Hypersensitivity to drugs. Hypersensitivity to drugs: causes, symptoms, diagnosis, treatment What is hypersensitivity to drugs

There are delayed and immediate hypersensitivity. Regardless of the characteristics of the manifestations, each of them can lead to certain consequences. For example, cause anaphylaxis or dermatitis. Sensitivity has several types, which arise due to various diseases.

Hypersensitivity is an increased reaction of the immune system to any substance. It is one of the types of allergies. Occurs at any age.

Types of hypersensitivity:

1. First type. This includes the reaction immediate type. It appears immediately after contact with an allergen irritant. The manifestation depends on the functionality of the cells that are responsible for the antigen. Including histamine. A popular immediate allergic reaction to bee venom. Diseases such as asthma, psoriasis, urticaria, eczema, occur more often with HT.
2. Second type. This reaction most often occurs due to blood group incompatibility during transfusion. The reason for its appearance is the connection of antibodies with antigens on the surface of cells. In this regard, phagocytosis occurs.
3. Third type. Most often occurs with serum sickness. In this case, disturbances appear in the immune system and the number of antigens and antibodies increases. Then immune cells cannot independently cope with foreign bodies in the blood. If such complexes are chronic, then the person suffers from skin bacteria such as staphylococcus and streptococcus. Malaria and hepatitis (in this case B) are rare. Type 3 hypersensitivity is accompanied by changes neurological nature. Occurs after the use of serum for tetanus and serum sickness.
4. Type 4 (delayed hypersensitivity). Its appearance is provoked by various viruses, bacteria, and fungi that penetrate the body. Often occurs when infected with helminths. Many inflammatory reactions appear in the blood, especially with the participation of T-lymphocytes. These cells react negatively to the introduction of the tuberculosis vaccine (tuberculin component). Undesirable skin reactions occur. Thus, there is a response to the penetration of foreign cells.

It is worth noting that each person experiences hypersensitivity individually. In all people, the immune system overreacts to foreign allergen cells that enter the body repeatedly and initially. This is where the term “hypersensitive” comes from.

Immediate hypersensitivity

Allergic reactions of the immediate type are quite common.

These include:

• Quincke's edema;
• bronchial asthma;
• seasonal allergies, which are accompanied by rhinitis and itching;
• almost all types of urticaria and rarely drug allergies.

Immediate hypersensitivity occurs when you first encounter an allergen. If a person experiences an allergic reaction for the first time. For example, an allergy to medicine or pollen. Antibodies focus on a specific irritant. In order for them to fully perform their function, the consent of macrophages is necessary.

Hypersensitivity reactions occur varying degrees difficulties: early and late. Immediate reaction depends on mast cells and basophils. After this, the participation of eosinophils begins. Initially, the allergy may be characterized by slight increase these cells. When an allergic reaction is active, the number of eosinophils increases rapidly.

The appearance of a hypersensitivity reaction of the immune system leads to increased vascular permeability. This causes damage to the kidneys, lungs, and skin. The risk of developing vasculitis increases.

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Delayed hypersensitivity

Delayed allergic reaction – occurs due to macrophages and Th1 lymphocytes. Stimulation of immune cells depends on them. This is type 4 hypersensitivity. It appears within 24-72 hours after the irritant allergen enters the body. A slow reaction provokes inflammation and tissue hardening.

There are certain forms of such a reaction. Their characteristics:

1. Contact - manifests itself within a period of up to 72 hours. Provoked by lymphocytes. In the form of a disease, the delayed type is defined as eczema and edema.
2. Tuberculin HRT occurs in the form of local reactions on the skin.
3. Granulomatous is characterized by fibrosis. Develops over 20-28 days. Epithelioid and giant cells and macrophages participate in this process. Lead to thickening of the skin.

Diseases such as tuberculosis and toxoplasmosis are infectious. A delayed hypersensitivity reaction provokes their development. In progress diagnostic studies perform subcutaneous allergy tests. The causative allergen is introduced and the reaction is observed. Use tuberculin, tularin, brucellin.

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Hypersensitivity in the human body

Hypersensitivity reactions may manifest as dysfunction of certain organs. Most often found:

• dental hypersensitivity (hyperesthesia);
• sensitivity of the glans penis;
• excessive sensitivity of the skin.

Hypersensitivity can manifest itself in a specific type and have varying degrees of complexity.

Tooth hypersensitivity

Hypersensitivity of teeth. In medicine, this type of reaction is called hyperesthesia. Easily identified by characteristic symptoms: severe pain that passes quickly. Occur due to contact of enamel with various stimuli: oral care products, toothbrushes. Pain may occur for the following reasons:

• due to cold and hot food and drinks;
• eating sweets;
• sour fruits.

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Hyperesthesia has stages of development:

• 1 – slight sensitivity that is not accompanied by pain,
• 2 – severe pain upon contact with irritants.

In the latter stage, a person may suffer pain even when breathing in cool air. Hyperesthesia belongs to the list of immediate allergic reactions. This type of reaction is encountered at different ages. Most often it appears after 25 years. This type of hypersensitivity is constantly present. With the help of medications you can achieve good result. Don't forget about good oral hygiene. In this case, it is necessary to use products for hypersensitive teeth.

Sensitivity of the glans penis

Hypersensitivity of the glans penis is familiar to many men. With this reaction comes discomfort, mainly in the intimate area. Therefore, a man has problems satisfying a woman. The type of temperament of such people is very characteristic. They are irritable, unconfident, and overly emotional. It is worth noting that hypersensitivity of the head is formed at the genetic level. If it occurs throughout life, then it is enough to limit contact with irritants. It is important to distinguish the types of hypersensitivity from premature erection and severe arousal. Condoms reduce sensitivity of the head and prolong sexual intercourse. If you constantly use lubricant, you can significantly reduce hypersensitivity.

Skin hypersensitivity. Accompanied by a strong skin reaction to various allergens. This is a pathology of the skin that provokes disorders of the central nervous system. Skin hypersensitivity reactions can manifest in different ways:

• 1 – locally;
• 2 – all over the skin.

May contribute to skin hypersensitivity the following factors and diseases:

• wounds;
• infectious skin lesions;
• burns.

Diseases such as atopic dermatitis, eczema, neuritis provoke the development of sensitivity. They have a bad effect on the type of temperament, as a person experiences irritation and suffers from insomnia. Diseases such as tumors, meningitis, encephalitis, sclerosis indicate serious disorders of the nervous system. Because of this there is central shape hypersensitivity.

There are certain types of hypersensitivity:

1. Thermal.
2. Polyesthesia.
3. Hyperplasia.
4. Paresthesia.

Type 1 occurs due to cold and heat influences. Accompanied by severe pain. Polyesthesia is easily recognized by a characteristic tingling sensation in the affected area. The patient feels that there are “goosebumps” in this place. Hyperplasia is determined severe pain at the slightest touch to the affected area. Type 4 has less strong reactions. Limb ischemia may be accompanied by slight numbness. Delayed allergic reactions in each patient have different symptoms and degrees of complexity. Treatment is mainly aimed at eliminating the irritant. To do this, you need to see a doctor and undergo comprehensive examination. Allergic reactions, immediate or delayed, require traditional treatment.

Treatment of hypersensitivity

Delayed allergic reactions are treatable. In this case, damage to the immune system is important. To do this, it is necessary to release cells that affect changes in the functionality of tissues and all organs. Mostly, immediate type allergies manifest themselves in the form of urticaria, asthma, and Quincke's edema. Refers to type 1 hypersensitivity and requires timely treatment. The following medications are used for this:

• antihistamines, antiallergic;
• medications to suppress immunological reactions;
• medications that prevent allergy mediators from being released;
• glucocorticosteroids.

Delayed allergic reactions are treated with such drugs.

Allergy (from the Greek alios - different, ergon - acting) is a typical immunopathological process that develops upon contact with an antigen (hapten) and is accompanied by damage to the structure and function of one’s own cells, tissues and organs. Substances that cause allergies are called allergens.

Sensitization

The basis of allergies is sensitization (or immunization) - the process of the body acquiring increased sensitivity to a particular allergen. Otherwise, sensitization is the process of producing an allergen specific antibodies or lymphocytes.

There are passive and active sensitization.

• Passive sensitization develops in a non-immunized recipient with the introduction of ready-made antibodies (serum) or lymphoid cells (during a lymphoid tissue transplant) from an actively sensitized donor.
• Active sensitization develops when an allergen enters the body due to

the formation of antibodies and immunocompetent lymphocytes upon activation of his own immune system.

Sensitization (immunization) itself does not cause disease - only repeated contact with the same allergen can lead to a damaging effect.

Thus, an allergy is a qualitatively altered (pathological) form of the body’s immunological reactivity.

Allergies and immunity have common properties:

1. Allergy, like immunity, is a form of species reactivity that contributes to the preservation of the species, although for an individual it has not only a positive, but also a negative meaning, since it can cause the development of a disease or (in some cases) death.
2. Allergies, like immunity, are protective in nature. The essence of this protection is localization, inactivation and elimination of the antigen (allergen).
3. Allergies are based on immune mechanisms development - the “antigen-antibody” reaction (AG + AT) or “antigen-sensitized lymphocyte” (“AG + sensitized lymphocyte”).

Immune reactions

Typically, immune reactions unfold covertly, and they lead either to the complete destruction of the antigenic aggressor or to the partial suppression of its pathogenic action, providing the body with a state of immunity. However, under some circumstances, these reactions can develop unusually.

In some cases, when a foreign agent is introduced into the body, they are so intense that they lead to tissue damage and are accompanied by the phenomenon of inflammation: then they speak of a hypersensitivity reaction (or disease).

Sometimes, under certain conditions, the body's cells acquire antigenic properties or the body produces antibodies that can react with normal cell antigens. In these cases we talk about diseases due to autoimmunization or autoimmune diseases.

Finally, there are conditions in which, despite the arrival of antigenic material, immune reactions do not develop. Such conditions are referred to as immune failure or immunodeficiency.

Thus, the immune system, which is normally involved in maintaining homeostasis, can serve as a source of pathological conditions caused by an excessive reaction or insufficient response to aggression, which are referred to as immunopathological processes.

Immune hypersensitivity

Hypersensitivity is a pathological overly strong immune reaction to a foreign agent, which leads to damage to body tissues. Four stand out various types hypersensitivity All forms, except type IV, have a humoral mechanism (that is, they are mediated by antibodies); Type IV hypersensitivity has a cellular mechanism. In all forms, the initial intake of a specific antigen (sensitizing dose) causes a primary immune response (sensitization). After short period(1 or more weeks), during which the immune system is activated, a hypersensitive response occurs to any subsequent intake of the same antigen (resolving dose).

Type I hypersensitivity (immediate) (atopy; anaphylaxis)

Development mechanism

The first arrival of an antigen (allergen) activates the immune system, which leads to the synthesis of antibodies - IgE (reagins), which have a specific reactivity against this antigen. They are then fixed on the surface membrane of tissue basophils and blood basophils due to the high affinity (affinity) of IgE for Fc receptors. The synthesis of antibodies in sufficient quantities for the development of hypersensitivity takes 1 or more weeks.

With subsequent administration of the same antigen, the antibody (IgE) interacts with the antigen on the surface of tissue or blood basophils, causing their degranulation. Vaso cells emerge from the cytoplasmic granules of tissue basophils into the tissue. active substances(histamine and various enzymes that are involved in the synthesis of bradykinin and leukotrienes), which cause vasodilation, increased vascular permeability and contraction of smooth muscle.

Tissue basophils also secrete factors that are chemotactic for neutrophils and eosinophils; When studying preparations from tissues where a type I hypersensitivity reaction occurred, a large number of eosinophils are determined, and an increase in the number of eosinophils is observed in the blood of patients. Eosinophils activate both blood coagulation and the complement system and promote further degranulation of blood basophils and tissue basophils. However, eosinophils also secrete arylsulfatase B and histaminase, which degrade leukotrienes and histamine, respectively; thus they weaken the allergic response. ====Disorders that occur with type I hypersensitivity====:

• Local manifestations - the local manifestation of type I hypersensitivity is called atopy. Atopy is an innate predisposition, which runs in families, to have an abnormal response against certain allergens. Atopic reactions are widespread and can occur in many organs.
  • Skin - when an allergen enters the skin, there is immediate redness, swelling (sometimes with blistering [urticaria]) and itching; in some cases, acute dermatitis or eczema develops. The antigen can come into contact with the skin directly, through injection (including insect bites) or orally into the body (through food and drug allergies).
  • Nasal mucosa - when allergens are inhaled (for example, plant pollen, animal hair), vasodilation and hypersecretion of mucus occurs in the nasal mucosa (allergic rhinitis).
  • Lungs - inhalation of allergens (pollen, dust) leads to contraction of bronchial smooth muscles and hypersecretion of mucus, which leads to acute obstruction of the airways and suffocation (allergic bronchial asthma).
  • Intestines - oral ingestion of an allergen (for example, nuts, shellfish, crabs) causes muscle contraction and fluid secretion, which manifests itself in the form of cramping abdominal pain and diarrhea (allergic gastroenteritis).

• Systemic manifestations - anaphylaxis - a rare but extremely life-threatening systemic type I hypersensitivity reaction. The entry of vasoactive amines into the bloodstream causes contraction of smooth muscle, widespread vasodilation and an increase in vascular permeability with the release of fluid from the vessels into the tissue.

The resulting peripheral vascular insufficiency and shock can lead to death within a few minutes (anaphylactic shock). In less severe cases, increased vascular permeability leads to allergic edema, which has its most dangerous manifestation in the larynx, since it can cause fatal asphyxia.

Systemic anaphylaxis usually occurs following injection of allergens (eg, penicillin, foreign serum, local anesthetics, X-ray contrast agents). Less commonly, anaphylaxis can occur when allergens are ingested orally (shellfish, crabs, eggs, berries) or when allergens enter the skin (bee and wasp stings).

In sensitized individuals, even small amounts of the allergen can trigger fatal anaphylaxis (eg, intradermal penicillin [penicillin hypersensitivity test]).

Type II hypersensitivity

Development mechanism

Type II hypersensitivity is characterized by the reaction of an antibody with an antigen on the surface of a host cell, which causes the destruction of that cell. The antigen involved may be one's own, but for some reason recognized by the immune system as foreign (an autoimmune disease occurs). The antigen can also be external and can accumulate on the surface of the cell (for example, a drug can be a hapten when it binds to a cell membrane protein and thus stimulates an immune response).

A specific antibody, usually IgG or IgM, produced against an antigen interacts with it on the cell surface and causes cell damage in several ways:

1. Cell lysis - activation of the complement cascade leads to the formation of the “membrane attack” complex C5b6789, which causes lysis of the cell membrane.
2. Phagocytosis - the antigen-bearing cell is engulfed by phagocytic macrophages, which have Fc or C3b receptors, which allows them to recognize antigen-antibody complexes on the cell.
3. Cellular cytotoxicity - the antigen-antibody complex is recognized by unsensitized "null" lymphocytes (K cells; see Immunity), which destroy the cell. This type of hypersensitivity is sometimes classified separately as type VI hypersensitivity.
4. Altering cell function—An antibody can react with cell surface molecules or receptors to cause either enhancement or inhibition of a specific metabolic response without causing cell necrosis (see Stimulation and Inhibition in Hypersensitivity, below). Some authors classify this phenomenon separately as type V hypersensitivity.

Manifestations of type II hypersensitivity reaction

Depends on the type of cell carrying the antigen. Note that blood transfusion reactions are actually normal immune responses against foreign cells. They are identical in the mechanism of type II hypersensitivity reactions and also adversely affect the patient, and therefore blood transfusion complications are often considered together with disorders that occur with hypersensitivity.

Reactions with destruction of red blood cells

• Post-transfusion reactions - antibodies in the patient's serum react with antigens on transfused red cells, causing either complement-mediated intravascular hemolysis or delayed hemolysis as a result of immune phagocytosis by splenic macrophages. There are a large number of erythrocyte antigens that can cause hemolytic reactions during transfusions (ABO, Rh, Kell, Kidd, Lewis). Also, hemolysis can occur when Rh+ blood is retransfused into an Rh- patient. In addition, transfused blood may directly contain antibodies that react against host cells, but due to the high dilution in the total blood volume, this reaction usually has little clinical consequence. To prevent these reactions, it is necessary to check blood compatibility.
• Hemolytic disease of newborns develops when maternal antibodies penetrate the placenta, which are active against fetal erythrocyte antigens (Rh and ABO) and destroy them. Hemolytic disease of the newborn is more common in Rh incompatibility, since anti-Rh antibodies in maternal plasma are usually IgG, which readily cross the placenta. Anti-A and anti-B antibodies are usually IgM, which normally cannot cross the placenta.
• Other hemolytic reactions - hemolysis can be caused by drugs that act as haptens in combination with red blood cell membrane proteins or it can develop when infectious diseases associated with the appearance of anti-erythrocyte antibodies, for example, in infectious mononucleosis, mycoplasma pneumonia.

Reactions with destruction of neutrophils

maternal antibodies to fetal neutrophil antigens can cause neonatal leukopenia if they cross the placenta. Sometimes post-transfusion reactions occur due to the activity of the host serum against the leukocyte HLA antigens of the donor.

Reactions with platelet destruction

posttransfusion febrile reactions and neonatal thrombocytopenia may result from the factors described above for leukocytes. Idiopathic thrombocytopenic purpura is a common autoimmune disease in which antibodies are formed against self-antigens of the platelet membrane.

Reactions on the basement membrane

antibodies against basement membrane antigens in the renal glomeruli and pulmonary alveoli occur in Goodpasture syndrome. Tissue damage occurs as a result of complement activation.

Stimulation and inhibition for hypersensitivity

• Stimulation - with the formation of antibodies (IgG), which bind to TSH receptors on follicular epithelial cells thyroid gland Graves' disease (primary hyperthyroidism) develops. This interaction leads to stimulation of the enzyme adenylate cyclase, which results in increased cAMP levels and the secretion of increased amounts of thyroid hormone.
• Inhibition - inhibitory antibodies play key role for myasthenia gravis (myasthenia gravis), a disease characterized by impaired neuromuscular transmission and the occurrence of muscle weakness. The disease is caused by antibodies (IgG) directed against acetylcholine receptors on the motor end plate. Antibodies compete with acetylcholine for the binding site on the receptor, thus blocking the transmission of nerve impulses.

The mechanism of inhibition also underlies pernicious anemia, in which antibodies bind to internal factor and inhibit the absorption of vitamin B12.

Hypersensitivity type III (immune complex damage)

Development mechanism

The interaction of antigen and antibody can lead to the formation of immune complexes, either locally at the site of damage, or generalized in the bloodstream. The accumulation of immune complexes in various parts of the body activates complement and causes acute inflammation and necrosis.

There are two types of immune complex damage:

• Reactions such as the Arthus phenomenon - in reactions such as the Arthus phenomenon, tissue necrosis occurs at the site of antigen injection. Repeated administration of the antigen leads to the accumulation of large amounts of precipitating antibodies in the serum. Subsequent administration of the same antigen leads to the formation of large antigen-antibody complexes, which are deposited locally in small blood vessels, where they activate complement, accompanied by the development of a severe local acute inflammatory reaction with hemorrhage and necrosis. This phenomenon is observed very rarely. It occurs in the skin after repeated administration of the antigen (for example, during rabies vaccination, when multiple injections of the vaccine are given). The severity of inflammation depends on the dose of antigen. Hypersensitivity Type III is believed to be responsible for the occurrence of hypersensitivity pneumonitis, a lung disease that presents with cough, dyspnea, and fever 6–8 hours after inhalation of certain antigens (Table 11.2). If the supply of antigen is repeated, then chronic granulomatous inflammation occurs. Types I and IV hypersensitivity can coexist with type III.
• Serum sickness type reactions - serum sickness type reactions, also caused by immune complex damage, are more common than reactions like the Arthus phenomenon. The course of reactions depends on the dose of antigen. Repeated intake of a large dose of antigen, for example, foreign serum proteins, drugs, viral and other microbial antigens, leads to the formation of immune complexes in the blood. In the presence of excess antigen, they remain small, soluble, and circulate in the bloodstream. They ultimately pass through the endothelial pores of small vessels and accumulate in the vessel wall, where they activate complement and lead to complement-mediated necrosis and acute inflammation of the vessel wall (necrotizing vasculitis).

Vasculitis can be generalized, affecting a large number of organs (for example, in serum sickness due to the introduction of foreign serum or in systemic lupus erythematosus, an autoimmune disease) or can affect a single organ (for example, in post-streptococcal glomerulonephritis).

Immune complex damage can occur in many diseases. In some of them, including serum sickness, systemic lupus erythematosus, and poststreptococcal glomerulonephritis, immune complex damage is responsible for the main clinical manifestations of the disease. For others, such as hepatitis B, infective endocarditis, malaria and some types malignant tumors, immune complex vasculitis occurs as a complication of the disease.

Diagnosis of immune complex diseases: A reliable diagnosis of immune complex disease can be established by detecting immune complexes in tissues by electron microscopy. Rarely large immune complexes may be visible by light microscopy (for example, with post-streptococcal glomerulonephritis). Immunological methods (immunofluorescence and immunoperoxidase method) use labeled anti-IgG, anti-IgM, anti-IgA or anti-complement antibodies that bind to immunoglobulins or complement in immune complexes. There are also methods for determining immune complexes circulating in the blood.

Hypersensitivity type IV (cellular)

Development mechanism

Unlike other hypersensitivity reactions, delayed-type hypersensitivity involves cells rather than antibodies. This type is mediated by sensitized T lymphocytes, which either directly exert cytotoxicity or through the secretion of lymphokines. Type IV hypersensitivity reactions usually occur 24 to 72 hours after administration of the antigen to a sensitized person, which distinguishes this type from type I hypersensitivity, which often develops within minutes.

At histological examination tissues in which type IV hypersensitivity reaction occurs, cell necrosis and pronounced lymphocytic infiltration are detected.

Direct cytotoxicity of T cells plays an important role in contact dermatitis, in the response against tumor cells, virus-infected cells, transplanted cells bearing foreign antigens, and in some autoimmune diseases.

T-cell hypersensitivity resulting from the action of various lymphokines also plays a role in granulomatous inflammation caused by mycobacteria and fungi. The manifestation of this type of hypersensitivity is the basis of skin tests used in the diagnosis of these infections (tuberculin, lepromin, histoplasmin and coccidioidin tests). In these tests, inactivated microbial or fungal antigens are injected intradermally. At positive reaction after 24-72 hours, granulomatous inflammation develops at the injection site, which manifests itself in the form of papule formation. Positive test indicates the presence of delayed hypersensitivity against the administered antigen and is evidence that the body has previously encountered this antigen. ===Disorders that occur with type IV hypersensitivity===delayed type hypersensitivity has several manifestations:

• Infections - for infectious diseases caused by facultative intracellular microorganisms, for example, mycobacteria and fungi, morphological manifestations delayed type hypersensitivity - epithelioid cell granuloma with caseous necrosis in the center.
• Autoimmune diseases - with Hashimoto's thyroiditis and autoimmune gastritis associated with pernicious anemia, the direct action of T cells against antigens on host cells (thyroid epithelial cells and parietal cells in the stomach) leads to the progressive destruction of these cells.
• Contact dermatitis - when an antigen comes into direct contact with the skin, a local hypersensitive response of type IV occurs, the area of ​​which exactly corresponds to the area of ​​contact. The most common antigens are nickel, drugs, and clothing dyes.

Morphological changes in organs with hypersensitivity

Morphologically, during antigenic stimulation (sensitization) of the body, the most pronounced changes observed in lymph nodes, primarily regional to the site of entry of the antigen.

• Lymph nodes are enlarged and full of blood. In types I-III of hypersensitivity, an abundance of plasmablasts and plasma cells is detected in the light centers of the follicles of the cortical and in the pulpal cords of the medulla. The number of T-lymphocytes is reduced. A large number of macrophages are noted in the sinuses. The degree of macrophage-plasmacytic transformation of lymphoid tissue reflects the intensity of immunogenesis and, above all, the level of production of antibodies (immunoglobulins) by plasmacytic cells. If, in response to antigenic stimulation, predominantly cellular immune reactions develop (type IV hypersensitivity), then in the lymph nodes in the paracortical zone, mainly sensitized lymphocytes proliferate, rather than plasmablasts and plasma cells. In this case, expansion of T-dependent zones occurs.
• The spleen enlarges and becomes full of blood. In types I-III of hypersensitivity, sharply enlarged large grayish-pinkish follicles are clearly visible on the section. Microscopically, hyperplasia and plasmatization of the red pulp and an abundance of macrophages are noted. In the white pulp, especially along the periphery of the follicles, there are also many plasmablasts and plasmacytes. In type IV hypersensitivity, the morphological changes are similar to the changes observed in the lymph nodes in the T-zones.

In addition, in organs and tissues in which an immediate-type hypersensitivity reaction develops - HNT (types I, II, III), acute immune inflammation. It is characterized by rapid development, the predominance of alterative and exudative changes. Alterative changes in the form of mucoid, fibrinoid swelling and fibrinoid necrosis are observed in the ground substance and fibrous structures connective tissue. In the focus of immune inflammation, plasmorrhagia is expressed, fibrin, neutrophils, and erythrocytes are detected.

In type IV hypersensitivity (delayed hypersensitivity reaction - DTH), lymphocytic and macrophage infiltration (sensitized lymphocytes and macrophages) at the site of immune conflict are an expression of chronic immune inflammation. To prove that morphological changes belong to the immune reaction, it is necessary to use an immunohistochemical method; in some cases, electron microscopic examination can help.

Literature

Pathophysiology: textbook: in 2 volumes / ed. V.V. Novitsky, E.D. Goldberg, O.I. Urazova. - 4th ed., revised. and additional - GEOTAR-Media, 2009. - T. 1. - 848 p. : ill.

Lecture by Prof. V.G.Shlopova

The reaction of the immune system to the effects of various components of origin that enter the body with air, food, during contact with the skin, or as a result of drug treatment is called hypersensitivity.

The causes of hypersensitivity are disorders of the body's immune functions. Hypersensitivity reactions are triggered by many antigens and the causes vary from person to person.

Hypersensitivity reactions are classified using the immunological mechanisms that cause them.

There are two forms of hypersensitivity reaction:

• immediate type hypersensitivity, which includes 3 types of hypersensitivity (I, II, III);
• delayed type hypersensitivity - type IV.

Diagnosis of immediate types of reactions

1. Allergological history. It is necessary to collect the information needed to carry out diagnosis and treatment.
2. Comprehensive physical examination. The respiratory organs, skin, eyes, and chest are subject to careful examination.
3. Laboratory research, thanks to which it is possible to refute or confirm the diagnosis that was made based on the results of the anamnesis, as well as taking into account physical examinations. Laboratory tests also help in assessing the effectiveness of treatment and help monitor the patient’s condition.
4. General blood analysis.
5. Sputum smears.
6. Skin tests.
7. Total level of immunoglobulins IgE in serum.
8. Provocative tests. This method is based on the introduction of allergens into the target organ, it allows you to identify sensitization.
9. Conducting respiratory function studies. This method is used to conduct a differential diagnosis of non-allergic and allergic lung diseases in order to assess the reactivity of the bronchi and the severity of these diseases, as well as the effectiveness of their treatment.
10. X-ray examination.

Diagnosis of delayed types of reactions

The following methods are used to diagnose these types of hypersensitivity reactions:

• determination of the level of serum immunoglobulins IgE;
• conducting skin and provocative tests using suspected allergens,
• determination of sensitized cells using tests, carrying out the blast transformation reaction of lymphocytes,
• carrying out a migration inhibition reaction in leukocytes;
• carrying out cytotoxic tests.

Anaphylactic reactions - type 1 reactions

This reaction is based on the mechanism of tissue damage, which usually occurs with the participation of immunoglobulins E and G. B in this case Biologically active substances (serotonin, histamine, heparin, bradykinins and others) penetrate into the blood. In this case, there is an increase in secretion, impaired membrane permeability, muscle spasm, and interstitial edema.

Hypersensitivity reactions of this type are divided into local and systemic.

Local reactions depend entirely on the site of entry of the antigen.

Symptoms of the disease:

• anaphylactic shock;
• conjunctivitis and nasal discharge;
• swelling of the skin;
• hay fever and bronchial asthma;
• allergic gastroenteritis.

A systemic reaction usually develops in response to intravenous administration antigen to which the host is already sensitized. After a few minutes, a state of shock may develop. This condition can be fatal.

This type of hypersensitivity reaction goes through two phases in development. Symptoms of the first phase:

• dilation of blood vessels, as well as increasing their permeability;
• secretion of glands or spasm of smooth muscles.

These symptoms appear 5-30 minutes after administration of the antigen.

The second phase often begins to develop after 2-8 hours and can last several days.

Late phase symptoms:

• intense infiltration of neutrophils, eosinophils, basophils and monocytes.
• tissue destruction.

Cytotoxic reactions - reactions of the second type

Circulating antibodies react with components of tissue and cell membranes. This type of reaction occurs with the participation of immunoglobulins G, M, and also during activation of the complement system. As a result, the cell membrane is damaged. This type of reaction appears with thrombocytopenia, hemolytic disease of newborns with Rh conflict, allergies, hemolytic anemia.

During this type of hypersensitivity reaction, antibodies appear in the body directed against antigens that are located on the surface of cells or other tissue components.

There are two ways in which antibodies can cause a type 2 hypersensitivity reaction: opsonization and direct lysis.

Clinical hypersensitivity reactions of type II occur in the following cases:

• during transfusion of incompatible blood, in which the donor’s cells react with the host’s antibodies;
• during erythroblastosis of the fetus, there is an antigenic difference between the fetus and the mother, and maternal antibodies, penetrating the placenta, can cause the destruction of red blood cells in the fetus;
• during thrombocytopenia, anemia and agranulocytosis, in which antibodies are formed against one’s own blood cells, which are then destroyed;
• During some drug reactions, antibodies are formed by reacting with the drugs.

Immune complex reactions - hypersensitivity reactions of the third type

The third type of hypersensitivity reaction is caused by the formation of precipitating antibody-antigen complexes in a small excess of antigens. The complexes, deposited on the walls of blood vessels, activating the complement system, thereby causing inflammatory processes, such as serum sickness, immune complex nephritis. The reaction mechanism is closely related to tissue damage by immune complexes and involves immunoglobulins G and M. This type of reaction is characteristic of allergic dermatitis, exogenous allergic conjunctivitis, systemic lupus erythematosus, immune complex glomerulonephritis, rheumatoid arthritis, serum sickness.

There are 2 types of immune complex lesions:

1. when exogenous antigens, such as proteins, bacteria, viruses, enter the human body;
2. during the formation of antibodies against self-antigens

Immune cell reactions - reactions of the fourth type

This type of reaction is caused by contact of a specific antigen with T lymphocytes. After repeated contact with the antigen, T-cell-dependent delayed inflammatory reactions begin to develop, which can be local or generalized. This, for example, could be allergic contact dermatitis. Any organs and tissues can be involved in the process. This type of reaction is characteristic of diseases such as brucellosis and tuberculosis.

Treatment of hypersensitivity reactions

Treatment consists of a number of activities. The most important thing is to stop exposure to the allergen. To do this, it is necessary to isolate the patient from animals, install air conditioners with filters, give up many medications and food products. If it is impossible to completely eliminate the allergen, then you need to reduce its intensity of exposure.

Antihistamines are also used for treatment.

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Types of allergic reactions (hypersensitivity reactions). Hypersensitivity of immediate and delayed type. Stages of allergic reactions. Step-by-step mechanism for the development of allergic reactions.

1. 4 types of allergic reactions (hypersensitivity reactions).

Currently, according to the mechanism of development, it is customary to distinguish 4 types of allergic reactions (hypersensitivity). All of these types of allergic reactions are generally rare in pure form, more often they coexist in various combinations or move from one type of reaction to another type.
At the same time, types I, II and III are caused by antibodies, are and belong to immediate hypersensitivity reactions (IHT). Type IV reactions are caused by sensitized T cells and belong to Delayed hypersensitivity reactions (DTH).

Note!!! is a hypersensitivity reaction triggered by immunological mechanisms. Currently, all 4 types of reactions are considered hypersensitivity reactions. However, true allergies mean only those pathological immune reactions that occur through the mechanism of atopy, i.e. according to type I, and reactions of types II, III and IV (cytotoxic, immunocomplex and cellular) types are classified as autoimmune pathology.

1. The first type (I) is atopic, anaphylactic or reagin type - caused by IgE class antibodies. When an allergen interacts with IgE fixed on the surface of mast cells, these cells are activated and the deposited and newly formed allergy mediators are released, followed by the development of an allergic reaction. Examples of such reactions are anaphylactic shock, Quincke's edema, hay fever, bronchial asthma, etc.
2. The second type (II) is cytotoxic. In this type, the body’s own cells become allergens, the membrane of which has acquired the properties of autoallergens. This occurs mainly when they are damaged as a result of exposure to drugs, bacterial enzymes or viruses, as a result of which the cells change and are perceived by the immune system as antigens. In any case, for this type of allergy to occur, antigenic structures must acquire the properties of autoantigens. The cytotoxic type is caused by IgG or IgM, which are directed against Ags located on modified cells of the body’s own tissues. The binding of Ab to Ag on the cell surface leads to the activation of complement, which causes damage and destruction of cells, subsequent phagocytosis and their removal. The process also involves leukocytes and cytotoxic T- lymphocytes. By binding to IgG, they participate in the formation of antibody-dependent cellular cytotoxicity. It is the cytotoxic type that causes the development of autoimmune hemolytic anemia, drug allergies, and autoimmune thyroiditis.
3. The third type (III) is immunocomplex, in which body tissues are damaged by circulating immune complexes involving IgG or IgM, which have a large molecular weight. That. in type III, as well as in type II, reactions are caused by IgG and IgM. But unlike type II, in a type III allergic reaction, antibodies interact with soluble antigens, and not with those located on the surface of cells. The resulting immune complexes circulate in the body for a long time and are fixed in the capillaries of various tissues, where they activate the complement system, causing an influx of leukocytes, the release of histamine, serotonin, lysosomal enzymes that damage the vascular endothelium and tissues in which the immune complex is fixed. This type of reaction is the main one in serum sickness, drug and food allergies, and in some autoallergic diseases (SLE, rheumatoid arthritis, etc.).
4. The fourth (IV) type of reaction is delayed-type hypersensitivity or cell-mediated hypersensitivity. Delayed reactions develop in a sensitized organism 24-48 hours after contact with the allergen. In type IV reactions, the role of antibodies is performed by sensitized T- lymphocytes. Ag, in contact with Ag-specific receptors on T cells, leads to an increase in the number of this population of lymphocytes and their activation with the release of mediators of cellular immunity - inflammatory cytokines. Cytokines cause the accumulation of macrophages and other lymphocytes, involving them in the process of destruction of antigens, resulting in inflammation. Clinically, this is manifested by the development of hyperergic inflammation: a cellular infiltrate is formed, the cellular basis of which is made up of mononuclear cells - lymphocytes and monocytes. The cellular type of reaction underlies the development of viral and bacterial infections(contact dermatitis, tuberculosis, mycoses, syphilis, leprosy, brucellosis), some forms of infectious-allergic bronchial asthma, transplant rejection and antitumor immunity.

Reaction type		Development mechanism		Clinical manifestations
Type I Reagin reactions		Develops as a result of the binding of an allergen to IgE fixed on mast cells, which leads to the release of allergy mediators from the cells, which cause clinical manifestations		Anaphylactic shock, Quincke's edema, atopic bronchial asthma, hay fever, conjunctivitis, urticaria, atopic dermatitis, etc.
Type II Cytotoxic reactions		Caused by IgG or IgM, which are directed against Ag located on the cells of their own tissues. Complement is activated, which causes cytolysis of target cells		Autoimmune hemolytic anemia, thrombocytopenia, autoimmune thyroiditis, drug-induced agranulocytosis, etc.
Type III Immune complex-mediated reactions		Circulating immune complexes with IgG or IgM are fixed to the capillary wall, activate the complement system, tissue infiltration by leukocytes, their activation and production of cytotoxic and inflammatory factors (histamine, lysosomal enzymes, etc.), damaging the vascular endothelium and tissue.		Serum sickness, drug and food allergies, SLE, rheumatoid arthritis, allergic alveolitis, necrotizing vasculitis, etc.
Type IV Cell-mediated reactions		Sensitized T- lymphocytes, in contact with Ag, produce inflammatory cytokines that activate macrophages, monocytes, lymphocytes and damage surrounding tissues, forming a cellular infiltrate.		Contact dermatitis, tuberculosis, mycoses, syphilis, leprosy, brucellosis, transplant rejection reactions and antitumor immunity.

2. Hypersensitivity of immediate and delayed type.

What is the fundamental difference between all these 4 types of allergic reactions?
And the difference is in what type of immunity, humoral or cellular, these reactions are caused. Depending on this they distinguish:

3. Stages of allergic reactions.

In most patients, allergic manifestations are caused by IgE-class antibodies, therefore we will consider the mechanism of allergy development using the example of type I allergic reactions (atopy). There are three stages in their course:

• Immunological stage– includes changes in the immune system that occur at the first contact of the allergen with the body and the formation of corresponding antibodies, i.e. sensitization. If by the time At is formed the allergen is removed from the body, no allergic manifestations occur. If the allergen is re-entered or continues to be in the body, an “allergen-antibody” complex is formed.
• Pathochemical– release of biologically active allergy mediators.
• Pathophysiological– stage of clinical manifestations.

This division into stages is quite arbitrary. However, if you imagine Allergy development process step by step, it will look like this:

1. First contact with an allergen
2. IgE formation
3. Fixation of IgE on the surface of mast cells
4. Sensitization of the body
5. Repeated contact with the same allergen and formation of immune complexes on the mast cell membrane
6. Release of mediators from mast cells
7. The effect of mediators on organs and tissues
8. Allergic reaction.

Thus, the immunological stage includes points 1 - 5, pathochemical - point 6, pathophysiological - points 7 and 8.

4. Step-by-step mechanism for the development of allergic reactions.

1. First contact with an allergen.
2. Ig E formation.
   At this stage of development, allergic reactions resemble a normal immune response, and are also accompanied by the production and accumulation of specific antibodies that can combine only with the allergen that caused their formation.
   But in the case of atopy, it is the formation of IgE in response to the incoming allergen, and in increased quantities in relation to the other 5 classes of immunoglobulins, which is why it is also called Ig-E dependent allergy. IgE is produced locally, mainly in the submucosa of tissues in contact with the external environment: in the respiratory tract, skin, and gastrointestinal tract.
3. Fixation of IgE to the mast cell membrane.
   If all other classes of immunoglobulins, after their formation, circulate freely in the blood, then IgE has the property of immediately attaching to the mast cell membrane. Mast cells are immune cells of connective tissue that are found in all tissues in contact with the external environment: tissues of the respiratory tract, gastrointestinal tract, as well as connective tissues surrounding blood vessels. These cells contain biologically active substances such as histamine, serotonin, etc., and are called mediators of allergic reactions. They have pronounced activity and have a number of effects on tissues and organs, causing allergic symptoms.
4. Sensitization of the body.
   For the development of allergies, one condition is required - preliminary sensitization of the body, i.e. the occurrence of hypersensitivity to foreign substances - allergens. Hypersensitivity to a given substance develops upon first encounter with it.
   The time from the first contact with an allergen to the onset of hypersensitivity to it is called the period of sensitization. It can range from a few days to several months or even years. This is the period during which IgE accumulates in the body, fixed to the membrane of basophils and mast cells.
   A sensitized organism is one that contains a reserve of antibodies or T cells (in the case of HRT) that are sensitized to that particular antigen.
   Sensitization is never accompanied by clinical manifestations of allergy, since only Ab accumulates during this period. Immune complexes Ag + Ab have not yet formed. Not single Abs, but only immune complexes are capable of damaging tissue and causing allergies.
5. Repeated contact with the same allergen and the formation of immune complexes on the mast cell membrane.
   Allergic reactions occur only when the sensitized organism encounters a given allergen again. The allergen binds to ready-made Abs on the surface of mast cells and the formation of immune complexes: allergen + Ab.
6. Release of allergy mediators from mast cells.
   Immune complexes damage the membrane of mast cells, and from them allergy mediators enter the intercellular environment. Tissues rich in mast cells (skin vessels, serous membranes, connective tissue, etc.) are damaged by the released mediators.
   At long-term exposure allergens, the immune system uses additional cells to repel the invading antigen. A number of more chemical substances - mediators - are formed, which causes further discomfort for allergy sufferers and increases the severity of symptoms. At the same time, the mechanisms of inactivation of allergy mediators are inhibited.
7. The action of mediators on organs and tissues.
   The action of mediators determines the clinical manifestations of allergies. Systemic effects develop - dilation of blood vessels and increased permeability, mucous secretion, nervous stimulation, smooth muscle spasms.
8. Clinical manifestations of an allergic reaction.
   Depending on the organism, the type of allergens, the route of entry, the place where the allergic process occurs, the effects of one or another allergy mediator, symptoms can be system-wide (classical anaphylaxis) or localized in individual systems of the body (asthma - in the respiratory tract, eczema - in the skin ).
   Itching, runny nose, lacrimation, swelling, shortness of breath, drop in pressure, etc. occur. And the corresponding picture develops allergic rhinitis, conjunctivitis, dermatitis, bronchial asthma or anaphylaxis.

In contrast to immediate hypersensitivity described above, delayed hypersensitivity is caused by sensitized T cells rather than antibodies. And it destroys those cells of the body on which the immune complex Ag + sensitized T-lymphocyte has been fixed.

Abbreviations in the text.

• Antigens – Ag;
• Antibodies – Ab;
• Antibodies = same as immunoglobulins(At=Ig).
• Delayed hypersensitivity - HRT
• Immediate hypersensitivity - IHT
• Immunoglobulin A - IgA
• Immunoglobulin G - IgG
• Immunoglobulin M - IgM
• Immunoglobulin E - IgE.
• Immunoglobulins- Ig;
• Antigen-antibody reaction – Ag + Ab

Main types of hypersensitivity reactions

Type I - anaphylactic. Upon initial contact with the antigen, IgE is formed, which is attached by the Fc fragment to mast cells and basophils. The reintroduced antigen cross-binds with IgE on the cells, causing them to degranulate and release histamine and other allergy mediators.

The initial intake of an allergen causes the production of IgE and IgG4 by plasma cells. Synthesized IgE is attached by the Fc fragment to the Fc-pe receptors (FceRl) of basophils in the blood and mast cells in the mucous membranes and connective tissue. When the allergen is re-entered, mast cells and basophils form IgE complexes with the allergen (cross-linking with FceRl antigen), causing cell degranulation.

Clinical manifestations of type I hypersensitivity can occur against the background of atopy. Atopy- hereditary predisposition to the development of HNT, caused by increased production of IgE antibodies to the allergen, increased amount Fc receptors for these antibodies on mast cells, features of mast cell distribution and increased permeability of tissue barriers.

Anaphylactic shock- occurs acutely with the development of collapse, edema, spasm of smooth muscles; often ends in death. Hives- vascular permeability increases, the skin turns red, blisters and itching appear. Bronchial asthma- inflammation, bronchospasm develop, mucus secretion in the bronchi increases.

Type II - cytotoxic. The antigen located on the cell is “recognized” by antibodies of the IgG and IgM classes. During the “cell-antigen-antibody” interaction, complement activation and cell destruction occur in three directions: complement-dependent cytolysis; phagocytosis; antibody-dependent cellular cytotoxicity. Reaction time - minutes or hours.

Close to type II hypersensitivity are antireceptor reactions (the so-called type IV hypersensitivity), which are based on antireceptor antibodies, for example antibodies against hormone receptors.

Clinical manifestations of type II. According to type II hypersensitivity, some autoimmune diseases caused by the appearance of autoantibodies to antigens of one’s own tissues: malignant myasthenia gravis, autoimmune hemolytic anemia, pemphigus vulgaris, Goodpasture's syndrome, autoimmune hyperthyroidism, insulin-dependent diabetes type II.

Autoimmune hemolytic anemia cause antibodies against the Rh antigen of erythrocytes; red blood cells are destroyed as a result of complement activation and phagocytosis. Drug-induced hemolytic anemia, granulocytopenia and thrombocytopenia are accompanied by the appearance of antibodies against the drug - hapten and cytolysis of cells containing this antigen.

Type III - immunocomplex. Antibodies of the IgG and IgM classes form immune complexes with soluble antigens that activate complement. With an excess of antigens or a lack of complement, immune complexes are deposited on the wall of blood vessels, basement membranes, i.e. structures having Fc receptors.

The primary components of type III hypersensitivity are soluble immune complexes antigen-antibody and complement (anaphylatoxins C4a, C3a, C5a). With an excess of antigens or a lack of complement, immune complexes are deposited on the wall of blood vessels, basement membranes, i.e. structures that have Fc receptors. Damage is caused by platelets, neutrophils, immune complexes, and complement. Proinflammatory cytokines are recruited, including TNF-a and chemokines. At later stages, macrophages are involved in the process.

The reaction may be general (eg, serum sickness) or involve specific organs, tissues, including the skin (eg, systemic lupus erythematous, Arthus reaction), kidneys (eg, lupus nephritis), lungs (eg, aspergillosis), or other organs. This reaction can be caused by many microorganisms. It develops 3-10 hours after exposure to the antigen, as in the Arthus reaction. The antigen can be exogenous (chronic bacterial, viral, fungal or protozoal infections) or endogenous, as in systemic lupus erythematosus.

Clinical manifestations of type III. Serum sickness occurs when high doses of antigen are administered, such as equine tetanus serum. After 6-7 days, antibodies against horse protein appear in the blood, which, interacting with this antigen, form immune complexes that are deposited in the walls of blood vessels and tissues. Systemic vasculitis, arthritis (deposition of complexes in the joints), nephritis (deposition of complexes in the kidneys) develop.

Arthus' reaction develops with repeated intradermal injection of an antigen, which locally forms immune complexes with previously accumulated antibodies. Manifested by edema, hemorrhagic inflammation and necrosis.

No. 68 Anaphylactic shock and serum sickness. Causes of occurrence. Mechanism. Their warning.

Anaphylaxis is an immediate type reaction that occurs during parenteral reintroduction antigen in response to the damaging effect of the antigen-antibody complex and characterized by a stereotypical clinical and morphological picture.

The main role in anaphylaxis is played by cytotropic IgE, which has an affinity for cells, in particular basophils and mast cells. After the first contact of the body with the antigen, IgE is formed, which, due to cytotropism, is adsorbed on the surface of the above-mentioned cells. When the same antigen enters the body again, IgE binds the antigen to form an IgE-antigen complex on the cell membrane. The complex damages cells, which in response to this release mediators - histamine and histamine-like substances (serotonin, kinin). These mediators bind to receptors located on the surface of functional muscle, secretory, mucous and other cells, causing their corresponding reactions. This leads to a reduction in the smooth muscles of the bronchi, intestines, bladder, increased vascular permeability and other functional and morphological changes that are accompanied clinical manifestation. Clinically, anaphylaxis manifests itself in the form of shortness of breath, suffocation, weakness, anxiety, convulsions, involuntary urination, defecation, etc. The anaphylactic reaction occurs in three phases: in the 1st phase, the antigen-antibody reaction itself occurs; in the 2nd phase, mediators of the anaphylactic reaction are released; in the 3rd phase, functional changes appear.

Anaphylactic reaction occurs several minutes or hours after repeated administration of the antigen. Flows in the form anaphylactic shock or how local manifestations. The intensity of the reaction depends on the dose of antigen, the amount of antibodies formed, the type of animal and can result in recovery or death. Anaphylaxis can be easily induced in animal experiments. The optimal model for reproducing anaphylaxis is the guinea pig. Anaphylaxis can occur when any antigen is administered by any route (subcutaneously, through Airways, digestive tract) provided that the antigen causes the formation of immunoglobulins. The dose of antigen that causes sensitization, i.e., hypersensitivity, is called sensitizing. It is usually very small, since large doses can cause not sensitization, but the development of immune defense. A dose of antigen administered to an animal already sensitized to it and causing anaphylaxis is called resolving. The permissive dose must be significantly greater than the sensitizing dose.

State of sensitization after encountering an antigen persists for months, sometimes years; the intensity of sensitization can be artificially reduced by introducing small resolving doses of antigen, which bind and remove part of the antibodies from circulation in the body. This principle has been used for desensitization (hyposensitization), i.e. prevention of anaphylactic shock with repeated injections of the antigen. The desensitization method was first proposed by the Russian scientist A. Bezredka (1907), which is why it is called the Bezredka method. The method consists in the fact that a person who has previously received any antigenic drug (vaccine, serum, antibiotics, blood products, etc.), upon repeated administration (if he has hypersensitivity to the drug), is first given a small dose (0.01 ; 0.1 ml), and then, after 1-1"/2 hours, the main one. This technique is used in all clinics to avoid the development of anaphylactic shock; this technique is mandatory.

Passive transfer of anaphylaxis with antibodies is possible.

Serum sickness is a reaction that occurs during a single parenteral administration of large doses of whey and other protein preparations. Usually the reaction occurs after 10-15 days. The mechanism of serum sickness is associated with the formation of antibodies against the introduced foreign protein (antigen) and the damaging effect of antigen-antibody complexes on cells. Clinically, serum sickness is manifested by swelling of the skin and mucous membranes, increased body temperature, swelling of the joints, rash and itching of the skin; changes in the blood are observed (increased ESR, leukocytosis, etc.). The timing of manifestation and severity of serum sickness depend on the content of circulating antibodies and the dose of the drug. This is explained by the fact that by the 2nd week after the administration of serum proteins, antibodies to serum proteins are produced and an antigen-antibody complex is formed. Prevention of serum sickness is carried out using the Bezredka method.

No. 69 Theories of immunity.

Mechnikov's theory of immunity- the theory according to which phagocytosis plays a decisive role in antibacterial immunity.

First, I.I. Mechnikov, as a zoologist, experimentally studied the marine invertebrates of the Black Sea fauna in Odessa and drew attention to the fact that certain cells (coelomocytes) of these animals absorb foreign substances (solid particles and bacteria) that had penetrated into the internal environment. Then he saw an analogy between this phenomenon and the absorption of microbial bodies by the white blood cells of vertebrates. These processes were observed by other microscopists before I.I. Mechnikov. But only I.I. Mechnikov realized that this phenomenon is not a process of nutrition of a given single cell, but is a protective process in the interests of the whole organism. I.I. Mechnikov was the first to consider inflammation as a protective rather than a destructive phenomenon. Against the theory of I.I. Mechnikov at the beginning of the 20th century. were the majority of pathologists, since they observed phagocytosis in areas of inflammation, i.e. in diseased areas, and considered white blood cells (pus) to be pathogenic rather than protective cells. Moreover, some believed that phagocytes are carriers of bacteria throughout the body, responsible for the dissemination of infections. But I.I. Mechnikov’s ideas survived; the scientist called those acting in this way protective cells are "eating cells". His young French colleagues suggested using Greek roots of the same meaning. I.I. Mechnikov accepted this option, and the term appeared "phagocyte". L. Pasteur liked these works and Mechnikov’s theory extremely much, and he invited Ilya Ilyich to work at his institute in Paris.

Ehrlich's theory of immunity- one of the first theories of antibody formation, according to which cells have antigen-specific receptors that are released as antibodies under the influence of an antigen.

In Paul Ehrlich's article, the author called the antimicrobial substances in the blood the term "antibody", since bacteria at that time were called the term "korper" - microscopic bodies. But P. Ehrlich “visited” a deep theoretical insight. Despite the fact that the facts of that time indicated that antibodies against a given microbe were not detected in the blood of an animal or person who had not been in contact with a specific microbe, P. Ehrlich somehow realized that even before contact with a specific microbe in the body has already antibodies in a form he called "side chains". As we now know, this is exactly the case, and Ehrlich’s “side chains” are those that have been studied in detail in our time lymphocyte receptors for antigens. Later, P. Ehrlich “applied” this same way of thinking to pharmacology: in his theory of chemotherapy, he assumed the pre-existence in the body of receptors for medicinal substances. In 1908, P. Ehrlich was awarded the Nobel Prize for humoral theory of immunity.

There are also some other theories.

Bezredky's theory of immunity- a theory that explains the body’s defense against a number of infectious diseases by the emergence of specific local cell immunity to pathogens.

Instructive theories of immunity - common name theories of antibody formation, according to which the leading role in the immune response is assigned to an antigen that directly participates as a matrix in the formation of a specific configuration of an antideterminant or acts as a factor that directionally changes the biosynthesis of immunoglobulins by plasma cells.

No. 70 Features of antiviral, antibacterial, antifungal, antitumor, transplantation immunity.

Antiviral immunity. The basis of antiviral immunity is cellular immunity. Target cells infected with the virus are destroyed by cytotoxic lymphocytes, as well as NK cells and phagocytes interacting with Fc fragments of antibodies attached to virus-specific proteins infected cell. Antiviral antibodies are capable of neutralizing only extracellularly located viruses, as well as factors of nonspecific immunity - serum antiviral inhibitors. Such viruses, surrounded and blocked by body proteins, are absorbed by phagocytes or excreted in urine, sweat, etc. (so-called “excretory immunity”). Interferons enhance antiviral resistance by inducing in cells the synthesis of enzymes that suppress the formation of nucleic acids and viral proteins. In addition, interferons have an immunomodulatory effect and increase the expression of major histocompatibility complex (MHC) antigens in cells. Antiviral protection of mucous membranes is due to secretory IgA, which, interacting with viruses, prevents their adhesion to epithelial cells.

Antibacterial immunity directed both against bacteria and their toxins (antitoxic immunity). Bacteria and their toxins are neutralized by antibacterial and antitoxic antibodies. Bacteria (antigens)-antibody complexes activate complement, the components of which attach to the Fc fragment of the antibody, and then form a membrane attack complex that destroys the outer membrane of the cell wall of gram-negative bacteria. Peptidoglycan of bacterial cell walls is destroyed by lysozyme. Antibodies and complement (C3b) envelop bacteria and “glue” them to the Fc and C3b receptors of phagocytes, acting as opsonins along with other proteins that enhance phagocytosis ( C-reactive protein, fibrinogen, mannan-binding lectin, serum amyloid).

The main mechanism of antibacterial immunity is phagocytosis. Phagocytes move directionally to the object of phagocytosis, reacting to chemoattractants: microbial substances, activated complement components (C5a, C3a) and cytokines. Antibacterial protection of mucous membranes is due to secretory IgA, which, interacting with bacteria, prevents their adhesion to epithelial cells.

Antifungal immunity. Antibodies (IgM, IgG) in mycoses are detected in low titers. The basis of antifungal immunity is cellular immunity. Phagocytosis occurs in the tissues, an epithelioid granulomatous reaction develops, and sometimes thrombosis of blood vessels. Mycoses, especially opportunistic ones, often develop after long-term antibiotic therapy and in immunodeficiencies. They are accompanied by the development of delayed-type hypersensitivity. It is possible to develop allergic diseases after respiratory sensitization with fragments of opportunistic fungi of the genera Aspergillus, Penicillium, Mucor, Fusarium, etc.

Antitumor immunity is based on a Th1-dependent cellular immune response that activates cytotoxic T lymphocytes, macrophages and NK cells. The role of the humoral (antibody) immune response is small, since antibodies, combining with antigenic determinants on tumor cells, shield them from the cytopathogenic actions of immune lymphocytes. Tumor antigen is recognized by antigen-presenting cells (dendritic cells and macrophages) and, directly or through T helper cells (Th1), is presented to cytotoxic T lymphocytes that destroy the target tumor cell.

In addition to specific antitumor immunity, immune surveillance of the normal composition of tissues is realized due to nonspecific factors. Nonspecific factors that damage tumor cells: 1) NK cells, a system of mononuclear cells, the antitumor activity of which is enhanced by the influence of interleukin-2 (IL-2) and α-, β-interferons; 2) LAK cells (mononuclear cells and NK cells activated by IL-2); 3) cytokines (α- and β-interferons, TNF-α and IL-2).

Transplant immunity is an immune reaction of a macroorganism directed against foreign tissue (graft) transplanted into it. Knowledge of the mechanisms of transplantation immunity is necessary to solve one of the most important problems of modern medicine - organ and tissue transplantation. Many years of experience have shown that the success of transplantation of foreign organs and tissues in the vast majority of cases depends on the immunological compatibility of the tissues of the donor and recipient.

The immune reaction to foreign cells and tissues is due to the fact that they contain antigens that are genetically foreign to the body. These antigens, called transplantation or histocompatibility antigens, are most fully represented on the CPM of cells.

A rejection reaction does not occur if full compatibility donor and recipient by histocompatibility antigens - this is only possible for identical twins. The severity of the rejection reaction largely depends on the degree of foreignness, the volume of transplanted material and the state of immunoreactivity of the recipient.

Upon contact with foreign transplantation antigens, the body reacts with factors of the cellular and humoral immunity. The main factor cellular transplantation immunity are T-killer cells. These cells, after sensitization by donor antigens, migrate into the graft tissue and exert antibody-independent cell-mediated cytotoxicity on them.

Specific antibodies that are formed against foreign antigens (hemagglutinins, hemolysins, leukotoxins, cytotoxins) are important in the formation of transplantation immunity. They trigger antibody-mediated cytolysis of the graft (complement-mediated and antibody-dependent cell-mediated cytotoxicity).

Adoptive transfer of transplantation immunity is possible using activated lymphocytes or with specific antiserum from a sensitized individual to an intact macroorganism.

The mechanism of immune rejection of transplanted cells and tissues has two phases. In the first phase, an accumulation of immunocompetent cells is observed around the graft and vessels ( lymphoid infiltration), including T-killers. In the second phase, destruction of the transplant cells by T-killers occurs, the macrophage link, natural killer cells, and specific antibody genesis are activated. Immune inflammation, thrombosis of blood vessels occurs, the nutrition of the graft is disrupted and its death occurs. Destroyed tissues are utilized by phagocytes.

During the rejection reaction, a clone of immune memory T and B cells is formed. A repeated attempt to transplant the same organs and tissues causes a secondary immune response, which is very violent and quickly ends in transplant rejection.

From a clinical point of view, acute, hyperacute and delayed graft rejection are distinguished. They differ in the reaction time and individual mechanisms.

No. 71 Concept of clinical immunology. Human immune status and factors influencing it.

Clinical immunology is a clinical and laboratory discipline that studies issues of diagnosis and treatment of patients with various diseases and pathological conditions, which are based on immunological mechanisms, as well as conditions in the treatment and prevention of which immunotherapy plays a leading role.

Immune status- it is structural and functional state the individual’s immune system, determined by a set of clinical and laboratory immunological parameters.

Thus, immune status characterizes the anatomical and functional state of the immune system, i.e. its ability to mount an immune response to a specific antigen at a given time.

For immune status the following factors influence:

Climatic-geographical; social; environmental (physical, chemical and biological); “medical” (the effect of drugs, surgical interventions, stress, etc.).

Among the climatic and geographical factors The immune status is influenced by temperature, humidity, solar radiation, day length, etc. For example, the phagocytic reaction and allergic skin tests are less pronounced in residents of northern regions than in southerners. Epstein-Barr virus in people of the white race it causes an infectious disease - mononucleosis, in people of the Negroid race - oncopathology (Burkitt's lymphoma), and in people of the yellow race - a completely different oncopathology (nasopharyngeal carcinoma), and only in men. Africans are less susceptible to diphtheria than Europeans.

To social factors that influence the immune status include nutrition, living conditions, occupational hazards, etc. A balanced and rational diet is important, since food supplies the body with substances necessary for the synthesis of immunoglobulins, for the construction of immunocompetent cells and their functioning . It is especially important that the diet contains essential amino acids and vitamins, especially A and C.

Living conditions have a significant impact on the immune status of the body. Living in poor housing conditions leads to a decrease in general physiological reactivity, respectively immunoreactivity, which is often accompanied by an increase in the level of infectious morbidity.

Occupational hazards have a great influence on the immune status, since a person spends a significant part of his life at work. Industrial factors that can have an adverse effect on the body and reduce immunoreactivity include ionizing radiation, chemicals, microbes and their metabolic products, temperature, noise, vibration, etc. Radiation sources are now very widespread in various industries industry (energy, mining, chemical, aerospace, etc.).

Salts of heavy metals, aromatic, alkylating compounds and other chemicals, including detergents, disinfectants, pesticides, and pesticides, which are widely used in practice, have an adverse effect on the immune status. Workers in chemical, petrochemical, metallurgical industries, etc. are exposed to such occupational hazards.

Microbes and their metabolic products (most often proteins and their complexes) have an adverse effect on the immune status of the body among workers in biotechnological industries associated with the production of antibiotics, vaccines, enzymes, hormones, feed protein, etc.

Factors such as low or heat, noise, vibration, insufficient lighting, can reduce immunoreactivity by exerting an indirect effect on the immune system through the nervous and endocrine systems, which are in close relationship with the immune system.

Environmental factors have a global effect on human immune status, first of all, environmental pollution with radioactive substances (spent fuel from nuclear reactors, leakage of radionuclides from reactors during accidents), wide application pesticides in agriculture, emissions chemical enterprises and motor transport, biotechnological production.

Various diagnostic and therapeutic medical procedures influence the immune status, drug therapy, stress. Unreasonable and frequent use of radiography and radioisotope scanning can affect the immune system. Immunoreactivity changes after injury and surgical operations. Many medications, including antibiotics, can have immunosuppressive side effects, especially with long-term use. Stress leads to disruptions in the functioning of the T-immune system, acting primarily through the central nervous system.

No. 72 Assessment of immune status: main indicators and methods for their determination.

Despite the variability of immunological parameters in normal conditions, immune status can be determined by performing a set of laboratory tests, including assessment of the state of nonspecific resistance factors, humoral (B-system) and cellular (T-system) immunity.

Assessment of immune status carried out in the clinic for organ and tissue transplantation, autoimmune diseases, allergies, to identify immunological deficiency in various infectious and somatic diseases, to monitor the effectiveness of treatment of diseases associated with disorders of the immune system. Depending on the capabilities of the laboratory, assessment of immune status is most often based on determining a set of the following indicators:

1) general clinical examination;

2) the state of natural resistance factors;

3) humoral immunity;

4) cellular immunity;

5) additional tests.

During a general clinical examination take into account the patient’s complaints, anamnesis, clinical symptoms, results of a general blood test (including the absolute number of lymphocytes), data from a biochemical study.

Humoral immunity determined by the level of immunoglobulins of classes G, M, A, D, E in the blood serum, the amount of specific antibodies, immunoglobulin catabolism, immediate hypersensitivity, the indicator of B-lymphocytes in the peripheral blood, blast transformation of B-lymphocytes under the influence of B-cell mitogens and other tests .

State of cellular immunity assessed by the number of T-lymphocytes, as well as subpopulations of T-lymphocytes in the peripheral blood, blast transformation of T-lymphocytes under the influence of T-cell mitogens, determination of thymic hormones, the level of secreted cytokines, as well as skin tests with allergens, contact sensitization with dinitrochlorobenzene. To perform skin allergy tests, antigens to which there should normally be sensitization are used, for example, the Mantoux test with tuberculin. The body's ability to induce a primary immune response can be provided by contact sensitization with dinitrochlorobenzene.

As additional tests To assess the immune status, you can use tests such as determination of bactericidal™ in blood serum, titration of C3 and C4 components of complement, determination of C-reactive protein in blood serum, determination of rheumatoid factors and other autoantibodies.

Thus, the assessment of the immune status is carried out on the basis of a large number of laboratory tests that allow assessing the state of both the humoral and cellular components of the immune system, and factors of nonspecific resistance. All tests are divided into two groups: 1st and 2nd level tests. Level 1 tests can be performed in any primary care clinical immunology laboratory and are used for the initial identification of individuals with obvious immunopathology. For more accurate diagnosis, level 2 tests are used.

No. 73 Immune system disorders: primary and secondary immunodeficiencies.

Immunodeficiencies- These are violations of the normal immune status caused by a defect in one or more mechanisms of the immune response.

Distinguish primary, or congenital (genetic), and secondary, or acquired, immunodeficiencies.

Primary, or congenital, immunodeficiencies.

As primary immunodeficiencies, conditions are distinguished in which a violation of the immune humoral and cellular mechanisms is associated with a genetic block, that is, genetically determined by the inability of the body to implement one or another link of immunological reactivity. Immune system disorders can affect both the main specific links in the functioning of the immune system and factors that determine nonspecific resistance. Combined and selective variants of immune disorders are possible. Depending on the level and nature of the disorders, humoral, cellular and combined immunodeficiencies are distinguished.

Congenital immunodeficiency syndromes and diseases are quite rare. The causes of congenital immunodeficiencies can be chromosome duplication, point mutations, defects in nucleic acid metabolism enzymes, genetically determined membrane disorders, genome damage in the embryonic period, etc. As a rule, primary immunodeficiencies appear in the early stages of the postnatal period and are inherited in an autosomal recessive manner. manifest primary immunodeficiencies may be in the form of insufficiency of phagocytosis, complement system, humoral immunity (B-system), cellular immunity (T-system) or in the form of combined immunological deficiency.