Symptoms of an immediate allergic reaction. Delayed-type allergic reactions: how does the lesion occur?
2. Allergic reactions (hypersensitivity) of the delayed type.
The classification is based on the time of occurrence of the reaction after contact with the allergen: reactions of the immediate type develop after 15-20 minutes, the delayed type - after 24-48 hours.
This classification, developed in the clinic, did not cover the whole variety of allergy manifestations, and therefore it became necessary to classify allergic reactions taking into account the peculiarities of their pathogenesis.
The first attempt to separate allergic reactions, taking into account the peculiarities of their pathogenesis, was made by A.D. Ado (1963). He divided these reactions according to pathogenesis into two groups:
1. True allergic reactions.
2. False allergic reactions(pseudo-allergic).
With true allergic reactions, hypersensitivity (sensitization) develops to the allergen that first enters the body. With repeated exposure to an already sensitized organism, the allergen combines with the resulting antibodies or lymphocytes.
False allergic reactions occur upon first contact with the allergen without prior sensitization. In external manifestations, they only resemble allergic ones, but do not have the main, leading (immunological) mechanism characteristic of true allergic diseases.
Currently, allergic reactions are divided according to the classification of damage reactions (hypersensitivity), proposed in 1969 by Gell and Coombs and later supplemented by Royt. This classification is based on the features of the mechanism of immune damage. Taking into account the peculiarities of the development of the immune response, they are isolated 5 main types of immune damage(immunopathological reactions) (Table 27, Fig. 39).
Type I (reaginic, anaphylactic) is associated with the formation of a special type of antibodies (IgE, IgG4) that have a high affinity (affinity) for certain cells (obese, basophils), the so-called cytotropic antibodies. The antigen, interacting with antibodies fixed on the cells, leads to the secretion of pre-existing and newly formed biologically active substances (mediators), which cause an increase in vascular permeability, tissue edema, mucus hypersecretion, and smooth muscle contraction. A typical example of this type of damage is allergic reactions such as atopic bronchial asthma, seasonal allergic rhinitis, conjunctivitis, anaphylactic shock, allergic urticaria, Quincke's edema, etc.
II type (cytotoxic or cytolytic) is associated with the formation of antibodies of the IgG (except IgG4) and IgM classes. Antigens are components of natural cell membranes or substances adsorbed on the cell surface, to which antibodies are formed. The antigen-antibody complex formed on the cell surface activates the complement system, resulting in cell damage and lysis. Examples of this type of cytotoxic injury are:
allergic reactions to certain medicinal substances - drug thrombocytopenic purpura, allergic drug agranulocytosis (an antigen is a drug or a product of its metabolism included in the cell surface); blood transfusion reactions resulting from incompatibility of blood groups (antigens are natural cellular structures);
autoimmune diseases - autoimmune hemolytic anemia, thrombocytopenia, myasthenia gravis, etc.
III type of immune damage associated with the formation of toxic immune complexes (antigen-antibody: IgM, IgG1, IgG3). An example is: allergic reactions - exogenous allergic alveolitis (when inhaled antigens enter), serum sickness, the Arthus phenomenon; autoimmune diseases (systemic lupus erythematosus, systemic vasculitis, etc.).
IV type of immune damage - cell-mediated ( HRT )
. This type includes: allergies that form in some infectious diseases (tuberculosis, leprosy, leprosy, brucellosis, syphilis), allergic contact dermatitis, transplant rejection, etc .; autoimmune diseases (rheumatoid arthritis, multiple sclerosis).
Type V immune damage(antireceptor) associated with the presence of antibodies(mainly IgG) to physiologically important cell membrane determinants - receptors(b-adrenergic receptors, acetylcholine and insulin receptors, receptors for TSH). Type V immune damage plays a special role in autoimmunization. The reaction of AG (receptor) + AT can lead to either stimulation or blockade of the effect.
The fifth type of immune damage is the leading one in the development of the immune type of diabetes mellitus, immune diseases of the thyroid gland, pituitary gland, etc. In the development of bronchial asthma, atopic dermatitis, and some others antireceptor type of damage may be one of the mechanisms complicating the course of the disease.
In many allergic diseases, it is possible to simultaneously detect the mechanisms of various types of damage. For example, mechanisms of types I and III are involved in anaphylactic shock, reactions of types II and IV are involved in autoimmune diseases, etc. However, for pathogenetically substantiated therapy, it is always important to establish the leading mechanism.
Allergy in humans has extremely diverse manifestations: bronchial asthma, hay fever (allergic rhinitis, conjunctivitis), urticaria, allergic dermatitis, Quincke's edema, anaphylactic shock, serum sickness, post-vaccination allergic complications (fever, hyperemia, edema, rash, Arthus phenomenon).
Along with independent, purely allergic diseases, there are diseases (mainly infectious), where allergic reactions and processes are involved as concomitant or secondary mechanisms: tuberculosis, brucellosis, leprosy, scarlet fever and a number of others.
7.5. GENERAL PATHOGENESIS OF ALLERGIC REACTIONS
Regardless of what type of damage an allergic reaction belongs to, three stages can be distinguished in its development.
I. Stage of immune reactions (immunological). It begins with the first contact of the body with the allergen and consists in the formation of allergic antibodies (or sensitized lymphocytes) in the body and their accumulation. As a result, the body becomes sensitized, or hypersensitive to a specific allergen. When a specific allergen enters the body again, the formation of AG-AT complexes (or AG-sensitized lymphocyte) occurs, which determine the next stage of the allergic reaction.
II. Stage of biochemical reactions (pathochemical). Its essence lies in the release of ready-made and the formation of new biologically active substances (allergy mediators) as a result of complex biochemical processes triggered by AG-AT complexes (or AG-sensitized lymphocyte).
III. Stage of clinical manifestations (pathophysiological). It is a response of cells, organs and tissues of the body to the mediators formed in the previous stage.
7.5.1. The mechanism of allergic reactions developing according to type I immune damage
In the pathogenesis of type I allergic reactions, which are also called atopic (reaginic, anaphylactic), the following stages are distinguished: IgE differ significantly in their properties from other antibodies (Table 28). First of all, they are cytotropic (cytophilic). It is believed that their inherent ability to attach to cells and be fixed in tissues is associated with the additional 110 amino acids acquired in phylogenesis on the Fc fragment of the molecule. The concentration of IgE in the blood serum is therefore low because the IgE molecules synthesized in the regional lymph nodes enter the bloodstream to a lesser extent, since they are mainly fixed in the surrounding tissues. Destruction or inactivation of this region of the Fc fragment by heating (up to 560C) leads to the loss of the cytotropic properties of these antibodies, i.e. they are thermolabile.
Fixation of antibodies by cells occurs with the help of a receptor embedded in the cell membrane. IgE receptors found on mast cells and blood basophils have the highest ability to bind IgE antibodies, so these cells are called target cells of the 1st order. From 3,000 to 300,000 IgE molecules can be fixed on one basophil. The receptor for IgE is also found on macrophages, monocytes, eosinophils, platelets and lymphocytes, but their binding capacity is lower. These cells are called second order target cells(Fig. 41).
IgE binding on cells is a time dependent process. Optimal sensitization can occur in 24-48 hours. Fixed antibodies can stay on the cells for a long time, so an allergic reaction can be caused after a week or more. A feature of IgE antibodies is also the difficulty of their detection, since they do not participate in serological reactions.
So, the primary entry of an allergen into the body triggers complex mechanisms for the synthesis of IgE, which are fixed on target cells, through the cooperation of dendritic cells, T- and B-lymphocytes. The repeated encounter of the body with this allergen leads to the formation of the AG-AT complex, and through the fixed IgE molecules, the complex itself will also become fixed on the cells. If the allergen turned out to be associated with at least two neighboring IgE molecules, then this is enough to disrupt the structure of target cell membranes and activate them. Stage II of the allergic reaction begins.
II. S t a d i i a b i o chemi cal and s to and x re - a to c and y. In this stage, the main role is played by mast cells and blood basophils, i.e. target cells of the first order. mast cells(tissue basophils) are connective tissue cells. They are found mainly in the skin, respiratory tract, along the course of blood vessels and nerve fibers. Mast cells are large (10-30 µm in diameter) and contain 0.2-0.5 µm diameter granules surrounded by a perigranular membrane. Granules of mast cells and blood basophils contain mediators: histamine, heparin, allergy eosinophil chemotaxis factor (FCE-A), allergy neutrophil chemotaxis factor (FCHN-A) (Table 29).
The formation of the AG-AT complex on the surface of the mast cell (or blood basophil) leads to the contraction of receptor proteins for IgE, the cell is activated and secretes mediators. Maximum cell activation is achieved by binding several hundred and even thousands of receptors.
As a result of the attachment of the allergen, the receptors acquire enzymatic activity and a cascade of biochemical reactions is triggered. Increases the permeability of the cell membrane for calcium ions. The latter stimulate endomembrane proesterase, which converts to esterase and converts phospholipase D, which hydrolyzes membrane phospholipids, into its active form. Hydrolysis of phospholipids promotes loosening and thinning of the membrane, which facilitates the fusion of the cytoplasmic membrane with the perigranular one and the rupture of the cytoplasmic membrane with the release of the contents of the granules (and mediators) to the outside, exocytosis of the granules occurs. In this case, processes associated with energy metabolism, especially glycolysis, play an important role. The energy reserve is important both for the synthesis of mediators and for the release of mediators through the intracellular transport system. As the process progresses, the granules move to the cell surface. For the manifestation of intracellular mobility, microtubules and microfilaments are of certain importance.
Energy and calcium ions are needed to convert the microtubules into a functioning form, while an increase in the level of cyclic adenosine monophosphate (cAMP) or a decrease in cyclic guanosine monophosphate (cGMP) has the opposite effect. Energy is also required to release histamine from loose bonds with heparin. At the end of the AG-AT reaction, the cell remains viable.
In addition to the release of mediators already present in the granules of mast cells and basophils, these cells rapidly synthesize new mediators (Table 29). They are derived from lipid breakdown products: platelet activating factor (PAF), prostaglandins, thromboxanes, and leukotrienes.
It should be noted that degranulation of mast cells and basophils can also occur under the influence of non-immunological activators, i.e. activating cells not through IgE receptors. These are ACTH, substance P, somatostatin, neurotensin, chymotrypsin, ATP. This property is possessed by the activation products of cells that are secondarily involved in an allergic reaction - the cationic protein of neutrophils, peroxidase, free radicals, etc. Some drugs can also activate mast cells and basophils, such as morphine, codeine, radiopaque agents.
As a result of the isolation of neutrophil and eosinophil chemotaxis factors from mast cells and basophils, the latter accumulate around first-order target cells. Neutrophils and eosinophils are activated and also release biologically active substances and enzymes. Some of them are also damage mediators (for example, PAF, leukotrienes, etc.), and some (histaminase, arylsulfatase, phospholipase D, etc.) are enzymes that destroy certain damage mediators. So, arylsulfatase from eosinophils causes the destruction of leukotrienes, histaminase - the destruction of histamine. The resulting group E prostaglandins reduce the release of mediators from mast cells and basophils.
III. Stage of clinical manifestations. As a result of the action of mediators, an increase in the permeability of the microvasculature develops, which is accompanied by the release of fluid from the vessels with the development of edema and serous inflammation. With the localization of processes on the mucous membranes, hypersecretion occurs. In the respiratory organs, bronchospasm develops, which, along with swelling of the walls of the bronchioles and hypersecretion of sputum, causes a sharp difficulty in breathing. All these effects are clinically manifested in the form of attacks of bronchial asthma, rhinitis, conjunctivitis, urticaria (blister + hyperemia), skin itching, local edema, diarrhea, etc. Due to the fact that one of the mediators is FChE-A, very often type I Allergy is accompanied by an increase in the number of eosinophils in the blood, sputum, serous exudate.
In the development of type I allergic reactions, early and late stages are distinguished. The early stage appears within the first 10-20 minutes in the form of characteristic blisters. It is dominated by the influence of primary mediators secreted by mast cells and basophils.
The late stage of the allergic reaction occurs 2-6 hours after contact with the allergen and is mainly associated with the action of secondary mediators. It is characterized by edema, redness, thickening of the skin, which is formed within 24-48 hours, followed by the formation of petechiae. Morphologically, the late stage is characterized by the presence of degranulated mast cells, perivascular infiltration with eosinophils, neutrophils, and lymphocytes. The following circumstances contribute to the end of the stage of clinical manifestations:
a) during stage III, the damaging principle, the allergen, is removed. The cytotoxic effect of macrophages is activated, the release of enzymes, superoxide radical and other mediators is stimulated, which is very important for protection against helminths;
b) thanks primarily to the enzymes of eosinophils, damaging mediators of an allergic reaction are eliminated.
7.5.2. Type II allergic reactions (cytotoxic type of allergy)
It is called cytotoxic because the antibodies formed against cell antigens combine with them and cause their damage and even lysis (cytolytic action). The outstanding Russian scientists I.I. Mechnikov, E.S. London, A.A. Bogomolets, G.P. Sakharov. I. I. Mechnikov published his first work on the so-called cell poisons (cytotoxins) back in 1901.
The cause of cytotoxic reactions is the occurrence in the body of cells with altered components of the cytoplasmic membrane. An important role in the process of acquiring autoallergenic properties by cells is played by the action on them of various chemicals, more often drugs. They can change the antigenic structure of cytoplasmic membranes due to conformational transformations of antigens inherent in the cell, the appearance of new antigens, the formation of complexes of allergens with membrane proteins, in which the chemical plays the role of a hapten (for example, 2-methyldopa is an antihypertensive drug). According to one of these mechanisms, autoimmune hemolytic anemia can develop. The pathogenesis of cytotoxic allergic reactions includes the following stages:
I. S and m u n n n y x reac - c and y. In response to the appearance of autoallergens, the production of autoantibodies of the IgG and IgM classes begins. They have the ability to fix complement and cause its activation. Some antibodies have opsonizing properties (enhancing phagocytosis) and usually do not fix complement. In some cases, after the connection with the cell, conformational changes occur in the region of the Fc fragment of the antibody, to which K cells (killers) can then join.
A common property of killer cells is the presence of a membrane receptor for the Fc fragment of IgG and the ability to have a cytotoxic effect (the so-called antibody-dependent cellular cytotoxicity), i.e. they are capable of destroying only those altered cells that are covered with antibodies. Such effector cells include: granulocytes, macrophages, platelets, cells from lymphoid tissue without characteristic markers of T- and B-cells and are called K-cells. The mechanism of lysis in all these cells is the same. Antibodies (IgG) are involved in K-cell lysis with Fab- and Fc-fragments (Fig. 42). It is believed that antibodies serve as a "bridge" between the effector cell and the target cell.
II. S t a d i a b i o chemi cal s k i x r e - a c t i y. At this stage, mediators appear, other than in reactions of the reagin type (Table 30).
1. The main mediators of complement-mediated cytotoxicity are classically activated (via the AG-AT complex) complement components: C4b2a3b; C3a; C5a; C567; C5678; C56789, which form a hydrophilic channel in the cell membrane, through which water and salts begin to pass.
2. During the absorption of opsonized cells, phagocytes secrete a number of lysosomal enzymes that can play the role of damage mediators (Fig. 43).
3. During the implementation of antibody-dependent cellular cytotoxicity, the superoxide anion radical secreted by blood granulocytes takes part.
III. Stage of clinical development. The final link in complement- and antibody-dependent cytotoxicity is cell damage and death, followed by their removal by phagocytosis. The target cell is a completely passive partner in the act of lysis, and its role is only to expose the antigen. After contact with the effector cell, the target cell dies, but the effector cell survives and can interact with other targets. The death of the target cell is due to the fact that cylindrical pores with a diameter of 5 to 16 nm are formed in the surface of the cell membranes. With the appearance of such transmembrane channels, an osmotic current appears (the entrance to the cell of water) and the cell dies.
The cytotoxic type plays an important role in the immune response when cells foreign to a given organism, such as microbes, protozoa, tumor cells, or end-of-life cells, act as an antigen. However, under conditions when normal cells of the body acquire autoantigenicity under the influence of exposure, this protective mechanism becomes pathogenic and the reaction changes from immune to allergic, leading to damage and destruction of tissue cells.
The cytotoxic type of reaction can be one of the manifestations of drug allergy in the form of leukopenia, thrombocytopenia, hemolytic anemia, etc. The same mechanism is also activated when homologous antigens enter the body, for example, when blood is transfused in the form of allergic blood transfusion reactions (to multiple blood transfusions), when hemolytic disease of the newborn.
The action of cytotoxic antibodies does not always end in cell damage. In this case, their number is of great importance. With a small amount of antibodies, instead of damage, a stimulation phenomenon can be obtained. For example, some forms of thyrotoxicosis have been associated with long-term stimulatory effects of naturally occurring thyroid autoantibodies.
7.5.3. Type III allergic reactions (immune complex reactions)
The damage in this type of allergic reactions is caused by antigen-AT immune complexes. Due to the constant contact of a person with any antigens in his body, immune reactions constantly occur with the formation of the AG-AT complex. These reactions are an expression of the protective function of the immune system and are not accompanied by damage. However, under certain conditions, the AG-AT complex can cause damage and the development of the disease. The concept that immune complexes (ICs) can play a role in pathology was expressed as early as 1905 by K. Pirke and B. Schick. Since then, a group of diseases in the development of which CI plays the main role has been called immune complex diseases.
The cause of immunocomplex diseases are: drugs (penicillin, sulfonamides, etc.), antitoxic sera, homologous g-globulins, food products (milk, egg whites, etc.), inhalation allergens (house dust, fungi, etc.), bacterial and viral antigens, membrane antigens, body cell DNA, etc. It is important that the antigen has a soluble form.
In the pathogenesis of reactions of immune complexes, the following stages are distinguished (Fig. 44):
In response to the appearance of an allergen or antigen, the synthesis of antibodies begins, mainly IgG and IgM classes. These antibodies are also called precipitating for their ability to form a precipitate when combined with the appropriate antigens.
When AT is combined with AG, ICs are formed. They can be formed locally, in tissues or in the bloodstream, which is largely determined by the routes of entry or the place of formation of antigens (allergens). The pathogenic significance of CIs is determined by their functional properties and the localization of the reactions they cause.
The size of the complex and the structure of the lattice depend on the number and ratio of AG and AT molecules. Thus, large-lattice complexes formed in excess of antibodies are quickly removed from the bloodstream by the reticuloendothelial system. Precipitated, insoluble ICs formed in an equivalent ratio are usually easily removed by phagocytosis and do not cause damage, except in cases of their high concentration or formation in membranes with a filtering function (in glomeruli, choroid of the eyeball). Small complexes formed in a large excess of antigen circulate for a long time, but have a weak damaging activity. The damaging effect is usually exerted by soluble complexes formed in a slight excess of the antigen, m.m. 900-1000 KD. They are poorly phagocytized and stay in the body for a long time.
The significance of the type of antibodies is determined by the fact that their different classes and subclasses have different abilities to activate complement and be fixed through Fc receptors on phagocytic cells. So, IgM and IgG1-3 bind complement, but IgE and IgG4 do not.
With the formation of pathogenic IC, inflammation of various localization develops. Inhalation antigens contribute primarily to reactions in the alveolar capillaries (allergic alveolitis).
Vascular permeability and the presence of certain receptors in tissues play a decisive role for CIs circulating in the blood.
II. ST A D I A. Under the influence of IC and in the process of their removal, a number of mediators are formed, the main role of which is to provide conditions conducive to phagocytosis of the complex and its digestion. However, under certain conditions, the formation of mediators may be excessive, and then they begin to have a damaging effect.
The main mediators are:
1. Complement, under conditions of activation of which various components and subcomponents have a cytotoxic effect. The leading role is played by the formation of C3, C4, C5, which enhance certain links of inflammation (C3b enhances the immune adhesion of IC to phagocytes, C3a plays the role of anaphylatoxin, like C4a, etc.).
2. Lysosomal enzymes, the release of which during phagocytosis enhances damage to basement membranes and connective tissue.
3. Kinins, in particular bradykinin. With the damaging effect of IC, the Hageman factor is activated, as a result, bradykinin is formed from blood a-globulins under the influence of kallikrein.
4. Histamine, serotonin play an important role in type III allergic reactions. Their source is mast cells, platelets and blood basophils. They are activated by the C3a and C5a complement components.
5. The superoxide radical anion also takes part in the development of this type of reaction.
The action of all the listed main mediators is characterized by increased proteolysis.
III. Stage. As a result of the appearance of mediators, inflammation develops with alteration, exudation and proliferation, vasculitis, leading to the appearance of erythema nodosum, periarteritis nodosa. Cytopenias (eg, granulocytopenia) may occur. Due to the activation of the Hageman factor and / or platelets, intravascular coagulation sometimes occurs.
The third type of allergic reactions is leading in the development of serum sickness, exogenous allergic alveolitis, some cases of drug and food allergies, autoimmune diseases (systemic lupus erythematosus, etc.). With significant complement activation, systemic anaphylaxis develops in the form of shock.
7.5.4. Allergic reactions type IV (mediated by T-cells)
This form of reactivity was formed at the later stages of evolution on the basis of immunological reactions and inflammation. It is aimed at recognizing and limiting the action of the allergen. Type IV immune damage underlies many allergic and infectious diseases, autoimmune diseases, transplant rejection, contact dermatitis (contact allergy), and antitumor immunity. Its most striking manifestation is the tuberculin reaction, which is used in clinical practice in the form of the Mantoux reaction. The relatively late manifestation of this reaction (not earlier than 6-8 hours later, redness occurs at the injection site, later the erythema increases and reaches its peak 24-48 hours after the introduction of the antigen) also made it possible to call it delayed-type hypersensitivity (DTH).
Etiology and features of antigenic stimulation in HRT. The antigens that induce HRT can be of various origins: microbes (eg, tuberculosis, brucellosis, salmonellosis, diphtheria, streptococci, staphylococci), vaccinia, herpes, measles, fungi, tissue proteins (eg, collagen), antigenic polymers of amino acids, low molecular weight compounds. By chemical nature, the antigens that can cause HRT are more often protein compounds.
Proteins that cause DTH are characterized by low molecular weight and "weak" immunogenic properties. Therefore, they are not able to sufficiently stimulate antibody formation. The immunological response in HRT has a number of distinctive features. The immune response is directed not only to the hapten, as is the case with immediate-type reactions, but also to the carrier protein, and the specificity for the antigen in HRT is much more pronounced than in immediate-type reactions.
The formation of HRT can be influenced by both the quality and quantity of the antigen entering the body. As a rule, a small amount of antigen (micrograms) is required to reproduce HRT.
In the pathogenesis of an allergic reaction of type IV, conditionally, as in allergic reactions of types I, II, III, three stages can be distinguished (Fig. 45).
I. STAGE OF IMMUNE REACTIONS. The antigen that enters the body most often meets with a macrophage, is processed by it, and then, in a processed form, is transmitted by Tx1, which has receptors for the antigen on its surface. They recognize the antigen, and then, with the help of interleukins, trigger the proliferation of inflammatory effector T cells with the CD4+ phenotype, as well as memory cells. The last one is important. Memory cells allow you to form a rapid immune response when the antigen enters the body again.
HRT-carrying lymphocytes capture the antigen, apparently in the immediate vicinity of the injection site. A necessary condition for the activation of lymphocytes is the simultaneous binding of the T cell to both the antigen and molecules of the major histocompatibility complex (HLA). As a result of the simultaneous "double recognition" of the antigen and HLA products, cell proliferation (transformation of lymphocytes) begins and their transformation from mature into blasts.
II. ST A D I A. Antigenic stimulation of lymphocytes is accompanied by their transformation, formation and further release of DTH mediators. Receptors were found on target cells for each mediator. The action of mediators is non-specific (no antigen is needed for their action). The biological effect of cytokines is varied (Table 31). They change cell mobility, activate cells involved in inflammation, promote cell proliferation and maturation, and regulate the cooperation of immunocompetent cells. Their target cells are macrophages and neutrophils, lymphocytes, fibroblasts, bone marrow stem cells, tumor cells, osteoclasts, etc. All DTH cytokines are proteins, most of which are glycoproteins.
Depending on the effect they have, cytokines are divided into two large groups:
1) factors that suppress the functional activity of cells (MCB, TNFb);
2) factors that enhance the functional activity of cells (transfer factor; MVB; mitogenic and chemotactic factors).
III. Stage. It depends on the nature of the etiological factor and the tissue where the pathological process is “played out”. These can be processes occurring in the skin, joints, internal organs. The inflammatory infiltrate is dominated by mononuclear cells (lymphocytes, monocytes, and macrophages). Violation of microcirculation in the lesion is explained by an increase in vascular permeability under the influence of protein mediators (kinins, hydrolytic enzymes), as well as activation of the blood coagulation system and increased fibrin formation. The absence of significant edema, which is so characteristic of immune lesions in immediate-type allergic reactions, is associated with a very limited role of histamine in HRT.
With HRT, damage can develop as a result of:
1) direct cytotoxic effect of CD4+ T-lymphocytes on target cells (TNFb and complement do not take part in this process);
2) the cytotoxic effect of TNFb (since the effect of the latter is nonspecific, not only the cells that caused its formation, but also intact cells in the zone of its formation can be damaged);
3) release in the process of phagocytosis of lysosomal enzymes that damage tissue structures (these enzymes are secreted primarily by macrophages).
An integral part of HRT is inflammation, which is added to the immune response by the action of mediators of the pathochemical stage. As with the immunocomplex type of allergic reactions, it is connected as a protective mechanism that promotes the fixation, destruction and elimination of the allergen. However, inflammation is at the same time a factor of damage and dysfunction of those organs where it develops, and it plays the most important pathogenetic role in the development of infectious-allergic, autoimmune and some other diseases.
7.6. PSEUDO-ALLERGIC REACTIONS
In allergological practice, the allergist increasingly has to deal with a large group of reactions that are clinically often indistinguishable from allergic ones. These reactions have pathochemical and pathophysiological stages similar to allergic ones and are called pseudo-allergic(non-immunological). It is not possible to reveal the participation of immune reactions in the mechanisms of their occurrence and development.
In the development of pseudo-allergic reactions, mediators such as histamine, leukotrienes, complement activation products, and the kallikrein-kinin system play a special role.
There are three groups of pseudo-allergic reactions:
1. Reactions associated with excessive release of mediators (histamine) and mast cells or with a violation of their inactivation.
Causes: high temperature, UVI, ionizing radiation, antibiotics, polysaccharides.
2. Reactions associated with a deficiency of the inhibitor of the first component of complement, as well as non-immunological activation of complement through an alternative pathway.
Causes: cobra venom, bacterial lipopolysaccharides, enzymes: trypsin, plasmin, kallikrein, activated when damaged.
3. Reactions associated with impaired metabolism of polyunsaturated fatty acids (primarily arachidonic).
Causes: acetylsalicylic acid, pyrazolone derivatives, non-steroidal anti-inflammatory drugs.
The main manifestations of pseudo-allergic reactions: urticaria, Quincke's edema, bronchospasm, anaphylactic shock.
TYPICAL PATHOLOGICAL PROCESSES
PATHOPHYSIOLOGY OF THE PERIPHERAL (ORGAN)
BLOOD CIRCULATION AND MICROC |
An allergic reaction is a change in the properties of the human body to respond to the effects of the environment with repeated exposure to it. A similar reaction develops as a response to the influence of substances of a protein nature. Most often they enter the body through the skin, blood or respiratory organs.
Such substances are foreign proteins, microorganisms and their metabolic products. Since they are able to influence changes in the sensitivity of the body, they are called allergens. If the substances that cause a reaction are formed in the body when tissues are damaged, they are called autoallergens, or endoallergens.
External substances that enter the body are called exoallergens. The reaction manifests itself to one or more allergens. If the latter case occurs, it is a polyvalent allergic reaction.
The mechanism of action of causing substances is as follows: when allergens first enter, the body produces antibodies, or counterbodies, - protein substances that oppose a specific allergen (for example, pollen). That is, a protective reaction is produced in the body.
Repeated contact with the same allergen entails a change in the response, which is expressed either by the acquisition of immunity (reduced sensitivity to a particular substance), or by an increase in susceptibility to its action up to hypersensitivity.
An allergic reaction in adults and children is a sign of the development of allergic diseases (bronchial asthma, serum sickness, urticaria, etc.). In the development of allergies, genetic factors play a role, which is responsible for 50% of the cases of the reaction, as well as the environment (for example, air pollution), allergens transmitted through food and air.
Malicious agents are eliminated from the body by antibodies produced by the immune system. They bind, neutralize and remove viruses, allergens, microbes, harmful substances that enter the body from the air or food, cancer cells that have died after injuries and tissue burns.
Each specific agent is opposed by a specific antibody, for example, the influenza virus is eliminated by anti-influenza antibodies, etc. Thanks to the well-functioning immune system, harmful substances are eliminated from the body: it is protected from genetically alien components.
In the removal of foreign substances, lymphoid organs and cells take part:
- spleen;
- thymus;
- The lymph nodes;
- peripheral blood lymphocytes;
- bone marrow lymphocytes.
All of them make up a single organ of the immune system. Its active groups are B- and T-lymphocytes, a system of macrophages, due to the action of which various immunological reactions are provided. The task of macrophages is to neutralize part of the allergen and absorb microorganisms, T- and B-lymphocytes completely eliminate the antigen.
Classification
In medicine, allergic reactions are distinguished depending on the time of their occurrence, the characteristics of the mechanisms of the immune system, etc. The most used is the classification according to which allergic reactions are divided into delayed or immediate types. Its basis is the time of occurrence of allergy after contact with the pathogen.
According to the reaction classification:
- immediate type- appears within 15–20 minutes;
- delayed type- develops a day or two after exposure to the allergen. The disadvantage of this division is the inability to cover the various manifestations of the disease. There are cases where the reaction occurs 6 or 18 hours after contact. Guided by this classification, it is difficult to attribute such phenomena to a particular type.
A classification is widespread, which is based on the principle of pathogenesis, that is, the features of the mechanisms of damage to cells of the immune system.
There are 4 types of allergic reactions:
- anaphylactic;
- cytotoxic;
- Arthus;
- delayed hypersensitivity.
Allergic reaction type I also called atopic, immediate type reaction, anaphylactic or reaginic. It occurs in 15–20 minutes. after the interaction of antibodies-reagins with allergens. As a result, mediators (biologically active substances) are released into the body, by which one can see the clinical picture of a type 1 reaction. These substances are serotonin, heparin, prostaglandin, histamine, leukotrienes, and so on.
Second type most often associated with the occurrence of drug allergies, which develop due to hypersensitivity to medications. The result of an allergic reaction is the combination of antibodies with modified cells, which leads to the destruction and removal of the latter.
Type III hypersensitivity(precitipine, or immunocomplex) develops as a result of the combination of immunoglobulin and antigen, which in combination leads to tissue damage and inflammation. The cause of the reaction is soluble proteins that are re-introduced into the body in large volumes. Such cases are vaccinations, transfusion of blood plasma or serum, infection of blood plasma with fungi or microbes. The development of the reaction is facilitated by the formation of proteins in the body during tumors, helminthiasis, infections and other pathological processes.
The occurrence of type 3 reactions may indicate the development of arthritis, serum sickness, visculitis, alveolitis, Arthus phenomenon, nodular periarteritis, etc.
Allergic reactions type IV, or infectious-allergic, cell-mediated, tuberculin, delayed, arise due to the interaction of T-lymphocytes and macrophages with carriers of a foreign antigen. These reactions make themselves felt during allergic contact dermatitis, rheumatoid arthritis, salmonellosis, leprosy, tuberculosis and other pathologies.
Allergies are provoked by microorganisms that cause brucellosis, tuberculosis, leprosy, salmonellosis, streptococci, pneumococci, fungi, viruses, helminths, tumor cells, altered body proteins (amyloids and collagens), haptens, etc. Clinical manifestations of reactions are different, but most often infectious -allergic, in the form of conjunctivitis or dermatitis.
Allergen types
So far, there is no single division of substances that lead to allergies. They are mainly classified according to the way of penetration into the human body and the occurrence of:
- industrial: chemicals (dyes, oils, resins, tannins);
- household (dust, mites);
- animal origin (secrets: saliva, urine, secretions of glands; wool and dander, mostly domestic animals);
- pollen (pollen of grasses and trees);
- (insect poisons);
- fungal (fungal microorganisms that enter with food or by air);
- (full or haptens, that is, released as a result of the metabolism of drugs in the body);
- food: haptens, glycoproteins and polypeptides contained in seafood, cow's milk and other products.
Stages of development of an allergic reaction
There are 3 stages:
- immunological: its duration begins from the moment the allergen enters and ends with the combination of antibodies with a re-emerged or persistent allergen in the body;
- pathochemical: it implies the formation in the body of mediators - biologically active substances resulting from the combination of antibodies with allergens or sensitized lymphocytes;
- pathophysiological: differs in that the resulting mediators manifest themselves by exerting a pathogenic effect on the human body as a whole, especially on cells and organs.
Classification according to ICD 10
The database of the international classifier of diseases, which includes allergic reactions, is a system created by physicians for ease of use and storage of data on various diseases.
Alphanumeric code is a transformation of the verbal formulation of the diagnosis. In the ICD, an allergic reaction is listed under the number 10. The code consists of a Latin letter and three numbers, which makes it possible to encode 100 categories in each group.
Under number 10 in the code, the following pathologies are classified depending on the symptoms of the course of the disease:
- rhinitis (J30);
- contact dermatitis (L23);
- urticaria (L50);
- allergy, unspecified (T78).
Rhinitis, which has an allergic nature, is divided into several subspecies:
- vasomotor (J30.2), resulting from autonomic neurosis;
- seasonal (J30.2) due to pollen allergy;
- pollinosis (J30.2), manifested during the flowering of plants;
- (J30.3) resulting from the action of chemicals or insect bites;
- unspecified nature (J30.4), diagnosed in the absence of a final response to the samples.
The ICD 10 classification contains the T78 group, which contains pathologies that occur during the action of certain allergens.
These include diseases that are manifested by allergic reactions:
- anaphylactic shock;
- other painful manifestations;
- unspecified anaphylactic shock, when it is impossible to determine which allergen caused the immune system reaction;
- angioedema (Quincke's edema);
- unspecified allergy, the cause of which - the allergen - remains unknown after testing;
- conditions accompanied by allergic reactions with an unspecified cause;
- other unspecified allergic pathologies.
Kinds
Anaphylactic shock belongs to the fast-type allergic reactions, accompanied by a severe course. Its symptoms:
- lowering blood pressure;
- low body temperature;
- convulsions;
- violation of the respiratory rhythm;
- disorder of the heart;
- loss of consciousness.
Anaphylactic shock occurs when a secondary allergen enters, especially when drugs are administered or when they are applied externally: antibiotics, sulfonamides, analgin, novocaine, aspirin, iodine, butadiene, amidopyrine, etc. This acute reaction is life-threatening, therefore, requires emergency medical care. Prior to this, the patient needs to provide an influx of fresh air, a horizontal position and warmth.
To prevent anaphylactic shock, you must not self-medicate, since uncontrolled medication provokes more severe allergic reactions. The patient should make a list of drugs and products that cause reactions, and report them to the doctor at the doctor's appointment.
Bronchial asthma
The most common type of allergy is bronchial asthma. It affects people living in a certain area: with high humidity or industrial pollution. A typical sign of pathology is asthma attacks, accompanied by scratching and scratching in the throat, coughing, sneezing and difficult exhalation.
Asthma is caused by airborne allergens: from and to industrial substances; food allergens that provoke diarrhea, colic, abdominal pain.
The cause of the disease is also sensitivity to fungi, microbes or viruses. Its beginning is signaled by a cold, which gradually develops into bronchitis, which, in turn, causes difficulty in breathing. The cause of the pathology is also infectious foci: caries, sinusitis, otitis media.
The process of formation of an allergic reaction is complex: microorganisms that act on a person for a long time do not clearly worsen health, but imperceptibly form an allergic disease, including a pre-asthma condition.
Prevention of pathology includes the adoption of not only individual measures, but also public ones. The first are hardening, carried out systematically, smoking cessation, sports, regular home hygiene (ventilation, wet cleaning, etc.). Public measures include an increase in the number of green spaces, including park areas, the separation of industrial and residential urban areas.
If the pre-asthma condition has made itself felt, it is necessary to immediately begin treatment and in no case self-medicate.
After bronchial asthma, the most common is urticaria - a rash on any part of the body, reminiscent of the effects of contact with nettles in the form of itchy small blisters. Such manifestations are accompanied by fever up to 39 degrees and general malaise.
The duration of the disease is from several hours to several days. An allergic reaction damages blood vessels, increases capillary permeability, as a result of which blisters appear due to edema.
The burning and itching are so severe that patients can scratch the skin until it bleeds, causing an infection. The formation of blisters is caused by exposure to the body of heat and cold (respectively, heat and cold urticaria are distinguished), physical objects (clothes, etc., from which physical urticaria occurs), as well as a violation of the functioning of the gastrointestinal tract (enzymopathic urticaria).
In combination with urticaria, angioedema, or Quincke's edema, occurs - an allergic reaction of a rapid type, which is characterized by localization in the head and neck, in particular on the face, sudden onset and rapid development.
Edema is a thickening of the skin; its sizes vary from a pea to an apple; while itching is absent. The illness lasts 1 hour - several days. It may reappear in the same place.
Quincke's edema also occurs in the stomach, esophagus, pancreas or liver, accompanied by discharge, pain in the spoon. The most dangerous places for the manifestation of angioedema are the brain, larynx, root of the tongue. The patient has difficulty breathing, and the skin becomes cyanotic. Perhaps a gradual increase in symptoms.
Dermatitis
One type of allergic reaction is dermatitis - a pathology that is similar to eczema and occurs when the skin comes into contact with substances that provoke a delayed-type allergy.
Strong allergens are:
- dinitrochlorobenzene;
- synthetic polymers;
- formaldehyde resins;
- turpentine;
- PVC and epoxy resins;
- ursols;
- chromium;
- formalin;
- nickel.
All these substances are common both in production and in everyday life. More often they cause allergic reactions in representatives of professions involving contact with chemicals. Prevention includes the organization of cleanliness and order in production, the use of advanced technologies that minimize the harm of chemicals in contact with humans, hygiene, and so on.
Allergic reactions in children
In children, allergic reactions occur for the same reasons and with the same characteristic signs as in adults. From an early age, symptoms of food allergies are detected - they occur from the first months of life.
Hypersensitivity observed to products of animal origin(crustaceans), vegetable origin (nuts of all kinds, wheat, peanuts, soybeans, citrus fruits, strawberries, strawberries), as well as honey, chocolate, cocoa, caviar, cereals, etc.
At an early age, it affects the formation of more severe reactions at an older age. Since food proteins are potential allergens, foods containing them, especially cow's milk, are most likely to cause a reaction.
Allergic reactions in children that have arisen in food, are diverse, since different organs and systems can be involved in the pathological process. The clinical manifestation that occurs most often is atopic dermatitis - a skin rash on the cheeks, accompanied by severe itching. Symptoms appear for 2-3 months. The rash spreads to the trunk, elbows and knees.
Acute urticaria is also characteristic - itchy blisters of various shapes and sizes. Along with it, angioedema is manifested, localized on the lips, eyelids and ears. There are also lesions of the digestive organs, accompanied by diarrhea, nausea, vomiting, and abdominal pain. The respiratory system in a child is not affected in isolation, but in combination with the pathology of the gastrointestinal tract and is less common in the form of allergic rhinitis and bronchial asthma. The cause of the reaction is hypersensitivity to egg or fish allergens.
Thus, allergic reactions in adults and children are diverse. Based on this, physicians offer many classifications based on the reaction time, the principle of pathogenesis, etc. The most common diseases of an allergic nature are anaphylactic shock, urticaria, dermatitis or bronchial asthma.
Delayed-type allergic reactions are reactions that occur only a few hours or even days after exposure to the allergen. The most characteristic example of this group of allergic manifestations turned out to be tuberculin reactions, therefore, sometimes the entire group of delayed-type allergic reactions is called tuberculin-type reactions. Delayed allergies include bacterial allergies, contact type allergic reactions (contact dermatitis), autoallergic diseases, transplant rejection reactions, etc.
bacterial allergy
Delayed bacterial allergy can occur with preventive vaccinations and with some infectious diseases (tuberculosis, diphtheria, brucellosis, coccal, viral and fungal infections). If an allergen is applied to a sensitized or infected animal on the scarified skin (or administered intradermally), then the response begins no earlier than 6 hours later and reaches a maximum after 24-48 hours. At the site of contact with the allergen, hyperemia, induration and sometimes skin necrosis occur. Necrosis appears as a result of the death of a significant number of histiocytes and parenchymal cells. With the injection of small doses of the allergen, necrosis is absent. Histologically, as with all types of delayed-type allergic reactions, bacterial allergy is characterized by mononuclear infiltration (monocytes and large, medium and small lymphocytes). In clinical practice, skin delayed reactions of Pirquet, Mantoux, Burne, and others are used to determine the degree of sensitization of the body in a particular infection.
Delayed allergic reactions can also be obtained in other organs, for example, in the cornea, bronchi. When tuberculin aerosol is inhaled in BCG-sensitized guinea pigs, severe shortness of breath occurs, histologically, infiltration of the lung tissue by polymorphonuclear and mononuclear cells, which are located around the bronchioles, is observed. If tuberculous bacteria are introduced into the lungs of sensitized animals, a strong cellular reaction occurs with caseous decay and the formation of cavities (Koch's phenomenon).
contact allergy
Contact allergies (contact dermatitis) are caused by a variety of low molecular weight substances (dinitrochlorobenzene, picrylic acid, phenols, etc.), industrial chemicals, paints (ursol is the active substance of poison ivy), detergents, metals (platinum compounds), cosmetics, etc. Molecular the weight of most of these substances does not exceed 1000, i.e. they are haptens (incomplete antigens). In the skin, they combine with proteins, probably through a covalent bond with free amino and sulfhydryl groups of proteins, and acquire allergenic properties. The ability to combine with protein is directly proportional to the allergenic activity of these substances.
The local reaction of the sensitized organism to the contact allergen also appears after about 6 hours and reaches a maximum after 24-48 hours. The reaction develops superficially, mononuclear infiltration of the epidermis occurs and the formation of small cavities in the epidermis containing mononuclear cells. The cells of the epidermis degenerate, the structure of the basement membrane is disturbed and the epidermis detaches. Changes in the deep layers of the skin are much weaker than with other types of local reactions of delayed type a.
Autoallergy
Delayed-type allergic reactions also include a large group of reactions and diseases resulting from damage to cells and tissues by so-called autoallergens, i.e., allergens that have arisen in the body itself. The nature and mechanism of formation of autoallergens are different.
Some autoallergens are found in the body in finished form (endoallergens). Some tissues of the body (for example, tissues of the lens, thyroid gland, testicles, gray matter of the brain) in the process of phylogenesis turned out to be isolated from the apparatus of immunogenesis, due to which they are perceived by immunocompetent cells as foreign. Their antigenic structure is an irritant for the apparatus of immunogenesis and antibodies are produced against them.
Of great importance are secondary or acquired autoallergens, which are formed in the body from its own proteins as a result of the action of any damaging environmental factors on them (for example, cold, high temperature, ionizing radiation). These autoallergens and antibodies formed against them play a certain role in the pathogenesis of radiation, burn disease, etc.
When exposed to the own antigenic components of the human or animal body with bacterial allergens, infectious autoallergens are formed. In this case, complex allergens may arise that retain the antigenic properties of the constituent parts of the complex (human or animal tissues + bacteria) and intermediate allergens with completely new antigenic properties. The formation of intermediate allergens is very clearly seen in some neuroviral infections. The relationship of viruses with the cells they infect is characterized by the fact that the nucleoproteins of the virus in the process of its reproduction extremely closely interact with the nucleoproteins of the cell. The virus at a certain stage of its reproduction, as it were, fuses with the cell. This creates especially favorable conditions for the formation of large-molecular antigenic substances - products of the interaction of the virus and the cell, which are intermediate allergens (according to A.D. Ado).
The mechanisms of occurrence of autoallergic diseases are quite complex. Some diseases develop, apparently, as a result of a violation of the physiological vascular tissue barrier and the release of natural or primary autoallergens from tissues, to which there is no immunological tolerance in the body. These diseases include allergic thyroiditis, orchitis, sympathetic ophthalmia, etc. But for the most part, autoallergic diseases are caused by antigens of the body's own tissues, altered under the influence of physical, chemical, bacterial and other agents (acquired or secondary autoallergens). For example, autoantibodies against one's own tissues (antibodies such as cytotoxins) appear in the blood and tissue fluids of animals and humans during radiation sickness. In this case, apparently, the products of water ionization (active radicals) and other products of tissue breakdown lead to protein denaturation, turning them into self-allergens. Against the latter, antibodies are produced.
Autoallergic lesions are also known, which develop due to the commonality of antigenic determinants of the tissue's own components with those of exoallergens. Common antigenic determinants have been found in the heart muscle and some strains of streptococcus, lung tissues and some saprophytic bacteria living in the bronchi, etc. The immunological reaction caused by the exoallergen, due to its cross antigenic properties, can be directed against its own tissues. In this way, some cases of allergic myocarditis, an infectious form of bronchial asthma, etc. may occur. systemic lupus erythematosus, acquired hemolytic anemia, etc.
A special group of lesions, close in mechanism to autoallergic reactions, are experimental diseases caused by cytotoxic sera. A typical example of such lesions is nephrotoxic glomerulonephritis. Nephrotoxic serum can be obtained, for example, after repeated subcutaneous administration of an emulsion of crushed rabbit kidney to guinea pigs. If guinea pig serum containing a sufficient amount of antirenal cytotoxins is injected into a healthy rabbit, they develop glomerulonephritis (proteinuria and death of animals from uremia). Depending on the dose of antiserum administered, glomerulonephritis appears soon (24-48 hours) after serum administration or 5-11 days later. Using the method of fluorescent antibodies, it was established that, according to these terms, foreign gamma globulin appears in the glomeruli of the kidneys in the early stages, and after 5-7 days, autologous gamma globulin. The reaction of such antibodies with a foreign protein fixed in the kidneys is the cause of late glomerulonephritis.
Homograft rejection reaction
As is known, true engraftment of a transplanted tissue or organ is possible only with autotransplantation or homotransplantation in identical twins. In all other cases, the transplanted tissue or organ is rejected. Transplant rejection is the result of a delayed-type allergic reaction. As early as 7-10 days after tissue transplantation, and especially abruptly after transplant rejection, a typical delayed reaction to intradermal administration of donor tissue antigens can be obtained. In the development of the body's response to the transplant, lymphoid cells are of decisive importance. When tissue is transplanted into an organ with a poorly developed drainage lymphatic system (anterior chamber of the eye, brain), the process of destruction of the transplanted tissue slows down. Lymphocytosis is an early sign of incipient rejection, and the imposition of a fistula of the thoracic lymphatic duct in the recipient, which allows to some extent to reduce the number of lymphocytes in the body, prolongs the life of the homotransplant.
The mechanism of graft rejection can be represented as follows: as a result of transplantation of a foreign tissue, the recipient's lymphocytes become sensitized (become carriers of a transfer factor or cellular antibodies). These immune lymphocytes then migrate to the graft, where they are destroyed and release the antibody, which causes the destruction of the transplanted tissue. Upon contact of immune lymphocytes with graft cells, intracellular proteases are also released, which cause further metabolic disorder in the graft. The introduction of tissue protease inhibitors (for example, s-aminocaproic acid) to the recipient promotes engraftment of transplanted tissues. Suppression of the function of lymphocytes by physical (ionizing irradiation of the lymph nodes) or chemical (special immunosuppressive agents) effects also prolongs the life of the transplanted tissues or organs.
Mechanisms of delayed-type allergic reactions
All allergic reactions of the delayed type develop according to the general plan: in the initial stage of sensitization (shortly after the introduction of the allergen into the body), a large number of pyroninophilic cells appear in the regional lymph nodes, from which, apparently, immune (sensitized) lymphocytes are formed. The latter become carriers of antibodies (or the so-called "transfer factor"), enter the blood, partly they circulate in the blood, partly settle in the endothelium of blood capillaries, skin, mucous membranes and other tissues. Upon subsequent contact with the allergen, they cause the formation of an allergen-antibody immune complex and subsequent tissue damage.
The nature of the antibodies involved in the mechanisms of delayed allergy is not fully understood. It is known that the passive transfer of a delayed allergy to another animal is possible only with the help of cell suspensions. With blood serum, such a transfer is practically impossible; the addition of at least a small amount of cellular elements is required. Among the cells involved in delayed allergy, cells of the lymphoid series seem to be of particular importance. So, with the help of lymph node cells, blood lymphocytes, it is possible to passively endure hypersensitivity to tuberculin, picryl chloride and other allergens. Contact sensitivity can be transmitted passively with the cells of the spleen, thymus, thoracic lymphatic duct. In people with various forms of insufficiency of the lymphoid apparatus (for example, lymphogranulomatosis), delayed-type allergic reactions do not develop. In the experiment, irradiation of animals with X-rays before the onset of lymphopenia causes suppression of tuberculin allergy, contact dermatitis, homograft rejection, and other delayed-type allergic reactions. The administration of cortisone to animals at doses that reduce the content of lymphocytes, as well as the removal of regional lymph nodes, suppresses the development of delayed allergies. Thus, it is lymphocytes that are the main carriers and carriers of antibodies in delayed allergies. The presence of such antibodies on lymphocytes is also evidenced by the fact that lymphocytes with delayed allergies are able to fix the allergen on themselves. As a result of the interaction of sensitized cells with the allergen, biologically active substances are released, which can be considered as delayed-type allergy mediators. The most important of them are the following:
1.
Macrophage migration inhibitory factor
. It is a protein with a molecular weight of about 4000-6000. It inhibits the movement of macrophages in tissue culture. When administered intradermally to a healthy animal (guinea pig), it causes a delayed-type allergic reaction. Found in humans and animals.
2.
lymphotoxin
- a protein with a molecular weight of 70,000-90,000. Causes the destruction or inhibition of growth and proliferation of lymphocytes. Suppresses DNA synthesis. Found in humans and animals
3.
Blastogenic factor
- protein. Causes the transformation of lymphocytes into lymphoblasts; promotes the absorption of thymidine by lymphocytes and activates the division of lymphocytes. Found in humans and animals.
4. In guinea pigs, mice, and rats, other factors have also been found as mediators of delayed-type allergic reactions that have not yet been isolated in humans, for example,skin reactivity factor
causing inflammation of the skinchemotactic factor
and some others that are also proteins with different molecular weights.
Circulating antibodies can appear in some cases with delayed-type allergic reactions in body fluids. They can be detected using an agar precipitation test or a complement fixation test. However, these antibodies are not responsible for the essence of delayed-type sensitization and do not participate in the process of damage and destruction of tissues of a sensitized organism during autoallergic processes, bacterial allergies, rheumatism, etc. According to their significance for the body, they can be classified as witness antibodies (but classification of antibodies A. D. Ado).
Effect of thymus on allergic reactions
The thymus influences the formation of delayed allergies. Early thymectomy in animals causes a decrease in the number of circulating lymphocytes, involution of lymphoid tissue and suppresses the development of delayed allergy to proteins, tuberculin, disrupts the development of transplantation immunity, but has little effect on contact allergy to dinitrochlorobenzene. Insufficiency of the thymus function affects primarily the state of the paracortical layer of the lymph nodes, i.e., the layer where pyroninophilic cells form from small lymphocytes during delayed allergy. With early thymectomy, it is from this area that lymphocytes begin to disappear, which leads to atrophy of the lymphoid tissue.
The effect of thymectomy on delayed allergy appears only if the thymus is removed early in the life of the animal. Thymectomy performed in animals a few days after birth or in adult animals does not affect the engraftment of the homograft.
Allergic reactions of the immediate type are also under the control of the thymus, but the influence of the thymus on these reactions is less pronounced. Early thymectomy does not affect the formation of plasma cells and the synthesis of gamma globulin. Thymectomy is accompanied by inhibition of circulating antibodies not to all, but only to some types of antigens.
Life without allergies
Manifestations of allergies, both immediate and delayed reactions - this is the topic of our conversation on the site of allergy sufferers allergozona.ru.
In response to the penetration of an allergenic substance into the body, a specific process is launched that has 3 stages currents:
1. The production of antibodies or the formation of lymphocytes aimed at interacting with the allergen. ( Immunological stage.)
2. With subsequent contact of the body with a specific allergen, biochemical reactions occur with the participation of histamine and other mediators that damage cells. ( pathochemical stage.)
3. The manifestation of symptoms of the clinical picture. ( Pathophysiological stage.)
All manifestations of allergies are divided into:
They tend to develop rapidly. An allergic reaction of an immediate type manifests itself after a short time interval (from half an hour to several hours) after repeated contact with the allergen. Among them are:
This is an extremely dangerous acute condition. Most often it develops against the background of intravenous or intramuscular administration of drugs.
Less common with other routes of penetration of the allergen into the body. As a result of hemodynamic disturbances, the development of circulatory failure and oxygen starvation in the organs and tissues of the body occurs.
Clinical symptoms are caused by a contraction of smooth muscles, an increase in the permeability of the walls of the vascular bed, disturbances in the endocrine system and blood clotting parameters.
Cardiovascular insufficiency develops. The pressure in the bloodstream drops sharply. On the part of the bronchopulmonary system, spasm, hypersecretion of mucus and pronounced edema of the respiratory tract are observed. Sharply growing in the larynx, it can lead to the death of the patient as a result of asphyxia.
Due to the release of their cells of an excess amount of heparin, complications develop due to a decrease in blood clotting, and with the development of DIC, there is a threat of numerous thromboses.
It is the basis of the following changes in the blood formula, as a result of drug allergies:
- decrease in the number of leukocytes and platelets of immune origin;
- development of hemolytic anemia.
The main pathogenetic mechanism of such conditions as serum sickness and allergic vasculitis.
It appears after a certain time. From the moment of contact with the allergen, it takes up to two days before the onset of signs of allergy.
- Type four or delayed hypersensitivity.
This type causes contact dermatitis, an allergic component in bronchial asthma.
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3 thoughts on “Types of allergic reactions (immediate and delayed type)”
I learned a lot about the types of allergic reactions, for general education in my case it is very necessary, since I am a recently manifested allergy sufferer.
Thank you very much for the site. I found answers to all my questions. Not so long ago I encountered an allergy, BA did not know much, the doctors are laconic, everything here is intelligible and understandable. Thank you!
I am familiar with this situation with different types of allergic reactions. Let's discuss in chat.
There are 2 types of allergic reactions: immediate and delayed. Immediate type reactions develop within a few minutes after the repeated intake of the allergen. It is believed that in this case the allergen attaches to the antibody fixed on the surface of the endothelium of blood capillaries, mast, nerve and smooth muscle cells.
According to A. D. Ado, the mechanism of development in this type of allergy goes through 3 successive phases:
- immunological, in which the allergen is combined with the antibody in liquid tissue media;
- cytochemical changes with cell damage under the influence of the antigen-antibody complex and the violation of enzyme systems on the membrane and inside the cells;
- pathophysiological, when biologically active substances formed in the second phase lead to damage to organs and tissues, violating their specific functions.
Immediate allergic reactions include anaphylaxis and anaphylactoid reactions, serum sickness, allergic bronchial asthma, hay fever, urticaria, Quincke's edema, hemorrhagic phenomena (Arthus, Overy, Schwartzman).
Delayed-type reactions occur several hours or even days after exposure to the allergen. More often they are caused by the reaction of bacterial allergens with antibodies fixed on the cells. In the transfer of the sensitizing factor to other cells, great importance is attached to blood lymphocytes. The participation of biologically active substances in the mechanism of delayed-type reactions is not clearly expressed.
Delayed-type allergic reactions include bacterial allergies, contact dermatitis, autoallergic reactions (encephalitis, thyroiditis, orchitis, myocarditis, etc.), transplant rejection reactions, reactions with purified protein.
Allergic reactions of immediate and delayed type
Allergic reaction of immediate type
According to the time of occurrence, allergic reactions of immediate and delayed types are distinguished. Immediate type reactions include skin and allergic systemic reactions that develop 15 to 20 minutes after contact with an allergen (specific). In this situation, a person has a number of characteristic symptoms - skin rashes, bronchospasm and indigestion. An example of this type of allergic reaction is hay fever, Quincke's edema, bronchial asthma (BA), urticaria and a life-threatening condition - anaphylactic shock.
Delayed allergic reaction
Allergic reactions of a delayed type can develop over many hours, often days. This type of reaction includes hypersensitivity to bacterial infectious agents in tuberculosis, glanders, brucellosis, tularemia and some other infectious diseases, as well as occupational contact dermatitis in persons employed in production in the chemical and pharmacological industries.
The mechanisms of development of allergies and normal immune responses have such clear similarities that at present, allergic reactions of immediate and delayed types are often referred to as T- and B-dependent.
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Allergic reactions of the immediate type appear directly upon contact with the allergen.
Allergy can be expressed in the form of various signs. Symptoms can appear immediately upon exposure to the allergen, or after some time. Damage to the body directly under the influence of an irritant is an allergic reaction of an immediate type. They are characterized by a high rate of occurrence and a strong impact on various systems.
Why the reaction can come instantly?
Allergy of the immediate type occurs at the time of exposure to the irritant. It can be any substance that contributes to negative changes in the body in hypersensitive people. They may not pose a danger to an ordinary person, they may not be toxins and harmful elements. But the immunity of an allergic person perceives them as foreign bodies and includes a fight against an irritant.
Most often, symptoms appear when the body reacts to:
medicinal preparations;
plant pollen;
food irritants (nuts, honey, eggs, milk, chocolate, seafood);
insect bites and poison released at the same time;
wool and proteins of animals;
synthetic fabrics;
chemicals in household products.
With delayed-type reactions, the allergen can accumulate in the body for a long time, after which a surge occurs. Allergic reactions of immediate type differ in etiology. They occur when the body is first irritated by damaging substances.
How does the reaction develop?
Human immunity, upon contact with the allergen, begins to actively produce antibodies, which leads to an allergic reaction.
To say that allergy symptoms occur at the time of the first entry of the irritant into the body is not entirely true. Indeed, by the time negative changes occur, the immune system is already familiar with the allergen.
At the first exposure, the process of sensitization begins. During it, the protective system releases the substance that has entered the body and remembers it as dangerous. Antibodies begin to be produced in the blood, which gradually eliminate the allergen.
With repeated penetration, immediate reactions begin. The immune defense, which has already remembered the irritant, begins to produce antibodies in full force, which leads to an allergy.
From the moment the irritant enters the body until the first signs of damage appear, about 20 minutes pass. The reaction itself goes through three stages of development. On each of them, mediators of an allergic reaction function differently.
During the immunological reaction, the antigen of the stimulus and the antibody come into contact. Antibodies are defined in the blood as immunoglobulins E. Their localization is mast cells. Granules of the cytoplasm of the latter produce allergy mediators. During this process, the creation of histamine, serotonin, bradykinin, as well as other substances.
At the next stage, a pathochemical type reaction occurs. Allergy mediators are released from mast cell granules.
In a pathophysical reaction, mediators act on the cells of body tissues, contributing to an acute inflammatory response.
The main goal of the whole process is to create a reaction in the body. In this case, the mediators of the allergic reaction influence the occurrence of symptoms.
Types of allergic reactions
Immediate type reactions include several types of characteristic symptoms. They are caused by various signs depending on the nature of the lesion of a particular organ or body system. These include:
Hives
When acute urticaria appears, the skin is damaged. As a result of exposure to the allergen on the body, an itchy rash forms on the surface of the skin. Most often it is represented by blisters.
Small formations are expressed in a regular round shape. When confluent, they can form large blisters that are oblong in shape.
Localization of urticaria is noted mainly on the arms, legs, body. Sometimes rashes appear in the mouth, on the surface of the mucous membrane of the larynx. A rash is a common occurrence when exposed to an allergen of a contact nature (insect bite).
From the moment the rash appears to its complete disappearance, it can take 3-4 hours. If the urticaria is characterized by a severe form, then the rash can persist for several days. In this case, a person may feel weakness, a rise in body temperature.
Urticaria is treated with topical ointments, creams and gels.
Angioedema
Angioedema, known to everyone as Quincke's edema, affects the subcutaneous fat and mucous membranes. As a result of its occurrence, a sharp swelling of the tissues is formed, resembling a giant urticaria.
Quincke's edema may occur:
-
in the intestines;
in the urinary system;
in the brain.
Especially dangerous is the swelling of the larynx. It can also be accompanied by swelling of the lips, cheeks, eyelids. For humans, angioedema of the larynx can be fatal. This is due to the fact that when the defeat is disturbed by the process of breathing. Therefore, complete asphyxia may occur.
The appearance of angioedema is noted with a drug allergy or in the course of a reaction to the penetration of the venom of a bee into the body, a wasp when bitten. Treatment of the reaction should be urgent. Therefore, the patient must be given emergency care.
Atopic bronchial asthma
With atopic bronchial asthma, an instant spasm of the bronchi occurs. It becomes difficult for the person to breathe. There are also symptoms such as:
Often the reaction occurs when you are allergic to dust, animal hair, plant pollen. The risk group includes people who suffer from bronchial asthma or have a genetic predisposition to the disease.
allergic rhinitis
The defeat of the body occurs under the influence of irritants penetrating through the respiratory tract. Suddenly, a person may have:
itching in the nasal passages;
mucous discharge from the nose.
Rhinitis also affects the eyes. A person may experience itching of the mucous membranes, the flow of tears from the eyes, as well as a strong reaction to light. With the addition of bronchospasm, serious complications appear.
Anaphylactic shock
Anaphylactic shock can be fatal
The most serious allergic reaction of the immediate type, anaphylactic shock, manifests itself very quickly in a person. It is characterized by obvious symptoms, as well as the speed of the flow. In some cases, if the patient is not helped, anaphylactic shock leads to death.
The reaction develops to some medicinal stimuli. One of the common allergens is penicillin, novocaine. Food allergies can also be a source. Most often it occurs in infants. In this case, a strong allergen (eggs, citrus fruits, chocolate) can cause a severe reaction in the child's body.
Signs of damage may appear within half an hour. If an allergic reaction of an immediate type, anaphylactic shock, occurs 5-10 minutes after the irritant enters the body, then it is much more difficult to bring the patient to his senses. At the first stage of the lesion, the appearance of:
weakening of the body;
tinnitus;
numbness of hands, feet;
tingling in the chest, face, feet, palms.
The skin of a person acquires a pale shade. Also often there is a cold sweat. During this period, there is a sharp decrease in blood pressure, increased heart rate, tingling behind the chest area.
Anaphylactic shock can be complicated if it is accompanied by a rash, rhinorrhea, lacrimation, bronchospasm, angioedema. Therefore, treatment consists in providing emergency care to the patient.
hay fever
Hay fever, also called hay fever, occurs when the body reacts to pollen from flowering plants and trees. A person may experience signs of:
conjunctivitis;
bronchial asthma.
When it occurs, there is frequent sneezing, discharge from the nose of a mucous consistency, congestion of the nasal passages, itching of the nose and eyelids, the flow of tears, pain in the eyes, itching on the surface of the skin.
Arthus-Sakharov phenomenon
The phenomenon is also known as the gluteal reaction. The name is due to the fact that signs of a reaction occur in the injection area when:
The lesion is characterized by a capsule in the area of injection, bulge of vessels in the area of necrosis. Patients may feel pain and itching at the site of the lesion. Sometimes seals appear.
Measures in the event of an immediate reaction
If there are warning signs that relate to the above reactions, then it is important to protect yourself from contact with the irritant. A person definitely needs to take antihistamines: Suprastin, Diazolin, Diphenhydramine, Claritin, Tavegil, Erius. They slow down the reaction, and also speed up the process of removing the allergen from the body. Only after the elimination of the primary signs, symptomatic treatment can be started.
The patient must be at rest. You can use improvised means (cold compress with ice) to soothe the affected area on the skin.
With strong reactions, injections of glucocorticoids are indicated: Prednisolone, Hydrocortisone. It is also mandatory to call an ambulance.
Doctors must urgently arrive on call to a patient who has experienced anaphylactic shock. They will administer hormonal drugs to the patient, normalize the pressure. When breathing stops and blood circulation is disturbed, cardiopulmonary resuscitation is performed. Tracheal intubation and oxygen administration may also be performed.
Immediate type reactions pose a serious danger to a person because of their unpredictability. Therefore, it is important to urgently seek medical help in order to prevent complications.
