Mechanisms of skin allergic reactions to infectious allergens. Allergy: manifestations and reactions

Institute of Allergology and Clinical Immunology in Moscow Tatyana Petrovna Guseva

What of the latest discoveries in the field of allergology can be called really significant - both for doctors and for patients?

The most important recent achievement can be considered the fact that we have learned almost everything about the mechanism of allergic reactions. Allergy is no longer a mysterious disease. More precisely, this is not one disease, but a whole group of conditions. Allergic diseases include bronchial asthma, allergic rhinitis, skin problems - acute and chronic urticaria, atopic dermatitis.

All these problems are based on the same reaction. And today it is fully deciphered. The essence of an allergy is that the immune system begins to overreact to substances that are relatively harmless to the body. Today we know all about the mechanisms that trigger an inadequate immune response. And we can act on allergies at any stage.

- How does this reaction take place?

Let's take allergic rhinitis as an example. An allergen enters the body - for example, pollen from a plant. In response to this, the level of a special protein, class E immunoglobulin, rises in the blood. It is produced only in people who are genetically predisposed to allergies. Immunoglobulin E binds to the allergen on the surface of the mast cell. The latter are found in different tissues and organs. So, quite a lot of them in the composition of the mucous membranes of the upper and lower respiratory tract, as well as the conjunctiva of the eyes.

Mast cells are "storage" of histamine. By itself, this substance is necessary for the body to carry out many important functions. But in the case of an allergic reaction, it is histamine that is responsible for the development of unpleasant symptoms. When the mast cell is activated, histamine is released into the blood. It provokes increased secretion of mucus and nasal congestion. At the same time, histamine also affects other structures, and we begin to sneeze, cough, and itching occurs.

- Science is advancing, and allergy sufferers are becoming more and more every year. How to be?

Allergies are indeed very common today. According to statistics, every fifth inhabitant of the Earth suffers from it. And worst of all it is necessary to inhabitants of the developed countries. This spread of the problem is associated with environmental degradation, people's excessive enthusiasm for antibiotics. Stress, malnutrition, an abundance of synthetic materials around us contribute.

But still, heredity plays a major role in triggering an allergic reaction. The allergy itself is not passed down from generation to generation. But you can inherit a predisposition. And of great importance is the way of life, and from the most tender age. It has been proven, for example, that children who have been breastfed for at least six months are much less likely to suffer from allergies. Today, children are breastfed less often, and they do not grow up in the most favorable conditions.

There is another problem here as well. Until now, there is a stereotype in society that allergies are a "non-serious" disease. Many self-prescribe drugs for themselves, use some folk recipes. Meanwhile, if you run an allergy, it can go into more severe forms. For example, allergic rhinitis without treatment can lead to the development of bronchial asthma. The conclusion is simple: the sooner you get professional help, the sooner you can deal with your problem.

- Where does the treatment of allergic problems begin?

With a visit to the doctor and diagnostics. It is important to know what exactly causes allergies. To do this, today there is a very wide range of methods. These are various skin tests, advanced blood tests.

Next, you need to avoid contact with the allergen if possible. When it comes to food, a hypoallergenic diet is prescribed. If you are allergic to house dust, plant pollen or pet hair, you will have to acquire. Modern models of these devices trap particles up to one tenth of a micron in size.

Now scientists are trying to approach this problem from the other side - to "teach" the body not to react to immunoglobulin E. In Germany, they are conducting clinical trials of the latest drug that allows this to be done. This is a revolutionary approach to the treatment of allergies.

- Recently, another method of prevention has been widely discussed - allergen-specific therapy.

This is a well-researched and effective technique. Its essence is that low doses of the allergen are introduced into the body according to a certain scheme. Gradually increase the dose. As a result, the sensitivity of the body to this substance is reduced. And instead of the "wrong" immunoglobulin E, protective antibodies begin to be produced in the body. This treatment takes time: on average, the course lasts from 3 to 5 years.

Previously, this method was associated with a large number of complications. But recently this method has become much safer. The fact is that therapeutic allergens today are thoroughly cleaned. They practically do not give complications and at the same time have a powerful immunostimulating effect. Another advantage is their prolonged effect.

Recently, another step forward has been taken in this direction. In Austria, medicinal allergens began to be created using genetic engineering. Now they are undergoing clinical trials in France. These drugs will reduce the chance of side effects. They also make healing faster.

- Does allergen-specific therapy work for all types of allergies?

Most often, this method is used for bronchial asthma and allergic rhinitis. It gives the best results for allergies to plant pollen and house dust mites. But it began to be successfully used in patients with epidermal and tick-borne allergies.

This therapy is carried out only during the period of remission and a few months before the start of flowering of allergenic plants. It is important that this method of treatment prevents the development of bronchial asthma in patients with allergic rhinitis.

- What other methods help fight allergies?

A very important component of the treatment program is basic therapy. Its purpose is to strengthen the mast cell membrane. This is necessary in order to prevent the release of histamine into the blood. Today, there are several drugs that have this effect. This, for example, zaditen, zyrtec or intal. To achieve a good effect, they should be taken for several months or even years. Each time, the allergic reaction will be milder, sensitivity to allergens will decrease.

- What if the reaction has already occurred?

Antihistamines are prescribed. So, with allergic rhinitis, nasal sprays are used today. With conjunctivitis - antiallergic eye drops. For skin reactions, topical hormone-containing preparations are used.

By the way, there has been a real breakthrough in the treatment of skin allergic reactions. Today, a whole generation of high-end cosmeceuticals has appeared. They are used to care for the affected skin after stopping the exacerbation. They allow you to increase the remission period, nourish and moisturize the skin well. During an exacerbation of an allergic disease, along with local treatment, it is necessary to take antihistamine drugs.

In recent years, preparations with improved properties have appeared: Telfast, Erius. They have practically no side effects, act quickly and effectively. Today in pharmacies there is a huge selection of such funds. But only a doctor should choose for a particular patient.

As you can see, today you can cope with an allergic reaction at almost any stage. Tune in to the fact that the treatment will take a certain period. But the result is sure to come.

Olga Demina

Allergy, the most common form of human pathology associated with inadequate manifestations of the activity of the immune system, is based on individual hypersensitivity, which is usually defined as hypersensitivity, i.e., an increased ability of the body to respond with reproducible damage to its tissues upon contact with certain, usually exogenous, compounds at concentrations to which normal individuals are tolerant.

Knowledge of the mechanisms of formation of allergic reactions has its own eventful history. Hypersensitivity to repeated parenteral administration of vaccine preparations, manifested in the form of rash and erythema, was first described in the 18th century by R.

Sutton. In 1890, R. Koch discovered delayed-type hypersensitivity with intradermal administration of tuberculin. In 1902, C. Richet and R. Portier described anaphylactic shock, which they observed when dogs were repeatedly injected with extracts of sea anemone tentacles (the term “anaphylaxis” they introduced comes from Latin anaphylaxic - counterprotection). In 1906, K. Pirke introduced the term "allergy" (from Latin alios ergon - another action) to denote an altered sensitivity to substances with which the body had previously been in contact, he also described serum sickness.

In 1923, A. Koka and R. Cook introduced the concept of "atopy" to denote a hereditary predisposition to the development of hypersensitivity reactions. An allergy is said to be when an overly strong or unusual immune response has pathological consequences. At the beginning of the last century, allergies were considered rare. This is also evidenced by the etymology of the term introduced by K. Pirke to designate "other", that is, not the usual, but the exceptional reactivity of the organism. Currently, allergies are detected with a steadily increasing frequency. In recent years, allergy has been understood as a collective definition of a group of typical immunopathological processes that develop in a sensitized organism of genetically predisposed individuals. The antigens that cause allergies are called allergens. These are mainly low molecular weight proteins or haptens that can bind to proteins in the body, which, when they first enter the body, cause the formation of IgE antibodies, and on subsequent intakes, allergic reactions.

Allergic reactions are the result of the activation of the immune system in response to the intake of a complex of molecules that is part of the allergen and contains not only proteins, but also sugars, lipids, nucleic acids and their compounds. Almost all the most common allergens - fungal, pollen, food, household, bacterial insect poisons - are multicomponent compounds in which proteins are present in minor amounts. Non-protein compounds are recognized by the immune system, the role of which in the formation of allergic reactions is clearly underestimated.

It is known that macrophages and other phagocytic cells are able to quickly become activated at the first encounter with a pathogen and eliminate it. This led to the discovery of the innate immune system. However, it is only recently that scientists have figured out exactly how this happens. In 1997, a homologue of the Drosophila Toll receptor found in mammals and called the Toll-like receptor was described. The TLR system refers to the innate immune system. TLRs recognize various types of pathogens and provide the body's first line of defense. To date, the TLR family is known, consisting of 10 members.

The structure of the receptors, the pathways of the signal passing through them to the nucleus, the structure of the recognized pathogen molecules and the mechanisms of their recognition by the TLR system have been established. TLRs recognize specific structures of pathogens that are fundamentally important for the survival of the latter. These structures are called pathogen-associated molecular structures. TLR ligands in most cases are non-protein molecules, such as bacterial peptidoglycans, lipoproteins, lipopolysaccharides, lipoteichoic acid, bacterial DNA, bacterial protein flagellin, galactomannan from fungi, double-stranded viral RNA, etc. Through the interaction between TLRs, the repertoire of pathogens is sorted, which allows a limited number of TLRs to cover the entire diversity of their molecular structures. Activation of innate immunity occurs immediately upon encountering a pathogen. This does not require the stage of cell differentiation, enhancement of TLR expression on their surface, proliferation and accumulation of specific clones. As such, the innate immune system is the first and most effective line of defense against pathogens.

One of the essential issues in the formation of an allergic reaction is to elucidate the reasons for the predominant induction of a humoral IgE response by allergens with a relatively low ability of atopics to induce the production of antibodies of other isotypes. The manifestation of allergenicity is facilitated by the small size of the molecules (the molecular weight is usually 5000-15000), which allows allergens to penetrate through the mucous membranes; their low concentrations favor the formation of T-helpers of the Th2 type, which contribute to increased production of IgE; allergens enter through the mucous membranes, in which one of the main populations of mast cells is concentrated, IgE-B cells migrate here, and Th2-type T-helpers are formed. However, all these factors only favor the development of an allergic reaction, but do not determine its course.

IgE antibodies are VB-globulins with a pier. weighing 188,000, which, according to the general plan, are structurally quite close to IgG. They include two H-(e) and two L-chains. The structure of L-chains (k or A) does not differ significantly from that in immunoglobulins of other classes. The e chain is a special isotype. It contains 5 m domains of 1V and 4 C-type, i.e., 1 C-domain more than in the y-chains. The e-chain contains 6 carbohydrate binding sites. IgE are quite labile to physical and chemical influences. The sites of binding to Fee receptors of mast cells and basophils are localized in the Ce2 and Ce3 domains: primary binding is carried out with the participation of CES, after which another locus is opened, located in Ce2 and C3, this locus provides stronger binding. The receptors for IgE found on mast cells and blood basophils are most capable of binding IgE antibodies, so these cells are called target cells of the 1st order. From 3,000 to 300,000 IgE molecules can be fixed on one basophil. Receptors for IgE are also found on macrophages, monocytes, eosinophils, platelets, and lymphocytes, but the binding capacity of these cells is lower, which is why they are called target cells of the 2nd order.

Binding of IgE on cell membranes is time dependent, so optimal sensitization can occur after 24-50 hours. Fixed antibodies can stay on cells for a long time, and therefore an allergic reaction may occur after a week or more.

A feature of IgE antibodies is also the difficulty of their detection, since they do not participate in serological reactions. To date, a fairly large number of monoclonal antibodies have been obtained that recognize epitopes in various regions of the IgE molecule. This served as the basis for the development of solid-phase ELISA test systems for the determination of IgE. As a rule, these are two-site systems - with the fixation of some antibodies on the plastic and the detection of their complex with IgE using antibodies that react with another epitope. To determine antigen-specific IgE antibodies, a radioimmunosorbent test is still used with fixation of an allergen on a solid basis and detection of binding of IgE antibodies to it using anti-IgE labeled with a radionuclide. Similar ELISA test systems have been created. The concentration of IgE is expressed in weight units and in units of activity IU/ml; 1 ME is equal to 2.42 ng. Analysis of the IgE response to a greater extent reflects the nature of the activation of a specific allergic immune response. In addition, the switch of B cells to the synthesis of IgE antibodies depends mainly on the production of IL-4 and/or IL-13 by T cells, that is, on the key cytokines for the allergic response.

The concentration of IgE in the blood serum of a healthy adult is 87-150 ng / ml, while in individuals with atopic diseases it can be several orders of magnitude higher. IgE is practically absent in newborns, but its concentration gradually increases from the 3rd month of life. The level of IgE in one-year-old children is about 10 times lower than in adults. Its amount, characteristic of adults, is reached by 10 years of age. In secrets, the content of IgE is approximately 10 times higher than in blood serum; especially a lot of it in colostrum. Even in the urine it is higher than in the blood. It has been established that most of the IgE is secreted in the lymphoid tissue associated with the mucous membranes. Serum IgE has a short half-life of 2.5 days.

It has been established that IL-4 is responsible for switching immunoglobulin isotypes to gene C (in addition to the CD4-CD154 interaction). Cells stimulated with bacterial lipopolysaccharide in the presence of IL-4 begin to secrete IgE.

Since IL-4 is a product of Th2-type T helpers, it is these cells that play a key role in providing an IgE response and the formation of allergic reactions. Both in normal and pathological conditions, IgE synthesis is associated predominantly with lymphoid tissue associated with mucous membranes, including mesenteric and bronchial lymph nodes. It is believed that this is due to the peculiarities of the microenvironment of these structures, which promotes the differentiation of activated CD+4 cells into Th2. Microenvironmental factors that have this effect include transforming growth factor-p, IL-4 produced by mast cells, and the steroid hormone 1,25-dihydroxyvitamin D3. It is also believed that the endothelium of postcapillary venules in lymph nodes associated with mucous membranes expresses (possibly under the influence of the same factors) the corresponding addressins, i.e. adhesion molecules that recognize the membrane structures of Th2 cells and promote their migration into the tissue. The key role of Th2 cells and their products IL-4 and IL-5 in the development of allergic reactions is quite well argued and manifests itself not only at the stage of IgE production.

Formation of specific Th2 cells and activation of IgE+-B-KJie currents occur in the lymph node, from where E+ blasts migrate to the lamina propria of the mucous membranes and submucosal layer. The combined effect of allergens and IL-4 on B-lymphocyte clones simultaneously with activation induces the expression of adhesive molecules that promote the migration of these cells into the lamina propria of the mucous membranes. Although there are typical cases when the place of deployment of the allergic process spatially corresponds to the route of entry of the allergen (for example, in bronchial asthma), this rule is not universal due to the ability of cells activated in one region of the lymphoid tissue of the mucous membranes to migrate to other regions and settle there in the submucosa layer and lamina propria.

An important place in the control of IgE secretion is given to the soluble form of the CD23 molecule. Being on the cell surface, it acts as a low-affinity receptor. This C-lectin receptor is present on the surface of 30% of B-lymphocytes, being associated with the complement receptor CR2 (CD21), and on 1% of T-cells and monocytes (this percentage increases significantly in allergic patients). Under the influence of IL-4, CD23 begins to be produced by B cells and monocytes in a soluble form. The soluble CD23 molecule interacts with the receptor complex of B cells containing CD 19, CD 21, and CD 81. At the same time, through the lyn tyrosine kinase associated with CD 19, a signal is launched into the cell to switch immunoglobulin isotypes to Ce, to increase the proliferation of IgE + -B- mieTOK and their secretion of IgE.

There are other factors that regulate the production of IgE. The role of the weakening of the suppressor control over the production of IgE has been established. The mechanisms of involvement of CD8+ suppeccors in the regulation of IgE synthesis and the development of allergy have not been studied; suggest that these cells produce the above-mentioned suppressor factor. At the same time, it is known that the function of suppressors of the IgE response can be performed by C04+ cells of the Th1 type, which suppress the differentiation of Th2 cells and their secretion of IL-4. This activity of Thl-cells is associated mainly with interferon-y. In this regard, any factor that promotes the differentiation of Th1 cells automatically inhibits the development of Th2 cells and allergic processes. These factors include, for example, IL-12 and interferon.

IgE secreted by plasma cells in the mucosa bind to the high-affinity FceRI receptors on mast cells located in the same mucosal compartment as the IgE-producing cells. The FceRI receptor has 4 chains: the a-chain has two extracellular domains, with the help of which the receptor interacts with the Ce2 and Ce3 domains of IgE, the p-chain, which spans the membrane 4 times, and two y-chains that transmit a signal to the cell, the y-chain homologous to the £-chain of the T-cell receptor TCR-CD3 and can even replace it in ub+ T-cells of the mucous membranes. Fixation of free IgE molecules is not accompanied by an activation signal entering the cell. IgE, the free form of which is characterized by rapid turnover, can remain on the surface of mast cells for a very long time (up to 12 months).

The state of the body in which IgE antibodies to a specific allergen are fixed on the surface receptors of mast cells is referred to as sensitization to this antigen. Since IgE antibodies that are identical in specificity but belong to different classes bind to the same epitopes, the formation of non-reaginic antibodies to allergens simultaneously with IgE antibodies can reduce the likelihood of IgE antibodies binding to the allergen and, therefore, reduce the manifestations of allergy. At this stage, this is one of the possible ways to control the allergic process. Indeed, IgG antibodies to allergens have been shown to reduce manifestations of hypersensitivity by competing with IgE reagins, which is why they are called blocking antibodies. Increasing their production is a possible way to prevent allergies, which consists in enhancing the IgG response and attenuating the IgE response to allergens. The first is achieved by increasing the immunogenicity of allergenic substances with the help of various kinds of adjuvants, the second is still practically unattainable due to the lack of accurate information about the relationship between the structure of allergens and their ability to preferentially induce an IgE response.

Autoallergy is a pathological process, which is based on damage caused by the reaction of the immune system to its own endoallergens. With allergies, the action of immune mechanisms is directed to an exogenous allergen and tissue damage becomes a side effect of this action. With autoallergy, the immune system interacts with antigens that have changed and become foreign to the body. The latter are formed during various types of pathological processes (necrosis, inflammation, infection, etc.) and are designated as autoallergens. In the process of interaction with the immune system, autoallergens are eliminated and additional damage to various tissues occurs.

Among the numerous classifications of allergic reactions, the classification proposed by Sooke in 1930, according to which all allergic reactions are divided into reactions of immediate and delayed types, based on humoral (IgE-mediated) and cellular (mediated by CD4 + T-lymphocytes) are widely used. mechanisms.

This classification is based on the time of manifestation of an allergic reaction after repeated contact with the allergen. Immediate-type reactions develop after 15-20 minutes, delayed-type reactions after 24-48 hours. Immediate-type reactions include anaphylactic shock, atopic form of bronchial asthma, hay fever, Quincke's edema, allergic urticaria, serum sickness, etc. Delayed-type reactions include allergic contact dermatitis, transplant rejection, post-vaccination encephalomyelitis, etc. Delayed-type hypersensitivity accompanies tuberculosis, brucellosis, syphilis, fungal diseases, protozoal infections, etc. It is important to note that the concept of immediate and delayed-type allergic reactions that has arisen in the clinic does not reflect the whole variety of manifestations and mechanisms of development of allergies.

Currently, the classification proposed by P. Gell, R. Coombs, which is based on the pathogenetic principle, is widespread. According to this classification, depending on the mechanism of the immune response, 4 main types of allergic reactions are distinguished.
. Type 1, which includes immediate allergic reactions, includes the reaginic subtype, associated with the production of IgE antibodies and underlying atopic diseases, and anaphylactic, due mainly to IgE and C4 antibodies and observed in anaphylactic shock.
. Type 2 - cytotoxic, which is associated with the formation of IgG (except IgGl) and IgM antibodies to determinants present on the body's own cells. Allergic diseases of this type include some forms of hematological diseases, for example, autoimmune hemolytic anemia, myasthenia gravis and some others.
. Type 3 - immunocomplex, associated with the formation of complexes of allergens and autoallergens with IgG or IgM antibodies and with the damaging effect of these complexes on body tissues. Serum sickness, anaphylactic shock, etc. develop according to this type.
. Type 4 - cell-mediated (often use a different definition - delayed-type hypersensitivity, delayed-type hypersensitivity) is associated with the formation of allergen-specific lymphocytes (T-effectors). Allergic contact dermatitis, transplant rejection, etc. develop according to this type. The same mechanism is also involved in the formation of infectious and allergic diseases (tuberculosis, leprosy, brucellosis, syphilis, etc.).

In the pathogenesis of many allergic diseases, it is possible to detect the mechanisms of simultaneously different types of allergic reactions. For example, in atopic bronchial asthma and anaphylactic shock, mechanisms of the 1st and 2nd types are involved, in autoimmune diseases - reactions of the 2nd and 4th types.

However, for pathogenetically substantiated therapy, it is always important to establish the leading mechanism for the formation of an allergic reaction.

Regardless of the type of allergic reaction, 3 stages are conditionally distinguished in its development.
. Stage I, the stage of immune reactions (immune), begins with the first contact of the body with the allergen and consists in the formation of allergic antibodies (or allergen-specific lymphocytes) and their accumulation in the body. As a result, the body becomes sensitized, or hypersensitive, to the specific allergen. When a specific allergen enters the body again, a complex of antigen antibodies is formed, which determine the development of the next stage of the allergic reaction.
. Stage II, the stage of biochemical reactions (pathochemical), is determined by the predominant release of ready-made (preformed) biologically active compounds and the formation of new substances (allergy mediators) as a result of sequential biochemical processes triggered by antibody allergen complexes or allergen-specific lymphocytes.
. Stage III, the stage of clinical manifestations (pathophysiological), is the reaction of cells, tissues and functional systems of the body to the mediators formed in the previous stage.

This term refers to a group of allergic reactions that develop in sensitized animals and humans 24-48 hours after exposure to an allergen. A typical example of such a reaction is a positive skin reaction to tuberculin in antigen-sensitized tuberculosis mycobacteria.
It has been established that the main role in the mechanism of their occurrence belongs to the action sensitized lymphocytes for allergen.

Synonyms:

Delayed type hypersensitivity (DTH);
Cellular hypersensitivity - the role of antibodies is performed by the so-called sensitized lymphocytes;
Cell-mediated allergy;
Tuberculin type - this synonym is not quite adequate, since it represents only one of the types of delayed-type allergic reactions;
Bacterial hypersensitivity is a fundamentally incorrect synonym, since bacterial hypersensitivity can be based on all 4 types of allergic damage mechanisms.

The mechanisms of a delayed-type allergic reaction are fundamentally similar to the mechanisms of cellular immunity, and the differences between them are revealed at the final stage of their inclusion.
If the activation of this mechanism does not lead to tissue damage, they say about cellular immunity.
If tissue damage develops, then the same mechanism is referred to as delayed allergic reaction.

The general mechanism of an allergic reaction of a delayed type.

In response to the ingestion of an allergen, the so-called sensitized lymphocytes.
They belong to the T-population of lymphocytes, and in their cell membrane there are structures that act as antibodies that can combine with the corresponding antigen. When the allergen enters the body again, it combines with sensitized lymphocytes. This leads to a number of morphological, biochemical and functional changes in lymphocytes. They manifest as blast transformation and proliferation, increased synthesis of DNA, RNA, and proteins, and secretion of various mediators called lymphokines.

A special type of lymphokines has a cytotoxic and inhibitory effect on cell activity. Sensitized lymphocytes also have a direct cytotoxic effect on target cells. Accumulation of cells and cell infiltration of the area where the connection of the lymphocyte with the corresponding allergen occurred, develop over many hours and reach a maximum after 1-3 days. In this area, there is destruction of target cells, their phagocytosis, and an increase in vascular permeability. All this manifests itself in the form of an inflammatory reaction of a productive type, which usually occurs after the elimination of the allergen.

If the elimination of the allergen or the immune complex does not occur, then granulomas begin to form around them, with the help of which the allergen is separated from the surrounding tissues. The granulomas may include various mesenchymal macrophage cells, epithelioid cells, fibroblasts, and lymphocytes. Usually, necrosis develops in the center of the granuloma, followed by the formation of connective tissue and sclerosis.

immunological stage.

At this stage, the thymus-dependent immune system is activated. The cellular mechanism of immunity is usually activated in cases of insufficient effectiveness of humoral mechanisms, for example, when the antigen is located intracellularly (mycobacteria, brucella, listeria, histoplasm, etc.) or when the cells themselves are the antigen. They can be microbes, protozoa, fungi and their spores that enter the body from the outside. Cells of own tissues can also acquire autoantigenic properties.

The same mechanism can be activated in response to the formation of complex allergens, for example, in contact dermatitis that occurs when the skin comes into contact with various medicinal, industrial and other allergens.

pathochemical stage.

The main mediators of type IV allergic reactions are lymphokines, which are macromolecular substances of a polypeptide, protein or glycoprotein nature, generated during the interaction of T- and B-lymphocytes with allergens. They were first discovered in in vitro experiments.

The secretion of lymphokines depends on the genotype of lymphocytes, the type and concentration of the antigen, and other conditions. Testing of the supernatant is carried out on target cells. The release of some lymphokines corresponds to the severity of an allergic reaction of a delayed type.

The possibility of regulating the formation of lymphokines has been established. Thus, the cytolytic activity of lymphocytes can be inhibited by substances that stimulate 6-adrenergic receptors.
Cholinergics and insulin enhance this activity in rat lymphocytes.
Glucocorticoids apparently inhibit the formation of IL-2 and the action of lymphokines.
Group E prostaglandins change the activation of lymphocytes, reducing the formation of mitogenic and inhibiting macrophage migration factors. Neutralization of lymphokines by antisera is possible.

There are various classifications of lymphokines.
The most studied lymphokines are the following.

Factor inhibiting macrophage migration, - MIF or MIF (Migration inhibitory factor) - promotes the accumulation of macrophages in the area of allergic alteration and possibly enhances their activity and phagocytosis. It also participates in the formation of granulomas in infectious and allergic diseases and enhances the ability of macrophages to destroy certain types of bacteria.

Interleukins (IL).
IL-1 is produced by stimulated macrophages and acts on T-helpers (Tx). Of these, Th-1 under its influence produce IL-2. This factor (T-cell growth factor) activates and maintains the proliferation of antigen-stimulated T-cells, regulates the biosynthesis of interferon by T-cells.
IL-3 is produced by T-lymphocytes and causes proliferation and differentiation of immature lymphocytes and some other cells. Th-2 produce IL-4 and IL-5. IL-4 enhances the formation of IgE and the expression of low-affinity receptors for IgE, and IL-5 - the production of IgA and the growth of eosinophils.

chemotactic factors.
Several types of these factors have been identified, each of which causes chemotaxis of the corresponding leukocytes - macrophages, neutrophilic, eosinophilic and basophilic granulocytes. The latter lymphokine is involved in the development of cutaneous basophilic hypersensitivity.

Lymphotoxins cause damage or destruction of various target cells.
In the body, they can damage cells located at the site of formation of lymphotoxins. This is the nonspecificity of this damage mechanism. Several types of lymphotoxins have been isolated from an enriched culture of human peripheral blood T-lymphocytes. At high concentrations, they cause damage to a wide variety of target cells, and at low concentrations, their activity depends on the type of cells.

Interferon secreted by lymphocytes under the influence of a specific allergen (the so-called immune or γ-interferon) and nonspecific mitogens (PHA). It is species specific. It has a modulating effect on the cellular and humoral mechanisms of the immune response.

Transfer factor isolated from dialysate of lymphocytes of sensitized guinea pigs and humans. When administered to intact gilts or humans, it transfers the "immunological memory" of the sensitizing antigen and sensitizes the organism to that antigen.

In addition to lymphokines, the damaging action involves lysosomal enzymes, released during phagocytosis and cell destruction. There is also some degree of activation Kallikrein-kinin system, and involvement of kinins in damage.

pathophysiological stage.

In a delayed-type allergic reaction, the damaging effect can develop in several ways. The main ones are the following.

1. Direct cytotoxic effect of sensitized T-lymphocytes on target cells, which, due to various reasons, have acquired autoallergenic properties.
Cytotoxic action goes through several stages.

In the first stage - recognition - the sensitized lymphocyte detects the corresponding allergen on the cell. Through it and the histocompatibility antigens of the target cell, contact of the lymphocyte with the cell is established.
In the second stage - the stage of a lethal blow - the induction of a cytotoxic effect occurs, during which the sensitized lymphocyte carries out a damaging effect on the target cell;
The third stage is the lysis of the target cell. At this stage, blistering of the membranes develops and the formation of a fixed frame with its subsequent disintegration. At the same time, swelling of mitochondria, pycnosis of the nucleus is observed.

2. Cytotoxic effect of T-lymphocytes mediated through lymphotoxin.
The action of lymphotoxins is nonspecific, and not only the cells that caused its formation, but also intact cells in the zone of its formation can be damaged. Cell destruction begins with damage to their membranes by lymphotoxin.

3. Release of lysosomal enzymes during phagocytosis damaging tissue structures. These enzymes are secreted primarily by macrophages.

An integral part of delayed-type allergic reactions is inflammation, which is connected to the immune response by the action of mediators of the pathochemical stage. As with the immunocomplex type of allergic reactions, it is connected as a protective mechanism that promotes the fixation, destruction and elimination of the allergen. However, inflammation is both a factor in damage and dysfunction of those organs where it develops, and it plays an important pathogenetic role in the development of infectious-allergic (autoimmune) and some other diseases.

In type IV reactions, in contrast to inflammation in type III, macrophages, lymphocytes and only a small number of neutrophilic leukocytes predominate among the focus cells.

Delayed-type allergic reactions underlie the development of some clinical and pathogenetic variants of the infectious-allergic form of bronchial asthma, rhinitis, autoallergic diseases (demyelinating diseases of the nervous system, some types of bronchial asthma, lesions of the endocrine glands, etc.). They play a leading role in the development of infectious and allergic diseases. (tuberculosis, leprosy, brucellosis, syphilis, etc.), transplant rejection.

The inclusion of a particular type of allergic reaction is determined by two main factors: properties of the antigen and the reactivity of the organism.
Among the properties of an antigen, its chemical nature, physical state and quantity play an important role. Weak antigens found in the environment in small quantities (plant pollen, house dust, dander and animal hair) often give an atopic type of allergic reactions. Insoluble antigens (bacteria, fungal spores, etc.) often lead to a delayed-type allergic reaction. Soluble allergens, especially in large quantities (antitoxic serums, gamma globulins, bacterial lysis products, etc.), usually cause an allergic reaction of the immunocomplex type.

Types of allergic reactions:

Immune complex type of allergy (I I I type).
Delayed type allergy (type IV).

Modern science describes allergy as an increased level of sensitivity of the body to foreign substances. The cause of allergies are allergens, which are substances that are predominantly of a protein nature, which, when penetrated into an organism that is sensitive to them, cause allergic reactions. Allergic reactions can in turn lead to damage to organs and tissues.

Allergen classification

Allergens are usually divided into two groups:

Exoallergens - allergens that enter the body from the external environment;

Endoallergens are allergens that form inside the body.

When considering allergic diseases among children, the most attention is paid tonon-infectious exoallergens . They also have their division into the following subgroups:

Household exoallergens - house dust is especially important in this subgroup;

pollen;

Food, which may be of animal and vegetable origin;

Chemical;

epidermal.

Infectious exoallergens divided as follows:

fungal;

Viral;

Bacterial.

Causes of allergic reactions

The impact of allergens on an organism sensitive to them provokes the development of allergic reactions; In addition, the following factors can serve as a trigger in this process:

Features of the body's immune system with a predisposition to allergies;

Changes in metabolic reactions and endocrine processes;

Influences of the external environment.

There are various types of allergic reactions, which, according to modern classification, are divided into four types:

Type I - immediate, reaginic, anaphylactic - determines the formation of reagin antibodies that are associated with the presence of IgE. When reagin and allergen interact, a biologically active substance is released - histamine, which is a slow-acting substance of anaphylaxin. In this case, a characteristic clinical picture of a certain allergic disease is manifested.

This type of allergic reaction is especially often observed in childhood and is characteristic of non-infectious atopic allergies.

Type II allergic reactions - cytolytic, cytotoxic - develops with the participation of IgM and IgE, closely associated with cell membranes. When an allergen interacts with an antibody, cell destruction occurs.

This type of allergic reaction is most characteristic of immune forms of blood diseases.

Type III - semi-slow, immunocomplex - similar in manifestation to the first two types of allergic reactions. This type is humoral, it is associated with the formation of precipitating antibodies that belong to IgG. In this case, the formation of immune complexes that damage blood vessels occurs.

Type IV - delayed, cellular - is accompanied by the formation of sensitized lymphocytes that specifically and selectively damage tissues. This type of allergic reaction is typical for manifestations of an infectious allergy.

The course of allergic diseases occurs with the participation of a certain type of allergic reactions. But at the same time, reactions of various types can proceed sequentially or simultaneously, and this greatly complicates the development of allergic pathology, as well as its diagnosis and treatment.

drug allergy

This type of allergy is an allergic disease and reactions that occur as a response to a specific drug. Drug allergies are now increasingly common among children in the process of taking certain medications.

Disease pathogenesis

In the emergence and development of drug allergies, the mechanisms of the immune system, as well as allergic reactions belonging to different types, play a leading role. Drug allergens can act on the body both as full antigens and, more commonly, as partial antigens (or haptens) that act as allergens after attaching body proteins.

This type of allergic disease develops most often in children who have increased allergic reactivity or already have a specific form of allergic pathology, for example, food allergies or bronchial asthma.

An important role here belongs to the allergenicity of the medicinal product, as well as (but to a lesser extent) the route of administration and the dose of the drug. Drug allergy most often develops with the use of a large number of drugs, as well as with unreasonably frequent use of antibiotics.

The formation of drug allergy is characterized by cross and group reactions, which depend on the chemical properties and molecular structure of the drugs used. At the same time, allergic reactions of medicinal origin can also be observed in newborns. This can occur as a result of the development of an allergy to medicines in the mother during pregnancy or when she comes into contact with the drug.

Clinical picture

Manifestations of drug allergy and the clinical picture that occurs during its development can be quite diverse both in its form and in the severity of the manifestation. The most severe allergic reactions develop in the following situations:

exposure of the body to several allergens at the same time, which can be medicinal and food;

due to the combination of the use of drugs with the action of preventive vaccinations;

allergenic effect of viral infections;

negative impact on the body of various non-specific factors.

Diagnosis of the disease

When diagnosing a drug allergy, the main thing is a carefully compiled allergic history. The use of laboratory methods for in vitro diagnostics is recommended - these include:

mast cell degranulation,

leukocyte agglomeration,

method of blast transformation of lymphocytes,

Skin testing with drugs is not recommended in children, as they are potentially hazardous to their health.

What preventive measures can be offered to prevent the occurrence of drug allergies?

Disease prevention

To prevent the development of this disease, preventive measures are of paramount importance. In order to prevent drug allergies, you should clearly justify the use of certain drugs, do not self-medicate.

In the presence of allergies, and especially of medicinal origin, the prescription of medications should be carried out carefully and as reasonably as possible, when they are used, the doctor's reaction to the body should be monitored in order to identify possible negative manifestations of the disease.

A clear fixation of allergic reactions to certain drugs in the child's medical records and bringing this information to his parents is a prerequisite for treatment if there is a tendency to allergic manifestations. At the first manifestations of an allergic reaction to medicines, it should be urgently canceled and prescribed hyposensitizing agent, apply a hypoallergenic diet. In especially severe cases, the use of glucocorticoid hormones is allowed.

food allergy

This type of allergy most often manifests itself in the first years of a child's life. Etiologically, it is associated with various food allergens of plant or animal origin.

The earliest food allergen is cow's milk used in baby food. It should be remembered about the high degree of lability of the composition of cow's milk, which depends on a combination of many factors. In addition to milk, foods such as sweets, citrus fruits, fish, chicken eggs have increased allergenicity. Carrots and tomatoes have a high degree of allergenicity among vegetables. Any food products can act as a source of allergens, and allergic reactions occur when allergens of different food products cross-action, for example, between those contained in beef and cow's milk.

The pathogenesis of this disease

The emergence and development of food allergies begins with antenatal development, especially when a pregnant woman abuses foods that cause allergic reactions in her. The factors that provoke the development of food allergies in a child include:

Reduced barrier of the immune defense of the digestive tract due to an insufficient level of formation of secretory igA;

Non-infectious and infectious diseases of the gastrointestinal tract, the development of which leads to the occurrence of dibacteriosis due to a violation of the normal breakdown of food components;

Frequent constipation, contributing to the decay of food debris in the intestines;

Clinical picture of the disease

Food allergies come in many forms, but the most common are:

angioedema,

hives,

neurodermatitis,

children's true eczema,

exanthems of various etiologies.

In addition, there may be such manifestations of food allergies:

pain abdominal and dyspeptic syndromes;

respiratory allergy symptoms

general reaction of the collaptoid type,

changes in peripheral blood (leukopenic and thrombocytopenic reactions),

skin and respiratory reactions, which are characterized by polyallergy with a fairly wide range of inhaled household and food allergens.

Manifestations of food allergies are observed most often after eating, after about 2 hours.

How is the disease diagnosed?

Diagnosis of the disease

The main types of diagnosis of this disease include an allergic history, as well as keeping a food diary. To identify specific allergens, provocative and laboratory tests are used, as well as sampling.

Respiratory Allergy

Allergic reactions can occur in any part of the respiratory tract, which in this case will become a springboard (or shock organ) for the development of allergies. As a result, various nosological forms of respiratory allergies may occur. The leading role here belongs to the impact of non-infectious exogenous allergens, in particular, house dust.

Also, the development of respiratory allergies is promoted by plant pollen, medicinal, food, fungal, epidermal allergens. Less commonly, respiratory allergies develop when exposed to infectious allergens.

The present time is characterized by the spread of epidermal and pollen allergies. Young children, and especially in the first year of life, are more likely to suffer from reactions of the respiratory tract that are of a food nature.

Most often, with the manifestation of respiratory allergies, allergic reactions of the immediate type are involved, but other types of allergic reactions may also be involved.

The pathogenesis of this type of allergy is complicated by the participation of pathoreceptor mechanisms in its development, which are typical for children with allergic reactivity with increased irritability of the respiratory tract. Strengthening it can occur when exposed to damaging and irritating environmental factors that injure the mucous membranes of the respiratory tract, as well as under the action of chemical agents, air pollution, meteorological effects and damage by respiratory viruses.

Clinical picture

Allergic diseases affecting the respiratory system are usually divided into the following types:

tracheitis;

laryngitis;

allergic rhinitis;

rhinosinusitis.

These diseases can have an independent course, and can be simultaneously observed in one person. With the development of diseases of the allergic nature of the upper respiratory tract, bronchial asthma is formed - the leading disease of the allergic nature of the respiratory system. For this reason, the listed diseases can be combined by the definition of "preasthma".

Diagnostics

Diagnosis of a certain form of a respiratory disease of an allergic nature is carried out taking into account the clinical picture, knowledge of the allergic history and mandatory information about the presence of allergic reactions in the family. Also an important factor in making a diagnosis is information about conditions in everyday life that can provoke the manifestation of allergic reactions.

In the absence of exacerbations of the disease, special diagnostics are carried out in allergological children's rooms in order to establish the causes of allergies and specific allergens.

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

bacterial allergy

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

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

contact allergy

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

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

Autoallergy

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

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

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

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

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

Autoallergic lesions are also known, which develop due to the commonality of antigenic determinants of the tissue's own components with those of exoallergens. Common antigenic determinants have been found in the heart muscle and some strains of streptococcus, lung tissues and some saprophytic bacteria living in the bronchi, etc. The immunological reaction caused by an exoallergen, due to its cross antigenic properties, can be directed against its own tissues. In this way, some cases of allergic myocarditis, an infectious form of bronchial asthma, etc. may occur. systemic lupus erythematosus, acquired hemolytic anemia, etc.

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

Homograft rejection reaction

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

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

Mechanisms of delayed-type allergic reactions

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

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

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

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

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

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

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

Effect of thymus on allergic reactions

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

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

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