Mechanisms of formation of allergic reactions. Allergy types, mechanism of action, clinical manifestations

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 gone mysterious disease. More precisely, this is not one disease, but a whole group of conditions. Allergic diseases are bronchial asthma, allergic rhinitis, skin problems- sharp and chronic urticaria, atopic dermatitis.

All these problems are based on the same reaction. And today it is fully deciphered. The point of allergy is 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 solve 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 respond to immunoglobulin E. In Germany, clinical trials the latest drug which allows you to do this. This is a revolutionary approach to the treatment of allergies.

- AT recent times Another method of prevention is widely discussed - allergen-specific therapy.

It is already well studied 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 body's sensitivity 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 likelihood 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. Best Results it gives 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. For achievement 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?

Appointed antihistamines. So, with allergic rhinitis, nasal sprays are used today. With conjunctivitis - antiallergic eye drops. At skin reactions local 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 need to take antihistamines.

AT last years drugs with improved properties 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

Over the past two decades, the frequency of allergic diseases has increased significantly, especially in economically developed countries and in countries with an unfavorable environmental situation. Some scientists predict that the 21st century will be the century of allergic diseases. Currently, more than 20 thousand allergens are already known, and their number continues to grow. Various factors appear today as the reasons for the increase in the frequency of allergic diseases.

1. Change in the structure of infectious morbidity. At present, it is generally accepted that the function of T-lymphocytes-helpers of the 2nd type normally prevails in the human immune system at birth. This is due to the peculiarities of the immune mechanisms that regulate the relationship in the mother-fetus system during pregnancy. However, after birth, during the period of maturation of the immune system, there should normally be a change in orientation in the ratio of the function of T-lymphocytes-helpers in favor of strengthening the function of type 1 T-helpers. In this they are helped by viral and bacterial antigens, which, by activating macrophages, contribute to the production of interleukin 12 by the latter. In turn, IL-12, acting on type 0 T-helpers, shifts their differentiation towards type 1 T-helpers, which produce gamma-IFN and suppress the function of type 2 T-helpers. It may sound paradoxical, but today there is every reason to say that improving the quality of life, reducing the number of viral and bacterial diseases in childhood, including tuberculosis, leads to an increase in the function of type 2 T-helpers and the development of allergic reactions in the future. .
2. Hereditary factors. Determined that genetic predisposition Allergy is polygenic in nature and includes:

genetic control of the enhanced function of type 2 T-helpers for the production of IL-4 and IL-5;

genetic control of increased IgE production; c) genetic control of bronchial hyperreactivity.

3. Environmental factors. In recent years, it has been shown that exhaust gases tobacco smoke due to the content of obvious pollutants such as NO2, SO2, or NO, they enhance the function of type 2 T-helpers and the production of IgE. In addition, by acting on the epithelial cells of the airways, they contribute to their activation and production of pro-inflammatory cytokines (IL-8, alpha-ONF, IL-6), which, in turn, have toxic effect on epithelial cells that contribute to the development of allergic inflammation.

Stages of a true allergic reaction:

The presence of primary contact of the body's immune system with an allergen (antigen);

The presence of a certain time interval for changing the reactivity of the development of the immune response, which in this context is understood as the occurrence of sensitization; ends with the formation of antibodies and/or cytotoxic sensitized T-lymphocytes;

The presence of repeated contact with the same (specific) allergen-antigen;

And, finally, the development of characteristic clinical manifestations, which are based on one or another effector immune mechanisms, which were mentioned in the general part of this book, i.e. an allergic reaction develops; action that causes damage.

Based on the above, today there are three stages of a true allergic reaction.

I. Immune stage - lasts from the moment of initial contact of the immune system with the allergen until the development of sensitization.

II.Pathochemical stage - turns on when the immune system re-contacts with a specific allergen and is characterized by the release a large number biologically active substances.

III.Pathophysiological stage - characterized by a violation of the functioning of cells and tissues of the body up to their damage under the influence of biologically active substances released by the immune system during the pathochemical stage.

We can also talk about the existence of stage IV - clinical, which completes the pathophysiological and is its clinical manifestation.

Thus, it should be remembered that the immune system of the body, developing an immune response, implementing humoral and cellular reactions as protective reactions aimed at maintaining immune homeostasis, in some cases can cause damage to its own cells and tissues. Such reactions, according to the historical tradition, are called allergic, or hypersensitivity reactions. However, even in cases of development of damage, allergic reactions are also considered as protective, contributing to the localization of the allergen that has entered the body and its subsequent removal from the body.

Conventionally, all hypersensitivity reactions, depending on the duration of the period between the onset of contact of the sensitized organism with the antigen and the onset of external (clinical) manifestations of an allergic reaction, are divided into three types:

Allergic reactions of immediate type (hypersensitivity of immediate type - HHT) - develop within 15-20 minutes (or earlier).

Late (delayed) allergic reactions HNT - develop within 4-6 hours.

Delayed-type allergic reactions (delayed-type hypersensitivity - HRT) - develop within 48--72 hours.

The classification of hypersensitivity reactions according to Gell and Coombs (1964), which provides for four types, is currently most widely used. In recent years, this classification has been supplemented by type V. The mechanism of the hypersensitivity reaction of types I, II, III and V is based on the interaction of the antigen with antibodies; IV hypersensitivity reactions depend on the presence in the body of sensitized lymphocytes carrying structures on their surface that specifically recognize the antigen. Below is a description of the different types of hypersensitivity reactions.

I. Anaphylactic type of hypersensitivity reactions. It is caused by the formation of a special type of antibodies related to IgE and having a high affinity (affinity) for tissue basophils (mast cells) and peripheral blood basophils. These antibodies are also called homocytotropic because of their ability to be fixed to the cells of the same animal species from which they are obtained.

When an allergen first enters the body, it is captured by antigen-presenting cells (macrophages, B-lymphocytes, dendritic cells) and is digested (processed). As a result of digestion under the influence of lysosomal enzymes, a certain amount of peptides is formed from the allergen, which are loaded into the peptide-binding grooves of the molecules of the major histocompatibility complex, transported to the surface of antigen-presenting cells and presented for recognition by T-helper lymphocytes. For certain reasons, allergenic peptides are recognized by type 2 T-helpers, which, at the moment of recognition, are activated and begin to produce IL-4, IL-5, IL-3, and other cytokines.

Interleukin-4 performs two important functions:

Under the influence of IL-4 and subject to the presence of a costimulation signal in the form of contact between two molecules of CD40L and CD40, the B-lymphocyte turns into a plasma cell that produces mainly IgE;

Under the influence of IL-4, IL-3, the proliferation of both types of basophils increases and the number of receptors for the IgE Fc fragment increases on their surface.

Thus, at this stage of the immune response, a fundamental basis is laid that distinguishes an immediate-type allergic reaction from all other hypersensitivity reactions: specific IgE (homocytotropic antibodies, or reagins) are “produced” and fixed on tissue basophils and peripheral blood basophils.

Under the influence of IL-5, IL-3, eosinophils are also included in the “combat readiness”: their migration activity increases, the ability to produce biologically active substances extending their lifespan. On the surface of eosinophils, adhesion molecules appear in large numbers, allowing eosinophils to attach to the epithelium, in particular ICAM.

When a specific allergen enters the body again, it binds to IgE (moreover, it is very important that the allergen has a certain molecular weight that allows it to bind the Fab fragments of two adjacent IgE molecules located on the basophil (or mast cell) membrane), which leads to degranulation of basophils both types with the release of thrombocyte-activating factor, histamine, leukotrienes, prostaglandins, etc. The release of biologically active substances during degranulation leads to:

activation of platelets with the release of serotonin;

complement activation with the formation of anaphylotoxins - C3a and C5a, activation of hemostasis;

release of histamine and increased vascular permeability;

increased contraction of smooth (non-striated) muscle tissue under the influence of leukotrienes and prostaglandins (in particular, PGT2alpha).

All this ensures the development of the acute phase of the reaction, and its clinical symptoms which are sneezing, bronchospasm, itching and lacrimation.

The mediators that are released during a type I allergic reaction are divided into reformed (i.e., already present in the granules of both types of basophils) and newly formed under the influence of phospholipase A2 during the breakdown of arachidonic acid cell membranes.

The participation of eosinophils in allergic reactions of the immediate type is characterized by two functions.

Mediators are released from eosinophils, which include the main basic protein of eosinophils, cationic proteins, peroxidase, neurotoxin, platelet-activating factor, leukotrienes, etc. Under the influence of these mediators, symptoms of the late phase develop, which are characterized by the development of cellular inflammation, destruction of the epithelium, hypersecretion of mucus, contraction of the bronchi .

Eosinophils produce a number of substances that help suppress the allergic reaction, reduce the consequences of its damaging power:

histaminase - destroying histamine;

arylsulfatase - contributing to the inactivation of leukotrienes;

phospholipase D - neutralizing platelet-activating factor;

prostaglandin E - reducing the release of histamine.

Thus, type I allergic reactions, like other immune reactions, have a dialectical character in terms of the realization of the protective potential, which can take on a damaging character. It's connected with:

release of mediators with destructive potential;

the release of mediators that destroy the function of the former.

At the first stage, the release of mediators leads to an increase in vascular permeability, promotes the release of Ig, complement into the tissues, enhances the chemotaxis of neutrophils, eosinophils. The inclusion of hemocoagulation mechanisms and the formation of blood clots in the microvascular bed localize the focus of penetration of the allergen into the body. All of the above leads to inactivation and elimination of the allergen.

At the second stage, the release of arylsulfatase, histaminase, phospholipase D, prostaglandin E2 contributes to the suppression of the function of mediators released at the first stage. The degree of clinical manifestations depends on the ratio of these mechanisms. In general, the pathophysiological stage of the T-type hypersensitivity reaction is characterized by:

increased permeability of the microvasculature:

the release of fluid from the vessels;

the development of edema;

serous inflammation;

increased formation of mucous excretions.

Clinically, this is manifested by bronchial asthma, rhinitis, conjunctivitis, urticaria, Quincke's angioedema, skin itching, diarrhea, an increase in the number of eosinophils in the blood and in secrets.

Concluding the review of type I allergic reactions, it should be noted that allergens that promote the production of IgE have a molecular weight in the range of 10-70 KD. Antigens (allergens) weighing less than 10 KD, if they are not polymerized, are not able to bind two IgE molecules on the surface of basophils and mast cells, and therefore are not able to “turn on” an allergic reaction. Antigens weighing more than 70 KD do not penetrate intact mucous membranes and therefore cannot bind to IgE present on cell surfaces.

II. Cytotoxic type of hypersensitivity reactions. It is realized in the same way as type I, by humoral antibodies, however, not IgE (as in type 1 reactions), but IgG (except IgG4) and IgM act as reactants. Antigens with which antibodies interact in type II allergic reactions can be both natural cellular structures (antigenic determinants), for example, when blood cells are damaged, and extracellular structures, for example, antigens of the basal membrane of the renal glomeruli. But in any case, these antigenic determinants must acquire autoantigenic properties.

The reasons for the acquisition of autoantigenic properties by cells can be:

conformational changes in cell antigens;

membrane damage and the appearance of new “hidden” antigens;

formation of an antigen + hapten complex.

As a result of the immune response, IgG and IgM are produced, which, by combining their F (ab) 2 fragments with cell antigens, form immune complexes. Under the influence of the formation of immune complexes, three mechanisms are activated:

Complement activation and implementation of complement-mediated cytotoxicity;

Activation of phagocytosis;

Activation of K-cells and realization of antibody-dependent cell-mediated cytotoxicity (ADCC).

During the pathochemical stage, complement activation is accompanied by opsonization. activation of inflammatory cell migration, increased phagocytosis, release of histamine under the influence of C3a, C5a, formation of kinins, destruction of the cell membrane. Activation of neutrophils, monocytes, eosinophils leads to the release of lysosomal enzymes from them, the formation of superoxide anion radical, singlet oxygen. All these substances are involved in the development of cell membrane damage, in the initiation and maintenance of free-radical lipid oxidation of cell membranes.

As clinical examples type II allergic reactions can lead to autoimmune hemolytic anemia, autoimmune thyroiditis, allergic drug agranulocytosis, thrombocytopenia, nephrotoxic nephritis, etc.

III. Immune complex type of hypersensitivity reactions. It is characterized in the same way as the cytotoxic type II by the participation of IgG and IgM. But unlike type II, here antibodies interact with soluble antigens, and not with antigens located on the surface of cells. As a result of the combination of antigen and antibody, a circulating immune complex is formed, which, when it is fixed in the microvasculature, leads to complement activation, release of lysosomal enzymes, formation of kinins, superoxide radicals, release of histamine, serotonin, endothelial damage and platelet aggregation with all subsequent events. leading to tissue damage. An example of type III reactions are serum sickness, local reactions like the Arthus phenomenon, exogenous allergic alveolitis (farmer's lungs, lungs of pigeon breeders, etc.), glomerulonephritis, some variants of drug and food allergies, autoimmune pathology.

The pathological potential of immune complexes in type III allergic reactions is determined by the following factors:

1. The immune complex must be soluble, formed with a slight excess of antigen and have a molecular weight of -900-1000 KD;
2. The composition of the immune complex should include complement-activating IgG and IgM;
3. The immune complex must circulate for a long time, which is observed when:

prolonged intake of the antigen;

in violation of the excretion of immune complexes as a result of overload of the monocyte-macrophage system, blockade of Fc-, C3b- and C4b-receptors;

4. Must be enhanced permeability vascular wall what happens under the influence of:

vasoactive amines from both types of basophils and platelets;

lysosomal enzymes.

With this type of reaction, neutrophils predominate in the focus of inflammation, then macrophages, and finally lymphocytes.

IV. Delayed-type hypersensitivity reactions (cell-mediated or tuberculin hypersensitivity). This type of hypersensitivity is based on the interaction of a cytotoxic (sensitized) T-lymphocyte with a specific antigen, which leads to the release of a whole set of cytokines from the T-cell, mediating the manifestations of delayed hypersensitivity.

The cellular mechanism is activated when:

Insufficient efficiency of the humoral mechanism (for example, with the intracellular location of the pathogen - tubercle bacillus, brucella);

In the case when foreign cells act as an antigen (some bacteria, protozoa, fungi, transplanted cells and organs), or cells of one's own tissues, the antigens of which are changed (for example, the inclusion of an allergen-hapten in skin proteins and the development of contact dermatitis).

Thus, during the immunological stage, cytotoxic (sensitized) T-lymphocytes mature in the body.

During repeated contact with the antigen (allergen), in the pathochemical stage, cytotoxic (sensitized) T-lymphocytes secrete the following cytokines:

Macrophage migration inhibitory factor (MIF, MIF), which has the ability to enhance phagocytosis and is involved in the formation of granulomas;

Factor stimulating the formation of endogenous pyrogens (IL-1);

Mitogenic (growth) factors (IL-2, IL-3, IL-6, etc.);

Chemotactic factors for each white cell line, especially IL-8;

Granulocyte-monocytic colony-stimulating factors;

Lymphotoxins;

Tumor-necrotizing factor;

Interferons (alpha, beta, gamma).

Cytokines released from sensitized T-lymphocytes activate and attract cells of the monocyte-macrophage series to the focus of inflammation.

In the event that the action of lymphocytes is directed against viruses that infect cells, or against transplantation antigens, stimulated T-lymphocytes are transformed into cells that have the properties of killer cells in relation to target cells that carry this antigen. These reactions include: allergies, which are formed with some infectious diseases, transplant rejection, some types of autoimmune lesions.

Thus, during the pathophysiological stage, damage to cells and tissues occurs due to:

Direct cytotoxic action of T-lymphocytes;

Cytotoxic action of T-lymphocytes due to non-specific factors (pro-inflammatory cytokines, apoptosis, etc.);

Lysosomal enzymes and other cytotoxic substances (NO, oxidants) of activated cells of the monocyte-macrophage series.

In type IV allergic reactions, among the cells infiltrating the focus of inflammation, macrophages predominate, then T-lymphocytes, and, lastly, neutrophils.

An example of delayed-type hypersensitivity is allergic contact dermatitis, allograft rejection, tuberculosis, leprosy, brucellosis, fungal infections, protozoal infections, and some autoimmune diseases.

V. Stimulating type of hypersensitivity reactions. When reactions of this type are implemented, cell damage does not occur, but, on the contrary, cell function is activated. A feature of these reactions is that they involve antibodies that do not have complement-fixing activity. If such antibodies are directed against the components of the cell surface involved in the physiological activation of the cell, for example, against the receptors of physiological mediators, then they will cause stimulation of this cell type. For example, the interaction of antibodies with antigenic determinants that are part of the structure of the thyroid-stimulating hormone receptor leads to a reaction similar to action the hormone itself: to the stimulation of thyroid cells and the production of thyroid hormone. In fact, such antibodies are referred to as autoimmune antibodies. This immune mechanism underlies the development of Graves' disease - diffuse toxic goiter. The considered classification of hypersensitivity reactions, despite the fact that it was proposed more than 30 years ago, allows you to make general idea about the types of immunologically mediated reactions affecting cells and tissues; allows you to understand the fundamental differences in the mechanisms underlying them, as well as in the basis of clinical manifestations; and, at last, allows to explain possible ways of medical control over the course of these reactions.

It is important to take into account that, as a rule, not one, but several types of hypersensitivity reactions are involved in the mechanisms of development of individual nosological forms.

Over the past two decades, the frequency of allergic diseases has increased significantly, especially in economically developed countries and in countries with an unfavorable environmental situation. Some scientists predict that the 21st century will be the century of allergic diseases. Currently, more than 20 thousand allergens are already known, and their number continues to increase. Various factors appear today as the reasons for the increase in the frequency of allergic diseases.

1. Change in the structure of infectious morbidity. At present, it is generally accepted that the function of T-lymphocytes-helpers of the 2nd type normally prevails in the human immune system at birth. This is due to the peculiarities of the immune mechanisms that regulate the relationship in the mother-fetus system during pregnancy. However, after birth, during the period of maturation of the immune system, there should normally be a change in orientation in the ratio of the function of T-lymphocytes-helpers in favor of strengthening the function of type 1 T-helpers. In this they are helped by viral and bacterial antigens, which, by activating macrophages, contribute to the production of interleukin 12 by the latter. In turn, IL-12, acting on type 0 T-helpers, shifts their differentiation towards type 1 T-helpers, which produce gamma-IFN and suppress the function of type 2 T-helpers. It may sound paradoxical, but today there is every reason to say that improving the quality of life, reducing the number of viral and bacterial diseases in childhood, including tuberculosis, leads to an increase in the function of type 2 T-helpers and the development of allergic reactions in the future. .

2. Hereditary factors. It has been established that the genetic predisposition to allergies is polygenic in nature and includes:

genetic control of the enhanced function of type 2 T-helpers for the production of IL-4 and IL-5;
genetic control of increased IgE production; c) genetic control of bronchial hyperreactivity.

3. Environmental factors. In recent years, it has been shown that exhaust gases, tobacco smoke, due to the content of obvious pollutants such as NO2, SO2, or NO, enhance the function of type 2 T-helpers and the production of IgE. In addition, by acting on epithelial cells of the airways, they contribute to their activation and production of pro-inflammatory cytokines (IL-8, alpha-ONF, IL-6), which, in turn, have a toxic effect on epithelial cells that contribute to the development of allergic inflammation. What is an allergy? What is the fundamental feature of its fundamental mechanisms and clinical manifestations?

Allergy today is commonly understood as manifestations of increased sensitivity of the body's immune system to an allergen (antigen) upon repeated contact with it, which is clinically characterized by damage primarily to those tissues of the body through which the allergen penetrates: bronchial mucosa, alimentary canal, nasal cavity, skin, conjunctiva. For the first time the term "allergy" was proposed in 1906 by the Austrian pediatrician K. Pirke to determine the changes in reactivity, which he observed in children with serum sickness and infectious diseases. K. Pirke wrote: “A vaccinated person is related to a vaccine, a syphilitic person is related to the causative agent of syphilis, a tubercular person is related to tuberculin, a person who has received serum is related to the latter, differently than an individual who has not encountered these antigens before. He is, however, very far from a state of insensitivity. All we can say about him is that his reactivity is altered. For this general concept to altered reactivity, I propose the expression “allergy” (from the Greek allo- other; ergon- action)”.

Thus, already at the very beginning of the development of the doctrine of allergies, fundamental points were noticed, the conditions for the occurrence of altered reactivity, which later began to be interpreted as stages of a true allergic reaction:
The presence of primary contact of the body's immune system with an allergen (antigen);
The presence of a certain time interval for changing the reactivity of the development of the immune response, which in this context is understood as the occurrence of sensitization; ends with the formation of antibodies and/or cytotoxic sensitized T-lymphocytes;
The presence of repeated contact with the same (specific) allergen-antigen;

Based on the above, today there are three stages of a true allergic reaction.

I. Immune stage - lasts from the moment of initial contact of the immune system with the allergen until the development of sensitization.

II.Patochemical stage - is activated by repeated contact of the immune system with a specific allergen and is characterized by the release of a large amount of biologically active substances.

We can also talk about the existence of stage IV - clinical, which completes the pathophysiological stage and is its clinical manifestation.

Allergic reactions of immediate type (immediate type hypersensitivity - HHT) - develop within 15-20 minutes (or earlier).
Late (delayed) allergic reactions HNT - develop within 4-6 hours.
Delayed-type allergic reactions (delayed-type hypersensitivity - DTH) - develop within 48-72 hours.

Interleukin-4 performs two important functions:

Under the influence of IL-4 and subject to the presence of a costimulation signal in the form of contact between two molecules of CD40L and CD40, the B-lymphocyte turns into a plasma cell that produces mainly IgE;
Under the influence of IL-4, IL-3, the proliferation of both types of basophils increases and the number of receptors for the IgE Fc fragment increases on their surface.

Under the influence of IL-5, IL-3, eosinophils are also included in the “combat readiness”: their migratory activity and the ability to produce biologically active substances increase, their life span lengthens. On the surface of eosinophils, adhesion molecules appear in large numbers, allowing eosinophils to attach to the epithelium, in particular ICAM.

activation of platelets with the release of serotonin;
complement activation with the formation of anaphylotoxins - C3a and C5a, activation of hemostasis;
release of histamine and increased vascular permeability;
increased contraction of smooth (non-striated) muscle tissue under the influence of leukotrienes and prostaglandins (in particular, PGT2alpha).

All this ensures the development of the acute phase of the reaction, and its clinical symptoms, which are sneezing, bronchospasm, itching and lacrimation.

The participation of eosinophils in allergic reactions of the immediate type is characterized by two functions.

Mediators are released from eosinophils, which include the main basic protein of eosinophils, cationic proteins, peroxidase, neurotoxin, platelet-activating factor, leukotrienes, etc. Under the influence of these mediators, symptoms of the late phase develop, which are characterized by the development of cellular inflammation, destruction of the epithelium, hypersecretion of mucus, contraction of the bronchi .
Eosinophils produce a number of substances that help suppress the allergic reaction, reduce the consequences of its damaging power:

histaminase - destroying histamine;
arylsulfatase - contributing to the inactivation of leukotrienes;
phospholipase D - neutralizing platelet-activating factor;
prostaglandin E - reducing the release of histamine.

Thus, type I allergic reactions, like other immune reactions, have a dialectical character in terms of the realization of a protective potential, which can take on a damaging character. It's connected with:

release of mediators with destructive potential;
the release of mediators that destroy the function of the former.

increased permeability of the microvasculature:
the release of fluid from the vessels;
the development of edema;
serous inflammation;
increased formation of mucous excretions.

Clinically, this is manifested by bronchial asthma, rhinitis, conjunctivitis, urticaria, angioedema, angioedema, skin itching, diarrhea, an increase in the number of eosinophils in the blood and in secrets.

The reasons for the acquisition of autoantigenic properties by cells can be:

conformational changes in cell antigens;
membrane damage and the appearance of new “hidden” antigens;
formation of an antigen + hapten complex.

Complement activation and implementation of complement-mediated cytotoxicity;
Activation of phagocytosis;
Activation of K-cells and realization of antibody-dependent cell-mediated cytotoxicity (ADCC).

As clinical examples of type II allergic reactions, one can cite autoimmune hemolytic anemia, autoimmune thyroiditis, allergic drug agranulocytosis, thrombocytopenia, nephrotoxic nephritis, etc.

III. Immune complex type of hypersensitivity reactions. It is characterized in the same way as the cytotoxic type II by the participation of IgG and IgM. But unlike type II, here antibodies interact with soluble antigens, and not with antigens located on the surface of cells. As a result of the combination of antigen and antibody, a circulating immune complex is formed, which, when it is fixed in the microvasculature, leads to complement activation, release of lysosomal enzymes, formation of kinins, superoxide radicals, release of histamine, serotonin, endothelial damage and platelet aggregation with all subsequent events. leading to tissue damage. Examples of type III reactions are serum sickness, local reactions like the Arthus phenomenon, exogenous allergic alveolitis (farmer's lungs, pigeon breeders' lungs, etc.), glomerulonephritis, some variants of drug and food allergies, autoimmune pathology.

The pathological potential of immune complexes in type III allergic reactions is determined by the following factors:

1. The immune complex must be soluble, formed with a slight excess of antigen and have a molecular weight of -900-1000 KD;

2. The composition of the immune complex should include complement-activating IgG and IgM;

3. The immune complex must circulate for a long time, which is observed when:

prolonged intake of the antigen;
in violation of the excretion of immune complexes as a result of overload of the monocyte-macrophage system, blockade of Fc-, C3b- and C4b-receptors;

4. The permeability of the vascular wall should be enhanced, which occurs under the influence of:

vasoactive amines from both types of basophils and platelets;
lysosomal enzymes.

With this type of reaction, neutrophils predominate in the focus of inflammation, then macrophages, and finally lymphocytes.

The cellular mechanism is activated when:

Insufficient efficiency of the humoral mechanism (for example, with the intracellular location of the pathogen - tubercle bacillus, brucella);
In the case when foreign cells act as an antigen (some bacteria, protozoa, fungi, transplanted cells and organs), or cells of one's own tissues, the antigens of which are changed (for example, the inclusion of an allergen-hapten in skin proteins and the development of contact dermatitis).

Thus, during the immunological stage, cytotoxic (sensitized) T-lymphocytes mature in the body.

During repeated contact with the antigen (allergen), in the pathochemical stage, cytotoxic (sensitized) T-lymphocytes secrete the following cytokines:

Macrophage migration inhibitory factor (MIF, MIF), which has the ability to enhance phagocytosis and is involved in the formation of granulomas;
Factor stimulating the formation of endogenous pyrogens (IL-1);
Mitogenic (growth) factors (IL-2, IL-3, IL-6, etc.);
Chemotactic factors for each white cell line, especially IL-8;
Granulocyte-monocytic colony-stimulating factors;
Lymphotoxins;
Tumor-necrotizing factor;
Interferons (alpha, beta, gamma).

Cytokines released from sensitized T-lymphocytes activate and attract cells of the monocyte-macrophage series to the focus of inflammation.

In the event that the action of lymphocytes is directed against viruses that infect cells, or against transplantation antigens, stimulated T-lymphocytes are transformed into cells that have the properties of killer cells in relation to target cells that carry this antigen. These reactions include: allergies that form in some infectious diseases, transplant rejection, some types of autoimmune lesions. On fig. 57 is a diagram of a type IV (delayed) allergic reaction.

Thus, during the pathophysiological stage, damage to cells and tissues occurs due to:

Direct cytotoxic action of T-lymphocytes;
Cytotoxic action of T-lymphocytes due to non-specific factors (pro-inflammatory cytokines, apoptosis, etc.);
Lysosomal enzymes and other cytotoxic substances (NO, oxidants) of activated cells of the monocyte-macrophage series.

In type IV allergic reactions, among the cells infiltrating the focus of inflammation, macrophages predominate, then T-lymphocytes, and, lastly, neutrophils.

V. Stimulating type of hypersensitivity reactions. When reactions of this type are implemented, cell damage does not occur, but, on the contrary, cell function is activated. A feature of these reactions is that they involve antibodies that do not have complement-fixing activity. If such antibodies are directed against the components of the cell surface involved in the physiological activation of the cell, for example, against the receptors of physiological mediators, then they will cause stimulation of this cell type. For example, the interaction of antibodies with antigenic determinants that are part of the structure of the thyroid-stimulating hormone receptor leads to a reaction similar to the action of the hormone itself: to the stimulation of thyroid cells and the production of thyroid hormone. In fact, such antibodies are referred to as autoimmune antibodies. This immune mechanism underlies the development of Graves' disease - diffuse toxic goiter. The considered classification of hypersensitivity reactions, despite the fact that it was proposed more than 30 years ago, allows you to get a general idea of the types of immunologically mediated reactions affecting cells and tissues; allows you to understand the fundamental differences in the mechanisms underlying them, as well as in the basis of clinical manifestations; and, at last, allows to explain possible ways of medical control over the course of these reactions.

It is important to take into account that, as a rule, not one, but several types of hypersensitivity reactions are involved in the mechanisms of development of individual nosological forms.

Modern science describes allergies as elevated level 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 - especially important in this subgroup is house dust;

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 different 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, cells are destroyed.

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. However, reactions can proceed sequentially or simultaneously. various types, which greatly complicates the development process 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 drug allergy the leading role is played by the mechanisms of the immune system, as well as allergic reactions belonging to different types. 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.

Allergenicity plays an important role here. 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 when using a large number of drugs, as well as when unreasonably frequent use antibiotics.

The formation of drug allergy is characterized by cross and group reactions, which depend on chemical properties and the 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. Recommended use laboratory methods in vitro diagnostics - these include:

mast cell degranulation,

leukocyte agglomeration,

method of blast transformation of lymphocytes,

Holding skin tests with medications 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 development 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 appointment medications should be carried out carefully and as reasonably as possible, when using them, the doctor should monitor the reaction of the body in order to identify possible negative manifestations of the disease.

Clear fixation of allergic reactions to certain medications in the medical records of the child 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. Carrots and tomatoes have a high degree allergenicity among vegetables. Any source of allergens can be food products, while there is a manifestation of allergic reactions with the cross action of allergens of different foods, 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:

lowered barrier immune protection digestive tract due to an insufficient level of formation of secretory igA;

Noncommunicable and infectious diseases of organs 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 enough a wide range 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 development respiratory allergies contributes to 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 specific form respiratory disease allergic nature is carried out taking into account the clinical picture, knowledge allergic history and mandatory information about the presence of allergic reactions in the family. Also an important factor when making a diagnosis, there 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.

Mechanism of development of allergy.

There are three agents of an allergic reaction: the allergen itself, the antibodies produced in response, and the cells that bind them.

Antibodies are the main factors of immunity directed against foreign substances that enter the body. Antibodies are produced in bone marrow, spleen, lymph nodes. The thymus gland plays an important role. The main place in the reactions of immunity is occupied by lymphocytes. Of the lymphocytic stem cells, some become cells that produce immunoglobulins - protective protein formations circulating in the blood serum. Such lymphocytes are called B - lymphocytes, and immunoglobulins circulating in the blood - humoral antibodies. There are 5 classes of immunoglobulins: IgA, IgG, IgM, IgE and IgD.

In the blood serum healthy people most of all contains IgG and IgA - they protect the body during infections, IgM acts in the same way. The content of IgE in the blood of healthy people is low. The concentration of immunoglobulins of this class in the blood increases significantly with allergic diseases. Its increase can help in the diagnosis of allergies. An increase in the content of IgE is observed with helminthic invasion. IgE plays important role in the implementation of allergic reactions of the immediate type. However, other classes of immunoglobulins may also be involved in the development of allergic reactions.

Part of the lymphoid stem cells enters the thymus gland (thymus), in which these cells mature and, leaving it, are called thymus-dependent, or T-lymphocytes. These T-lymphocytes are cellular antibodies. They also play a large role in the body's defense reactions against infections and in the development of delayed-type allergic reactions. There are several subpopulations of T-lymphocytes: T-helpers (helpers), T-suppressors (suppressors), T-killers (killers). Subpopulations of T-cells interact with each other and regulate the production of all classes of immunoglobulins by B-lymphocytes.

Allergens are antigens that can cause sensitization of the body and participate in the development of type I hypersensitivity reactions. Allergens can enter the body different ways- with food, through the mouth, Airways through the skin, and sometimes by injection.

Allergens can be a variety of substances: foods of animal and vegetable origin, plant pollen, medicines, house dust, pillow feathers, pet hair and dander, fish food, various bacteria and viruses as well chemical substances.

There are the following large groups of allergens:

1) Allergens entering the body from outside (exogenous), which include:

a) household and epidermal (house dust, wool and dander of domestic animals, fluff and feathers of birds, food for fish and others);

b) food ( egg yolk and protein, chocolate, cocoa, fish, strawberries, nuts, caviar, cow's milk, oranges, honey, wheat flour, tomatoes and others);

c) pollen (pollen of various plants, trees, shrubs, meadow grasses, flowers of birch, alder, poplar, rye, fescue, timothy grass, ambrosia, and others);

d) medicinal allergens;

e) chemical and industrial allergens;

f) bacterial, fungal and viral allergens.

2) Allergens of the body's own (endogenous). Sometimes, when the tissues of the body are subjected to some harmful effects(chemicals, radiation, inflammatory process caused by microbes or viruses), the immune system no longer recognizes these tissues (they are called autoallergens) as their own, and antibodies are produced on them (they are called autoantibodies). This process is called autoallergic. Autoallergic processes play an important role in the development of diseases such as rheumatism, lupus erythematosus, nephritis and some others.

Phases of allergic reactions.

Once in the body, allergens are connected to the surface of the cells of various organs (depending on how the allergen entered the body). Sometimes allergens get inside the cells.

After the allergen enters the body, antibodies begin to be produced against it. These antibodies are different from the usual protective ones. They are called aggressive antibodies or reagins. They belong to IgE. Reagins bind to allergens on the cell surface. Academician Ado calls this period, this phase of allergic reactions the immunological phase.

The combination of an allergen with an antibody on cells leads to disruption of the function of these cells and even to their destruction. At the same time, a number of biologically active substances are released from damaged cells. This phase of the allergic reaction is called pathochemical. These biologically active substances are also called mediators. Each of them has the ability to cause a number of changes in the body: expand capillaries, reduce arterial pressure, cause spasm of smooth muscles, disrupt capillary permeability, as a result, disturbances in the activity of the organ in which the incoming allergen met with the antibody develop. Ado called this phase of the allergic reaction pathophysiological - this phase is already visible to both the patient and the doctor, because the clinical picture develops.

Allergic reactions can develop quickly - within 20 minutes-1 hour after meeting with allergens, in which case the reactions are called immediate type or atopic reaction, or type 1 reaction.

However, it is possible to develop an allergy many hours after exposure to the allergen. This is a delayed allergic reaction. Cellular antibodies are associated with blood cells (lymphocytes), which reach the site of allergen entry, interact with allergens much later (after many hours) and cause delayed-type allergies.

Of particular importance for the development of allergies are allergic antibodies - class E immunoglobulins - reagins. They are found in people with allergies in very large quantities. Reagins are firmly connected with cells, most of all with mast cells, which are present in greater numbers in the subcutaneous tissue, under the mucous membranes, in the nose, bronchi, and intestines. With their other endings, reagins are connected to the allergen (2 reagin molecules with 1 allergen molecule).

Mediators of allergic reactions.

When reagin interacts with an allergen, a number of substances are released from mast cells, which before this interaction were contained in the cell, but in an inactive state. These are the so-called mediators - biologically active substances. These include: histamine, leukotrienes, prostaglandins. As a result of the action of these substances in the organs in which the allergen enters and meets it with reagins, the permeability of the vascular wall increases, edema develops, vasospasm, muscle contraction and blood pressure drops. The clinical picture depends on the organ in which the allergic reaction has developed. Such an organ is called shock.

Eosinophils rush to such a "shock" organ under the influence of secreted factors. They can be found in patients in large quantities in the blood, in the mucus of the nose and bronchi. A platelet activating factor is also produced.

The most important of the mediators is histamine - a biogenic amine formed from histidine. When injected under the skin, it causes the formation of a characteristic blister, similar to that resulting from a nettle burn, and when injected into a vein in animals, it causes a picture anaphylactic shock. Inhalation of a histamine solution causes bronchospasm. Histamine in healthy people is found in small quantities, and, in addition, the blood of healthy people contains substances that can bind histamine. In allergic diseases of the immediate type, histamine is found in the blood in large quantities, and the ability to bind histamine in such patients is reduced.

Slowly active ingredients anaphylaxis (MRSA) can dramatically increase the permeability of the walls of blood vessels and cause spasm of smooth muscles. This contraction occurs more slowly than when exposed to histamine. MRSA is a mixture of leukotrienes - derivatives of arachidonic acid. The inactivation of MRSA involves arylsulfatase, which is contained in large quantities in eosinophils. Especially strong action MRSA on the peripheral airways (bronchioles). MRSA occurs during an allergic reaction. The maximum amount is observed 15 minutes after exposure to the allergen, then there is a slow decline.

In allergic reactions, an eosinophilic chemotactic factor is also released, due to which eosinophils involved in the allergic reaction accumulate in the shock organ.

Neutrophil chemotaxis factor, a factor that activates platelets, is also released. Due to the action of these substances, neutrophils and platelets, which are also involved in the allergic reaction, are attracted to the site of the allergic reaction.

Prostaglandins are also conversion products of arachidonic acid, some of them are capable of causing smooth muscle spasm, and in particular bronchospasm.