Classification of allergic reactions according to Jell and Coombs. Principles of classification of allergic conditions. Atopic bronchial asthma

Coombs and Jell (1968) identified the following types of allergic reactions:

1. Type I - reagin (anaphylactic). Antibodies are sorbed on the cell, and antigens come from outside. Antigen-antibody complexes form on cells bearing antibodies. In the pathogenesis of reactions, the interaction of the antigen with IgE and IgG (reagins) sorbed on tissue basophils and the subsequent degranulation of these cells is essential (Fig. 7.3). The complement system is not activated. This type of reaction includes general and local anaphylaxis. General anaphylaxis occurs during anaphylactic shock. Local anaphylaxis is divided into: anaphylaxis in the skin (urticaria, Overy's phenomenon) and anaphylaxis in other organs (bronchial asthma, hay fever).

2. Type II - cytolysis reactions, or cytotoxic reactions. The antigen is a component of the cell or is sorbed on it, and the antibody enters the tissue. An allergic reaction begins as a result of the direct damaging effect of antibodies on cells; complement activation; activation of a subpopulation of killer B cells; activation of phagocytosis. The activating factor is the antigen-antibody complex. Cytotoxic allergic reactions include the effect of large doses of Bogomolets antireticular cytotoxic serum (ACS).

3. Type III - Arthus phenomenon or immune complex reactions. Neither antigen nor antibody are components of cells, and the formation of the antigen-antibody complex occurs in the blood and intercellular fluid. The role of precipitating antibodies is performed by IgM and IgG. Microprecipitates are concentrated around the vessels and in the vascular wall. This leads to disruption of microcirculation and secondary tissue damage, including necrosis. IgM, IgG - IgG, activate complement, and through it the production of other active substances, chemotaxis and phagocytosis. A leukocyte infiltrate is formed - a delayed component of the Arthus phenomenon.

4. Type IV - delayed hypersensitivity reactions (DHT)). The main feature of delayed-type reactions is that T-lymphocytes interact with the antigen. The delayed hypersensitivity reaction is no less specific to the antigen than the reaction with immunoglobulins, due to the presence of receptors in T-lymphocytes that can specifically interact with the antigen. These receptors are probably IgM, truncated and embedded in the T-lymphocyte membrane, and histocompatibility antigens (see below). However, in the tissue where this reaction occurs, among the many cells that destroy the antigen and the tissue, only a few percent of T lymphocytes are found that can specifically react with the antigen. This fact became clear after the discovery of lymphokines - special substances secreted by T-lymphocytes. Thanks to them, immune T-lymphocytes, even in small numbers, become organizers of the destruction of antigen by other blood leukocytes (see below).

5. Type V - stimulating allergic reactions. As a result of the action of antibodies on cells bearing the antigen, the function of these cells is stimulated. The mechanism of stimulation is explained by the fact that the produced antibodies can specifically react with cell receptors intended for activating hormones or mediators. The stimulating type of allergic reactions includes the autoimmune mechanism of Graves' disease, which leads to hyperfunction of the thyroid gland.

Depending on the time of occurrence of the reaction after contact with the allergen, allergic reactions of the immediate type (immediate-type hypersensitivity - IHT) and allergic reactions of the delayed type (delayed-type hypersensitivity - DTH) are also distinguished according to the classification proposed by R. A. Cooke (1930). In the first case, the reaction develops within 15-20 minutes, in the second - after 1-2 days. This classification still exists, but it does not reflect the full variety of manifestations of allergies, including the pathogenetic features that underlie the classification of Jell and Coombs.

Features of the immune stage of delayed (cellular) type reactions. T lymphocytes recognize antigenic determinants with a high degree of specificity using receptors that include the MHC major histocompatibility complex antigen.

The genes encoding MHC antigens are located in humans on chromosome 6, there are 4 alleles, each gene is found in the gene pool in many (dozens) of variants. MHC antigens are substances built into cell membranes, including the membranes of leukocytes, so they are designated HLA-A, HLA-B, HLA-C, HLA-D (from the English Human Leucocytes Antigen - human leukocyte antigen).

Based on their participation in the immune reactions of lymphocytes, substances of the major histocompatibility complex MHC were divided into two groups: group HI includes HLA-A, HLA-B, HLA-C, group HII includes HLA-D. T-killer receptors include substances of group HI. In the same organism, T-helper receptors contain substances from the NI group (HLA-D allele). It has been established that body cells integrate foreign antigens into their membrane into the substance of the MHC complex, for example, virus antigens when a cell is infected. A T-lymphocyte can recognize a foreign antigen if this foreign substance in the carrier cell is embedded in the same antigen of the major histocompatibility complex that the T-lymphocyte itself has, i.e., associated immune recognition occurs.

Bronchial asthma. With this disease, in response to the action of the allergen, spasm and swelling of the mucous membrane of the bronchioles develop, hypersecretion of mucus, which accumulates in the bronchi. Ventilation of the lungs and gas exchange are disrupted, and severe shortness of breath occurs. In approximately 50% of cases, bronchial asthma is caused by a component of room dust, which is a carbohydrate - a product of natural or bacterial breakdown of cellulose from cotton. This allergen is absent from street dust and dust from empty buildings, but is found in dust from residential premises. It also turned out that in 85% of children with bronchial asthma, the allergen originated from house dust mites (Dermatophagoides). In other cases, bronchial asthma is caused by other allergens contained in the air (plant pollen, desquamated epidermis, animal hair), substances entering the body parenterally, as well as enterally, including drugs - acetylsalicylic acid, antipyrine, morphine, etc.

In the immune stage of bronchial asthma, IgE is of great importance (in patients with bronchial asthma, the production of antibodies of this class is increased). Antibodies are found in the bronchioles, where they can react with an inhaled allergen.

In the biochemical stage of bronchial asthma, acetylcholine, MRS-A, histamine, PGF2, PGE deficiency and other biologically active compounds play an important role. Along with MPC-A, which is leukotriene D, prolonged spasm of bronchial muscles is also caused by platelet activating factor (PAF).

Under the influence of the BAS complex, spasm of the bronchioles, accumulation of viscous mucus in their lumen and swelling of the mucous membrane occur, which leads to narrowing and even blocking of the lumen of the bronchioles.

It is also important to reduce the production of adrenaline and cortisol - hormones that are counter-regulatory to acetylcholine and histamine.

Hay fever (from the English pollen - pollen)- an allergic disease caused by pollen or essential oils of plants and characterized by acute inflammatory changes in the mucous membranes, mainly of the respiratory tract and eyes: hay fever, spring catarrh, pollen rhinopathy, pollen bronchial asthma.

Serum sickness. Under this name, Pirquet and Schick in 1905 described pathological phenomena that sometimes occur in patients after parenteral administration of foreign serum for therapeutic purposes. The disease can occur not only after repeated administration of the serum, but also after its initial single administration. This happens when a large amount of serum is administered, the proteins of which are stored in the tissues until antibodies to it appear.

The first type of allergic reaction is an immediate allergic reaction (reagin, IgE-mediated, anaphylactic or atopic type of reaction). Its development is associated with the formation of antibodies called “reagins”. They belong mainly to the IgG class. Reagins are fixed on mast cells (mast cells) and basophilic leukocytes. When reagins are combined with the corresponding allergen, mediators are released from these cells - histamine, leukotrienes, chemotactic factors, heparin, platelet-activating factor ( rice. 1 ). Clinical manifestations of the reaction usually occur within 15-20 min after contact of a sensitized organism with a specific allergen (hence the name “immediate type reaction”). An immediate allergic reaction that occurs when an allergen is administered parenterally is referred to as “anaphylaxis.” Allergic reactions of immediate type are the basis of anaphylactic shock , hay fever , hives , atopic bronchial asthma , Quincke's edema , atopic dermatitis , allergic rhinitis .

Atopic bronchial asthma, atopic dermatitis, allergic rhinitis, hay fever belong to the group of so-called atopic diseases. Hereditary predisposition plays an important role in their development - an increased ability to respond with the formation of IgE and an allergic reaction to the actions of exogenous allergens. So, if both parents have any of these diseases, then allergic diseases occur in children in more than 70% of cases (if one of the parents is sick - up to 50% of cases). Depending on the type of allergen and the routes through which it enters the body, an allergic disease in a child can manifest itself in any form. Moreover, it is not an allergic disease that is inherited, but only a tendency to develop it, therefore, with a burdened heredity, it is especially necessary to observe preventive measures, which can prevent the development of the disease.

The main path of development of an immediate allergic reaction is often joined by a second path. It is due to the fact that on the surface of monocytes, eosinophils and platelets there are also receptors for reagins that can be fixed on them. The allergen binds to the fixed reagins, as a result of which these cells release a number of mediators with pro-inflammatory activity (cationic proteins, reactive oxygen species, etc.). This leads to development within 4-8 h the so-called late, or delayed, phase of an immediate allergic reaction. The late phase of immediate-type allergic reactions leads to increased sensitivity of the bronchi in patients with bronchial asthma, sometimes to the development of status asthmaticus; a recurrence of anaphylactic shock several hours after the patient was brought out of this state is described.

The second type of allergic reactions is cytotoxic ( rice. 2), in which tissue cells become allergens. This usually occurs as a result of the damaging effects of drugs, bacterial and viral enzymes during infectious processes, as well as lysosomal enzymes of phagocytes. In response to the appearance of altered cells, antibodies are formed, represented mainly by the IgG and IgM classes. Antibodies combine with the corresponding cells, which leads to the activation of one of two cytotoxic mechanisms - complementary or the mechanism of antibody-dependent cellular cytotoxicity. The type of mechanism depends on the nature of the antibodies (class, subclass) and their quantity fixed on the cell surface. In the first case, complement activation occurs, its active fragments are formed, causing cell damage and even their destruction. In the second case, so-called K-cells attach to the antibodies fixed on the surface of the target cell. Typically, this is a special type of lymphocyte that produces a superoxide anion radical (a reactive form of oxygen) that damages the target cell. Damaged cells are phagocytosed by macrophages. The cytotoxic type of reactions includes such manifestations of drug allergies as leukopenia, thrombocytopenia, hemolytic anemia, etc. The same type of reaction is observed when allogeneic antigens enter the body, for example, during blood transfusion (in the form of allergic blood transfusion reactions), with hemolytic disease of newborns.

The third type of allergic reactions is tissue damage by immune complexes (Arthus type reaction, immune complex type; rice. 3 ). In these cases, the allergen is present in soluble form (bacterial, viral, fungal antigens, drugs, nutrients). The resulting antibodies belong mainly to the IgG and IgG classes. These antibodies are called precipitating antibodies for their ability to form a precipitate when combined with the corresponding antigen. Under certain conditions, such an immune complex can be deposited in tissues, which is facilitated by increased permeability of the vascular wall; formation of a complex in a small excess of antigen; a decrease in the activity of phagocytic cells, which leads to inhibition of the process of cleansing the body of immune complexes and to an increase in the time of their circulation in the body. The complexes deposited in the tissues interact with complement. Its active fragments are formed, which have chemotactic activity, stimulate the activity of neutrophils, increase vascular permeability and promote the development of inflammation. Neutrophils phagocytose immune complexes and secrete lysosomal enzymes. Proteolysis increases in places where immune complexes are deposited. The kallikrein-kinin system is activated. As a result, tissue damage occurs and inflammation occurs as a reaction to this damage. The third type of allergic reactions is the leading one in the development of serum sickness , exogenous allergic alveolitis , in some cases of drug allergies and food allergies, in a number of autoallergic diseases ( rheumatoid arthritis , systemic lupus erythematosus, etc.).

The fourth type of allergic reactions is a delayed-type allergic reaction (delayed-type hypersensitivity, cellular hypersensitivity). In this type of reaction, the role of antibodies is performed by sensitized lymphocytes that have structures on their membranes similar to antibodies ( rice. 4 ). A delayed-type reaction in a sensitized organism manifests itself after 24-48 h after contact with an allergen.

Delayed reactions are based on the formation of so-called sensitized T-lymphocytes (T-killers). In chronic infections, such as tuberculosis, brucellosis, toxoplasmosis, viral hepatitis, the pathogen multiplies intracellularly, and there is a need to destroy infected cells, which is carried out by T-killers - a subpopulation of T-lymphocytes capable of recognizing infected cells. During this reaction, interleukins and other mediators are released, which initially attract neutrophils to the scene of events. Then the neutrophil infiltration gives way to mononuclear infiltration, epithelioid cells appear and a granuloma is formed. Contact dermatitis is also caused by delayed reactions: simple chemical compounds, such as chromium salts, attach to the proteins of skin cells, and these proteins become foreign to the body (autoallergens); sensitization develops, and with repeated contact with the allergen, disease occurs. Delayed allergic reactions to opportunistic microorganisms (staphylococci, streptococci, fungi) underlie such allergic diseases as infectious-allergic bronchial asthma and rhinitis, allergic conjunctivitis, etc.

The activation of one or another immune mechanism is determined by the properties of the antigen and the reactivity of the body. Among the properties of an antigen, its chemical nature, physical state and quantity are of greatest importance. Antigens found in the environment in small quantities (plant pollen, house dust, dander and animal fur) are more likely to cause atopic allergic reactions. Corpuscular, insoluble antigens (bacteria, fungal spores) usually lead to delayed allergic reactions. Soluble allergens (antitoxic serums, gamma globulins, bacterial lysis products), especially in large quantities, usually cause allergic reactions of the third (immune complex) type. The appearance of foreign antigens on cells causes the development of allergic reactions of the cytotoxic type.

An allergen, as the cause of an allergic disease, acts on the body under certain conditions, which can either aggravate its effect, leading to the development of the disease, or complicate it, thereby preventing the occurrence of the disease. Conditions can be external (amount of allergen, duration and nature of its action) and internal. Internal conditions are presented in a generalized form by the reactivity of the body. It depends on the hereditary characteristics of the structure and functioning of the body's systems and those properties that the body acquires during its life. This combination of hereditary and acquired properties largely determines whether a disease will exist or not. Therefore, it is possible to change the body’s reactivity in a direction that makes it difficult to realize the effects of potential allergens.

Any irritant has a dual effect on the body: specific and nonspecific. The first is related to the quality of the stimulus, its ability to cause strictly defined changes in the body. A nonspecific effect is a consequence of the ability of a stimulus to lead to an imbalance in the system, regardless of where it is caused. Allergen (antigen) is no exception. The specific action of the allergen is aimed at the immune system, which has the corresponding receptors. The immune system responds to the allergen with a certain reaction in accordance with the internal laws of functioning according to the program that is embedded in it. The effect of the program is determined by hereditary and acquired properties, for example, it has been established that the immune response to each antigen is determined genetically. The class, subclass, allotype and idiotype of the antibodies formed depend on the characteristics of the functioning of the structural genes of immunoglobulins. Immune response genes (lr-genes) determine the intensity of the immune response by the number of antibodies formed and (or) the severity of a delayed-type allergic reaction mediated by sensitized lymphocytes. Hereditary or acquired defects in certain parts of the immune system can contribute to the development of allergic reactions. Thus, with insufficient activity of a certain subpopulation of T-suppressors, the formation of lgE increases, which can lead to the occurrence of atopic sensitization. Deficiency of secretory lgA contributes to the penetration of allergens through the mucous membranes of the respiratory tract or gastrointestinal tract and the development of allergic reactions of both atopic and other types .

The immune system functions according to its own internal laws and programs, but its activity, like all other systems, is integrated and regulated in the interests of the whole organism by the neuroendocrine system. Through it, the body adapts to constantly changing environmental conditions and to the action of its various factors. These factors, often unfavorable for the body, either directly or through the neuroendocrine system have a modulating effect on the function of the immune system. The possibility of such an influence is ensured by the presence on its cells of appropriate receptors for nervous system mediators and hormones.

Clinical observations show that the course and development of allergic diseases depend on the state of the higher parts of the nervous system (for example, exacerbation of the course of allergic diseases against the background of psycho-emotional stress under the influence of negative emotions, the development of acute allergic reactions to a number of food and other allergens after traumatic brain injury). Higher departments of the c.s.s. have a pronounced effect on the manifestations of bronchial asthma. Various types of such influence have been described: from the typical psychogenic development of bronchial asthma in a certain situation to cases where strong negative emotions inhibited a previously developed attack of bronchial asthma. The influence of the higher departments of the central scientific research team largely realized through the Hypothalamus . This explains the fact that dysfunction of the hypothalamus itself also affects the development of allergic reactions. Thus, with A., signs of pathology of the autonomic nervous system are often detected. Activation of its sympathetic or parasympathetic departments has different effects on the development and course of an allergic disease. At the same time, many researchers point to the role of local, rather than generalized dystonia of both parts of the autonomic nervous system. The influence of the nervous system is realized in tissues through cholinergic and adrenergic receptors present on cells, by changing the activity of endocrine glands, the regulatory centers of which are located in the hypothalamus, as well as through the formation of neuropeptides.

Clinical and experimental observations show that changes in the hormonal profile of the body can significantly influence the occurrence and course of allergic processes, and their development is accompanied by dysfunction of the endocrine glands. Activation of the pituitary-adrenal and sympathetic-adrenal systems under stressful conditions inhibits the development of inflammation and allergic reactions in some cases. On the contrary, anaphylactic shock and a number of other allergic reactions in adrenalectomized animals are severe. A severe allergic reaction, as well as stress, causes activation of the pituitary-adrenal system. This activation is non-specific, secondary and is a response to damage. At the same time, allergic alteration occurring in the adrenal glands themselves blocks the synthesis of cortisol to one degree or another and often enhances the formation of corticosterone. Repeated exacerbations of allergic processes lead to depletion of this system, therefore, in patients with long-term severe allergic diseases, a certain degree of insufficiency of the adrenal cortex is always detected.

The role of sex hormones in the development and course of allergic processes is indicated by numerous clinical observations. In some cases, the development of allergic diseases is associated with menstrual irregularities or the onset of menopause. There is a connection between the intensity of the clinical manifestations of the disease and the phase of the menstrual cycle. The premenstrual period is critical in this regard. Urticaria and allergic rhinitis become especially acute during this period. During pregnancy, an improvement in the course of some allergic diseases was noted.

Dysfunction, especially hyperfunction, of the thyroid gland is a factor contributing to the development of A. Against the background of hyperthyroidism, the drugs used often cause drug allergies. Experiments have established that modeling hyperthyroidism promotes the occurrence of sensitization and allergic reactions, and reproducing hypothyroidism inhibits them. At the same time, the introduction of a large amount of thyroid hormones stops the development of allergic reactions. In patients with bronchial asthma, both hypofunction and (more often) hyperfunction of the thyroid gland are detected, which is determined by the form, severity and duration of the disease.

Insulin and closely related states of hyper- and hypoglycemia have a certain effect on A. It is believed that hyperglycemia (for example, with alloxan diabetes) inhibits the development of a delayed-type reaction of anaphylactic shock, and hypoglycemia (insulin administration) enhances them. There is evidence that allergic diseases in diabetes mellitus and diabetes mellitus in patients with allergic diseases are somewhat less common than in the general population.

The role of the parathyroid glands is evidenced by the development of some signs of hypoparathyroidism (Erb's and Chvostek's symptoms, sometimes short-term tetanic convulsions of the limbs) in patients with bronchial asthma and the beneficial therapeutic effect of parathyroid hormone in bronchial asthma and urticaria.

The thymus gland (thymus) has a significant influence on the development of allergic reactions. Many humoral factors obtained from thymus extracts have been described, but so far the existence of only four hormones has been recognized as reliable: thymosin-1, thymopoietin, thymic humoral factor and the zinc-containing hormone thymulin. They are polypeptides and act at different stages of T-cell maturation. Insufficient formation of these hormones causes varying degrees of insufficiency of the immune system, which leads to inhibition of the development of delayed-type allergic reactions, a decrease in antibody synthesis to varying degrees, and often to an increase in IgE antibodies.

Under the influence of the neuroendocrine system, the activity of processes occurring in the immunological, pathochemical and pathophysiological stages of the allergic process changes. In the immunological stage, the intensity of antibody formation, their ratio and belonging to different classes of immunoglobulins, as well as the formation of sensitized lymphocytes depend on the influence of this system. This does not mean that in the c.s.s. there is a special center for the regulation of immunological reactions, although such a point of view has been expressed. The antigen response program is centered in the immune system. The influence of mediators and hormones in the immunological stage is realized through changes in intercellular interaction, migration and recycling of hematopoietic stem cells, intensity of antibody synthesis, through the formation and action of lymphokines, monokines and other regulatory signals within the immune system. In particular, through the opioid receptors of lymphoid cells, the activity of natural killer cells increases, the formation of α-interferon and interleukin-2, the release of histamine from mast cells and the number of different T-cell subpopulations increase.

In the pathochemical stage, the neuroendocrine system influences the amount of mediators produced. Thus, IgE-mediated release of histamine from basophils and mast cells is enhanced by stimulation of the parasympathetic nerve. The sympathetic department inhibits its release. The ratio between mediators is of great importance, because they often had opposite effects (for example, prostaglandins of group E and F), as well as the relationship between mediators and enzymes that cause their inactivation (for example, histamine - histaminase, leukotrienes - arylsulfase, etc.).

In the pathophysiological stage, the neuroendocrine system changes the sensitivity of tissues to the action of mediators. An important role in this belongs to the activity and number of receptors, because all mediators exert their influence on cells through the corresponding receptors (for example, a decrease in the activity of β-adrenergic receptors on smooth muscle and other cells in patients with bronchial asthma). This leads to a predominance of activity of cholinergic receptors, kinin receptors and, obviously, some others. Therefore, sensitivity to acetylcholine and kinins, which cause a bronchoconstrictor effect at concentrations that have no effect on healthy people, increases. The state of permeability of the microvasculature also plays an important role in the manifestation of the pathophysiological stage. Increased permeability, as a rule, increases the manifestations of allergic reactions.

All hormones also exert their influence on cells through the corresponding receptors. Some of them are located in the cytosol, others on the cell surface. In this regard, hormones of one group (androgens, estrogens, progestins and corticosteroids) penetrate the cell and bind to cytosolic receptors. The main effect of corticosteroid hormones is the activation of a particular gene, which is accompanied by increased formation of the corresponding enzyme.

Another group of mediators and hormones controls various metabolic processes in the cell from its surface. It includes protein and peptide hormones, catecholamines, kinins, histamine and other biogenic amines, acetylcholine. Lymphokines obviously act in the same way. These substances bind to the corresponding receptor on the surface of target cells, which leads to the activation of a number of intracellular mechanisms that regulate the functional state of cells.

It is becoming increasingly clear that the concentration and ratio of two nucleotides, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), are of primary importance in intracellular regulatory mechanisms. The therapeutic effect of a number of drugs ultimately depends on the concentration of these nucleotides. Thus, the β-adrenergic receptor is associated with the enzyme adenyl cyclase, under the influence of which cyclic AMP is formed from ATP. One of the known functions of the latter is that it either closes the calcium channel in the membrane and thereby inhibits the entry of Ca 2+ into the cell, or promotes its excretion. The resulting cAMP is hydrolyzed by phosphodiesterase to form an inactive product, which goes back to the formation of ATP. Pharmacologically, the content of cAMP in the cell can be increased either by stimulators of β-adrenergic receptors, or by phosphodiesterase inhibitors, or by a combined effect of both. The cholinergic receptor is associated with guanyl cyclase; its activation leads to the formation of cGMP, which stimulates the entry of calcium into the cell, i.e. its effect is opposite to that of cAMP. Hydrolysis of cGMP is carried out by its phosphodiesterase. The role of calcium is to activate protein kinases and phosphorylate proteins, which contributes to the implementation of the corresponding function.

In patients with allergic diseases, sensitivity to various environmental factors is altered. for example, an increase in the sensitivity of patients with infectious-allergic bronchial asthma, rheumatism, tuberculosis, and brucellosis to adverse meteorological conditions has been described. This is manifested by exacerbation of the underlying disease, instability of thermoregulation, vascular reactivity and other signs of dysfunction of the autonomic and central nervous system.

Various factors influence changes in the body's reactivity during sensitization. First of all, this is due to two sides of the action of the allergen - specific and nonspecific. As a specific irritant, an allergen activates the immune system. This change in activity is transmitted through the nerve pathways innervating the lymphoid organs, and possibly through the humoral route, to the central nervous system. and nonspecifically changes the activity of the corresponding structures. This allergen can also act as a stressor, also causing an imbalance in the system, which is accompanied by activation of certain brain structures. All this changes, usually briefly, the excitability of various parts of the central nervous system. and, accordingly, the body’s reaction to nonspecific irritation. These mechanisms are repeatedly enhanced and prolonged if the process is not limited only to sensitization. This can damage the tissues of various organs and the nervous system, which leads to long-term changes in the body’s reactivity.

II. Allergy (allergia; Greek allos other, other + ergon action)

a state of altered reactivity of the body in the form of increased sensitivity to repeated exposure to any substances or to components of its own tissues; A. is based on an immune response that occurs with tissue damage.

Nutritional allergy - see Food allergy.

Bacterial allergy (a. bacterialis) - A. to any type (or types) of bacteria or their metabolic products.

Viral allergy (a. viralis) - A. to components of viral particles or products of interaction of the latter with the cell.

Helminthic allergy (a. helminthica) - A. to any helminths or their metabolic products.

Gastrointestinal allergy (a. gastrointestinalis) - A. to any allergen, except food, manifested by severe reactions from the gastrointestinal tract.

Contact allergy (a. contactilis) - A. to substances that enter the body naturally through the skin, conjunctiva or oral mucosa.

Latent allergy (a. latens) - A., occurring during a given period of time without visible clinical manifestations.

Drug allergy (a. medicamentosa) - A. to any medications.

Microbial allergy (a. microbica) - A. to any microorganisms or products of their vital activity.

Food allergy (a. alimentaria; synonym A. alimentary) - A. to any food products.

Post-vaccination allergy (a. postvaccinalis) - A. that occurs as a result of vaccination.

Protozoal allergy (a. protozoalis) - A. to any organisms such as protozoa or to their metabolic products.

Occupational allergy (a. professionalis) - A. to any elements of the work environment (environment during professional activities).

Dust allergy (a. pulverea) - A. to house (household) dust.

Pollen allergy (a. pollinis) - see hay fever.

Heat allergy (a. thermalis) - physical A. to the effects of heat.

Tuberculin allergy (a. tuberculinica) - A. to mycobacterium tuberculosis or their metabolic products.

Physical allergy (a. physicalis) - A. to the action of any physical factors.

Cold allergy (a. ex frigore) - physical A. to the effects of cold.

Rice. 4. General mechanism for the development of a delayed type allergic reaction. After the formation of a complex consisting of a sensitized lymphocyte (1) and a target cell (2) containing an allergen (3), various lymphokines are released - interleukin-2, which stimulates B-lymphocytes, chemotactic factors causing chemotaxis of leukocytes, a factor that inhibits movement macrophages (MIF) and causing their accumulation, as well as lymphotoxin, which damages nearby cells, and other factors.

Rice. 3. General mechanism for the development of an allergic reaction of the immune complex type. The immune complex formed as a result of the combination of antigen (1) with antibody (2) is deposited in the wall of the vessel. Complement is fixed on it (3). The complexes are phagocytosed by neutrophils, which secrete lysosomal enzymes (indicated by arrows). Increased permeability is facilitated by the release of histamine and platelet-activating factor by basophils, which causes platelet aggregation (4) on endothelial cells (5) and stimulates the release of histamine and serotonin from platelets.

Rice. 2. General mechanism for the development of an allergic reaction of the cytotoxic type. In the upper part of the picture you can see a cell with antibodies fixed on it (1), complement (2) is depicted in the form of crescents. I - complement-mediated cytotoxicity is caused by complement (2) attached to antibodies (1) fixed on the target cell. As a result of activation, complement causes damage to the target cell membrane, which leads to its lysis. II - antibody-dependent cell-mediated cytotoxicity is caused by the attachment of K cells (3), which form a superoxide anion radical (O 2 -), damaging the target cell (indicated by an arrow). III - phagocytosis of a target cell opsonized by antibodies occurs through the interaction of antibodies fixed on the cell (1) with the Fc receptors of the phagocyte, absorption of the target cell by the phagocyte (4) and digestion of it. In addition, phagocytes engulf target cells damaged by complement-mediated (I) antibody-dependent cell-mediated cytotoxicity (II).

Rice. 1. The general mechanism for the development of an immediate-type allergic reaction, which has two phases: the development of the early phase of the reaction, or the classical pathway (I), and the development of the late phase of the reaction (II). In the development of the early phase of the reaction, mast cells (mast cells) and basophils take part, on which reagin antibodies are fixed (1). When the corresponding allergens (2) are attached to these antibodies, mediators are released from mast cells: histamine, which increases vascular permeability and causes spasm of smooth muscles, eozonophilic chemotactic factors (ECF), causing chemotaxis of eosinophils, high molecular weight neutrophil chemotactic factor (HNHF), ensuring chemotaxis of neutrophils, platelet-activating factor (TAF), which causes platelet aggregation and the release of histamine and serotonin from them. Eozonophils activated by mediators release secondary mediators: diamine oxidase (DAO), arylsulfatase (AS). Activated neutrophils release TAF and leukotrienes (LT). Macrophages, eosinophils and platelets take part in the development of the late phase of the reaction (II). Reagin antibodies are also fixed on them (1). When combined with the corresponding allergen (2), mediators are released from the cells that cause damage and the development of inflammation - cationic proteins, reactive oxygen species (ROS), peroxidase, as well as platelet-activating factor (TAF), leukotriene (LTV 4).

Question

General and specific immunoreactivity.

Reactivity is understood as the body’s ability to respond to irritations by changing its vital activity, which ensures adaptation to environmental conditions. It can be insufficient, excessive or perverted to the same antigenic stimulus. Reactivity was developed in the process of evolution. The higher an animal stands phylogenetically, the more complex its reaction to various environmental influences.

A narrower concept of reactivity is immunological reactivity - the body’s ability to exhibit protective immunological functions against pathogens of infectious diseases and provide a specific response to antigenic exposure.

There are general and specific immunological reactivity.

General - the potential ability of the body to respond with an immunological reaction to any antigenic stimulus.

Specific - the body’s ability to respond with an immunological reaction to a specific pathogen or antigen. As a rule, it develops after an encounter with the corresponding pathogen or antigen. Specific reactivity is part of general immunoreactivity.

For the formation of immunity, both categories are essential, i.e. general and specific immunoreactivity. These concepts correspond to the terms “nonspecific and specific resistance”.

Reactivity is the body's reaction to a foreign agent, and resistance is the state of the body's stability due to the body's reactivity.

According to modern concepts, pathogens of infectious diseases or antigens of any nature cause two types of reactions in the animal’s body: nonspecific - which are associated with general immunoreactivity (nonspecific-natural) and specific - which are associated with the qualitative originality of a given microorganism and are determined by the specific immunoreactivity of the body (specific resistance or immunity ).

Immunological reactivity is the most important expression of reactivity in general. This concept combines a number of interrelated phenomena.

1. Immunity of humans and animals to contagious (infectious) diseases, or immunity in the proper sense of the word.

2. Reactions of biological incompatibility of tissues:

a. heterogeneous, or phylogenous - when tissues of animals of one species enter the body of another species (for example, when horse serum is administered to a rabbit);

b. isogenic - when tissues of an animal of one immunological group enter the body of an animal of another immunological group within a given species (for example, transfusion of a different blood group to a person, organ transplantation);

c. individual - when the tissues of one animal enter the body of another within the same type of immunological group during the formation of pathologically altered tissues in the body (tumors, exudates, etc.);

d. reactions of interaction of embryonic tissues with tissues of an adult organism or with each other.

3.Hypersensitivity reactions (anaphylaxis and allergies).

4.Phenomena of addiction to poisons of various origins.

All these seemingly heterogeneous phenomena are united by the following characteristics.

1. All of the above phenomena and reactions occur in the body when “foreign” living beings (microbes, viruses), normal or painfully altered tissues, more or less denatured proteins, various antigens, toxins, alkaloids, etc. enter it. Reactions occupy a special place between embryonic tissues, the foreignness of which to each other is determined by the stage of embryo development.

2. These phenomena and reactions in a broad sense are reactions of biological protection aimed at preserving and maintaining the constancy, stability, composition and properties of each individual integral animal organism. Even severe hypersensitivity reactions in the form of anaphylactic shock are accompanied by destruction and cleansing of the body from the agent that caused the shock. Local hypersensitivity reactions are always accompanied by fixation of the pathogenic agent at the site of the reaction, which protects the body from the entry of this agent into the blood.

3. In the mechanism of the vast majority of reactions themselves, the processes of interaction of antigens with antibodies are essential.

In practice, the most important phenomena are immunity to infectious diseases. These phenomena are the most studied and form the basis of the doctrine of immunity.

Question

Allergy is the body's increased sensitivity to the effects of certain environmental factors called allergens.

Classification of allergic reactions according to Jell and Coombs, 1968.

The classification of allergic reactions according to Jell and Coombs is based on their division according to the type of pathogenetic immune mechanisms of development. There are 4 types of allergic reactions (see table).

The term “allergy” comes from two words: alios - different, different and ergon - act and is translated as a different, altered reaction. Allergy is a specifically increased sensitivity of the organism of a pathogenic nature to substances with antigenic properties. In 1963, Gell and Coombs divided allergic reactions into 4 groups depending on the type of immune tissue damage.

Type I. Anaphylactic reactions. They are caused by the interaction of antigens entering the body with antibodies (Ig E) deposited on the surface of mast cells and basophils. These target cells are activated. Biologically active substances (histamine, serotonin) are released from them. This is how anaphylaxis and atopic bronchial asthma develop.

Type II. Cytotoxic reactions. Antibodies circulating in the blood interact with antigens fixed on cell membranes (for example, blood group antigens Rh factor). As a result, the cells are damaged - cytolysis occurs. Type II reactions include autoimmune hemolytic anemia and hemolytic disease of the newborn.

Type III. These are reactions of immune complexes. Antibodies circulating in the blood interact with circulating antigens. The resulting complexes settle on the walls of blood capillaries, damaging the vessels. Type III is serum sickness of daily injections.

Type IV. Cell-mediated immune responses. They do not depend on the presence of antibodies, but are associated with the reactions of thymus-dependent lymphocytes (T-lymphocytes). T lymphocytes damage foreign cells. This is how transplant rejection and bacterial allergies develop.

Later, type V reactions were described - antireceptor (or stimulating) reactions. Antibodies interact with hormone receptors on the cell membrane. This leads to cell activation. This is how Graves' disease develops, characterized by an increase in the content of thyroid hormones in the blood.

24. Allergens: definition of the concept, classification.

Allergens are antigens that cause specifically increased sensitivity of the body - allergies. Allergens are divided into exogenous, which enter the body from the external environment, and endogenous, which are present or formed in the body itself. Exogenous allergens are divided into infectious and non-infectious by origin.

Infectious allergens: bacteria, viruses, fungi and their metabolic products. Non-infectious allergens are divided into:

Household (house dust);

Epidermal (dandruff, hair);

Medicinal drugs (antibiotics, sulfonamides, aspirin, novocaine);

Food;

Pollen;

Simple chemical compounds (washing powder).

The following ways of penetration of exogenous allergens into

organism:

Percutaneous (cutis - skin),

Inhalation,

Enteral,

Injectable.

Endogenous allergens (autoallergens) are divided into natural (primary) and acquired (secondary). Natural autoallergens are contained in “beyond-barrier” organs and tissues (in the lens of the eye, thyroid colloid, gray matter of the brain, testes). In the process of evolution, they were separated from immune cells by barriers. When these barriers are disrupted due to injury or inflammation, the cells and tissues behind the barrier are perceived by lymphocytes as “foreign,” with subsequent damage.

Acquired autoallergens can be non-infectious and infectious. Non-infectious ones are formed from their own proteins under the influence of high and low temperatures and ionizing radiation. Infectious autoallergens are formed due to the influence of microorganisms on the proteins of the macroorganism.

There are several classifications of allergies, which are based on different criteria. The most reasonable, significant and informative are the criteria based on the characteristics of the pathogenesis of hypersensitivity reactions (Gell and Coombs classification), the nature of the allergens, the origin of the allergenic AT or sensitized lymphocytes and the time of development of clinical manifestations after exposure to the resolving agent.

Types of allergic reactions

The widely accepted classification of Gell and Coombs divides hypersensitivity into four main types (depending on the mechanisms involved in their implementation). Many immunopathological processes are mediated by a combination of several hypersensitivity reactions.

Type 1 – reagin (anaphylactic). Antibodies are on the cell, antigens come from outside. Urticaria, bronchial asthma, hay fever.

Type 2 – cytolysis reactions. The antigen is a component of the cell or is sorbed on it, and the antibody enters the tissue. Effect of large doses of Bogomolets antireticular cytotoxic serum.

Type 3 – reactions such as the Arthus phenomenon. Antigen and antibody are found in the blood and intercellular fluid. Precipitates form around the vessels and in the vascular wall.

Type 4 – delayed hypersensitivity reactions. T lymphocytes interact with the antigen. Tuberculosis, syphilis, viral infections, contact dermatitis, implant rejection.

Type 5 – stimulating allergic reactions. As a result of the action of antibodies on cells with antigen, the function of these cells is stimulated. Autoimmune mechanism of Graves' disease (hyperfunction of the thyroid gland).

The nature of sensitizing and resolving allergens

Specific allergy. In most cases, a clinically pronounced allergic reaction is caused by repeated entry into the body or the formation in it of the same allergen (it is called resolving), which, upon first exposure, sensitized this organism (i.e., caused the production of specific AT and T-lymphocytes). This type of allergy is called specific.
Nonspecific allergy. So-called nonspecific allergic reactions often develop.
- Paraallergy. When protein allergens (both sensitizing and permissive) have a close, but not identical structure, paraallergic reactions develop (for example, during mass vaccinations against various diseases with short time intervals between them).
- Heteroallergy. Another option for nonspecific allergies is heteroallergy. It occurs in cases where the resolving agent is some non-antigenic effect - cooling, overheating, intoxication, irradiation of the body, etc. An example of heteroallergy is the development of acute diffuse glomerulonephritis or periodic exacerbation of chronic glomerulonephritis after exposure of the patient to any of the above factors. The direct resolving agent in such cases is, obviously, not the cooling itself, intoxication or irradiation, but those substances (allergens) that are formed in the body under the influence of these factors.

Genesis of allergenic AT or sensitized lymphocytes

Active allergy. In most cases, an allergic reaction is actively formed in the body, i.e. in response to the introduction or formation of an allergen in the body. This type of allergy is called active.
Passive allergy. If the development of an allergic reaction is the result of the ingestion of blood or its components containing allergic ATs into the body (for example, blood transfusion or blood plasma), or lymphocytes from a previously allergenic organism, then such a reaction is called passive, transferred, transplanted.