I. Classification of allergic reactions
III. The role of biologically active substances in allergic reactions
Iv. Delayed type allergy
V. Cellular changes in allergic reactions
Vi. Immunological tolerance
VII. Allergic syndromes in the experiment
Viii. Large allergic syndromes in the clinic
Ix. Allergic Tests
X. Autoallergic diseases
Xi. General principles of treatment of allergic diseases
Allergy (from the Greek. Alios - another and ergon - action) - altered sensitivity or reactivity of the organism in relation to a particular substance.
Along with the so-called purely allergic diseases (hay fever, urticaria, some types of asthma, etc.), there are diseases, mainly infectious, where the allergic component overlaps (allergic phases according to A. A. Koltypin) and infectious-allergic diseases (collagenosis and etc.). Substances that can cause allergies in humans and animals are called allergens. Currently, there are many diseases based on allergic reactions (bronchial asthma, urticaria, drug allergies, rheumatism, contact dermatitis, the reaction of "graft rejection", etc.). Various quantitative and qualitative changes in the state of allergy are designated by special terms. Those forms of allergic reactions that develop particularly rapidly and are distinguished by a high intensity of the damaging effect on the tissue are called hyperergy. Hyperargic inflammation is called, for example, Arthus phenomenon (see). Reducing the allergic reactivity of an organism is sometimes called hypergy. The complete lack of reactivity of the organism, for example, to tuberculin, is called anergy. Positive anergy is called a decrease in the body's reactivity to the causative agent of an infectious disease on the background of recovery, for example, in case of tuberculosis. Negative anergy refers to the lack of reactivity of the patient's organism to the pathogen against the background of severe intoxication and depletion of the body from infection (tuberculosis, pneumonia). Paraallergy refers to the state of allergy caused by one allergen to another (for example, a positive skin reaction to tuberculin in a child after a smallpox vaccination). Metallergy refers to the resumption of a specific allergic reaction after exposure to a nonspecific irritant (for example, the resumption of a tuberculin reaction in a patient with tuberculosis after administering a typhoid vaccine).Go
Human allergy can occur in relation to many groups of allergens (pollen, food, dust, etc.). So, with pollinosis (see hay fever), hypersensitivity to pollen of many species is often observed. Allergens of meadow grass pollen are proteins with a mol. weighing less than 10,000, strongly associated with the pigment - carbohydrate complex. One of the causes of paraallergy in pollinosis is the presence of many species of common antigens in plant pollen. The polyvalence of allergic reactions is also explained by the hereditary constitutional predisposition of some individuals to allergic diseases, i.e. the presence of the so-called allergic constitution, or allergic diathesis. Predisposition to allergic bronchial asthma, urticaria and other allergic diseases is inherited as a recessive trait, defined by several pairs of alleles (see Hereditary diseases). Allergic diathesis is caused, firstly, by a sharp increase in the permeability of blood capillaries and in general histohematic barriers, in connection with which allergens easily penetrate through the respiratory organs, digestive tract and other pathways into the blood and tissues of the patient; secondly, by the fact that proteins of the patient’s blood and tissues easily attach various chemicals (drugs, antibiotics, etc.) with the formation in the body of complex compounds with antigenic properties; Finally, in allergic diathesis, there is a high reactivity of the apparatus that produces antibodies: the “immunologically competent” cells of the patient are capable of producing specific antibodies against various allergens in large quantities. All these features, taken together, create allergic diathesis in a patient [exudative-catarrhal, according to Czerny (A. Czerny)] predisposition to various allergic diseases (bronchial asthma, urticaria, allergic rhinitis, etc.), often combined with the same the patient.
The clinical picture and many aspects of the pathogenesis of diseases associated with various allergic reactions are completely different, but each of them is based on the damaging effect on the tissue of an allergic reaction allergen - antibody. In 1930, Cook (K. Cooke) made an attempt to divide allergic reactions into two groups: immediate and delayed types. Immediate allergic reactions - skin blister, bronchospasm, disorder of the gastrointestinal tract, etc., are reactions of the skin, respiratory, digestive and other apparatus that occur a few minutes or hours after exposure to a specific allergen. Allergic reactions of the delayed type Cook suggested calling those that occur only many hours and even days after exposure to the allergen, for example, tuberculin reactions, skin reactions in case of allergies to poison ivy, certain types of eczema and urticaria caused by food (chocolate, milk, fish) or medicinal (potassium iodide) substances. Bacterial allergy was also classified as a delayed type of allergy.
Allergens can be a variety of substances, ranging from simple, such as iodine, bromine, to complex proteinaceous (serum allergy, pollinosis), protein-lipoid (bacterial, fungal allergy), etc. Allergens can also be complex compounds of non-protein nature. These include many polysaccharides, compounds of polysaccharides with lipids or with other substances (allergy to various types of dust, bacterial allergy). A large group of substances with allergenic properties, are various dyes, many compounds used in medicine for therapeutic purposes.
Thus, it was established that penicillin, streptomycin, chlormycetin, terramycin and other antibiotics can cause a variety of allergic reactions in the form of anaphylactic shock, serum sickness, contact dermatitis, bronchial asthma, urticaria, etc. Skin allergic reactions to penicillin are accompanied by the appearance of antibodies in the blood and can be transmitted passively from person to person. These reactions, attributable to medicinal diseases, present serious complications. Allergic reactions can be caused by various medicinal substances: acetylsalicylic acid (aspirin), zincophen (atofan), atropine, barbiturates, chloral hydrate, digitalis, iodides, morphine, quinine, pantopon, sulfonamides, insulin, etc.Go
Under experimental conditions, allergens can be obtained by artificially attaching various chemicals to proteins. Allergens that enter the body from the external environment are called “exoallergens” and are divided into the following main groups.
1. Exoallergens of non-infectious origin: a) household (house dust, etc.); b) epidermal (wool, hair and "dandruff" of animals); c) pollen (pollen of grassy and woody plants); d) medicinal (antibiotics, sulfonamides, arsenic preparations, barbiturates, etc.); e) chemicals (gasoline, benzene, chloramine, ursol, etc.); f) food, subdivided into allergens of animal (meat, fish) and vegetable (vegetables, fruits) origin.
2. Exoallergens of infectious origin: a) bacterial (pathogenic and non-pathogenic bacteria and their metabolic products); b) fungal (various types of non-pathogenic fungi) and c) viral (various types of viruses and products of their interaction with tissues).
Recently, the study of the allergenic properties of denaturation products of various tissues or products of animal tissue combination with bacterial antigens, toxins or components of a bacterial cell has been started. Such allergens are sometimes called autoallergens, although this name is inaccurate, since only a few human and animal tissues (lens, myelin of nervous tissue, thyroid tissue and testicles) are true autoallergens. Such autoallergens include heart tissue for myocardial infarction (and the allergen is both necrotic tissue itself and morphologically unchanged myocardium tissue), kidney tissue for nephrosonephritis, liver tissue for hepatitis, etc.
Endoallergens are divided into the following main groups.
I. Natural endoallergens, primary (normal lens tissue, nerve tissue, etc.).
Ii. Acquired endoallergens, secondary (pathological tissues):
1) non-infectious (burn, radiation, cold); 2) infectious: a) intermediate antigenic products (tissue damage by pathogenic microbes and viruses); b) complex antigenic products (tissue and microbe, tissue and toxin).
The existence of several types of antibodies involved in the formation of allergic reactions (present in the blood, lymph and tissue fluid in a free state and fixed on the tissues) has been established. Antibodies such as precipitinov are involved in the mechanism of only a small group of allergic reactions, which are affected by the Arthus phenomenon in a rabbit, human allergic reactions to egg white, horse epidermis, and some other antigens. Passive transmission of anaphylaxis in gilts is possible with antibodies that do not have the properties of precipitin. These non-precipitating antibodies, produced by sensitization in gilts, even in greater quantities than precipitin, are called Marrack (JR Marrack) “incomplete antibodies”. Allergic antibodies of reagin type or atopen are also found in humans. An electrophoretic analysis of proteins containing skin sensitizing antibodies showed that they are in fractions of the ү- or β2M- or β2A-globulin of human blood. Reagins are thermolabile. The specificity of skin sensitizing antibodies is relative. People who are immediately sensitive to many allergens contain skin sensitizing antibodies capable of combining with several allergens from the set to which a given person is sensitive. In addition to skin sensitizing antibodies, “blocking antibodies” have also been identified that can combine with the corresponding allergen without causing skin sensitization to the allergen with which they are connected. Blocking antibodies are monospecific and, therefore, with respect to regagins, even less valuable antibodies. They are found in the ү2- or β2A-globulin fraction of human blood. The relationship of various types of allergic antibodies can be represented as the following scheme:
The pathogenesis of immediate-type allergic reactions is based on the damaging effect of the allergen-antibody reaction on the surface of cells of a sensitized organism. This reaction develops in mast cells of loose connective tissue, on leukocytes and blood platelets, on the endothelial cells of the blood capillaries. An antibody like regagin, attached by one part to the cell, by another active group, fixes the allergen. This reaction of joining an allergen - antibody causes allergic injury (alteration) of the cell. Such an alteration of the mast cell leads to disintegration and destruction of the granules, resulting in the release of biologically active substances from the cell - histamine and others. Histamine, in turn, causes dilation of blood capillaries, contraction of smooth muscles, increased mucus secretion of the mucous membranes, and stimulation of nerve cells. For example, in bronchial asthma, a reduction in the smooth muscles of the bronchi and an increase in the secretion of the mucous membrane of the bronchi leads to a fit of asphyxiation. The ventilation of the lungs is also complicated by the hypertrophy of the mucous membrane of the small and medium bronchi. According to modern data, the reaction itself allergen - antibody (in addition to histamine) can cause the expansion of blood capillaries and an increase in their permeability. This leads to the fact that on the skin and mucous membrane of patients under the influence of an allergen blisters form easily. The blistering reaction is widely used today to determine the state of allergy in humans with respect to a particular allergen (see Allergic diagnostic test). A blistering reaction can develop on the mucous membranes of the internal organs (gastrointestinal tract, urinary tract), in the meninges and cause a second severe neurological disorder. From a morphological point of view, immediate-type allergic reactions cause damage to the vascular capillary network, the basic substance and the collagen fibers of the connective tissue. In the vascular capillary network, there is an expansion of capillaries, an increase in their permeability, exudation and emigration of neutrophils, eosinophils, basophils, lymphocytes; typical accumulation in the tissue of eosinophils. Abundant exudation with loss of fibrin and other proteins (ү-globulins, etc.) in the glomeruli of the kidneys characterizes the picture of allergic glomerulonephritis. The presence of soluble and precipitated complexes of allergen-antibody is shown by fluorescent analysis of proteins found in areas of immediate-type allergic inflammations (glomerulonephritis, lymphadenitis, neuritis, and many others). It is assumed that these complexes in some cases (the Arthus phenomenon, etc.) are formed in the blood or other liquid tissue media and subsequently have a secondary effect on the blood capillaries and cells of the affected tissue. Great importance to these complexes is attached to the pathogenesis of autoallergic lesions of various organs (autoallergic gastritis, nephritis, thyroiditis, orchitis, etc.).
In loose connective tissue and lymph nodes, immediate-type allergic reactions are accompanied by characteristic changes in the basic substance and connective tissue fibers. The essence of such a “disorganization” consists in the “mucoid” swelling of the main substance and fibrous structures, which later turns into “fibrinoid” swelling and “fibrinoid” necrosis. When mucoid swelling falls basophilic granular protein mass (blood globulins and immune complexes trapped in tissue from the blood). In addition, the basis of mucoid swelling is the change in the properties of mucopolysaccharides and glycoproteins of the main substance and collagen fibers, which increases the hydrophilicity of the connective tissue (A. I. Strukov). Fibrinoid swelling consists in the deposition of blood fibrin on the surface of collagen fibers and between them, the products of the connection of fibrin with the sulfonic polysaccharide of connective tissue and, possibly, the products of DNA breakdown. In the future, under the influence of the enzyme collagenase, collagen fibers are destroyed, further disorganization of the connective tissue and its necrosis (“fibrinoid”). These changes are most striking when exposed to protein allergens on sensitized skin tissue (see Arthus phenomenon), blood vessels, kidneys, and other organs. In case of some allergic reactions, following the described changes in the connective tissue, there are proliferation processes of histiomonocytic cells with the formation of granulomas, and further sclerotic processes (see Collagenoses).
Allergic reactions of the delayed type, depending on the type of allergens causing them, can be divided into five main groups [Waksman (W. Waksman)]: 1) allergic reactions of the tuberculin type; 2) allergic reactions of the contact type (contact dermatitis); 3) experimental autoallergic (encephalomyelitis, thyroiditis, orchitis, etc.) reactions; 4) allergic reactions to purified proteins; 5) allergic reactions "transplant rejection". These groups have both common and distinctive features. In a comparatively histological study of the phenomenon of Arthus and tuberculin reactions, Jella distinguishes three main pathogenetic components: 1) “perivascular islet response” - perivascular lymphohisto-monocytic infiltration of the connective tissue; 2) “vascular-necrotic reaction” - non-specific necrosis of the connective tissue and partly parenchymal skin elements, in many cases accompanied by edema, hemorrhage and fibrinous exudation; 3) "transformation of plasma cells" - the histiomonocytic elements of the slow-type allergic reaction site metaplasse into immature and mature pyroninophilic plasma cells. Waksman distinguishes the fourth component of morphological changes in delayed-type allergic reactions - the “invasive-destructive reaction”, which is closely associated with the Jella perivascular islet response. In reactions such as contact dermatitis in humans, the perivascular islet response and its invasive-destructive component essentially determine the histological picture of this type of inflammation. Macroscopically, the reaction is expressed by thickening of the skin and erythema, microscopically - by vacuolization and desquamation of the epidermis. In autoallergic reactions, these two components often also determine the complete histological picture. Often, the damage pattern is one “invasive-destructive” process, for example, demyelination of nerve conductors, destruction of follicles in the thyroid gland, etc. In some organs, such as the eye, the leading component may be a “perivascular-islet response” accompanied by an accumulation of mononuclear cells. In the tuberculin reaction, as well as in delayed-type allergic reactions caused by the introduction of proteins (bovine blood globulins), the histological changes consist almost exclusively of the perivascular-island response of mononuclear cells, macroscopically expressed in compaction and redness. The neurocrotic reaction here appears only as a complication, for example, with necrosis of cavities in the lungs in patients with tuberculosis. The reaction of plasma cells with small doses of tuberculin or purified protein antigen in an appropriately sensitized animal may be almost absent. In cases of rejection of the primary homotransplantation, the perivascular islet and invasive destructive reactions determine the whole picture of the process. The result is a slight swelling and blackening of the graft. The reaction from the plasma cells is missing. Most typically, this pattern is seen in guinea pigs.
Allergic skin reactions of a delayed type are transmitted from one person to another using lymphoid cells (lymph node cells, blood lymphocytes). Thus, it is possible to passively passively delayed-type allergy to tuberculin, to picryl chloride, to experimental allergic encephalomyelitis, to skin graft. Contact sensitivity was also transferred with the cells of the spleen, goiter, thoracic lymphatic duct. Clinical observations of people with various forms of lymphoid insufficiency (for example, Beck's sarcoid, lymphogranulomatosis, some lymphomas) have shown that in these cases delayed-type allergies do not develop. The importance of lymphoid elements in the mechanism of delayed type allergies is supported by the fact that lymphoid cells accumulate in each focus of the inflammatory reaction that develops in these cases, and observations on the effect of lymphocyte-reducing influences on the body on the development of this type of allergic reactions.
Thus, irradiation of animals with x-rays caused suppression of tuberculin and contact allergies of experimental allergic encephalomyelitis. The introduction of cortisone in doses that reduce the content of lymphocytes, also suppressed the development of the above reactions of the delayed type. Thus, cells of the lymphoid series in case of delayed-type allergies bear the function of both sensitization and the formation of a picture of allergic inflammation and the general allergic reaction of a sick person or a sensitized animal. In the process of sensitization in delayed-type allergies, mononuclear cells of the skin are likely to be involved. Schild (N. Schild) suggests that these cells after exposure to them a sensitizing agent secrete biologically active substances that cause inflammation. Mononuclear cells, apparently, can cause metaplasia of sensitized epidermis cells involved in the reaction of a delayed type (for example, in contact dermatitis). See also Anaphylaxis, Idiosyncrasy, Serum sickness.
Allergy is a change in the sensitivity of an organism that occurs under the influence of certain factors of the external and internal environment, called allergens.
In the vast majority of cases, allergens enter the body from the external environment, sometimes they are formed in the body itself (see Autoallergy ). Allergens can enter the body through the respiratory tract (plant pollen, household dust , dry fish food, etc.), digestive organs (food allergens - egg white, milk, tomatoes, chocolate, strawberries, crabs, etc., some medicines - acetylsalicylic acid, amidopyrin , antibiotics , etc.), through the skin and mucous membranes during medical manipulations ( injections of serums, vaccines , antibiotics, local application of drugs on the wound surfaces). Allergens can also be bacteria and viruses .
As a result of repeated exposure to the allergen, sensitization occurs - the process of acquiring an increased sensitivity to this allergen by the body. The time between the first ingestion of an allergen and the onset of an allergic disease is called the period of sensitization. It can vary from several days (with serum sickness) to several months, and even years (with drug allergies). In the process of sensitization, antibodies are formed and accumulate in the body (human allergic antibodies are called reagins). The chemical composition of the antibodies are modified serum globulins . Their most important property is the immunological specificity, that is, the ability to connect only with the allergen that caused their formation.
The state of sensitization has no clinical manifestations. Allergic reactions appear only after repeated, so-called permissive, contacts of the body with the same allergen. Allergens, reintroduced into an already sensitized organism, bind to specific antibodies, either fixed on cells or circulating in the blood. Complexes of allergens and antibodies are formed on the cell surface. This causes damage to the surface cell membranes, and then the internal structures of the cell. As a result of allergic damage, potassium ions and biologically active substances (histamine, etc.) come out of the cells, which enter the body fluids (blood, lymph) and act on various body systems (smooth muscles of the bronchi , capillary walls, nerve fiber endings and . d.), disrupting their normal function. As a result, there are general and local manifestations of allergic reactions (bronchospasm, inflammation, swelling, skin rashes, itching , a drop in vascular tone - anaphylactic shock, etc.).
The outlined mechanism is characteristic of an immediate type allergy; it includes anaphylaxis (see), serum sickness (see), hay fever (see), urticaria (see), Quincke swelling (see), bronchial asthma , etc. A common sign of an immediate type allergy is the rapidity of the reaction . So, the skin allergic reaction in these cases appears a few minutes after the intradermal administration of the allergen. Skin reaction after many hours (24-72) after exposure to an allergen is characteristic of a delayed-type allergy. Such reactions can be observed with sensitization to bacteria (for example, with tuberculosis, brucellosis , sapa , tularemia , etc.), with contact dermatitis in the chemical industry , pharmacists, medical staff. The change in the reactivity of the organism after transplantation of foreign tissues and organs, expressed in their rejection, also represents an allergic reaction of a delayed type.
In pathogenesis, allergy is a delayed type of antibody and biologically active substances are not of great importance. The decisive role is played by the so-called cellular antibodies, strongly associated with sensitized lymphocytes, which come from the lymphoid organs into the blood and participate in the general and local manifestations of delayed-type allergies.
In the occurrence of allergies, genetic predisposition is of great importance. Family members with hereditary predispositions have allergic diseases more often, although there is no direct transmission of a particular disease from parents to offspring. In such families, so-called parallergy is more often observed.
Parallel allergy is a state of hypersensitivity of an organism not only to the main specific allergen, but also to some other nonspecific factors, only sometimes having similarities with the main allergen in chemical structure. For example, when sensitizing to penicillin, a person may have an increased sensitivity to other antibiotics, and sometimes to a rather large number of very different drugs. Often there is an increased sensitivity to physical factors (heat, cold). Parallel allergy usually goes away with the elimination of sensitization to the main allergen, that is, with desensitization.
Desensitization is called the reduction or removal of the state of sensitization. In the experiment in animals, it occurs after anaphylactic shock (see Anaphylaxis ) or as a result of repeated injections of small doses of a specific allergen (specific desensitization). The introduction of the allergen begins with very small doses, gradually increasing the dose. As a result, special “blocking” antibodies are produced in the body to overcome the disease . Perhaps they are connected with reagins, modified in reaction with the allergen. As a result, cell damage is prevented and the sensitization state is removed. In addition to specific methods of treating allergies, there are non-specific, somewhat reducing allergic reactions - the use of antihistamines (diphenhydramine, etc.), calcium chloride (10% solution), calcium gluconate, vitamins, corticosteroids ( prednisone , etc.).
The section on the modern level describes the mechanism of allergic reactions of the delayed and immediate type, the most common allergens. Some phenomena important for understanding allergic processes are considered. The question of the connection between allergic reactions of immediate and delayed type, as well as the problem of immunological tolerance and species immunospecificity, which is currently very important in connection with organ transplantation, is highlighted. The etiology, mechanisms and principles of treatment of the most common diseases such as bronchial asthma, urticaria and angioedema, contact dermatitis, eczema are described. A special chapter is devoted to autoallergic diseases with a description of some experimental data and immunological reactions that help make a diagnosis in the clinic. The principles and results of specific desensitization are described and the immunological mechanism and prospects of this treatment method are highlighted.
Designed for immunologists, general practitioners, allergists, dermatologists.
The famous French scientist Bernard Alpern is a member of the French Academy of Sciences, a broad-based immunologist. He is the creator of many antihistamine drugs.
In his laboratory, studies were conducted to study the mechanisms of anaphylaxis of smooth muscle organs and the role of the reticuloendothelial system in the reactivity of the organism.
The book of B. Alpern "Allergy" is devoted to the actual problem of modern medicine. In her at a high scientific level and quite popular various issues of allergy and its relationship with the immune system.
The author presents a modern classification of allergic reactions, expounds immunological aspects of immediate and delayed allergy, tissue changes characteristic of allergic reactions, experimental models of allergic reactions, stops the important problem of immunological tolerance, the role of various biologically active substances in allergic reactions.
The book describes a number of allergic diseases (atopic diseases — bronchial asthma, allergic rhinitis, urticaria, as well as serum sickness, contact dermatitis, various manifestations of drug allergy and their immunological mechanism); immunological aspects of autoallergy are given, the principles of specific diagnostics and treatment of certain allergic diseases, outlines the prospects for the development of allergology.
The book is of great interest for doctors of various specialties.
Academician of the Academy of Medical Sciences of the USSR prof. A.D. Ado