Hypersensitivity of immediate and delayed types. Hypersensitivity reactions, their morphological characteristics

Contents of the topic " Autoimmune reactions. Hypersensitivity reactions. Transplant immunity.":

Hypersensitivity reactions. Types of hypersensitivity reactions. Hypersensitivity reactions of the first type (type I). Anaphylactic reactions.

At infectious pathology binding of Ag AT provides reduced h sensitivity to the action of various microorganisms and their toxins. Repeated contact with Ag causes the development of a secondary response, which is much more intense. Ags do not always stimulate the production of ATs, which reduce sensitivity to them. Under certain conditions, ATs are produced, the interaction of which with Ag increases the body’s sensitivity to its re-penetration ( hypersensitivity reactions).

like this increased sensitivity, conditioned immune mechanisms, denoted by the term “ allergy“, and the substances that cause it are “allergens”. A separate science deals with the study of hypersensitivity reactions and the diseases caused by them - allergology.

Allergic reactions may differ significantly from each other, primarily in the time of their manifestation after repeated contact with the allergen. In accordance with this, hypersensitivity reactions are distinguished immediate type(develop after a few minutes) and HRT reactions (develop after 6-10 hours and later). According to the classification of Jell and Coombs, all allergic reactions, depending on the mechanisms of development, are divided into four types. This classification is conditional because Various types tissue damage can occur simultaneously or replace each other.

Pathogenesis of type 1 allergic reaction

Types of hypersensitivity reactions. Hypersensitivity reactions of the first type (type I).

Type 1 hypersensitivity reactions (Type I) are caused by the interaction of the allergen with IgE sorbed on the membranes of mast cells and basophils (therefore, these reactions are also called IgE-mediated). Due to its cytophilic properties (the ability to react with the surface of mast cells and basophils), IgE is also referred to as reagins. The cytophilicity of IgE is due to the presence of special receptor structures in the region of the Fc fragment of the AT molecule. Otherwise, the ability to bind to one’s own cells is called homocytotropy. It is this property that is expressed in IgE, while other ATs (for example, IgG) also interact with foreign cells (that is, they are heterocytotropic). The interaction of the allergen with IgE sorbed on mast cells and basophils leads to the release of biologically active substances (histamine, serotonin, eosinophilic and neutrophilic chemotactic factors, proteases).

These substances (so-called preformed picks) are formed even before contact with the allergen. After the interaction of the latter with IgE, new mediators are synthesized - platelet activating factor (PAF), a slow-reacting substance of anaphylaxis (leukotrienes B4, C4 D4) and other metabolic products of cell membrane phospholipids (prostaglandins and thromboxanes). Mediators interact with receptors of muscle, secretory and many other cells, which leads to contraction smooth muscle(for example, bronchi), increased vascular permeability and edema. Clinically, reactions of the first type are manifested mainly by anaphylaxis and atopic diseases. Acute urticaria and angioedema are less common. The development of anaphylaxis can be blocked by circulating AT (IgM, IgG), which, unlike sorbed IgE, can bind Ag more quickly. But usually they are formed in small quantities, which gives the allergen the opportunity to freely reach the surface of mast cells and basophils with IgE fixed on their surface.

Anaphylactic reactions

Anaphylactic reactions are immunospecific and develop after exposure to an allergen to which the body was previously sensitized. The hypersensitivity state develops 7-14 days after the first contact with Ag and persists for years. Reactions may be systemic or local. Systemic manifestations in the form of anaphylactic shock can develop after exposure to an allergen via almost any route (subcutaneous, parenteral, inhalation). Manifestations local reactions- atopy Goth Greek. atopia, strangeness]. Their development is due to the formation of IgE in response to long-term exposure allergens. Clinically manifested by rhinitis, conjunctivitis, bronchial asthma, Quincke's edema.

Hypersensitivity is an increased reaction immune system the body into, as a rule, normally harmless substances that are inhaled by a person through the air, consumed with food, liquids, injected, or simply exposed to the skin.

First of all, it is worth noting that most people do not experience hypersensitivity reactions and are hypersensitive only to 1-2 (or several) substances. Some, however, are predisposed to hypersensitivity reactions to a wide range of substances.

Such people are called atopics, and this disorder is hereditary. The severity of hypersensitivity reactions is also manifested in the widest spectrum from minimal irritation to a rare and very dangerous shock condition called anaphylaxis.

How does hypersensitivity manifest?

A fairly common hypersensitivity reaction to allergens in the air is hay fever. This disease has a pronounced seasonal character, coinciding with the flowering time of certain plants.

Many different substances and components - animal dander, spices, house dust, and fungal spores - can often cause hypersensitivity reactions that are symptomatically similar to hay fever. Asthma attacks, characterized by increasing shortness of breath and difficulty breathing, are caused by inhalation of such substances. It is worth noting that one of the most common causes of an asthma attack is dust mites.

If we talk about what can cause hypersensitivity reactions, then you should definitely pay attention to some foods. The most common allergens among food products are fish, milk, egg white and other seafood, as well as nuts and grains.

Food allergy symptoms are very diverse - from nausea and indigestion to asthma, atonic eczema and urticaria. This disorder is characterized by such manifestations as dryness and flaking of the skin of the cheeks and forehead, which further spread to the skin of the scalp, chin and subsequently to chest area, palms, forearms, and also the popliteal area.

As a rule, wasp and bee stings are characterized by pain, but for one person in a thousand who is hypersensitive to the venom of such insects, their bite can cause the most serious consequences. Extreme hypersensitivity in rare cases for the victim of the bite it manifests itself in the form of difficulty breathing, pallor and fainting. This condition, as we have already noted, is called anaphylactic shock and requires emergency medical care.

Very severe hypersensitivity reactions can be caused by drugs: penicillin and its derivatives (sulfonamides), barbituric acid derivatives, and especially aspirin.

One of the most common allergic reactions on medicinal substances is skin rash, which extends to the entire body. Moreover, with a deeper degree of hypersensitivity to drugs, anaphylactic shock. Moreover, an allergic reaction to medications may determine serious damage kidneys, liver, heart and blood cells.

Another sign of hypersensitivity is contact dermatitis, a condition that develops when an allergen comes into contact with the skin. As a rule, contact allergens can be metals (in particular, nickel impurities in many jewelry), ingredients included in cosmetics and medicines, or chemical substances, which are dealt with in view of professional duties. As a result of physical contact with these substances, skin redness and itching develop in the area where the allergen comes into contact with the skin.

If you exhibit the indicated signs of hypersensitivity, consult an allergist or immunologist for an appointment.

Read more about the condition of hypersensitivity in our next reviews.

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 immune functions body. Hypersensitivity reactions are triggered by many antigens and the causes vary from person to person.

Classify hypersensitivity reactions using 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

Allergological history. It is necessary to collect the information needed to carry out diagnosis and treatment.
Comprehensive physical examination. The respiratory organs, skin, eyes, and chest are subject to careful examination.
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.
General analysis blood.
Sputum smears.
Skin tests.
General level immunoglobulins IgE in serum.
Provocative tests. This method is based on the introduction of allergens into the target organ, it allows you to identify sensitization.
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.
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 penetrate into the blood active substances(serotonin, histamine, heparin, bradykinins and others). 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 membranes of tissues and cells. This type of reaction occurs with the participation of immunoglobulins G, M, and also during activation of the complement system. As a result, it is damaged cell membrane. This type reactions appear with thrombocytopenia, hemolytic disease 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 incompatible blood, while the donor cells react with the host 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 reactions to drugs, 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:

when exogenous antigens, such as proteins, bacteria, viruses, enter the human body;
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, and give up many medications and foods. If it is impossible to completely eliminate the allergen, then you need to reduce its intensity of exposure.

Antihistamines are also used for treatment.

Drug hypersensitivity is an immune-mediated reaction. Symptoms range from mild to severe and include skin rash, anaphylaxis, and serum sickness. Diagnosis is made clinically; Skin tests are informative. Treatment consists of stopping the medication, prescribing antihistamines (as indicated), and sometimes desensitization.

Pathogenesis

Some proteins and most polypeptide drugs (such as insulin, therapeutic antibodies) can directly stimulate the production of antibodies. However, most drugs act as haptens, which covalently bind to serum or cellular proteins, including proteins that are part of the MHC molecules. This binding makes these proteins immunogenic, stimulating the production of antidrug antibodies, an antidrug T cell response, or both. Haptens can also bind directly to MHC class II molecules, directly activating T lymphocytes. Prohaptens become haptens during metabolic reactions; for example, penicillin itself is not an antigen, but it main product degradation, benzylpenicilloic acid can combine with tissue proteins to form benzylpenicilloyl (BPO), the main antigenic determinant. Some drugs bind directly to T-lymphocyte receptors (TCR, TCR - T-cell receptor) and stimulate them; clinical significance The binding of nehaptens to TCR remains to be established.

It is not clear how primary sensitization occurs and how the innate immune system is initially recruited, but once a drug has stimulated an immune response, cross-reactivity between drugs within and between drugs of the same class is observed. For example, it is very likely that penicillin-sensitized patients will react to semisynthetic penicillins (eg, amoxicillin, carbenicillin, ticarcillin), and about 10% of such patients will react to cephalosporins with a similar beta-lactam structure. However, some apparent cross-reactions (eg, between sulfonamide antibiotics and non-antibiotics) are primarily a consequence of predisposition to allergic reactions rather than a consequence of specific immune cross-reaction. Thus, not every visible reaction is an allergic reaction; for example, amoxicillin causes a rash, but it is not immune-mediated and does not preclude future use of the drug.

Symptoms of drug hypersensitivity

Symptoms and signs vary greatly depending on the patient and the drug, and the same drugs can cause different reactions in different patients. The most serious manifestation is anaphylaxis; Exanthema, urticaria and fever are more common. Persistent drug reactions are rare.

There are other distinctive clinical syndromes. Serum sickness usually begins 7 to 10 days after exposure to the drug and manifests as fever, arthralgia, and rash. The developmental mechanism involves the formation of drug-antibody complexes and complement activation. Some patients develop severe arthritis, swelling, or gastrointestinal symptoms. Symptoms are self-limiting and last from 1 to 2 weeks. Beta-lactam antibiotics and sulfonamide drugs, iron dextran and carbamazepine most often cause this condition.

Hemolytic anemia occurs when an antibody-drug-red blood cell complex forms or when a drug (eg, methyldopa) alters the red blood cell membrane, exposing antigens that induce the production of autoantibodies. Some drugs induce lung damage. Tubulointerstitial nephritis is a common allergic reaction of the kidneys; methicillin, antimicrobials, cimetidine often causes this condition. Hydralazine and procainamide can lead to the development of an SLE-like syndrome. This syndrome proceeds relatively favorably, sparing the kidneys and central nervous system; the antinuclear antibody test is positive. Penicillamine can cause SLE and other autoimmune diseases(for example, myasthenia gravis).

Diagnosis of drug hypersensitivity

The diagnosis is made when a reaction to the drug develops within a short time: from a few minutes to hours after taking the drug. However, many patients report a late reaction of uncertain nature. In some cases, when it is not possible to find an equivalent substitute (for example, penicillin in the treatment of syphilis), skin testing is necessary.

Skin tests. Skin tests for immediate hypersensitivity (IgE-mediated) help in diagnosing reactions to beta-lactam antibiotics, foreign (xenogeneic) serum, some vaccines and polypeptide hormones. However, usually only 10-20% of patients who react to penicillin have positive skin tests. For many drugs (including cephalosporins), the tests are unreliable, and because they only diagnose IgE-mediated allergies, they do not predict the development of morbilliform rash, hemolytic anemia, or nephritis.

Penicillin skin testing is necessary in patients with a history of immediate hypersensitivity who must be prescribed penicillin. BPO-polylysine conjugate and penicillin G are used with histamine and saline solution as a control. First, a pricking technique (prick test) is used. If the patient has a history of severe violent reactions, for the initial sample it is necessary to dilute the reagents 100 times. If the prick test result is negative, intradermal tests can be performed. If the result skin test positive, then treating the patient with penicillin may cause anaphylactic reaction. If the test results are negative, a serious reaction is unlikely but not impossible. Although penicillin skin tests do not induce hypersensitivity de novo, patients are tested immediately before starting penicillin therapy.

When performing skin tests for xenogeneic serum, patients who do not have a history of atopy and who have not previously received preparations from horse serum are first given a prick test using a 1:10 dilution; if the test result is negative, 0.02 ml in a 1:1000 dilution is administered intradermally. In sensitive patients, a blister larger than 0.5 cm in diameter forms within 15 minutes. In all patients who may have previously received serum preparations - whether they have had a reaction or not - and with a suspected history of allergies, the first test is carried out at a dilution of 1:1000. Negative results exclude the possibility of anaphylaxis, but do not predict the occurrence of serum sickness in the future.

Other samples. To conduct drug provocative tests, drugs that can cause hypersensitivity reactions are used in increasing doses until a reaction occurs. This test appears to be safe and effective when performed under supervision. Tests for hematological drugs include direct and indirect antiglobulin tests. Tests for drugs that cause other types of hypersensitivity (eg, RAST, histamine release, mast cell or basophil degranulation, lymphocyte transformation) are unreliable or are in experimental development.

Differential diagnosis

Drug hypersensitivity must be differentiated from toxic and side effects which may occur when taking individual medications or a combination of them.

Treatment of drug hypersensitivity

Treatment consists of stopping taking medications, causing a reaction; most symptoms and complaints become most clear within a few days after the drug is stopped. Maintenance therapy for acute reactions consists of prescribing antihistamines to relieve itching, NSAIDs for arthralgia, glucocorticoids for more severe reactions(for example, exfoliative dermatitis, bronchospasm) and adrenaline for anaphylaxis. Conditions such as drug fever, non-pruritic skin rash, mild reactions from other organs and systems, do not require treatment (treatment of specific clinical reactions see other chapters of this publication).

Desensitization. Rapid desensitization may be necessary in cases of well-established sensitivity and if treatment with this drug is necessary in the absence of alternative options. If possible, desensitization is best done in collaboration with an allergist. The procedure is not performed on patients with Stevens-Johnson syndrome. Before carrying out desensitization, 0 2 , adrenaline, and other equipment for carrying out resuscitation measures in case of anaphylaxis.

Desensitization is based on a gradual increase in the dose of the allergen administered every 30 minutes; it begins with the minimum dose that induces subclinical anaphylaxis, bringing the exposure to therapeutic dose. The effect of this procedure is based on the constant presence of the drug in the blood serum and its administration should not be interrupted; Desensitization is followed by the full therapeutic dose. A hypersensitivity reaction usually occurs 24-48 hours after stopping the drug. During desensitization, minimal reactions (eg, itching, rash) are often observed.

For penicillin, oral or intravenous routes of administration can be used; subcutaneous or intramuscular route of administration is not recommended. If the intradermal test is positive, 100 units (or mcg)/ml is administered intravenously for the first time in a 50 ml balloon (total amount 5000 units) very slowly. If no symptoms are observed, the rate of administration is gradually increased until the balloon is completely empty within 20-30 minutes. Then the procedure is repeated with a concentration of 1000 or 10,000 units/ml, followed by the administration of the full therapeutic dose. If any symptoms develop during the procedure allergic symptoms, the rate of administration should be reduced and the patient undergoes appropriate drug therapy. If the penicillin prick test is positive or if the patient has had severe allergic reactions, the initial dose should be lower.

During desensitization per os the dose starts at 100 units (mcg); the dose is doubled every 15 minutes to 400,000 units (dose 13). The drug is then administered parenterally, and if allergic symptoms appear, they are controlled with appropriate anti-anaphylactic drugs.

For trimethoprim-sulfamethoxazole and vancomycin, the same methodology is used as for penicillin.

For xenogeneic serum. If the skin test for xenogeneic serum is positive, then the risk of anaphylaxis is very high. If treatment with serum is necessary, it should be preceded by desensitization. To determine the appropriate starting dose for desensitization, skin tests are used and the minimum dose obtained through a series of dilutions (the concentration at which there is no or very weak reaction) is selected. 0.1 ml of this solution is injected subcutaneously or slowly intravenously; the intravenous route of administration, although non-standard, requires medical supervision until a therapeutic concentration and rate of administration are achieved. If no reaction occurs within 15 minutes, the dose is doubled after 15 minutes to reach 1 ml of undiluted serum. The administration of this dose is repeated intramuscularly, and if no reaction is noted in the next 15 minutes, the full dose is administered. If a reaction occurs, treatment may still be possible; the dose is reduced, prescribed antihistamines, as in acute urticaria, and then the dose is increased very slightly.

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Normally healthy person the body works like a clock, all its organs and systems are well balanced with each other and constantly interact. In addition, they respond adequately to various external influences, adapting to them or eliminating them Negative consequences. However, in certain cases, the body's functioning may malfunction. So, in certain cases, a person may experience hypersensitivity of the nervous or immune system. Let's try to understand these pathological conditions in a little more detail.

Immune system hypersensitivity

This pathology is inherently an inadequate or excessive manifestation of the acquired immune response. It is based on a useful and normal immune response, but in this case it works completely inadequately and can cause serious pathological conditions - inflammation and tissue damage.

With immune hypersensitivity, the body can react aggressively to a variety of components that enter our body along with food or air, as well as those that come into contact with the skin or are medications.

The main reason for this pathological condition- This is a violation of the immune functions of our body. The immune system reacts to the penetration of various foreign particles by releasing histamine, which causes itching, swelling and inflammation.

Moreover, such a reaction can vary in severity - be moderate or quite dangerous (anaphylaxis).

Increased sensitivity the body may occur in response to the influence of various highly allergenic particles - plant pollen, animal hair, household dust, waste products of fleas or dust mites. In this case, the person experiences asthmatic attacks or shortness of breath. If we talk about food products that cause pathological allergic reactions, the most common of them are milk and eggs, some fruits, nuts and seafood. This type of immune hypersensitivity is manifested by skin problems - peeling, dryness, redness, dermatitis and eczema. In some cases, violations also appear digestive processes.

Contact dermatitis can occur as a result of hypersensitivity of the epidermis to various aggressive irritants, which may include metals, cosmetics, household chemicals etc. If the body reacts aggressively to insect bites or medications, the patient may develop anaphylactic shock and damage to cells of various vital important organs.

Treatment of immune system hypersensitivity involves identifying the allergen and, if possible, eliminating contact with it. Certain symptoms Such pathologies are eliminated by consuming antihistamines. Treatment may also involve systematic administration of minimum quantity allergen to reduce intensity immune reactions. To correct severe shock states It is customary to use antihistamines, as well as hormonal drugs.

Most often, the tendency to immune hypersensitivity is hereditary. The development of such a pathology can be provoked by the most various factors, among which the influence environment, as well as lifestyle and social environment.

Hypersensitivity nervous system

This pathology is observed in many people, regardless of gender and age. However, most often it is diagnosed in male children, as well as in adolescents. Doctors classify this pathological condition as hyperexcitability syndrome. A person with this diagnosis is quite easy to recognize - his facial muscles are asymmetrical, and his movement is also impaired. eyeballs. In addition, hypersensitivity of the nervous system impairs orientation in time and space and makes the patient uncollected and awkward. Among other things, such people are constantly bothered by headaches and insomnia; they are characterized by insignificant delay mental development.

Most often, this diagnosis is given to children, because their nervous system is quite imperfect; it can suffer from an unfavorable psychological environment, as well as from sitting in front of a computer or TV. In adults, the disease develops against the background constant stress and too fast pace of life, it can be provoked poor nutrition and lack of quality rest and sleep.

Therapy for this pathological condition can be quite successful; for this purpose, the patient may be prescribed various medications, among which the most popular are sedative compounds for plant based, for example, motherwort tincture or valerian extract. In addition, doctors often prescribe Barboval or Valocardin; the cardiac medication Tricardin and the metabolic composition Glycine are very popular. Good results can also be achieved by using homeopathic medicines, for example, Calm or Cardioica. To common medicinal compositions for the treatment of hypersensitivity of the nervous system also include Piracetam, Klimadion and Magnefar B6.

At reasonable approach hypersensitivity reactions of the nervous and immune systems are completely correctable.