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19.07.2019

Allergic reaction type 4 pathophysiology. Allergy. Criteria for an allergic condition

Allergy is a qualitatively altered reaction of the body to the action of substances, often of an antigenic nature (a type of immunopathology). It is based on immune mechanisms. Unlike immunity, allergic reactions lead to damage to tissues and organs.
The substance that causes an immune reaction is called an antigen, and the allergic reaction is called an allergen. The occurrence of allergies is associated with altered (increased) reactivity of the body, as well as with the nature and amount of allergen entering the body.
When an allergen is introduced, antibodies are formed in the body, which, if exposed again, can lead to the development of an allergic reaction. Children more often suffer from allergic diseases due to the immaturity of the histohematic barriers of the gastrointestinal tract, respiratory tract, easier penetration of the allergen into the body and other characteristics of the child’s body.
Allergens that enter the body from the environment are called exoallergens, and those formed in the body and representing the body's own, but modified proteins are called endoallergens, or autoallergens. Exoallergens are classified into infectious and non-infectious.
Non-infectious allergens:
1. pollen allergens: pollen of any plants, trees, meadow grasses, pollen of cereals (rye, corn, sunflower, etc.).
2. epidermal: dander and hair of domestic and wild animals (cats, dogs, cows, horses), feathers and down of birds.,
3. household: house and library dust, fish food, etc.,
4. drug allergens: antibiotics, iodine, novocaine, etc.,
5. food: milk, eggs, honey, chocolate, etc.,
6. chemical allergens: varnishes, paints, cosmetics, washing powders, etc.
Autoallergens (endoallergens) are divided into natural and acquired. Natural tissue includes lens tissue, thyroid gland, testicles, and nervous tissue. Autoallergens can also form in other organs due to the action of infectious agents during burns, cooling, etc.
There are certain differences between an allergen and an antigen. An antigen is a high-molecular compound (usually a protein) that leads to the formation of antibodies. An allergen does not always have antigenic properties; sometimes it is a low-molecular compound that interacts with body proteins.
Of the classifications based on the pathogenetic principle, the most recognized is that proposed in 1968 by Jell and Coombs. In accordance with it, 4 types of allergic reactions are distinguished.

Type Name
I Anaphylactic (reaginic)
II Cytotoxic
III Immunocomplex
IV HRT (delayed hypersensitivity)

Type I reactions (anaphylactic) are mainly IgE-mediated. This includes anaphylactic shock, bronchial asthma, Quincke's edema, etc.
Anaphylaxis is a state of acquired hypersensitivity of the body to repeated parenteral administration of a foreign protein. Anaphylaxis, depending on the conditions of its occurrence, can manifest itself in the form of a local or general reaction. The general reaction is anaphylactic shock. Anaphylactic reactions can occur in people. This can be due to insect bites (bees, wasps, etc.), administration of drugs (penicillin, novocaine, serums) and in other cases.
Classic anaphylactic shock was first reproduced in guinea pigs in 1912 by A.M. Frequently. Pigs are sensitized by subcutaneous injection of a very small dose of foreign serum. Active sensitization occurs. 2-3 weeks after the administration of the sensitizing dose, the pigs are intravenously injected with protein in a much larger dose, after which she develops anaphylactic shock. (Fig.3)
If serum from a sensitized pig that has the appropriate immunoglobulins is injected into an intact pig, then the second will experience passive sensitization, which, depending on the route of administration, can last from several minutes to several hours.
The development of shock can be prevented by desensitization. This is achieved by repeated injections of small doses of the allergen subcutaneously or intradermally. Desensitization according to A.M. It is often carried out for the purpose of administering medicinal serums and other medicinal drugs to which there is increased sensitivity. People have diseases similar to anaphylactic reactions in animals, but they differ significantly in the mechanism of development and a number of signs. These diseases were called atopic (Greek: Atopia - unusual). In the development of atopic diseases, hereditary predisposition and the participation of nonspecific factors play a greater role than in anaphylaxis. These diseases include atopic bronchial asthma, hay fever, year-round rhinitis, etc.
There are 3 stages in the development of allergic reactions.
In the first - immune stage - after the first injection of the antigen, the formation of antigen-specific antibodies (IgE and IgG), sensitized T-lymphocytes, occurs. Antibodies bind mainly to mast cells and basophils.
In the second, pathochemical stage, the allergen, when reintroduced, combines with antibodies and sensitized lymphocytes. A large number of allergy mediators are released from mast cells, basophils, etc., the main ones being histamine and serotonin.
The third - pathophysiological stage is characterized by the development, under the influence of mediators, of dysfunctions of cells, organs and systems.
Allergic reactions of the first (anaphylactic) type include anaphylactic shock, allergic form of bronchial asthma, conjunctivitis, urticaria, hay fever, etc.
Allergic reactions of the 2nd type are cytotoxic. In this case, the allergens are the body’s own modified cells. This occurs as a result of changes in cells (usually blood cells) under the influence of drugs, viruses, bacteria, etc. In this regard, many infectious diseases and the administration of medications can lead to allergic reactions.
Allergic reactions of the 3rd type - immunocomplex - allergens (bacterial, viral, fungal, drugs, food, etc.), combining with antibodies, form immune complexes (IC), which, after their fixation on the vascular wall, lead to its damage. ICs are phagocytosed by leukocytes, which leads to inflammation of the corresponding tissues and organs. This type of reaction leads to local anaphylaxis: Arthus phenomenon, serum sickness, allergic alveolitis, etc.
Allergic reactions of the 4th type - delayed type hypersensitivity (DSHT). They are characterized by the participation not of antibodies, but of specific effector T-lymphocytes. The lymphokines released from them activate macrophages and the processes of leukocyte emigration, which leads to the development of a dense infiltrate. Reactions of this type include transplant rejection reactions, contact dermatitis, tuberculin-type reactions, etc.
The most dangerous allergic reaction is anaphylactic shock. The course of shock varies among different animal species. The differences depend on the type of “shock organ”. In dogs, spasm of the sphincters of the hepatic veins and stagnation of blood in the liver occurs; in rabbits, the leading cause is spasm of the pulmonary arteries and a sharp expansion of the right half of the heart; in guinea pigs, bronchospasm predominates, leading to suffocation. In humans, the course of anaphylactic shock is possible in one of 4 options: 1) hemodynamic (drop in blood pressure), 2) respiratory (suffocation), 3) gastrointestinal tract (diarrhea), 4) cerebral (convulsions). (The course of anaphylactic shock in humans is described in the chapter “Extreme Conditions”).
Urticaria is accompanied by the appearance of itchy red spots or blisters, often of food origin, which can disappear within an hour after the antigen enters the skin from the environment. Urticaria can transform into life-threatening angioedema (giant urticaria or angioedema). The accumulation of large amounts of exudate in the area of ​​the lips, eyelids, and genitals is also life-threatening.
Bronchial asthma is characterized by the development of obstructive syndrome (usually at the level of the lower respiratory tract), which can lead to respiratory failure and asphyxia. The main mechanisms of obstruction of small bronchi and bronchioles are spasm, swelling of the mucous membrane and hypersecretion of mucus.
Hay fever (from the Latin pollen - pollen) is an allergic reaction caused by pollen. They are characterized by rhinitis and conjunctivitis, which are seasonal.
Serum sickness occurs after parenteral administration of serum for therapeutic purposes. It is characterized by the appearance of symptoms (rash, swelling, malaise, headache, pain in joints, muscles) after the first introduction of the allergen.
In some cases, with allergic reactions, an increase in organ function is observed. Thus, the formation of antibodies to thyroglobulin of the thyroid gland can have an effect similar to thyroid-stimulating hormone, which in many cases leads to the development of thyrotoxicosis (Graves' disease).

Pathological physiology Tatyana Dmitrievna Selezneva

LECTURE No. 8. IMMEDIATE ALLERGIC REACTIONS

Allergy(Greek “allos” - another, other, “ergon” - action) is a typical immunopathological process that occurs against the background of the influence of an allergen antigen on the body with a qualitatively altered immunological reactivity and is accompanied by the development of hyperergic reactions and tissue damage.

There are immediate and delayed allergic reactions (humoral and cellular reactions, respectively). Allergic antibodies are responsible for the development of allergic reactions of the humoral type.

For the clinical picture of an allergic reaction to manifest, at least 2 contacts of the body with the allergen antigen are necessary. First dose of exposure allergen (small) is called sensitizing. Second dose of exposure– large (resolving) is accompanied by the development of clinical manifestations of an allergic reaction. Allergic reactions of the immediate type can occur within a few seconds or minutes, or 5–6 hours after repeated contact of the sensitized organism with the allergen.

In some cases, long-term persistence of the allergen in the body is possible and, in connection with this, it is almost impossible to draw a clear line between the effects of the first sensitizing and repeated resolving doses of the allergen.

Classification of immediate allergic reactions:

1) anaphylactic (atopic);

2) cytotoxic;

3) immune complex pathology.

Stages of allergic reactions:

I – immunological

II – pathochemical

III – pathophysiological.

 From the book General and Clinical Immunology: Lecture Notes by N.V. Anokhin

LECTURE No. 5. Pathological immune reactions of the body. Allergic diseases The possibility of a pathological reaction is especially high in cases where a change in a person’s living conditions occurs in a short period of time. Such examples are climate change, regime change

author

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Drug allergy- allergic reactions caused by medications. Their prevalence is quite high and ranges from 3.7 to 6.4 per 1000 population in the USSR. In the United States, approximately 1-2% of the population suffers from drug allergies.

The mechanism of allergic reactions to drugs is diverse and complex. There are true allergic and pseudoallergic reactions. The former are based on immunological reactions of one type or another, the interaction of a drug as an allergen with antibodies belonging to immunoglobulins of classes E, G and M or with sensitized lymphocytes. This kind of specific interaction is followed by the release or formation and subsequent release of allergy mediators of immediate or delayed type (pathochemical stage). Then the pathophysiological processes underlying the clinical manifestations of drug allergies develop. Pseudoallergic reactions to drugs do not have an immunological stage as the basis for their pathogenesis.
These reactions are not determined by the interaction of the drug with recognizing immunological structures. The most important mechanism of pseudoallergic reactions to drugs is the release of histamine and other allergy mediators from mast cells (mast cells) and basophils in the blood under the influence of the drug, the activation of the components of the complement system by the drug, the effect on the metabolic pathways of arachidonic acid and the effect on the body’s kinin system. In addition, the development of pseudoallergic reactions depends on the properties of the administered drug (histamine liberator, etc.), on genetic factors affecting the metabolism of the drug, as well as on existing pathological changes in various organs and systems of the body (dysfunction of the liver, gastrointestinal tract , c.s.s., etc.). Drug allergies are mainly caused by the following groups of drugs: 1) full antigens: xenogeneic serums and immunoglobulins, which are administered for therapeutic or prophylactic purposes, some hormones (adiurecrin, corticotropin, insulin), but most drugs or their metabolic products in the body are haptens; 2) beta-lactam antibiotics of the penicillin group are the most studied and typical group of medicinal allergens that cause predominantly true allergic reactions; reactions occur under the influence of conjugates of metabolic products; 3) sulfonamide drugs (there is evidence of the possibility of true allergic reactions, in rare cases with the participation of JgE); 4) mainly contact sensitizers that cause allergic dermatitis (aminoglycosides, formaldehyde, metal compounds, anesthesin, nitrofuran drugs, etc.).
The overwhelming majority of groups of other drugs give pseudo-allergic reactions (x-ray contrast agents, plasma replacement solutions containing dextran, pyrazolone derivatives, antibiotics of various groups, etc.).

The clinical picture is characterized by the development of allergic reactions of immediate or delayed type: anaphylactic shock, acute allergic urticaria or angioedema, bronchospasm, a picture resembling serum sickness, contact allergic dermatitis, etc. For true LA. characterized by a high degree of sensitization, for example, well-known cases of extremely high sensitivity to drugs of the penicillin group. Allergic reactions in drug allergies, as a rule, occur not to one specific drug, but to a group of them, causing cross-reactions due to the antigenic affinity of the metabolites and their conjugates formed in the body. In other cases, similar pathways by which drugs influence pathochemical processes (eg, arachidonic acid metabolism) are common.

The diagnosis is made primarily on the basis of a clinical picture typical of allergic reactions and a carefully collected allergological history.
Laboratory diagnosis is associated with a number of difficulties associated with the diversity of pathogenetic mechanisms. The presence of a pseudoallergic reaction to drugs in this group excludes immunological diagnosis. Laboratory tests can only be informative for true drug allergies, taking into account the type of allergic reaction and when using an adequate drug allergen in a series of tested concentrations (for example, penicilloyl protein). For immediate type allergies, a radioallergosorbent test, an enzyme immunoassay test, a basophil test, a mast cell destruction test, and a specific histamine release reaction are used; for delayed type allergies - a reaction of inhibition of leukocyte migration in its various variants. A reaction of inhibition of the natural emigration of leukocytes into the oral cavity has been proposed to identify allergies of various types and mechanisms. Skin allergy tests with drugs are not recommended due to the nonspecific effects of most drugs.
As for true medicinal allergens (penicillin group), tests with them are potentially dangerous for the patient. Only patch tests with contact sensitizers are acceptable. Allergic reactions should be differentiated from complications of drug therapy associated with the toxic effect of administered substances, their overdose, and undesirable side effects of drugs.

Emergency care for acute allergic reactions to drugs - see Anaphylactic shock. Nonspecific therapy for developed allergic complications of drug therapy is carried out according to general principles. Prevention of subsequent allergic reactions is important. It must be carried out through strict elimination of both the drug that caused the reaction and related drugs and complex drugs containing them. It is necessary to carry out sanitary and hygienic measures among medical staff and pharmacists to prevent occupational drug allergies.

PATHOPHYSIOLOGY OF ALLERGY

Allergic diseases account for up to 30% of the population's morbidity and their frequency is constantly growing. The most common diseases are rhinitis, urticaria, and bronchial asthma.

Allos - different, ergon - action

Therefore, an allergy is a different action.

Allergy is a typical pathological process, manifested by the body's high sensitivity to repeated exposure to irritants of an antigenic nature. In addition to the concept of “allergy”, there are the terms “sensitization” and “hypersensitivity”. Substances that cause allergies are called allergens.

Allergy refers to a pathology of the immune system, reflecting a new form of sensitivity in the body.

Immunity

Allergen FSIO

Allergy

There are 3 periods in the development of allergies:

1. Sensitization. It occurs after the first contact with the allergen and does not manifest itself in any way. During this period, the body's sensitivity increases.

2. Period of clinical manifestations. It is characterized by contraction of smooth muscles, increased secretion of endocrine glands, pain reactions, development of fever, inflammation, and shock.

3. The period of hyposensitization is a period of decreased hypersensitivity.

Etiology of allergies

The etiology of allergies includes:

1. Extreme irritant

2 Terms

3. Entrance gate

4. Body reactivity

Extreme irritant

These are antigens, foreign substances. They have weak sensitivity and weak antigenicity. They can be complete or incomplete (haptens). Full antigens are macromolecular compounds of animal, plant, food origin, autoantigens. Incomplete antigens are haptens. These include medications.

Classification of antigens

ALLERGENS

Endogenous Exogenous

Non-infectious Infectious

medicinal household herbal food

penicillin, homemade herbs, flowers, cow milk insects -

medicinal dust, wool, pollen and juice, co, chicken proteins

serum, domestic plant eggs, fish, pathogens

sulfanyl-animal citrus fruits,

amides, iodine, mites, fluff, honey, coffee, bacteria, vi-

vitamins that wash meat, rusa nuts, mushrooms and

Group B means, their fragments

aniline

dyes

2. Conditions: high and low temperatures, ionizing radiation, ultraviolet rays, electromagnetic fields, environmental factors (ozone, nitrogen oxides), diet (excessive load of carbohydrates and proteins).

3. Entrance gate. When plant allergens enter the respiratory tract, cough and bronchial asthma more often develop. When an allergen enters through the gastrointestinal tract, manifestations in the form of inflammation are observed. If the allergen enters parenterally, for example, anaphylactic shock may develop into the blood. If the allergen enters through the skin, dermatitis, rashes, and even eczema can develop.

4. Reactivity of the body.

More often, people with an allergic constitution suffer from allergic diseases. In general, immunological reactivity in humans is determined by the state of the central nervous system, endocrine system, and genetic mechanisms.

The role of the nervous system. Increased sensitivity to allergic irritants is associated with neuroticism. Activation of cholinergic innervation (activation of the PSNS) contributes to the development of allergies.

Cholinesterase Ca 2+ cGMP

Endocrine system. The predominance of proallergic hormones - growth hormone, thyroxine, mineralocorticoids, TSH - form allergies. Hormones such as ACTH, glucocorticoids, and sex hormones are antiallergic.

The role of the physiological immune response system

Allergic predisposition is caused by mutations in the genome. The physiological immune response system is under the regulatory influence of the genome. The main role is played by the genes of the major histocompatibility system (HLA) (6th pair of chromosomes), which is capable of

HLA Ir Is to distinguish between one's own and someone else's. This system regulates the immune gene

Tx Tc response (Ir) and immune suppression gene (Is). These genes

form the degree of sensitivity Tx and Tc. With mutations, the Tc function is mainly affected. This changes the activity of the immune response. The sensitivity of the body increases, immunity is impaired.

The central nervous system, hormones, and genetic mechanisms shape age-related reactivity. In children of the first three years, allergies to food irritants predominate. Manifests itself in the form of exudative diathesis, dermatitis. At the age of 3-7 years, manifestations from the respiratory system are observed - allergic bronchitis, bronchial asthma. Until the age of 30, allergy symptoms subside. After 30 years, there is an exacerbation of allergic reactions from the respiratory system or skin manifestations.

Pathophysiological mechanisms of development of allergic reactions

These mechanisms are divided into:

1. Delayed type hypersensitivity (DSH)

2. Immediate type hypersensitivity (IHS)

PCZT: these reactions develop after a few hours or a little (up to 3 days). These are cellular reactions, this is a T-dependent allergy.

Allergic reactions of the immediate type develop within a few minutes. These are humoral reactions, B-dependent allergies. Mixed reactions are characteristic of autoallergy.

PCTs are cell-mediated reactions, type IY

The following stages are distinguished in the development of these reactions:

1. Pathoimmune

2. Pathochemical

3. Pathophysiological stage

Pathoimmune stage

Antigen Macrophage Tl Tsens. Tp

IL-1 IL-2 Tx

The antigen reacts with the macrophage (A cell). Incomplete phagocytosis of the antigen by the macrophage leads to the fact that allergen particles come to the surface of cell A. They interact with Tx with the participation of interleukin-1. Activation of Th enhances its effect on Th through interleukin-2. Tl become sensitized (T-effector). T-effectors are antigen-sensitive lymphocytes that have specific receptors on their surface.

T-effectors give a clone of cells: 1) T-memory cells are long-lived cells. They determine the allergic constitution and are able to react to the antigen. 2) T-cytotoxic lymphocytes. They damage any cell where there is antigen (even when the antigen initially enters). When the antigen is re-entered, memory T cells transform into Tc lymphocytes. 3) During the initial exposure to an antigen, T-helpers, T-suppressors and T-tolerant lymphocytes are also formed in the body. T-suppressors inhibit the development of allergies, and T-tolerant lymphocytes participate in the mechanisms of hyposensitization (reducing hypersensitivity). TCs play a major role in the development of allergies. They interact with somatic cells on which the antigen is fixed. The cell is excited and, under the influence of lysosomal enzymes, the cell is destroyed. This interaction leads to the development of the pathochemical stage. During the primary action of the antigen, the duration of the sensitization period is 3-5 days.

Pathochemical stage

As a result of the interaction of TC with the somatic cell, allergy mediators are released. They are released from lymphocytes and in delayed reactions are called lymphokines.

1. Transfer factor (transfer factor). It has a sensitizing effect on intact lymphocytes. This factor plays a role in blood transfusion.

2. Mitogenetic factor. It stimulates the proliferation of lymphocytes, their division, and promotes the population of T-sensitized lymphocytes.

3. Macrophage migration inhibitory factor (MIF)). It promotes the accumulation of macrophages in the area of ​​allergic alteration and causes the development of inflammation.

4. Lymphotoxin. It has a cytotoxic effect, causing destruction and death of the target cell.

5. Chemotaxis factor. It promotes the accumulation of neutrophils and monocytes at the site of inflammation.

6. Skin reactive factor. It causes the development of skin manifestations

7. Interferon. It inhibits the ability of viruses to infect cells.

8. Prostaglandins. They contribute to the development of fever and activate TC lymphocytes.

All these factors cause the formation of typical pathological processes: inflammation, fever and shock.

Lymphokines cause the development of clinical manifestations

Pathophysiological stage

This stage manifests itself as:

1. Bacterial allergies (tuberculin-type diseases)

2. Contact allergies

Bacterial allergy

If the body is sensitized, then an inflammatory infiltrate forms at the site of injection of the filtrate from the killed bacteria after 2-3 days. Bacterial allergies are

an indicator not only of allergies, but also of vaccination.

Contact allergy

It occurs upon contact with a foreign substance (bromine preparations, heavy metal salts, dyes, cosmetics, novocaine, penicillin, detergents). These substances are haptens, but when they combine with skin proteins, they become complete allergens. Contact allergies manifest themselves as skin reactions - hyperemia, dermatitis, itching, rash.

Immediate hypersensitivity

These are humoral reactions; B lymphocytes participate in them.

Development mechanisms

1. Pathoimmune stage

2. Pathochemical stage

3. Pathophysiological stage

Pathoimmune stage

This stage reflects the mechanisms of sensitization.

Antigen Macrophage Vl Alls. VP

Plasmatic

Tx cell

The antigen interacts with the macrophage and with the participation of Tx, IL-1 and IL-2, B lymphocytes become sensitized and antigen-sensitive.

Upon primary exposure to an antigen from the Alls. lymphocytes form memory B cells, which retain increased sensitivity to the antigen, B lymphocytes and plasma cells. Plasma cells produce immunoglobulins IgE and IgG. The main role in allergic reactions is played by IgE - allergic antibodies. IgE binds to somatic cells, in particular mast cells. The cell becomes sensitive to the antigen. In its structure, IgE has heavy and light chains. The Fc (heavy chain) region has an affinity for mast cells. Light chains are antigen-sensitive: antigen reacts with them. In this way, IgE becomes a receptor for the antigen. In addition to IgE, IgG is produced in plasma cells. They can exhibit IgE properties, that is, be allergic antibodies. The IgG portion is blocking antibodies.

IgE is capable of forming a pathoimmune complex with the antigen, which causes destruction, cell lysis and release of allergy mediators.

Pathochemical stage

Under the influence of the pathoimmune complex, allergy mediators are released from the cells, which contribute to clinical manifestations. The main mediators in immediate allergic reactions are:

1. Histamine - it is released from mast cells, dilates blood vessels, increases vascular permeability, causes spasm of the bronchi and smooth muscles, and increases mucus secretion.

2. Heparin - released from mast cells, enhances the fibrinolytic activity of the blood

3. Slowly reacting allergy substance - is a derivative of arachidonic acid, formed in mast cells of the lungs. MRSA causes slow spasm of bronchioles in bronchial asthma. The spasm is not relieved by antihistamines. Sputum is formed, clogging the bronchi.

4. Bradykinin causes an increase in vascular permeability, dilates blood vessels, causes pain and itching.

5. Acetylcholine has the same properties as histamine and bradykinin, but to a lesser extent.

6. Prostaglandins cause an effect similar to histamine and bradykinin and contribute to the development of fever.

7. Eosinophil chemotaxis factor promotes eosinophil chemotaxis. Eosinophilia indicates allergization of the body.

8 Complement - participates in the implementation of type II reactions.

Manifestations of the action of mediators are inflammation, fever, shock.

Pathophysiological stage

At this stage, typical pathological processes and allergic diseases are formed. There are 3 groups of allergic reactions:

1. Allergic reactions type I: IgE plays a role in these reactions

2. Allergic reactions type II: IgG is involved in these reactions

3. Allergic reactions of type III (reactions of free immune complexes).

Group I allergic reactions include atopic reactions and anaphylaxis.

Atopic reactions

These include hay fever, bronchial asthma, urticaria, and Quincke's edema.

Hay fever is caused by exposure to plant pollen. The disease is manifested by rhinitis, conjunctivitis, itching, lacrimation, cough, sometimes fever, bronchitis. All these symptoms are caused by the participation of histamine.

Bronchial asthma occurs under the influence of household allergens - house dust, which contains mites. The disease is characterized by paroxysmal disturbances of bronchial obstruction, the clinical expression of which is attacks of expiratory (with difficulty exhaling) suffocation. The main role in bronchospasm is played by the slowly reacting allergy substance.

Urticaria is an allergic disease characterized by the rapid formation of focal edema. The pathogenesis of urticaria is based on an increase in vascular permeability under the influence of histamine. The disease develops under the influence of various allergens. It is characterized by fever, headache, general malaise, and itching. Urticaria ranks second after bronchial asthma.

Angioedema (Quincke's edema) is a locally limited swelling of the skin and subcutaneous tissue with a predominant localization in the face, mucous membranes of the oral cavity, and extremities. Quincke's edema is one of the types of urticaria. The disease occurs under the influence of medications, food allergens, and plant pollen. Histamine plays a role in the pathogenesis of Quincke's edema.

Anaphylaxis

Anaphylaxis - defenselessness. Anaphylaxis is manifested by general and local reactions. General anaphylaxis manifests itself as anaphylactic shock.

Anaphylactic shock can develop when antibiotics, antitoxic serums, sulfonamides are introduced into the body, or when taking certain foods. In anaphylaxis, along with IgE, circulating IgG takes part in the development of shock. The mediator anaphylatoxin takes part in the formation of the pathoimmune complex. Its action is realized through the release of histamine. Shock is characterized by a drop in blood pressure, vasodilation and the development of collapse, the development of cardiac and respiratory failure. Anaphylactic shock can develop from bee stings. In this case, shock develops with the participation of acetylcholine.

Local anaphylaxis (Arthus phenomenon) occurs at the site of repeated administration of the drug, horse serum in a dose of 0.5-1.0 ml to a rabbit with an interval of 5-6 days. Local anaphylaxis is accompanied by the development of aseptic inflammation, hyperemia, edema, and emigration of leukocytes. The reaction appears after 4-5 injections of the drug. IgG is involved in the development of the Arthus phenomenon.

Cytolytic reactions

The allergen is fixed on blood cells. A pathoimmune complex with IgG is formed in the presence of complement (C-3, C-5). This complex is fixed on the membranes of blood cells and, with the participation of cytolysin, causes cell destruction. According to this mechanism, allergic hemopathy develops (anemia, hemolytic jaundice, leukopenia, thrombocytopenia with symptoms of hemorrhage and bleeding).

Free immune complex diseases

Circulating IgG acts as antibodies in these reactions. The pathoimmune complex is formed in the blood with the participation of complement and is then fixed on the membranes of the kidneys, lymph nodes, and endothelium of the microvasculature. An allergic reaction in the form of an inflammatory process develops in any organ.

An example of these reactions is serum sickness, which occurs after the administration of therapeutic serum, antibiotics, hormones, and protein preparations. The disease is manifested by a generalized reaction of the lymph nodes, fever, and skin manifestations in the form of urticaria. The pathological process includes the kidneys, myocardium, and joints. Conglomerates form in the blood, which clog capillaries and disrupt microcirculation.

Autoallergy

Autoallergy develops in response to the action of autoallergens (endogenous allergens). The physiological immune response system responds to autoallergens by producing autoantibodies.

Autoallergens

Natural Acquired

(primary) (secondary)

normal proteins I II III IY

ny fabrics

Autoallergy is a state of autoaggression of immunocompetent cells capable of reacting with proteins of their own tissues.

Autoallergy refers to mixed allergies. It develops according to the mechanism of delayed-type hypersensitivity and immediate-type hypersensitivity.

AAG FSIO

PCNT IgE, IgG, IgM

Mechanisms of development of autoallergy

There are several views on the mechanisms of development of autoallergy.

    Primary AAG. Some tissues of the body during embryogenesis developed without contact with FSIO. These tissues are isolated behind the histohematic barrier, and the proteins of these organs and tissues do not have histocompatibility genes. These proteins are incompatible with immunocompetent cells (B and T lymphocytes) and become autoallergens. These lymphocytes and A cells treat these proteins as foreign. These are proteins of the retina, lens, nervous system, thyroid gland, male reproductive gonads. When the histohematic barrier is disrupted, these proteins are released into the blood and lymphocytes perceive them as foreign. When proteins and lymphocytes interact, an autoallergic reaction develops. By this mechanism, diseases such as thyroiditis, encephalomyelitis, and ophthalmia (inflammatory processes of the damaged eye) develop.

    The second mechanism that contributes to the development of autoallergic reactions is associated with a violation of the tolerance mechanisms of immunocompetent cells, in particular T cells. According to Burnet's theory, these lymphocytes form a forbidden clone. During the development of the body, these lymphocytes are not able to distinguish between self and foreign. This clone of lymphocytes either disappears at birth or is in a depressed state under the control of the immune suppression gene (Is). When gene control is weakened, the function of T-suppressors becomes insufficient and aggressive lymphocytes (lymphocytes of the forbidden clone) are expressed, become active and begin to act as autoallergens. Thus, autoallergic reactions develop in this case as a result of a violation of the gene mechanism.

According to the second view, under the influence of mutagenic factors, mutant lymphocytes are formed in the body that can act as autoantigens. A number of diseases develop with the participation of this mechanism.

Rheumatoid arthritis: This is an autoallergic inflammation of the joints. The disease develops with the participation of rheumatoid factor (IgM). This is an antibody. IgM is formed when exposed to an allergen (some portions of IgG). IgG has antigenic determinants - idiotypes. B lymphocytes respond to them. In response to idiotypes, an anti-idiotype (IgM) is produced. An “idiotype-antiidiotype” complex is formed, which affects the synovial membranes of the joints.

Disseminated lupus erythematosus. Connective tissue DNA is often exposed to pathological lymphocytes. In this case, DNA acts as an autoallergen. In response to the formation of autoallergens, autoantibodies are formed. During the AAG + AAT reaction, a pathoimmune complex is formed, which is fixed on the skin, kidneys, myocardium, and vascular walls, causing damage to these tissues.

Myasthenia. Pathological lymphocytes (B cells) are able to perceive acetylcholine receptors as foreign, as self-antigens. Anti-acetylcholine antibodies are formed, which block acetylcholine receptors. Muscle weakness develops, muscles do not contract.

Diseases caused by the action of secondary (acquired) autoallergens

I. Modified, denatured proteins are capable of acquiring the properties of autoallergens. The physiological immune response system responds to these proteins by producing autoantibodies. The cause of the appearance of such proteins is extensive burns. A pathoimmune complex is formed, causing an autoallergic reaction.

II. A number of infectious pathogens and tissue allergens have common determinant groups. Some strains of E. coli and intestinal mucosal proteins share common determinants. By this mechanism, ulcerative colitis of autoallergic origin develops. Rheumatic carditis. Streptococcus A has similar determinant groups with cardiomyocytes. A pathoimmune complex is formed that damages the myocardium. Infectious-allergic bronchial asthma develops according to this mechanism. Its development is due to the fact that the microflora of the respiratory tract has common determinant groups with the proteins of lung tissue.

III. Ionizing radiation can cause tissue destruction and the appearance of autoallergens. During myocardial infarction and necrosis of the heart muscle, cardiomyocytes are damaged and become autoallergens. They cause the formation of autoantibodies followed by the formation of a pathoimmune complex.

IY. Autoallergens include intermediate allergens. In this case, complex autoallergens can form in the body. Most often, this group of autoallergic diseases occurs with the participation of viruses. Viruses enter the cell and damage it. The physiological immune response system responds to destroyed cells by developing an autoallergic process.

Hyposensitization

Hyposensitization is a decrease in the body's increased sensitivity to the action of an antigen.

The mechanisms of hyposensitization underlie the principles of treatment and prevention of allergic diseases.

The nervous and endocrine systems and biological active substances are involved in the mechanisms of hyposensitization.

Endocrine Biological

SNS system PSNS active

substances

A cells, T and B cells

There are methods of nonspecific and specific hyposensitization.

Non-specific methods

1. The use of sedatives that cause increased inhibitory processes in the central nervous system. It has been shown that anaphylactic shock does not develop during anesthesia.

2. The predominance of the sympathetic nervous system (in particular, -adrenergic innervation) reduces the activity of the allergic reaction. Adrenaline injection can be used. Hyposensitization is associated with inhibition of the parasympathetic nervous system, the predominance of cholinergic mechanisms. Atropine can be used for this purpose.

3. Reducing the activity of allergic reactions is possible with the use of antiallergic hormones, in particular cortisol and ACTH.

4. The use of antihistamines, since histamine is involved in the development of many allergic reactions.

5. Use of large doses of biological active substances.

Specific hyposensitization

1. Elimination of the allergen.

2. Antigen load. Large doses of antigen and small but frequently administered doses of antigen cause hyposensitization. In this case, tolerance develops: the formation of T- and B-tolerant cells is stimulated, T-suppressors are activated, and blocking antibodies (IgG) are formed.

3. Antibody load. The introduction of antibodies in large doses leads to blockade and neutralization of the antigen.

Pathophysiology of allergies(Lecture No. VIII) Part 2.

1. Immunocomplex type of damage.

2. Delayed allergic reactions.

3. Diagnosis of immediate allergic reactions.

4. Diagnosis of delayed-type allergic reactions.

5. Treatment of allergic reactions.

Damage by immune complexes(AG + AT) – III type- (synonyms - immunocomplex, Arthus type). On AG, which has a soluble form, the body forms AT of G and M classes (precipitating) capable of forming a precipitate in vitro when combined with AG. Immune reactions constantly occur in the body with the formation of the Ag+AT complex, because Some antigens constantly enter the body from outside or are formed endogenously, but these reactions are an expression of the protective or homeostatic function of the immune system and are not accompanied by damage. However, under certain conditions, the AG + AT complex can cause damage and the development of disease through complement activation, release of lysosomal enzymes, generation of superoxide radical and activation of the kallikrein-kinin system.

Many exo- and endogenous antigens and allergens are involved in the formation of immune complexes: antibiotics, sulfonamides, antitoxic serums, homologous gamma globulins, food products, inhalation allergens, bacteria and viruses. The formation of the immune complex depends on the site of entry or formation of Ag. The damaging effect is usually caused by complexes formed in a small excess of antigen with a molecular weight of 900,000 - 1 million daltons.

Pathochemical stage. Under the influence of the complex and in the process of its removal, a number of mediators are formed for phagocytosis and digestion of the complex: these are complement, lysosomal enzymes (acid phosphatase, ribonuclease, cathepsins, collagenase, elastase); kinins, causing spasm of bronchial smooth muscles, vasodilation, chemotaxis of leukocytes, pain effect, increased permeability of the microcirculatory bed. Activation of Hageman factor (XII) and (or) the plasmin system and the release of histamine, serotonin, platelet-activating factor, which causes platelet aggregation on the endothelium and the release of histamine and serotonin from platelets, can also occur.

Pathophysiological stage: circulating immune complexes are deposited in the vessels of the glomeruli of the kidneys and cause various types of glomerulonephritis, in the lungs - alveolitis, in the skin - dermatitis. In severe cases, inflammation can take on an alterative character with tissue necrosis, partial or complete thrombosis, and hemorrhage. Initially, neutrophils predominate in the lesion, actively phagocytizing immune complexes, releasing lysosomal enzymes and factors that increase permeability and chemotaxis for macrophages. Macrophages accumulate in the site of inflammation and phagocytose destroyed cells, cleaning the affected area. Inflammation ends with the proliferation of cellular elements.

The third type of immune damage is leading in the development of serum sickness, exogenous allergic alveolitis, some cases of drug and food allergies, a number of autoimmune diseases(lupus erythematosus, rheumatoid arthritis). With significant complement activation, systemic anaphylaxis may develop in the form of anaphylactic shock.

Serum sickness- an allergic disease of immediate type, caused by the introduction of heterologous or homologous serums or serum preparations and is characterized by predominant inflammatory damage to blood vessels and connective tissue, which develops 7-12 days after the introduction of foreign serum.

In response to the introduction of antigens, various classes of antigens are formed in the body, mainly precipitating ones. Immune complexes are formed and undergo phagocytosis, as in a normal immune reaction. But due to certain conditions (a certain amount of the allergen/AT complex, a small excess of allergen, and other factors), this complex is deposited in the vascular wall, its permeability increases, complement is activated, and mediators are released. Symptoms of serum sickness develop after 6-8-12 days: body temperature begins to rise, papulovesicular rashes appear on the skin (urticaria) up to hemorrhagic ones, most often at the site of injection of AG. The rash is accompanied by severe itching and hemodynamic disorder. Immune complexes are more often deposited in the glomeruli of the kidneys (glomerulonephritis) with swelling and proliferation of endothelial cells and mesangiocytes and narrowing or obliteration of the lumen of the glomerular capillaries. Often enlarged spleen, damage to the heart (from angina attacks to MI), lungs (emphysema, acute edema). In the blood - leukopenia with relative lymphocytosis, sometimes thrombocytopenia, glypoglycemia. Treatment depends on the form of the disease: in severe cases in the form of anaphylactic shock, emergency care is required, steroid hormones, antihistamines are prescribed, in case of edema - diuretics, etc.

Characteristics of HRT - T-type allergic response (autoimmune diseases, tuberculin-type reactions and contact dermatitis). The stages are the same.

IN immunological stage in 10-12 days, a clone of sensitized T-lymphocytes accumulates, into the cell membrane of which structures are built that act as ATs capable of connecting to the corresponding allergen. Lymphocytes do not need to be fixed; they are the repository of allergy mediators. Upon repeated application of the allergen, T-lymphocytes diffuse from the bloodstream to the site of application and combine with the allergen. Under the influence of the immuno-allergo-receptor + allergen complex, lymphocytes are irritated ( pathochemical stage) and release HRT mediators:

1) skin reactivity factor,

2) lymphocyte blast transformation factor,

3) transfer factor,

4) chemotaxis factor,

5) macrophage migration inhibitory factor (MIF),

6) lymphotoxin,

7) interferon,

8) a factor that stimulates the formation of endogenous pyrogens by macrophages,

9) mitogenic factors.

Clinically 3rd stage- a focus of allergic exudative inflammation of dense consistency. The leading place among HRT is autoimmune diseases.

Pathogenesis of autoimmune diseases to endoallergens:

There are three possible options:

1) the formation of autoATs to primary allergens that enter the blood when the corresponding organ is damaged (since in utero during the formation of the immune system they did not come into contact with lymphocytes, were isolated by histo-hematological barriers or developed after birth),

2) production of sensitized lymphocytes against foreign flora that have common specific antigen determinants with human tissues (group A streptococcus and heart and kidney tissue, E. coli and colon tissue, timothy grass glycoproteins and UDP glycoproteins),

3) removal of the inhibitory effect of T-suppressors, disinhibition of suppressed clones against their own tissues, components of the cell nucleus, causes generalized inflammation of the connective tissue - collagenosis.

Diagnosis of allergic diseases- search for a specific allergen, based on serological and cellular reactions based on the antibodies or lymphocytes present in the allergic person.

To identify reagin type sensitization:

1) radioallergosorbent test (RAST),

2) radioimmunosorbent test (RIST),

3) direct skin test,

4) Praustnitz-Kustner reaction,

5) Shelley test.

To identify cytotoxic type:

a) various variants of the immunofluorescence method,

b) Coombs test,

c) Steffen reaction,

d) radioimmunological method.

To identify immunocomplex type:

a) various methods for determining circulating immune complexes,

b) determination of the rheumatoid complex,

c) various methods for determining precipitating antibodies.

Diagnosis of HRT- identifying the effects of mediators:

2) blast transformation reaction,

3) reaction of inhibition of macrophage migration,

4) lymphotactic effect.

Allergy treatment - specific:

1. Etiotropic- prevention, cessation and elimination of allergens: with medications, food, hay fever, household allergens.

Specific to HNT is hyposensitization (fractional, continuous long-term administration of the allergen to the patient in increasing doses).

Pathogenetic therapy- identify the leading type of allergic reaction and have a blocking effect on the development of each stage.

IN immunological stage is applied levamisole and thymic hormones that regulate the immune response.

IN pathochemical stage: at reagin type of blockade of the release of mediators from mast cells: intal, ketotifen, antihistamines, histaglobulin(histaminopexy), antiserotonin drugs.

At cytotoxic And immunocomplex types of antienzyme drugs that inhibit the activity of proteolytic enzymes and thereby block the complement system and kallikrein, etc.

In pathophysiological The stage of treatment depends on the type of allergy.

2. Desensitization- urgent removal of sensitization in order to prevent anaphylactic shock.

Three types:

1) natural- after suffering anaphylactic shock (for 2 weeks),

2) nonspecific- introduction of the allergen under the protection of anesthesia and antihistamines,

3) specific according to Bezredko A.M. (repeated fractional doses every 30 minutes 2-3 times). The first small doses bind the bulk of the AT, losing the minimal reaction, and then the main dose of the drug.

3. Nonspecific- symptomatic: bronchodilators, antihistamines, anti-inflammatory hormones, anticoagulants for type 3 immune damage.
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