's edema), acute glomerulonephritis (see) and more.

Delayed reactions, in contrast to reactions of an immediate type, develop over many hours and sometimes days. They occur with tuberculosis, diphtheria, brucellosis; caused by hemolytic streptococcus, pneumococcus, vaccine virus, and more. A delayed-type allergic reaction in the form of damage to the cornea is described for streptococcal, pneumococcal, tuberculosis and other infections. In allergic encephalomyelitis, the reaction also proceeds according to the type of delayed Allergy. Delayed-type reactions also include reactions to plant (primula, ivy, etc.), industrial (ursols), medicinal (penicillin, etc.) allergens in so-called contact dermatitis (see).

Allergic reactions of immediate type differ from delayed allergic reactions in a number of ways.

1. Immediate allergic reactions develop 15-20 minutes after the contact of the allergen with sensitized tissue, delayed - after 24-48 hours.

2. Immediate allergic reactions are characterized by the presence of circulating antibodies in the blood. With delayed reactions, antibodies in the blood are usually absent.

3. With reactions of the immediate type, passive transfer of hypersensitivity to a healthy organism with the patient's blood serum is possible. With delayed allergic reactions, such a transfer is possible, but not with blood serum, but with leukocytes, cells of lymphoid organs, cells of exudate.

4. Delayed-type reactions are characterized by the cytotoxic or lytic effect of the allergen on sensitized leukocytes. For immediate allergic reactions, this phenomenon is not typical.

5. For reactions of the delayed type, the toxic effect of the allergen on tissue culture is characteristic, which is not typical for immediate reactions.

Partly an intermediate position between immediate and delayed reactions is occupied by the Arthus phenomenon (see Arthus phenomenon), which in the initial stages of development is closer to reactions of an immediate type.

The evolution of allergic reactions and their manifestations in ontogenesis and phylogenesis were studied in detail by N. N. Sirotinin and his students. It is established that in the embryonic period anaphylaxis (see) cannot be caused in an animal. In the neonatal period, anaphylaxis develops only in mature animals, such as guinea pigs, goats, and yet in a milder form than in adult animals. The emergence of allergic reactions in the process of evolution is associated with the appearance in the body of the ability to produce antibodies. Invertebrates have almost no ability to produce specific antibodies. To the greatest extent, this property is developed in higher warm-blooded animals and especially in humans, therefore it is in humans that allergic reactions are observed most often and their manifestations are diverse.

Recently, the term " immunopathology" (see). Immunopathological processes include demyelinating lesions of the nervous tissue (post-vaccination encephalomyelitis, multiple sclerosis, etc.), various nephropathies, some forms of inflammation of the thyroid gland, testicles; an extensive group of blood diseases adjoins these processes (hemolytic thrombocytopenic purpura, anemia, leukopenia), united in the immunohematology section (see).

An analysis of the factual material on the study of the pathogenesis of various allergic diseases by morphological, immunological and pathophysiological methods shows that allergic reactions are the basis of all diseases combined into the immunopathological group and that immunopathological processes do not fundamentally differ from allergic reactions caused by various allergens.

Mechanisms of development of allergic reactions

Allergic reactions of immediate type

The mechanism of development of allergic reactions of the immediate type can be divided into three stages closely related to each other (according to A. D. Ado): immunological, pathochemical and pathophysiological.

Immunological stage is the interaction of allergens with allergic antibodies, that is, the allergen-antibody reaction. Antibodies that cause allergic reactions when combined with an allergen, in some cases have precipitating properties, that is, they are able to precipitate when reacting with an allergen, for example. with anaphylaxis, serum sickness, Arthus phenomenon. An anaphylactic reaction can be induced in an animal not only by active or passive sensitization, but also by the introduction of an allergen-antibody immune complex prepared in a test tube into the blood. Complement, which is fixed by the immune complex and activated, plays an important role in the pathogenic action of the resulting complex.

In another group of diseases (hay fever, atonic bronchial asthma, etc.), antibodies do not have the ability to precipitate when reacting with an allergen (incomplete antibodies).

Allergic antibodies (reagins) in atonic diseases in humans (see Atopy) do not form insoluble immune complexes with the corresponding allergen. Obviously, they do not fix the complement, and the pathogenic action is carried out without its participation. The condition for the occurrence of an allergic reaction in these cases is the fixation of allergic antibodies on the cells. The presence of allergic antibodies in the blood of patients with atonic allergic diseases can be determined by the Prausnitz-Küstner reaction (see Prausnitz-Küstner reaction), which proves the possibility of passive transfer of hypersensitivity with blood serum from the patient to the skin of a healthy person.

pathochemical stage. The consequence of the antigen-antibody reaction in allergic reactions of the immediate type are profound changes in the biochemistry of cells and tissues. The activity of a number of enzyme systems necessary for the normal functioning of cells is sharply disrupted. As a result, a number of biologically active substances are released. The most important source of biologically active substances are mast cells of the connective tissue that secrete histamine (see), serotonin (see) and heparin (see). The process of release of these substances from mast cell granules proceeds in several stages. Initially, "active degranulation" occurs with the expenditure of energy and activation of enzymes, then the release of histamine and other substances and the exchange of ions between the cell and the environment. The release of histamine also occurs from leukocytes (basophils) of the blood, which can be used in the laboratory to diagnose Allergy. Histamine is formed by decarboxylation of the amino acid histidine and can be contained in the body in two forms: loosely associated with tissue proteins (for example, in mast cells and basal cells, in the form of a loose bond with heparin) and free, physiologically active. Serotonin (5-hydroxytryptamine) is found in large quantities in platelets, in the tissues of the digestive tract, and in the nervous system, and in a number of animals in mast cells. A biologically active substance that plays an important role in allergic reactions is also a slowly acting substance, the chemical nature of which has not been fully disclosed. There is evidence that it is a mixture of neuraminic acid glucosides. During anaphylactic shock, bradykinin is also released. It belongs to the group of plasma kinins and is formed from plasma bradykininogen, destroyed by enzymes (kininases), forming inactive peptides (see Mediators of allergic reactions). In addition to histamine, serotonin, bradykinin, a slow-acting substance, allergic reactions release substances such as acetylcholine (see), choline (see), norepinephrine (see), etc. Mast cells emit mainly histamine and heparin; heparin, histamine are formed in the liver; in the adrenal glands - adrenaline, norepinephrine; in platelets - serotonin; in the nervous tissue - serotonin, acetylcholine; in the lungs - a slow-acting substance, histamine; in plasma - bradykinin and so on.

Pathophysiological stage It is characterized by functional disorders in the body that develop as a result of the allergen-antibody (or allergen-reagin) reaction and the release of biologically active substances. The reason for these changes is both the direct impact of the immunological reaction on the cells of the body, and numerous biochemical mediators. For example, histamine, when injected intradermally, can cause so-called. "triple Lewis response" (itching at the injection site, erythema, wheal), which is characteristic of an immediate type of skin allergic reaction; histamine causes a contraction of smooth muscles, serotonin - a change in blood pressure (rise or fall, depending on the initial state), contraction of the smooth muscles of the bronchioles and the digestive tract, narrowing of larger blood vessels and expansion of small vessels and capillaries; bradykinin can cause smooth muscle contraction, vasodilation, positive leukocyte chemotaxis; the musculature of the bronchioles (in humans) is especially sensitive to the influence of a slowly acting substance.

Functional changes in the body, their combination and make up the clinical picture of an allergic disease.

The pathogenesis of allergic diseases is often based on certain forms of allergic inflammation with different localization (skin, mucous membrane, respiratory, digestive tract, nervous tissue, lymphatic glands, joints, and so on, hemodynamic disturbances (with anaphylactic shock), spasm of smooth muscles (bronchospasm in bronchial asthma).

Delayed allergic reactions

Delayed Allergy develops with vaccinations and various infections: bacterial, viral and fungal. The classic example of such Allergy is tuberculin hypersensitivity (see Tuberculin Allergy). The role of delayed Allergy in the pathogenesis of infectious diseases is most demonstrative in tuberculosis. With the local administration of tuberculosis bacteria to sensitized animals, a strong cellular reaction occurs with caseous decay and the formation of cavities - the Koch phenomenon. Many forms of tuberculosis can be considered as Koch's phenomenon at the site of superinfection of aerogenic or hematogenous origin.

One type of delayed allergy is contact dermatitis. It is caused by a variety of low molecular weight substances of plant origin, industrial chemicals, varnishes, paints, epoxy resins, detergents, metals and metalloids, cosmetics, drugs, and more. To obtain contact dermatitis in the experiment, sensitization of animals with skin applications of 2,4-dinitrochlorobenzene and 2,4-dinitrofluorobenzene is most often used.

A common feature that unites all types of contact allergens is their ability to combine with protein. Such a connection probably occurs through a covalent bond with free amino and sulfhydryl groups of proteins.

In the development of allergic reactions of a delayed type, three stages can also be distinguished.

immunological stage. Non-immune lymphocytes after contact with an allergen (for example, in the skin) are transported through the blood and lymph vessels to the lymph nodes, where they are transformed into an RNA-rich cell - a blast. Blasts, multiplying, turn back into lymphocytes, capable of "recognizing" their allergen upon repeated contact. Some of the specifically trained lymphocytes are transported to the thymus. The contact of such a specifically sensitized lymphocyte with the corresponding allergen activates the lymphocyte and causes the release of a number of biologically active substances.

Modern data on two clones of blood lymphocytes (B- and T-lymphocytes) allow us to reimagine their role in the mechanisms of allergic reactions. For a delayed-type reaction, in particular with contact dermatitis, T-lymphocytes (thymus-dependent lymphocytes) are needed. All influences that reduce the content of T-lymphocytes in animals sharply suppress delayed-type hypersensitivity. For an immediate type reaction, B-lymphocytes are required as cells capable of transforming into immunocompetent cells that produce antibodies.

There is information about the role of the hormonal influences of the thymus, which take part in the process of "learning" of lymphocytes.

pathochemical stage characterized by the release by sensitized lymphocytes of a number of biologically active substances of a protein and polypeptide nature. These include: a transfer factor, a factor that inhibits the migration of macrophages, lymphocytotoxin, a blastogenic factor, a factor that enhances phagocytosis; chemotaxis factor and, finally, a factor that protects macrophages from the damaging effects of microorganisms.

Delayed-type reactions are not inhibited by antihistamines. They are inhibited by cortisol and adrenocorticotropic hormone, and are passively transmitted only by mononuclear cells (lymphocytes). Immunological reactivity is implemented to a large extent by these cells. In the light of these data, the long-known fact of an increase in the content of lymphocytes in the blood with various types of bacterial Allergy becomes clear.

Pathophysiological stage characterized by changes in tissues that develop under the action of the above mediators, as well as in connection with the direct cytotoxic and cytolytic action of sensitized lymphocytes. The most important manifestation of this stage is the development of various types of inflammation.

physical allergy

An allergic reaction can develop in response to exposure to not only a chemical, but also a physical stimulus (heat, cold, light, mechanical or radiation factors). Since physical stimulation does not in itself cause the production of antibodies, various working hypotheses have been put forward.

1. We can talk about substances that arise in the body under the influence of physical irritation, that is, about secondary, endogenous autoallergens that take on the role of a sensitizing allergen.

2. The formation of antibodies begins under the influence of physical irritation. Macromolecular substances and polysaccharides can induce enzymatic processes in the body. Perhaps they stimulate the formation of antibodies (the onset of sensitization), primarily skin sensitizing (reagins), which are activated under the influence of specific physical stimuli, and these activated antibodies like an enzyme or catalyst (as strong liberators of histamine and other biologically active agents) cause the release of tissue substances .

Close to this concept is Cook's hypothesis, according to which the spontaneous skin sensitizing factor is an enzyme-like factor, its prosthetic group forms an unstable complex with whey protein.

3. According to Burnet's clonal selection theory, it is assumed that physical stimuli, just like chemical stimuli, can cause the proliferation of a "forbidden" clone of cells or mutations of immunologically competent cells.

Tissue changes in immediate and delayed type allergies

The morphology of immediate and delayed allergy reflects various humoral and cellular immunological mechanisms.

For allergic reactions of the immediate type that occur when antigen-antibody complexes are exposed to the tissue, the morphology of hyperergic inflammation is characteristic, which is characterized by rapid development, the predominance of alterative and vascular-exudative changes, and the slow course of proliferative-reparative processes.

It has been established that alterative changes in immediate allergy are associated with the histopathogenic effect of the complement of immune complexes, and vascular-exudative changes are associated with the release of vasoactive amines (inflammatory mediators), primarily histamine and kinins, as well as with chemotactic (leukotactic) and degranulating (in relation to obese cells) by the action of complement. Alterative changes mainly concern the walls of blood vessels, paraplastic substance and fibrous structures of the connective tissue. They are represented by plasma impregnation, mucoid swelling and fibrinoid transformation; the extreme expression of alteration is fibrinoid necrosis characteristic of immediate-type allergic reactions. Pronounced plasmorrhagic and vascular-exudative reactions are associated with the appearance of coarse proteins, fibrinogen (fibrin), polymorphonuclear leukocytes, "digesting" immune complexes, and erythrocytes in the area of ​​immune inflammation. Therefore, fibrinous or fibrinous-hemorrhagic exudate is most characteristic of such reactions. Proliferative-reparative reactions in case of allergy of the immediate type are delayed and weakly expressed. They are represented by the proliferation of cells of the endothelium and perithelium (adventitia) of the vessels and coincide in time with the appearance of mononuclear-histiocytic macrophage elements, which reflects the elimination of immune complexes and the onset of immunoreparative processes. Most typically, the dynamics of morphological changes in immediate type Allergy is presented with the Arthus phenomenon (see Arthus phenomenon) and the Overy reaction (see Cutaneous anaphylaxis).

Many human allergic diseases are based on immediate-type allergic reactions that occur with a predominance of alterative or vascular-exudative changes. For example, vascular changes (fibrinoid necrosis) in systemic lupus erythematosus (Fig. 1), glomerulonephritis, periarteritis nodosa and others, vascular-exudative manifestations in serum sickness, urticaria, Quincke's edema, hay fever, lobar pneumonia, as well as polyserositis, arthritis in rheumatism, tuberculosis, brucellosis and more.

The mechanism and morphology of hypersensitivity are largely determined by the nature and amount of the antigenic stimulus, the duration of its circulation in the blood, the position in the tissues, as well as the nature of the immune complexes (circulating or fixed complex, heterologous or autologous, formed locally by combining antibodies with the structural tissue antigen) . Therefore, the assessment of morphological changes in immediate type allergies, their belonging to the immune response requires evidence using the immunohistochemical method (Fig. 2), which allows not only talking about the immune nature of the process, but also identifying the components of the immune complex (antigen, antibody, complement ) and set their quality.

For delayed-type allergies, the reaction of sensitized (immune) lymphocytes is of great importance. The mechanism of their action is largely hypothetical, although the fact of a histopathogenic effect caused by immune lymphocytes in tissue culture or in an allograft is beyond doubt. It is believed that the lymphocyte comes into contact with the target cell (antigen) with the help of antibody-like receptors present on its surface. Activation of the target cell lysosomes during its interaction with an immune lymphocyte and "transfer" of the H3-thymidine DNA label to the target cell was shown. However, the fusion of the membranes of these cells does not occur even with deep penetration of lymphocytes into the target cell, which has been convincingly proven using microcinematographic and electron microscopy methods.

In addition to sensitized lymphocytes, delayed-type allergic reactions involve macrophages (histiocytes), which enter into a specific reaction with the antigen using cytophilic antibodies adsorbed on their surface. The relationship between immune lymphocyte and macrophage has not been elucidated. Only close contacts of these two cells have been established in the form of so-called cytoplasmic bridges (Fig. 3), which are revealed by electron microscopic examination. Possibly, cytoplasmic bridges serve to transmit antigen information (in the form of RNA or RNA-antigen complexes) by the macrophage; it is possible that the lymphocyte, for its part, stimulates the activity of the macrophage or exhibits a cytopathogenic effect in relation to it.

It is believed that a delayed-type allergic reaction occurs with any chronic inflammation due to the release of self-antigens from decaying cells and tissues. Morphologically, there is much in common between delayed-type allergy and chronic (intermediate) inflammation. However, the similarity of these processes - lymphohistiocytic tissue infiltration in combination with vascular-plasmorrhagic and parenchymal-dystrophic processes - does not identify them. Evidence of the involvement of infiltrate cells in sensitized lymphocytes can be found in histoenzymatic and electron microscopic studies: with delayed-type allergic reactions, an increase in the activity of acid phoephatase and dehydrogenases in lymphocytes, an increase in the volume of their nuclei and nucleoli, an increase in the number of polysomes, hypertrophy of the Golgi apparatus.

Contrasting the morphological manifestations of humoral and cellular immunity in immunopathological processes is not justified, therefore, combinations of morphological manifestations of immediate and delayed type allergies are quite natural.

Allergy due to radiation injury

The problem of allergy in radiation injury has two aspects: the effect of radiation on hypersensitivity reactions and the role of autoallergy in the pathogenesis of radiation sickness.

The effect of radiation on immediate-type hypersensitivity reactions has been studied in most detail using anaphylaxis as an example. In the first weeks after irradiation, carried out a few days before the sensitizing antigen injection, simultaneously with sensitization or on the first day after it, the state of hypersensitivity is weakened or does not develop at all. If the permissive injection of the antigen is carried out at a later period after the restoration of antibody genesis, then anaphylactic shock develops. Irradiation carried out a few days or weeks after sensitization does not affect the state of sensitization and antibody titers in the blood. The effect of radiation on cellular delayed-type hypersensitivity reactions (for example, allergic tests with tuberculin, tularin, brucellin, and so on) is characterized by the same patterns, but these reactions are somewhat more radioresistant.

With radiation sickness (see), the manifestation of anaphylactic shock may be intensified, weakened or changed depending on the period of illness and clinical symptoms. In the pathogenesis of radiation sickness, a certain role is played by allergic reactions of the irradiated organism in relation to exogenous and endogenous antigens (self-antigens). Therefore, desensitizing therapy is useful in the treatment of both acute and chronic forms of radiation injury.

The role of the endocrine and nervous systems in the development of allergies

The study of the role of the endocrine glands in the development of allergies was carried out by removing them from animals, introducing various hormones, and studying the allergenic properties of hormones.

Pituitary-adrenal glands

Data on the effect of pituitary and adrenal hormones on allergies are contradictory. However, most evidence suggests that allergic processes are more severe against the background of adrenal insufficiency caused by pituitary or adrenalectomy. Glucocorticoid hormones and ACTH, as a rule, do not inhibit the development of immediate-type allergic reactions, and only their long-term administration or the use of large doses inhibits their development to one degree or another. Allergic reactions of the delayed type are well suppressed by glucocorticoids and ACTH.

The antiallergic effect of glucocorticoids is associated with inhibition of antibody production, phagocytosis, the development of an inflammatory reaction, and a decrease in tissue permeability.

Obviously, the release of biologically active mediators also decreases and the sensitivity of tissues to them decreases. Allergic processes are accompanied by such metabolic and functional changes (hypotension, hypoglycemia, increased insulin sensitivity, eosinophilia, lymphocytosis, an increase in the concentration of potassium ions in the blood plasma and a decrease in the concentration of sodium ions), which indicate the presence of glucocorticoid deficiency. It has been established, however, that this does not always reveal insufficiency of the adrenal cortex. Based on these data, V. I. Pytsky (1968) put forward a hypothesis about extra-adrenal mechanisms of glucocorticoid insufficiency caused by an increase in the binding of cortisol to plasma proteins, a loss of cell sensitivity to cortisol, or an increase in cortisol metabolism in tissues, which leads to a decrease in the effective concentration of the hormone in them.

Thyroid

Consider that the normal function of the thyroid gland is one of the main conditions for the development of sensitization. Thyroidectomized animals can only be passively sensitized. Thyroidectomy reduces sensitization and anaphylactic shock. The shorter the time between permissive antigen injection and thyroidectomy, the less its effect on shock intensity. Thyroidectomy before sensitization inhibits the appearance of precipitates. If thyroid hormones are given in parallel with sensitization, then the formation of antibodies increases. There is evidence that thyroid hormones enhance the tuberculin reaction.

Thymus

The role of the thymus gland in the mechanism of allergic reactions is being studied in connection with new data on the role of this gland in immunogenesis. As you know, the spectacle gland plays an important role in the organization of the lymphatic system. It contributes to the settlement of the lymphatic glands with lymphocytes and the regeneration of the lymphatic apparatus after various injuries. The thymus gland (see) plays an essential role in formation of an allergy of the immediate and delayed type and first of all at newborns. Rats thymectomy immediately after birth do not develop the Arthus phenomenon to subsequent injections of bovine serum albumin, although nonspecific local inflammation caused, for example, by turpentine, is not affected by thymectomy. In adult rats, after simultaneous removal of the thymus and spleen, immediate allergic reactions are inhibited. In such animals, sensitized with horse serum, there is a distinct inhibition of anaphylactic shock in response to intravenous administration of a permissive dose of antigen. It has also been established that the introduction of an extract of the thymus gland of a pig embryo into mice causes hypo- and agammaglobulinemia.

Early removal of the thymus gland also causes inhibition of the development of all delayed-type allergic reactions. In mice and rats after neonatal thymectomy, it is not possible to obtain local delayed reactions to purified protein antigens. Repeated injections of antithymic serum have a similar effect. In newborn rats after removal of the thymus gland and sensitization with killed tuberculous mycobacteria, the tuberculin reaction on the 10-20th day of the animal's life is less pronounced than in control non-operated animals. Early thymectomy in chickens significantly prolongs the period of homograft rejection. The thymectomy has the same effect on newborn rabbits and mice. Transplantation of thymus or lymph node cells restores the immunological competence of the recipient's lymphoid cells.

Many authors associate the development of autoimmune reactions with dysfunction of the thymus gland. Indeed, thymectomized mice with thymus transplanted from donors with spontaneous hemolytic anemia show autoimmune disorders.

gonads

There are many hypotheses about the influence of the gonads on Allergy. According to some data, castration causes hyperfunction of the anterior pituitary gland. Hormones of the anterior pituitary gland reduce the intensity of allergic processes. It is also known that hyperfunction of the anterior pituitary leads to stimulation of adrenal function, which is the direct cause of increased resistance to anaphylactic shock after castration. Another hypothesis suggests that castration causes a lack of sex hormones in the blood, which also reduces the intensity of allergic processes. Pregnancy, like estrogens, can suppress the delayed-type skin reaction in tuberculosis. Estrogens inhibit the development of experimental autoimmune thyroiditis and polyarthritis in rats. A similar effect cannot be obtained by using progesterone, testosterone.

These data indicate the undoubted influence of hormones on the development and course of allergic reactions. This influence is not isolated and is realized in the form of a complex action of all endocrine glands, as well as various parts of the nervous system.

Nervous system

The nervous system is directly involved in each of the stages of development of allergic reactions. In addition, the nervous tissue itself can be a source of allergens in the body after exposure to various damaging agents, an allergic reaction of an antigen with an antibody can unfold in it.

Local application of the antigen to the motor area of ​​the cerebral cortex of sensitized dogs caused muscle hypotension, and sometimes an increase in tone and spontaneous muscle contractions on the side opposite to the application. The impact of the antigen on the medulla oblongata caused a decrease in blood pressure, impaired respiratory movements, leukopenia, hyperglycemia. Application of the antigen to the region of the gray tubercle of the hypothalamus led to significant erythrocytosis, leukocytosis, and hyperglycemia. Introduced primarily heterogeneous serum has a stimulating effect on the cerebral cortex and subcortical formations. During the period of the sensitized state of the body, the strength of the excitatory process is weakened, the process of active inhibition is weakened: the mobility of nervous processes worsens, the limit of the efficiency of nerve cells decreases.

The development of the reaction of anaphylactic shock is accompanied by significant changes in the electrical activity of the cerebral cortex, subcortical ganglia and formations of the diencephalon. Changes in electrical activity occur from the first seconds of the introduction of foreign serum and subsequently have a phase character.

Participation autonomic nervous system(see) in the mechanism of an anaphylactic shock and various allergic reactions many researchers assumed at experimental studying of the phenomena of an allergy. In the future, considerations about the role of the autonomic nervous system in the mechanism of allergic reactions were also expressed by many clinicians in connection with the study of the pathogenesis of bronchial asthma, allergic dermatosis and other diseases of an allergic nature. Thus, studies of the pathogenesis of serum sickness have shown the significant importance of disorders of the autonomic nervous system in the mechanism of this disease, in particular, the significant importance of the vagus phase (low blood pressure, sharply positive Ashner's symptom, leukopenia, eosinophilia) in the pathogenesis of serum sickness in children. The development of the theory of mediators of excitation transmission in the neurons of the autonomic nervous system and in various neuroeffector synapses was also reflected in the theory of allergies and significantly advanced the question of the role of the autonomic nervous system in the mechanism of some allergic reactions. Along with the well-known histamine hypothesis of the mechanism of allergic reactions, cholinergic, dystonic and other theories of the mechanism of allergic reactions appeared.

When studying the allergic reaction of the small intestine of a rabbit, a transition of significant amounts of acetylcholine from a bound state to a free one was found. The relationship of mediators of the autonomic nervous system (acetylcholine, sympathin) with histamine during the development of allergic reactions has not been elucidated.

There is evidence of the role of both the sympathetic and parasympathetic parts of the autonomic nervous system in the mechanism of development of allergic reactions. According to some reports, the state of allergic sensitization is expressed at first in the form of a predominance of the tone of the sympathetic nervous system, which is then replaced by parasympathicotonia. The influence of the sympathetic division of the autonomic nervous system on the development of allergic reactions was studied both by surgical and pharmacological methods. Studies by A. D. Ado and T. B. Tolpegina (1952) showed that with serum, as well as with bacterial allergies, an increase in excitability to a specific antigen is observed in the sympathetic nervous system; exposure of the heart of appropriately sensitized guinea pigs to the antigen causes the release of sympathin. In experiments with an isolated and perfused upper cervical sympathetic ganglion in cats sensitized with horse serum, the introduction of a specific antigen into the perfusion current causes excitation of the node and, accordingly, contraction of the third eyelid. The excitability of the node to electrical stimulation and to acetylcholine increases after protein sensitization, and decreases after exposure to a permissive dose of antigen.

A change in the functional state of the sympathetic nervous system is one of the earliest expressions of the state of allergic sensitization in animals.

An increase in the excitability of parasympathetic nerves during protein sensitization has been established by many researchers. It has been established that anaphylotoxin excites the endings of the parasympathetic nerves of smooth muscles. The sensitivity of the parasympathetic nervous system and the organs innervated by it to choline and acetylcholine increases during the development of allergic sensitization. According to the Danpelopolu hypothesis (D. Danielopolu, 1944), anaphylactic (paraphylactic) shock is considered as a state of increasing the tone of the entire autonomic nervous system (Danielopolu amphotonia) with an increase in the release of adrenaline (sympatin) and acetylcholine into the blood. In a state of sensitization, the production of both acetylcholine and sympathin increases. Anaphylactogen causes a non-specific effect - the release of acetylcholine (precholine) in the organs and a specific effect - the production of antibodies. The accumulation of antibodies causes specific phylaxis, and the accumulation of acetylcholine (precholine) causes non-specific anaphylaxis, or paraphylaxis. Anaphylactic shock is considered as "hypocholinesterase" diathesis.

Hypothesis of Danielopoulu is generally not accepted. However, there are numerous facts about a close relationship between the development of a state of allergic sensitization and a change in the functional state of the autonomic nervous system, for example, a sharp increase in the excitability of the cholinergic innervation apparatuses of the heart, intestines, uterus and other organs to choline and acetylcholine.

According to A. D. Ado, there are allergic reactions of the cholinergic type, in which the leading process is the reactions of cholinergic structures, reactions of the histaminergic type, in which histamine plays a leading role, reactions of the sympathergic type (presumably), where the leading mediator is sympathy, and, finally, various mixed reactions. The possibility of the existence of such allergic reactions is not excluded, in the mechanism of which other biologically active products, in particular a slowly reacting substance, will take the leading place.

The role of heredity in the development of allergies

Allergic reactivity is largely determined by the hereditary characteristics of the organism. Against the background of a hereditary predisposition to allergies in the body, under the influence of the environment, a state of an allergic constitution, or allergic diathesis, is formed. Exudative diathesis, eosinophilic diathesis, etc. are close to it. Allergic eczema in children and exudative diathesis often precede the development of bronchial asthma and other allergic diseases. Drug allergy occurs three times more often in patients with allergic reactivity (urticaria, pollinosis, eczema, bronchial asthma, etc.).

The study of hereditary burden in patients with various allergic diseases showed that about 50% of them have relatives in a number of generations with certain manifestations of Allergy. 50.7% of children with allergic diseases also have a hereditary burden for allergies. In healthy individuals, allergy in a hereditary history is noted in no more than 3-7%.

It should be emphasized that it is not an allergic disease as such that is inherited, but only a predisposition to a wide variety of allergic diseases, and if the examined patient has, for example, urticaria, then his relatives in different generations. Allergy can be expressed in the form of bronchial asthma, migraine, Quincke's edema , rhinitis and so on. Attempts to discover patterns of inheritance of predisposition to allergic diseases have shown that it is inherited as a recessive trait according to Mendel.

The influence of hereditary predisposition on the occurrence of allergic reactions is clearly demonstrated in the study of allergies in identical twins. Numerous cases of completely identical manifestations of allergy in identical twins to the same set of allergens are described. When titrating allergens by skin tests, identical twins show completely identical titers of skin reactions, as well as the same content of allergic antibodies (reagins) to the allergens that cause the disease. These data show that the hereditary conditionality of allergic conditions is an important factor in the formation of the allergic constitution.

When studying the age characteristics of allergic reactivity, two rises in the number of allergic diseases are noted. The first - in the earliest childhood - up to 4-5 years. It is determined by a hereditary predisposition to an allergic disease and manifests itself in relation to food, household, microbial allergens. The second rise is observed during puberty and reflects the completion of the formation of the allergic constitution under the influence of the factor of heredity (genotype) and the environment.

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Tissue changes in A.

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V. A. Ado; R. V. Petrov (rad.), . V. V. Serov (stalemate. An.).