Household allergens Among them, the main role is played by house dust, which includes dust particles from carpets, clothes, bed linen; fungi on the walls of damp rooms; particles of domestic insects (bugs, cockroaches, bed mites). This group also includes the so-called

Food allergens Almost all of them can be food products. But more often than others, allergies are caused by milk, eggs, meat, fish, crayfish, tomatoes, citrus fruits, strawberries, wild strawberries, and chocolate. When allergens enter the body through gastrointestinal tract(GIT)

A point that stimulates the development of intelligence, consciousness and internal discipline, as well as growth and physical development in children. Impact on the Tai-Bai point (Fig. 2) with a tonic or harmonizing method in the period from noon to midnight promotes development of intelligence,

Chapter 2 Types of allergic reactions All allergic reactions can be divided into 2 according to the time of occurrence large groups: if allergic reactions between the allergen and body tissues occur immediately, then they are called immediate-type reactions, and if after

Types of allergic reactions Depending on the time of occurrence, all allergic reactions can be divided into 2 large groups: if allergic reactions between the allergen and body tissues occur immediately, then they are called immediate-type reactions, and

Type I allergic reactions The first type includes allergic reactions (hypersensitivity) of the immediate type. They are called atopic. Allergic reactions immediate type are the most common immunological diseases. They amaze

Type II allergic reactions The second type of allergic reactions is called cytotoxic immune reactions. This type of allergy is characterized by connections first of the allergen with cells, and then of antibodies with the allergen-cell system. With such a triple connection and

III type allergic reactions The third type of allergic reactions is immunocomplex, it is also called “disease immune complexes" Their main difference is that the antigen is not associated with the cell, but circulates in the blood in a free state, without attaching to components

Type IV allergic reactions Antibodies are not involved in type IV reactions. They develop as a result of the interaction of lymphocytes and antigens. These reactions are called delayed-type reactions. Their development occurs 24-48 hours after entering the body

Stages of allergic reactions All allergic reactions progress through certain stages. As is known, when an allergen enters the body it causes sensitization, that is, immunologically increased sensitivity to the allergen. The concept of allergy includes

Allergens Many people suffer from common foods due to food allergies. Over 170 foods have been identified as causing immediate allergic reactions, which can range from mild (stomach upset) to life-threatening (asthma and anaphylactic reactions).

Introduction

In recent decades, it has been celebrated all over the world a sharp increase cases of allergy diseases. What is this connected with? First of all, with the deteriorating environmental situation. The so-called antigens that provoke an allergic reaction can enter the body with food, inhaled air, or through contact with mucous membranes or skin. Contact with pets, various chemicals, pollen or dust results in unpleasant symptoms for many. To cope with allergies, you need qualified help from an allergist. It is he who will order an examination and identify the real reason allergies and prescribe adequate treatment. Self-medication in case of allergies will not only not help, but can also cause irreparable harm. Medicine has described cases of fatal allergic reactions to the most seemingly ordinary foods or after contact with animals. About what happens in the body after an antigen enters, how to prevent the development of allergies, what are the urgent measures If an allergic reaction occurs, you will find out by reading this book.

This guide describes in detail modern methods diagnostics allergic diseases, traditional and unconventional methods and the principles of their treatment, a description of the drugs used for allergies is given, as well as the nutritional features of patients with allergies and physical therapy exercises. A separate chapter is devoted to the prevention of allergic diseases.

Chapter 1
Allergic reactions – hypersensitivity reactions

The immune response is a series of molecular and cellular reactions that occur in the body after exposure to an antigen, resulting in the formation of humoral or cellular immunity. The development of one or another type of immunity is determined by the properties of the antigen, the genetic and physiological capabilities of the body. During this period, the body’s ability to quickly respond to this is formed by neutralizing and removing microorganisms and substances that have invaded the body and change the properties of the antigen. In some cases, with excessively strong and long-term exposure antigen, the immune reaction becomes damaging to the body. This reaction is called a hypersensitivity reaction, or allergic reaction.

Depending on the rate of development, an immediate-type hypersensitivity reaction and a delayed-type reaction are distinguished.

Features of humoral immunity

Three types of cells take part in humoral immunity:

– macrophages;

– T-lymphocytes;

– B lymphocytes.

Macrophages phagocytose the antigen and, after intracellular proteolysis, present its peptide fragments on their cell membrane to T helper cells. T-helpers cause activation of B-lymphocytes, which begin to profile, transform into blast cells, and then, through a series of successive mitoses, into plasma cells that synthesize antibodies specific to a given antigen. Immune-competent cells produce regulatory substances, cytokines.

To activate T-helper cells, the effect of interleukin 1, secreted by a macrophage upon contact with an antigen, is necessary, interleukin 2, and for the activation of B-lymphocytes - lymphokines produced by T-helper cells - interleukins 4, 5, 6.

Plasma cells synthesize antibodies in the form of immunoglobulin molecules. There are 5 classes of immunoglobulins - A, M, G, D and E.

JgA (immunoglobulins A) make up 15% of the total number of immunoglobulins, they are contained in secretions and provide protection against toxins and pathogenic substances.

JgM (immunoglobulin M) is a high molecular weight immunoglobulin found in blood serum. It makes up 10% of the total number of immunoglobulins. These are the first antibodies that are produced after infection and immunization, but more often by antibodies to immunoglobulin G.

JgG (immunoglobulin G) makes up 75% of serum immunoglobulins. They can be found in the intercellular fluid and are capable of fixing complement. These immunoglobulins effectively appotylite particles, neutralize particles, bacteria.

JgD (immunoglobulin D) is found in traces and, together with JgM, can bind antigens.

JgE (immunoglobulin E) is found in very small quantities. When mast cells bind antigens, they trigger the release of histamine, the slow-reacting substance of anaphylaxis, eosinophil chemotaxis factor and other mediators responsible for immediate hypersensitivity reactions. When antibodies combine with an antigen, they form immune complexes.

Elimination of the allergen occurs due to activation of the complement system, leading to the destruction of bacterial or other foreign cells.

The complement system is a group of plasma proteins, the activation of which leads to the release of histamine from mast cells and platelets, an increase in vascular permeability, and a reduction in smooth muscle, neutralization of certain substances, cell lysis.

Features of cellular immunity

T lymphocytes take part in cellular immunity, which manifests itself in delayed-type hypersensitivity. These cells recognize antigen bound to the cell membrane. In the presence of antigens, T cells turn into T-blast forms of cells, then transform into T-effectors, which secrete biologically active substances - lymphokines (or mediators of delayed-type hypersensitivity). Under their influence, these cells accumulate in places of antigenic irritation. Due to this, macrophages, neutrophils, basophils, and eosinophils are attracted to the site of antigenic irritation. Target cells can be lysed due to the synthesis of lymphotoxin.

Another group of T-killer cells is represented by lymphocytes that are cytotoxic to cells infected with viruses, tumor cells, and allografts.

In another mechanism of cytotoxicity, antibodies recognize target cells and effector cells respond to these antigens.

Zero cells, monocytes, and lymphocytes have this ability.

Allergens

As a result of the interaction of the body's immunocompetent system with the allergen, specific sensitization develops, which is accompanied by clinical manifestations that are considered an allergic disease.

Allergens are all substances that carry genetically foreign information and, when they enter the body, cause specific immune reactions. They can be substances of organic or inorganic nature (antigenic or non-antigenic, simple substances - iodine, chromium, platinum) or complex protein or protein-polysaccharide and protein-lipid complexes (serum, tissue, bacterial, fungal), as well as false compounds of non-protein nature , for example allergens house dust.

Allergens can be medicines, dyes and detergents, various synthetic polymers, cosmetics and perfumes.

Simple low-molecular-weight products can acquire allergenic properties in the body after binding to serum and tissue proteins. Exoallergens are numerous substances that enter the body from the outside.

Exoallergens include allergens of non-infectious origin:

1) household (house dust, library dust, daphnia);

2) medicinal (antibiotics, etc.);

3) epidermal (human epidermis, animal epidermis, bird feathers, wool, hair, fur);

4) pollen (flowers of cultivated plants, flowers wild plants, meadow grasses, weeds, trees, shrubs, agricultural crops);

5) chemical substances(gasoline, benzene, etc.);

6) food allergens (livestock meat, poultry meat and eggs, fish products, herbal products, as well as dairy products);

7) insects (stinging, blood-sucking, arachnids).

Infectious allergens include:

1) bacterial – different kinds pathogenic and non-pathogenic bacteria, their metabolic products;

2) fungal allergens (pathogenic and non-pathogenic fungi), pathogens of fungal diseases, mold; 3) various types of viruses; 4) various types of protozoa; 5) saprophytes and opportunistic organisms.

Molds cause allergies in 30% of cases, food additives – in 21%, house dust mites – 20%, pollen – 16%, food – 14%, medications– 12%, pets – 8%.

The most common food allergens (listed in order of frequency of reaction):

- cow's milk;

– chicken eggs;

– vegetables (celery, tomatoes);

– grains;

– spices;

- yeast.

One patient may be allergic to several pathogens.

Main allergens and factors causing exogenous allergic diseases

Types of allergic reactions

The main cause of allergic reactions is congenital or acquired failure of the function of regulatory suppressor cells.

Genetic predisposition in patients is associated with inherited characteristics of the body. If allergies are registered in both parents, then their children inherit atopy in 50%. If only one parent had an allergy, the risk of getting sick is 30%. Action of products environment does not need explanation, but an important place is occupied by allergy mediators, including histamine, which is an endogenous toxin and is eliminated through the liver. If the liver is overloaded and the body cannot remove histamine, allergic symptoms occur.

The variety of allergic reactions has led to the creation of a large number of classifications of allergic reactions.

Ado A.D. (1978) divides all true allergic reactions into 2 large groups:

1) immediate type reactions (or reactions with circulating antibodies);

2) slow reactions (or cellular type).

In the pathogenesis of immediate-type allergic reactions, 3 stages are distinguished: immunological, pathochemical and pathophysiological.

The immunological reaction is an allergen-antibody reaction; it determines the development of the entire complex of processes and its specificity. The pathochemical stage develops as a result of an antigen-antibody, when a number of biologically active substances. The third stage is a consequence of the second stage and is a complex of disorders that characterize the clinical picture of allergic reactions.

The allergic response consists of 3 phases: sensitization, immediate allergic reaction and delayed allergic reaction.

The sensitization process can take up to 4 years until mast cells begin to stimulate an allergic response to a specific allergen.

At cross allergies an allergic response can occur without prior sensitization (for example, to penicillin drugs). Previous sensitization may be caused by an environmental allergen. Therefore, the first contact can provoke a severe allergic reaction.

Cross-allergy is typical for food allergens: grass pollen can cause cross-reactions to tomatoes and cereals, natural latex can cause cross-reactions to bananas and avocados.

An immediate allergic reaction develops after preliminary exposure of the allergen to mast cells with the formation of JgE.

Mediators, such as histamine, increase vascular permeability and fluid flow. Leukotrienes and prostaglandins cause inflammation. Basophils and other immunocompetent cells are involved in the process. Clinical manifestations of this reaction are itching and sneezing.

The delayed-type reaction is due to the action of cytokines that are produced by mast cells and T-2 lymphocytes 4–10 hours after repeated exposure. The main cells associated with a delayed allergic reaction.

Depending on the type of tissue damage, there are 4 types of allergic reactions.

Type I – anaphylactic reaction. This is an immediate hypersensitivity reaction with anaphylaxis and reagin reaction. At the first contact with the antigen, predisposed individuals produce antibodies - reagins, JgE, they are fixed on the membrane of mast cells, basophils, and smooth muscle cells. Upon repeated contact with the antigen, immune complexes are formed. This stimulates mast cell degranulation and the release of biologically active substances such as histamine, slow-reacting substance of anaphylaxis, eosinophil chemotactic factor.

Clinical type I reaction is detected when:

– anaphylactic shock;

– urticaria;

– angioedema;

– vasomotor rhinitis;

– bronchial asthma.

Type II – cytotoxic reaction. In this type of reaction, antibodies such as immunoglobulin JgG and JgM circulate freely in the blood, while endogenous or exogenous antigens are attached to the cell membrane.

The complement system is involved in antibodies (JgM).

With the participation of complement, the metic or inflammatory activity of the cell is manifested. The antibodies produced are specific to the popular membrane and wall of the lungs blood vessels. These antigen-antibody reactions lead to glomerulonephritis and pulmonary vasculitis. This is manifested by hemoptysis. In addition, a type II reaction can cause the formation of cytotoxic antibodies against any tissue.

A cytotoxic reaction occurs during immunohemolysis with drug allergies, post-transfusion complications.

Type III is an immune complex reaction, which can be characterized by an Arthus phenomenon type reaction (or an immune complex reaction). This reaction of the humoral type occurs 2–6 hours after antigenic stimulation, during which precipitating antibodies combine with the antigen. This is accompanied by the formation of microprecipitates inside and around small vessels, leading to thrombosis and destruction of the vessels. The higher the level of antibodies, the greater the intensity and duration of reactions in which neutrophils are destroyed with the release of lysosomal enzymes. Allergic reactions of this type include systemic lupus erythematosus, characterized by the deposition of immune complexes in various areas, as well as the glomerulonephric membrane, pleura, pericardium, synovial membranes, vessels, complexes.

In addition, an example of an allergic reaction of this type can be systemic serum sickness and local reaction, which develops in the event of the introduction of an antigen, eye damage in the form marginal keratitis and some other damage to the organs of vision.

Among the diseases of the “complexes” are exogenous allergic alveolitis, post-streptococcal glomerulonephritis, ulcers small intestine for typhoid fever, rheumatoid arthritis and etc.

Type IV allergic reaction is a delayed-type hypersensitivity reaction. It is cellular. Humoral antibodies and the complement system do not take part in it. Sensitized T lymphocytes, activated by antigens, turn into cytotoxic cells capable of killing bacteria on other target cells. Effector T lymphocytes, using hypersensitivity mediators, stimulate other lymphocytes, neutrophils and macrophages.

The latter also cause damage. These reactions of cellular immunity occur during tuberculosis and fungal diseases, in addition, they cause the development of goiter and contact dermatitis. This type of reaction is observed in transplants and also in bone marrow transplants.

IN clinical settings In the pathogenesis of many allergic diseases, it is difficult to differentiate the types of reactions, since there is often a combination of these reactions. In each specific case, it is important to correctly identify the predominance of one or another type of allergic reaction.

Characteristics of immediate and delayed types of hypersensitivity (according to V.V. Medunitsin)

Chapter 2
Diagnosis of allergic diseases

To make a diagnosis of an allergic disease, a thorough general clinical examination is necessary, as well as additional methods studies to identify specific allergens. To identify allergies in a patient, you need:

– taking anamnesis;

– physical examination;

– immunological study.

Specific diagnosis of allergic diseases includes, in addition to collecting anamnesis, allergological, immunological and instrumental research methods.

Anamnesis

Taking an anamnesis is the most universal method for diagnosing allergies; it is necessary for the correct selection of further examination, exclusion of non-allergic diseases, and prescribing adequate effective treatment. Main factors of the study allergy history: 9 causes and time of appearance of the first symptoms of the disease;

– general well-being, characteristics of the patient’s main complaints by organs and systems;

– the dynamics of the occurrence of symptoms depending on the season, by day, month, year, season, in different places;

– hereditary predisposition;

– factors influencing the course of pregnancy (factors of intrauterine sensitization, excess carbohydrates in the pregnant woman’s diet, taking medications, blood group incompatibility, smoking, various diseases and etc.);

– study of the food regime, diet features, food diary, reactions to various foods;

– if possible, identify causes that may predispose to allergies (for example, diseases digestive system, taking antibiotics, preventive vaccinations, perinatal lesions central nervous system, contact with animals, insect bites, changes in residence, season of the year, weather conditions, etc.);

– previous antiallergic treatment, its effectiveness;

– results of previously conducted examinations, their results;

– living conditions of the patient;

– the patient’s profession and occupational hazards.

A correctly collected anamnesis allows the allergist to suspect an allergen or group of allergens for specific diagnosis.

Skin tests

The method is based on the determination of antibodies not only in the shock organ, but also on the skin (reagins).

The following skin tests are distinguished:

– drip;

– application;

– scarification;

– scarification and application;

– intradermal.

In allergy diagnostics, skin tests, as they are more accessible, are used quite often. When the corresponding allergen is applied to the skin, it provokes specific reaction antigenantibody, accompanied by the release of biologically active substances (histamine, etc.), which after 15–20 minutes cause the formation of a blister surrounded by a zone of hyperemia (immediate type reaction, blistering), which occurs after 15–20 minutes. In delayed-type reactions, lymphoid cells are of primary importance with the formation of an infiltrate after 24–48 hours. The history and clinical picture of the disease indicate which allergens need to be tested with skin.

To avoid local and general complications, skin tests are performed no earlier than 7–10 days after the acute allergic reaction has subsided. Antihistamines and corticosteroids are discontinued 1–2 days before the study. With general hormone therapy, which suppresses general and local allergic reactions, skin tests are performed only 2 months after discontinuation of corticosteroids.

Indications for skin tests are medical history, indications of the role of a particular allergen or group of allergens in the history.

Currently, many both infectious and non-infectious allergens are known. Infectious allergens include:

– microbial;

– mold allergens;

– helminth allergens.

Non-infectious allergens include:

– pollen;

– household;

– epidermal;

– food;

– insect allergens.

Contraindications for skin testing are:

– exacerbation of the underlying disease;

– exacerbation of concomitant diseases;

– decompensated diseases internal organs;

– spicy infectious diseases;

– pregnancy, lactation, the first 2 days of the menstrual cycle.

A drop and skin test with rubbing of the allergen into intact skin is carried out if there is a suspicion of very high sensitivity. The test technique involves applying a drop of allergen to the skin of the forearm treated with 70% alcohol and after 15–20 minutes measuring the size of the papule and hyperemia.

Sometimes a drop of the food allergen is rubbed into intact skin with a stick. If there are no changes on the skin after 15–20 minutes, the tests are considered negative.

Usually, to control these tests, a drop of an isotonic solution is placed in parallel at a distance of 4–5 cm from the first sample. The test is usually performed with only one allergen.

The patch test is used more often for drug allergies. A drop is applied to the skin of the forearm medicinal substance, which is fixed with a piece of sterile gauze, and on top - with compress paper and adhesive tape. But it is more convenient to carry out tests using ready-made testoplast (a tape made of indifferent material, divided into squares, in the center of which a circle of 1 layer of filtered paper is fixed). An allergen or control solution is placed into the hole in the tape. Testoplast is removed after 24 hours. If skin itching the bandage is removed earlier.

The test is recorded 30 minutes after removal of the testoplast, 48 hours or more (up to 7 days) from the moment the sample is taken. Negative reaction is a skin reaction similar to the reaction with saline solution.

At positive reaction delayed type inflammatory phenomena occur in the form of erythema, edema, infiltration, papules, vesicles, depending on the degree of their severity.

The results of a positive reaction are assessed:

– erythema – +;

– erythema and swelling – ++;

– erythema, edema, onset of vesiculation – +++;

– erythema, edema, vesicles or ulcers – ++++.

Scarification tests are often carried out with various groups nonbacterial allergens. This test is specific and less dangerous than the intradermal test.

The test is performed on inner surface forearms: 0.5 cm long incisions are made with a scarifier at a distance of 3 cm from each other, an allergen or control examination is applied to the damaged skin. Up to 20–25 allergens are used in a single examination. The results of the reaction are assessed after 15–20 minutes.

The reaction is considered positive if a blister larger than 5 mm in diameter appears at the scarification site.

In the light of the problem under consideration, allergic reactions of the immediate type (or humoral) and delayed type (or cellular) are distinguished. Reactions of the humoral type are characterized by very rapid development (within a few seconds or minutes after the interaction of the sensitized organism and the allergen antigen). The mechanism for the development of such reactions is based on superficial serous inflammation, which disappears without a trace after a few hours. IN in this case great therapeutic effect give antihistamines.

Various protein substances (proteins of animal and plant origin) can have antigenic properties. They are capable of causing the induction (formation) of antibodies or specific cellular reactions. There are a huge number of substances that come into contact with antibodies, after which no further synthesis of antibodies follows. These are haptens.

By combining with body proteins, they acquire antigenic properties. The stronger the antigen, the higher and more rigid its molecular structure and the greater the mass of the molecule. Strong antigens are soluble allergens, weak antigens are insoluble, corpuscular, bacterial cells. There are endogenous allergens, which are present or formed in the body itself, and exogenous, which enter the human body from the environment. A.D. Ado proposed to classify exogenous allergens by origin into non-infectious and infectious. Non-infectious include:
1) simple chemical compounds ( detergents, perfumes, gasoline);
2) household (pollen, house dust);
3) food allergens of animal and plant origin (citrus fruits, egg whites, etc.);
4) epidermal (dandruff, wool);
5) medicinal (aspirin, sulfonamides, antibiotics
and etc.).

Non-infectious allergens are divided according to their source into: industrial (wool, flour dust); household (dust, wool) and natural (pollen from flowers, cereals and plants).

Infectious allergens are represented by fungi, viruses, bacteria and the products of their metabolism (life activities).

Exogenous allergens enter the body in various ways, for example, parenterally, enterally, inhalation and percutaneously (through the skin).
Endogenous allergens, or autoallergens, are divided into primary (natural) and secondary (acquired).

Natural antigens are found in the colloid of the thyroid gland, the gray matter of the brain, the lens of the eye, and the testes.

In some pathologies, due to the increased permeability of physiological barriers (blood-brain or histohematic), the so-called dystopia of these antigens from the above tissues and organs occurs, followed by their contact with immunocompetent cells, as a result of which autoantibodies begin to be produced. As a result, damage to the corresponding organ occurs.
Acquired (secondary) autoallergens are synthesized from the proteins of one’s own body under the influence of certain harmful agents ( ionizing radiation, low or high temperature, etc.). In particular, these mechanisms underlie radiation and burn illness.

Low temperature and cold are, of course, not an allergen, but this factor promotes agglutination (sticking together) of red blood cells with the active participation of anti-erythrocyte antibodies. The resulting agglutinins (clumped formations) trigger the activation of the complement system, which leads to the death of red blood cells.

Such phenomena can occur, for example, when alcoholic cirrhosis liver, infectious mononucleosis, mycoplasma infections.
It should be noted that under the influence of microorganisms, the proteins of the macroorganism form complex endoallergens and intermediate ones. Complex ones appear as a result of contact of the body’s own tissues with microorganisms or their toxins, which promotes the production of antibodies, their interaction with antigens and ultimately tissue damage.

Intermediate endoallergens are formed due to the combination of microorganisms with body tissues, but in this case a structure with completely new antigenic properties is formed.

There are thymus-independent antigens (when the immune response does not require the participation of T-lymphocytes-helpers) and thymus-dependent antigens (when the response of the immune system is possible with the obligatory participation of T-lymphocytes, B-lymphocytes and macrophages).

The classification of immediate allergic reactions includes:
1) anaphylactic (atopic) reactions;
2) cytotoxic reactions;
3) immune complex pathology.

1. Anaphylactic reactions are most often caused by allergens such as house and industrial dust, plant pollen and fungal spores, cosmetics and perfumes, epidermis and animal hair. They are called local anaphylactic reactions (urticaria, Quincke's edema, atopic bronchial asthma, allergic conjunctivitis and rhinitis). Sources of generalized allergic reactions ( anaphylactic shock) are allergens of hormones, antitoxic serums, blood plasma proteins, medications, and X-ray contrast agents. So the locals anaphylactic reactions occur when antigen enters naturally into the body and are found in places of fixation (mucous membranes, skin, etc.). Aggressor antibodies are isolated, belonging to the class of immunoglobulins E and G4, which have the ability to attach, for example, to mast cells, macrophages, platelets, basophils, neutrophils, eosinophils. In this case, there is a release of allergy mediators, in particular eosinophils produce cationic proteins, phosphatase D, histominase, arylsulfatase B; platelets release serotonin, mast cells and basophils - histamine, heparin arylsulfatase A, galactosidase, chemotrypsin, leukotrienes, prostaglandins, superoxide dismutase, neutrophil and eosinophil chemotoxic factors.
2. Also platelets, neutrophils, basophils, lymphocytes and endothelial cells are sources of platelet-activating factor. Allergy mediators are biologically active substances, with their help the so-called slow-reacting substance of anaphylaxis (MRS-A) is activated, which, in fact, causes anaphylaxis (a type of allergic reaction).

The development of such allergic reactions is represented by three stages:
1) immunological;
2) pathochemical;
3) pathophysical.

The stage of immune reactions, or immunological, begins with the accumulation of antibodies in the body after the introduction of a foreign antigen, which leads to the development of sensitization, or hypersensitivity body to this allergen. At this time, a clone of sensitized (sensitive) T-lymphocytes is formed. During the latent (hidden) period of sensitization, recognition and absorption of the allergen by the macrophage takes place, resulting in most of the antigen is destroyed under the influence of hydrolytic enzymes. The remaining part of the antigen is fixed on the A-cell membrane in complex with proteins. This complex is called a superantigen; it has a certain immunogenicity and is capable of activating the production of antibodies. This process is influenced by T-helpers and T-suppressors. It has been proven that even minor changes in their ratio can lead to serious disorders immunogenesis. The formation and release of allergy mediators constitutes the next stage of immune reactions - the pathochemical stage, in which the energy reserve of cells is of particular importance for the synthesis of mediators. The body becomes sensitized after about two weeks. When the allergen is re-entered, antigen-antibody complexes are formed. This moment is the trigger. Metabolism increases, new media are synthesized and released. There are two types of mediators that are released during immediate reactions.
Primary - this group is represented by serotonin, histamine, they are formed at the time of the antigen-antibody reaction.

Secondary - synthesized during the action of other cells and enzymes (for example, the mediator bradykinin).

According to their biological activity and chemical structure, mediators are divided into:
1) chemotactic (attracting certain cells
blood);
2) proteoglycans;
3) enzymes;
4) acting on smooth muscles and blood vessels.

1. Chemotactic mediators include the chemotaxis factor of neutrophils (a type of leukocyte) (FCN) and eosinophils (a type of leukocyte) (PCE). Neutrophil chemotaxis factors are responsible for stopping local action mediators, take part in modulating the release of biologically active substances. The most significant is histamine, which enhances or inhibits neutrophil chemotaxis, acting indirectly through H2 receptors or H2 receptors, respectively. The oxidation products of arachnoidic acid (leukotriene B4) also play an important role. After the start of the “antigen-antibody” contact, the release of a high-molecular neutrophil chemotaxis factor is observed within 5-15 minutes. Eosinophils migrate and accumulate in the lesion due to the eosinophil hemotaxis factor. The chemotaxis of eosinophils is also enhanced by other metabolic products, in particular arachnoidic acid, leukotriene B4, mono and hydroxy fatty acids, and histamine.

2. Proteoglycans. After the antigen is introduced into the body, a mediator is released that modulates (changes) the activity of trypsin (a destructive enzyme) and inhibits the functioning of the blood coagulation system. This is heparin, which is found in the granules of mast cells in the human skin and lungs and is closely related to histamine. Heparin contributes to the inhibition of complement functions. Proteoglycans such as chondrotin sulfates, found in basophils, have anticoagulant properties similar to heparin, but are approximately five times less active.

3. Enzymes as mediators of allergies are represented by neit; ral proteases (that break down proteins) (active bradykinin, pulmonary factor Hageman, tryptase) and acidic (peroxidase and hydrolase). Increased inflammatory processes, fibrin deposition near mast cells, inhibition of blood clotting - all this is controlled by enzymes such as acid hydrolases, in particular arylsulfatase, superoxide dismutase, peroxidase, beta-glucuronidase, beta-hexaminase.

4. Mediators acting on smooth muscles and blood vessels. A prominent representative is histamine, which is found in mast cells of the skin, lungs, and submucosal layer of the intestine. Histamine is in close ionic bond with heparin. Histamine is also found in basophils (a type of white blood cell), but in smaller quantities. The greater the concentration of antigen that enters the body, the higher the rate of histamine release. In small doses, it affects β-receptors, which, in turn, leads to a narrowing of the bronchi, pulmonary and coronary vessels, increased chemotaxis of eosinophils and neutrophils, increased synthesis of prostaglandins F2-alpha, E2, thromboxane and other products of arachnoidic acid metabolism. Activation of H receptors ensures increased secretion of mucus in the upper respiratory tract, an increase in the concentration of cGMP inside the cell, an increase in the permeability of blood vessels and their dilation, and, finally, stimulation of H receptors causes partial disconnection of connections between cells, which causes the development of urticaria or edema.

H2-histamine receptors are mostly located in the heart. Stimulation of these receptors is accompanied by dilation of the coronary vessels of the heart. Under their influence, secretion also increases of hydrochloric acid in the stomach. Normal level in the blood of this mediator should be 0.6 ± 0.2 ng/ml. Increasing it to 1.6 ng/ml leads to an increase in heart rate by 30%, to 2.4 ng/ml - headache, redness skin, up to 4.6 ng/ml - an even greater increase in the rate of contraction of the left ventricle and moderate hypotension, and above 30 ng/ml leads to cardiac arrest. It is necessary to take into account the fact that when any intravenous drug is administered, 10-30% of individuals may experience a release of several ng of histamine into the blood. The combination of such drugs sometimes leads to a total increase in histamine levels, which sometimes causes various complications.
In some cases, with an increase in histamine levels, activation of H2 receptors located on T-suppressors is observed, which is a trigger for the occurrence of attacks in patients with atopic bronchial asthma.

Another mediator that plays an important role is serotonin, which also affects blood vessels and smooth muscles. Serotonin is involved in the migration of sensitized leukocytes through the vascular endothelium (inner layer). Serotonin ensures platelet aggregation (sticking together) and also stimulates the secretion of lymphokines by T lymphocytes. In the presence of serotonin, permeability increases vascular wall and the smooth muscles of the bronchi contract.

In the third pathophysiological stage of immediate allergic reactions, after the formation and release of allergy mediators (in the pathochemical stage), the biological effects of these mediators develop and clinical manifestations. The most serious and dangerous manifestation of allergies is anaphylactic shock, in the development of which metabolites of arachnoidic acid play an important role. They are classified into:
1) cycloxygenase products: prostacyclin, thromboxanes,
prostaglandins;
2) lipoxygenase products: leukotrienes.

Prostaglandins are mediators that are synthesized
from arachnoidic acid with the participation of the enzyme cycloxygenase, the process occurs in most cases in mast cells of the parenchyma (tissue) of the lungs. These are mediators of inflammatory reactions, bronchospasm, and hypertension in the pulmonary artery system.
Leukotrienes are formed from fatty acids under the influence of the enzyme lipoxygenase. Three of them: C4, D4 and E4 constitute a slow-reacting substance (MRS-A). The effect of leukotriene C4 appears within ten minutes after the antigen enters the body and disappears after twenty-five to thirty minutes. This mediator increases the permeability of the microvasculature, causes bronchospasm, helps reduce cardiac output and increase systemic and pulmonary hypertension accompanied by leukopenia and hemoconcentration. Leukotriene D4 is much stronger in its histamine characteristics, especially in its ability to constrict small bronchi, coronary vessels and pulmonary circulation vessels. Leukotriene E4 activates the formation of thromboxane in the bronchi, causing their swelling, increased mucus secretion and thereby causing prolonged bronchospasm.

(1) Cytotropic (cytophilic) type reactions . The following substances act as initiators of a generalized anaphylactic reaction (anaphylactic shock) of this type of allergy:

allergens of antitoxic serums, allogeneic preparations of γ-globulins and blood plasma proteins;

allergens of hormones of protein and polypeptide nature (ACTH, insulin and others);

medications [antibiotics (penicillin), muscle relaxants, anesthetics, vitamins and others];

radiopaque agents;

insect allergens.

Local anaphylactic reactions - atopic bronchial asthma, allergic rhinitis and conjunctivitis, urticaria, Quincke's edema) - can occur under the influence of such antigens as:

allergens of plant pollen (hay fever), fungal spores);

house and industrial dust allergens;

epidermal allergens of pets;

allergens contained in cosmetics and perfumes, etc.

As a result of primary contact with the allergen, the ICS organizes an immune response in the body, the specificity of which lies in the synthesis of Ig E- and/or Ig G 4-class immunoglobulins (reagins, atopenes) by B-lymphocytes and plasma cells. The production of Ig G 4 and E-class immunoglobulins by B lymphocytes depends on the presentation of the allergen by APC and cooperation between T and B lymphocytes. Locally synthesized E-class Ig initially sensitizes mast cells at the site of its formation, after which the antibody spreads through the bloodstream to all organs and tissues of the body (Fig. 1;).

Rice. 1. Schematic representation of reactino-

vogo (cytotropic, cytophilic) mechanism

immediate hypersensitivity

Subsequently, the bulk of the Ig E- and Ig G 4 classes interact with high-affinity receptors and their subsequent fixation at the site of localization of Fc receptors on the cytoplasmic membranes of first-order target cells - mast cells (mast cells) and basophils. The remaining immunoglobulins of the Ig E and Ig G 4 classes interact with low-affinity receptors of second-order target cells - granulocytes, macrophages, lymphocytes, platelets, Langerhans cells of the skin and endothelial cells, also using a fragment of the Fc receptor. For example, on each mast cell or basophil, from 3,000 to 300,000 Ig E molecules can be fixed. Here they are able to remain for several months, and during this entire period of time, increased sensitivity to the allergen of first- and second-order target cells remains.

When the allergen re-enters, which can occur at least a week or more after the initial contact, an immune complex Ag+AT is formed at the site of localization of the IgE class, which is also fixed on the membranes of target cells of the first and second order. This leads to the withdrawal of receptor proteins for Ig E from the surface of the cytoplasmic membrane and subsequent activation of the cell, which is expressed in increased synthesis, secretion and release of HNT mediators. Maximum cell activation is achieved by binding of several hundred or thousands of receptors by immune complexes Ag+AT. The degree of activation of target cells depends on the content of calcium ions, the energy potential of the cell, as well as the ratio of cyclic adenosine monophosphate (cAMP) and guanosine monophosphate (cGMP) - a decrease in cAMP and an increase in cGMP.

As a result of the formation of the AG + AT complex and the activation of target cells (for example, mast cells), their cytolemma is destroyed, and the contents of the cytoplasmic granules are poured into the pericellular space. Mast cells, or mast cells, belong to the components of connective tissue and are localized mainly in those structures that directly or indirectly interact with the environment - skin, respiratory tract, digestive tract, along the nerve fibers and blood vessels.

In the process of destruction of the cytoplasmic and intracellular membranes, a large number of presynthesized biologically active substances are poured into the pericellular space, which are called immediate-type allergy mediators - vasoactive amines (histamine, serotonin), arachidonic acid metabolites (prostaglandins, leukotrienes, thromboxane A 2), cytokines that mediate local and systemic tissue damage [interleukins-1-6, IL-8, 10, 12, 13, platelet activating factor - PAF, neutrophil and eosinophil chemotaxis factors, TNF-α, γ-INF, eosinophil proteins, eosinophil neurotoxins, adhesins, selectins (P and E), granulocyte-monocyte colony-stimulating factor, lipid peroxidation products) and many other biologically active substances (heparin, kinins, arylsulfatases A and B, galactosidase, superoxide dismutase, histaminase, phospholipases A  and D, chymotrypsin, lysosomal enzymes, cationic proteins )]. Most of them are found in granules, primarily basophils, mast cells, as well as neutrophils, eosinophils, macrophages and others, and the process of releasing granules from first- and second-order target cells containing HNT mediators is called degranulation. Mediators of an immediate allergic reaction provide both protective and pathogenic effect. The latter is manifested by symptoms of various diseases. The classic way of releasing allergy mediators leads to immediate reactions that develop in the first half hour - the so-called first wave of mediator release. It is caused by the release of allergy mediators from cells with high affinity receptors (mast cells and basophils).

An additional pathway associated with the formation of a second wave of release of reagin allergy mediators initiates the development of the so-called late, or delayed, phase of HNT, associated with the release of biologically active substances from second-order target cells (granulocytes, lymphocytes, macrophages, platelets, endothelial cells). It appears after 6-8 hours. The severity of the late reaction may vary. Most HNT mediators have a predominant effect on vascular tone, the permeability of their walls and the state of smooth muscle fibers of hollow organs (relaxation or spasm). For example, the spasmogenic effect of leukotriene D 4 is hundreds of times higher than that of histamine.

This type of reaction is called cytotropic, or cytophilic, due to the high affinity (affinity) of Ig E for target cells. Degranulation of mast cells can occur under the influence of non-immunological activators - ACTH, substance P, somatostatin, neurotensin, ATP, as well as products of activation of granulocytes and macrophages: cationic proteins, myeloperoxidase, free radicals. Some drugs (eg, morphine, codeine, radiocontrast agents) have a similar ability.

Genetic aspects of reagin allergy. It is well known that atopy (reagin or anaphylactic type allergies) occurs only in a certain category of patients. In such subjects it is synthesized noticeably large quantity E-class immunoglobulins, a higher density of Fc receptors and their higher sensitivity to Ig E are detected on first-order target cells, and a deficiency of suppressor T lymphocytes is detected. In addition, the skin and airways of such patients have a higher sensitivity to the action of specific and nonspecific stimuli compared to those of other subjects. In families where one of the parents suffers from allergies, atopy in children occurs in 30-40% of cases. If similar form Since both parents suffer from allergies, anaphylaxis (or the reagin form of GNT) is detected in children in 50-80% of cases. Predisposition to atopy is determined by a group of genes that control the immune response, the synthesis of anti-inflammatory cytokines, the development of hyperreactivity of the smooth muscles of blood vessels, bronchi, hollow organs, etc. It has been proven that these genes are localized on chromosomes 5, 6, 12, 13, 20 and possibly other chromosomes.

(2) Cytotoxic type reactions . This mechanism began to be called cytotoxic because when a type II allergic reaction occurs, damage and death of target cells are observed, against which the action of the ICS was directed (Fig. 2;).

Rice. 2. Schematic representation of cytotoxic

(cytolytic) mechanism of hypersensitivity

immediate type. Designations: C – complement, K –

activated cytotoxic cell.

The reasons for the development of cytotoxic type of reactions may be:

firstly, antigens that are part of their own modified cytoplasmic membranes (most often, blood cells, kidney cells, liver, heart, brain and others);

secondly, exogenous Ags, secondarily fixed on the cytoplasmic membrane (drugs, metabolites or components of microorganisms, and others);

thirdly, non-cellular tissue components (for example, AG of the glomerular basement membrane, collagen, myelin, etc.).

There are three known mechanisms of cytotoxic (cytolytic) tissue damage in this type of allergy.

Complement mediated cytotoxicity;

Activation of phagocytosis of cells marked with antibodies;

Activation of antibody-dependent cellular toxicity;

The next stage is that this immune complex adsorbs on itself and activates complement components according to the classical type. Activated complement forms a membrane attack complex, which perforates the membrane, followed by lysis of the target cell. Therefore, this type of reaction was called cytolytic. Th 1 takes part in the induction of cytolytic reactions, producing IL-2 and γ-IFN. IL-2 ensures autocrine activation of Th, and γ-IFN – switches the synthesis of immunoglobulins from Ig M to Ig G.

Many autoimmune diseases develop through this mechanism - autoimmune and drug-induced hemolytic anemia, thrombocytopenia, leukopenia, Hashimoto's thyroiditis, autoimmune aspermatogenesis, sympathetic ophthalmopathy, transfusion shock when transfused with incompatible blood group or Rh factor, Rh conflict of mother and fetus, etc. P. The main mediators of complement dependent type allergies are

activated complement components (C4b2a3b, C567, C5678, C56789, etc.),

oxidants (O - , OH - and others),

lysosomal enzymes.

2. Another mechanism of cytolytic damage to target cells (cells with altered membrane properties) is associated with the activation of a subpopulation of cytotoxic cells and their attachment through the Fc receptor and Ig G- or Ig M classes to the cytoplasmic membrane with altered antigenic properties. Such cytotoxic cells can be natural killer cells (NK cells), granulocytes, macrophages, platelets, which recognize target cells to be destroyed through immunoglobulins fixed on them and their own Fc receptors, attach to them and inject toxic principles into the target cell, destroying her. It is assumed that Abs can act as “bridges” between the target cell and the effector cell.

3. The third mechanism of a type II allergic reaction is considered to be the destruction of the target cell through phagocytosis carried out by macrophages. Fc receptors of macrophages recognize antibodies fixed on the target cell and through them attach to the cell, followed by phagocytosis. This mechanism of destruction of target cells is typical, for example, in relation to platelets with ATs fixed on them, as a result of which the blood platelets become the object of phagocytosis, passing through the sinuses of the spleen.

In general, the mechanisms of type II allergic reactions include autoimmune hemolytic anemia and thrombocytopenia, diabetes mellitus, bronchial asthma, allergic drug agranulocytosis, post-infarction and post-commissurotomy myocarditis, endocarditis, encephalitis, thyroiditis, hepatitis, drug allergies, myasthenia gravis, components of the transplant rejection reaction and others.

(3) Immune complex formation reactions . Immune complex pathology has a certain place in the mechanisms of development of diseases such as glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, scleroderma, arteritis, endocarditis and others. This type of reaction occurs when the following allergens enter the sensitized body in a known high dose and in soluble form:

allergens of antitoxic serums,

allergens of certain medications (antibiotics, sulfonamides and others),

allergens of food proteins (milk, eggs, etc.),

household allergens,

bacterial and viral allergens,

cell membrane antigens,

allogeneic γ-globulins,

Precipitating (Ig G 1-3) and complement-fixing (Ig M) immunoglobulins synthesized for these allergens interact equivalently with a specific allergen and form medium-sized circulating immune complexes (CIC) of Ag + Ab, soluble in plasma and other body fluids. Such complexes are called precipitins (Fig. 3). Th 1 takes part in the induction of the immune response. Exogenous and endogenous Ags are constantly detected in the human body, which initiate the formation of immune complexes Ag+Abs. These reactions are an expression of the protective, or homeostatic, function of the immune system and are not accompanied by any damage. Immune complexes are required for rapid and efficient phagocytosis. However, under certain conditions they can acquire aggressive properties and destroy the body's own tissues. The damaging effect is usually caused by soluble complexes medium-sized, appearing with a slight excess of AG. An important role in the occurrence of this pathology is played by disturbances in the system of elimination of complexes (deficiency of complement components, Fc fragments of antibodies or receptors on erythrocytes for immune complexes, disturbances in the macrophage reaction), as well as the presence of chronic infection. In such cases, their damaging effect is realized through the activation of complement, the kallikrein-kinin system, the release of lysosomal enzymes, and the generation of superoxide radical.

Rice. 3. Schematic representation

immune complex mechanism of hypersensitivity

immediate type. Designations as in Fig. 1.

Precipitins can be found either in the blood, where they are localized on the inner wall of small vessels, or in tissues. Deposits, which include Ig G, penetrate the vascular wall, stratify endothelial cells and accumulate in its thickness on the basement membrane, resulting in the formation of larger and larger conglomerates of immune complexes. Unlike the CEC, they can activate not only complement components, but also the kinin, coagulation and fibrinolytic systems of the blood, as well as granulocytes, mast cells and platelets. As a result, at the site of their precipitation, for example, in the lumen of peripheral vessels, accumulations of leukocytes and other blood cells are formed, thrombosis is formed, and the permeability of the vascular wall increases. All this leads to the development of allergic (hyperergic) inflammation with a predominance of alteration and exudation processes. Being activated, fixed complement components enhance inflammatory reactions, causing the formation of anaphylotoxins (C3a and C5a), and inflammatory and allergic mediators (in particular, chemotactic factors) attract more and more leukocytes to the lesion site. Anaphylotoxins C3a and C5a cause the release of histamine by mast cells, contraction of smooth muscles and increase vascular permeability, promoting the further development of inflammation.

This type is a generalized form of allergy, for example, serum sickness. It is characterized by the development of systemic vasculitis, hemodynamic disorder, edema, rash, itching, arthralgia, hyperplasia of lymphoid tissue (see also below).

Glomerulonephritis of immunocomplex origin is characterized by impaired filtration, reabsorption and secretory functions of the kidneys.

Rheumatoid arthritis is accompanied by the formation of rheumatoid factor (IgM19S, IgG7S), autoantigens of inflammatory origin and autoantibodies, immune complexes and the involvement of synovial membranes in the pathological process with the development of systemic vasculitis (cerebral, mesenteric, coronary, pulmonary).

The formation of systemic lupus erythematosus is accompanied by the formation of immune complexes consisting of native DNA and nuclear proteins, antibodies to them and complement, which are subsequently fixed on the basement membrane of the capillaries, causing damage to the joints (polyarthritis), skin (erythema), serous membranes (exudative and adhesive process up to proliferation), kidneys (glomerulonephritis), nervous system (neuropathy), endocardium (Liebman-Sachs endocarditis), blood cells (anemia, leukopenia, thrombocytopenia, pancytopenia), and other organs.

If immune complexes are fixed in individual organs or tissues, then subsequent damaging processes are localized precisely in these tissues. For example, during vaccination, the antigen is fixed at the injection site with the subsequent development of a local allergic reaction similar to the Arthus phenomenon. The main mediators in this type of allergic reactions are

activated complement,

lysosomal enzymes,

• histamine,

  serotonin,

  superoxide anion radical.

The formation of immune complexes, their activation of leukocytes and other cellular elements, as well as their direct damaging effect, cause secondary reactions of immunoallergic origin. These include the development of allergic inflammation, cytopenias, intravascular coagulation, thrombus formation, immunodeficiency states and others. As mentioned above, specific manifestations of allergic diseases occurring in this type GNT are serum sickness, glomerulonephritis, arteritis, exogenous allergic alveolitis (“farmer’s lung”, “poultry farmer’s lung” and others), rheumatoid arthritis, endocarditis, anaphylactic shock, systemic lupus erythematosus, bacterial, viral and protozoal infections (for example, streptococcal diseases , viral hepatitis B, trypanosomiasis and others), bronchial asthma, vasculitis and others.

(4) Receptor-mediated reactions . This type IV allergic reaction mechanism is called antireceptor. It is associated with the presence of antibodies (mainly Ig G) to physiologically important determinants of the cell membrane, causing stimulating or inhibitory effects on the target cell through its receptors. As a result, for example, blockades are switched off from active functioning of numerous receptors of target cells, with the help of which they exchange molecular material with the pericellular space, including biologically active substances (ligands) necessary for normal cell activity (β-adrenergic receptors, acetylcholine, insulin and others receptors). An example of such a blocking effect is myasthenia gravis, which develops as a result of the formation of Ig G to the receptors of the neurotransmitter acetylcholine, localized on the postsynaptic membrane of skeletal muscle myocytes. The binding of AT to acetylcholine receptors blocks them, preventing the connection of acetylcholine with them and the subsequent formation of the muscle plate potential. Ultimately, the transmission of impulses from the nerve fiber to the muscle and its contraction are disrupted.

An example of a receptor-mediated stimulating type of allergic reaction is the development of a hyperthyroid state when AT antibodies imitate the effects of thyroid-stimulating hormone. Thus, in hyperthyroidism (allergic thyrotoxicosis), which is an autoimmune disease, autoantibodies activate receptors for thyroid-stimulating hormone. The latter stimulate thyrocytes of the thyroid follicles, which continue to synthesize thyroxine, despite the limited production of thyroid-stimulating hormone by the pituitary gland.

General patterns of development of delayed-type allergic reactions

Immunological stage of HRT . In cases of HRT, active sensitization is associated with the formation of an antigen–nonspecific receptor complex on the surface of the APC—macrophage, in which most of the antigens are destroyed during endocytosis. Passive sensitization is achieved by introducing pre-sensitized T-lymphocytes into the blood or transplanting lymphoid tissue lymph nodes from an animal previously sensitized with this AG . Determinant allergen groups (epitopes) in combination with MHC class I and II proteins are expressed on the APC membrane and presented to antigen-recognizing T lymphocytes.

CD4 lymphocytes take part in the induction of HRT, i.e. Th 1 cells (helper cells). The main effector cells are CD8 lymphocytes, among which are T-cytotoxic lymphocytes and T-lymphocytes that produce lymphokines. CD4 lymphocytes recognize allergen epitopes in complex with MCH class II glycoproteins, while CD8 lymphocytes recognize them in complex with MCH class I proteins.

Next, APCs secrete IL-1, which stimulates the proliferation of Th 1 and TNF. Th 1 secretes IL-2, γ-IFN and TNF. IL-1 and IL-2 promote the differentiation, proliferation and activation of Th 1 and T-cytotoxic lymphocytes. γ-IFN attracts macrophages to the site of allergic inflammation, which, through phagocytosis, increase the degree of tissue damage. γ-IFN, TNF and IL-1 enhance the generation of nitric oxide and other reactive oxygen-containing radicals at the site of inflammation, thereby exerting a toxic effect.

T-cytotoxic lymphocytes and T-killer cells destroy genetically foreign cells of the transplant, tumor and mutated cells of their own body, performing immunological surveillance functions. T-producers of lymphokines participate in HRT reactions, releasing numerous (more than 60) HRT mediators (lymphokines).

Pathochemical stage of HRT . Since during HRT sensitized lymphocytes come into contact with the allergen, the BAS they produce - lymphokines - determine the further course of pathological reactions. Among the lymphokines, the following groups are distinguished:

lymphokines acting on macrophagocytes: macrophage migration inhibitory factor, macrophage aggregation factor, chemotactic factor for macrophages and others;

lymphokines that determine the behavior of lymphocytes: helper factor, suppression factor, blast transformation factor, Lawrence transfer factor, IL-1, IL-2 and others;

lymphokines affecting granulocytes: factors of emigration of neutrophils and eosinophils, factor inhibiting granulocyte migration and others;

lymphokines affecting cell cultures: interferons, factor inhibiting the proliferation of tissue culture cells and others;

lymphokines acting in the whole organism: a factor causing skin reaction, a factor that increases vascular permeability, an edema factor and others.

Pathophysiological stage of HRT . Structural and functional lesions during HRT are caused mainly by the development of an inflammatory reaction with a pronounced emigration of predominantly mononuclear cells - lymphocytes, monocytes and macrophages, followed by cellular infiltration by them and other tissue phagocytes.

(5) Response mediated by cellular immune mechanisms . This type of reaction is provided by sensitized T-lymphocytes belonging to a special category of helper cells - first-order T-helpers, which exert a cytotoxic effect directed against cell membrane antigens using two known mechanisms: they can attack the target cell with its subsequent destruction or influence it indirectly through the lymphokines they synthesize (Fig. 4).

Rice. 4. Schematic representation of cells

indirect mechanism of allergy development (HRT).

Designations: T – cytotoxic lymphocyte.

The action of lymphokines in HRT reactions is aimed at activating certain target cells - macrophages, monocytes, neutrophils, lymphocytes, fibroblasts, bone marrow stem cells, osteoclasts and others. The target cells activated by lymphokines, mentioned above, damage or destroy the altered cells on which antigens are fixed, already with their mediators (for example, lysosomal enzymes, peroxide compounds and others). This type of reaction develops when the following allergens-antigens enter the body:

foreign protein substances (for example, collagen), including those contained in vaccine solutions for parenteral administration;

haptens, for example, drugs (penicillin, novocaine), simple chemical compounds (dinitrochlorophenol and others), herbal preparations that can be fixed on the membranes of their own cells, changing their antigenic structures;

protein histocompatibility antigens;

specific tumor antigens.

The mechanisms of HRT are fundamentally similar to other mechanisms of the formation of cellular immunity. The differences between them are formed at the final stage of reactions, which in delayed-type allergic reactions reduce to damage to one’s own organs and tissues.

The entry of an allergen antigen into the body forms an ICS immune response associated with the activation of T-lymphocytes. The cellular mechanism of immunity is activated, as a rule, in cases of insufficient efficiency of humoral mechanisms, for example, when the antigen is intracellularly localized (mycobacteria, Brucella, and others) or when the cells themselves are the antigens (microbes, protozoa, fungi, transplant cells, and others). Cells of one's own tissues can also acquire autoallergic properties. A similar mechanism may be activated in response to the formation of autoallergens when a hapten is introduced into the protein molecule (for example, in cases of contact dermatitis and others).

Typically, T-lymphocytes, sensitized to a given allergen and arriving at the site of an allergic reaction, are formed in a small amount - 1-2%, however, other non-sensitized lymphocytes change their functions under the influence of lymphokines - the main mediators of HRT. More than 60 different lymphokines are now known, which demonstrate a wide variety of their effects on various cells at the site of allergic inflammation. In addition to lymphokines, lysosomal enzymes, components of the kinin-kallikrein system and other mediators of allergic reactions that enter the site of damage from polymorphonuclear leukocytes, macrophages and other cells take part in damaging reactions, although to a lesser extent.

Manifestations of HRT in the form of cell accumulation, cellular infiltration, etc. appear 10-12 hours after repeated administration of a specific allergen and reach their maximum after 24-72 hours. It is important to note that during the formation of HRT reactions, tissue swelling is practically absent due to the limited participation of histamine in it. But an integral part of HRT is the inflammatory process, which occurs at the second, pathochemical stage of this reaction due to the destruction of target cells, their phagocytosis, and the action of allergy mediators on tissue. The inflammatory infiltrate is dominated by mononuclear cells (lymphocytes, macrophages, monocytes). The inflammation that develops during HRT is both a factor of damage and dysfunction of the organs where it occurs, and it plays a major pathogenetic role in the formation of infectious-allergic, autoimmune and some other diseases.

The inflammatory reaction is productive and usually normalizes after the allergen is eliminated. If the allergen or immune complexes are not excreted from the body, then they are fixed at the site of introduction and delimited from the surrounding tissues by forming a granuloma (see above). The granuloma may include various mesenchymal cells - macrophages, fibroblasts, lymphocytes, epithelioid cells. The fate of the granuloma is ambiguous. Typically, necrosis develops in its center, followed by the formation of connective tissue and sclerosis. Clinically, HRT reactions manifest themselves as

autoallergic diseases,

infectious and allergic diseases (tuberculosis, brucellosis and others),

contact allergic reactions ( contact dermatitis, conjunctivitis and others),

transplant rejection reactions.

The division of allergic reactions into 5 types is schematic and is intended to facilitate understanding of the complex processes of allergy. All types of allergic reactions can be observed in a patient simultaneously or follow each other.

Now let’s make a final comparison of the changes that are characteristic of HNT and HRT. The GNT is characterized by the following:

rapid type of reaction development (in minutes and hours);

the presence in the blood of freely circulating immunoglobulins to this allergen, the synthesis of which is due to the activation of the ICS B-subsystem;

antigens are, as a rule, non-toxic substances;

occurs during active and passive sensitization by parenteral administration of sera containing ready-made antibodies (immunoglobulins) to a given antigen;

an important role is played by biologically active substances – HNT mediators: histamine, serotonin, bradykinin and others, including cytokines;

manifestations of HNT are suppressed antihistamines(diphenhydramine, pipolfen, suprastin, tavegil and others), as well as glucocorticoids;

local reactions are accompanied by pronounced vascular components (hyperemia, exudation, edema, emigration of leukocytes) and alteration of tissue elements.

The manifestations of HRT are characterized by the following:

the response occurs after 12-48 hours or more;

antigens are in most cases toxic substances;

sensitization is associated with activation of cellular immunity;

sensitized T-lymphocytes, interacting with antigen, destroy it or induce other phagocytes to do so with their cytokines;

passive sensitization is achieved by parenteral administration of sensitized lymphocytes or tissue transplantation of lymph nodes removed from the body of a sensitized animal;

there is no histamine release reaction, and lymphokines act as allergy mediators;

the reaction is inhibited by glucocorticoids;

local reactions are mild;

The inflammatory reaction is most often accompanied by proliferation processes and the appearance of granulomas.

Allergy(from the Greek alios - “other”, other, ergon - “action”) is a typical immunopathological process that occurs against the background of exposure to an allergen antigen on the body with a qualitatively altered immunological reactivity and is accompanied by the development of hyperergic reactions and tissue damage. There are immediate and delayed allergic reactions (humoral and cellular reactions, respectively). Allergic antibodies are responsible for the development of allergic reactions of the humoral type. For the clinical picture of an allergic reaction to manifest, it is necessary to: at least, two contacts of the body with an allergen antigen.

The first dose of allergen exposure (small) is called sensitizing. The second dose of exposure is large (permissive), accompanied by the development of clinical manifestations of an allergic reaction. Immediate allergic reactions can occur within a few seconds or minutes, or 5–6 hours after repeated contact of the sensitized organism with the allergen. In some cases it is possible long-term persistence allergen in the body, and therefore it is almost impossible to draw a clear line between the effects of the first sensitizing and repeated resolving doses of the allergen.

Antigens-allergens are divided into antigens of bacterial and non-bacterial nature.

Non-bacterial allergens include:

1) industrial;

2) household;

3) medicinal;

4) food;

5) vegetable;

6) of animal origin.

There are complete antigens that can stimulate the production of antibodies and interact with them, as well as incomplete antigens, or haptens, consisting only of determinant groups and not inducing the production of antibodies, but interacting with ready-made antibodies. There is a category of heterogeneous antigens that are similar to the structure of determinant groups.

Allergens can be strong or weak. Strong allergens stimulate the production of large amounts of immune or allergic antibodies.

Soluble antigens, usually of a protein nature, act as strong allergens. An antigen of a protein nature is stronger, the higher its molecular weight and the more rigid the structure of the molecule. Weak are corpuscular, insoluble antigens, bacterial cells, antigens of damaged cells of the body's own.

There are also thymus-dependent and thymus-independent allergens. Thymus-dependent antigens are those that induce an immune response only with the mandatory participation of three cells: macrophage, T-lymphocyte and B-lymphocyte. Thymus-independent antigens can induce an immune response without the participation of helper T lymphocytes.