I. Classification of allergic reactions
III. The role of biologically active substances in allergic reactions
IV. The delayed-type Allergy
V. Cellular changes in allergic reactions
VI. Immunological tolerance
VII. Allergic syndromes in experiment
VIII. Large allergic syndromes in the clinic
IX. Allergy tests
X. Autoimmune diseases
XI. General principles of treatment of allergic diseases
Allergies (from the Greek. alios and ergon - action) - altered sensitivity or reactivity of the organism in relation to a particular matter.
Along with the so-called pure allergic diseases (hay fever, urticaria, some types of asthma and other) diseases, primarily infectious, where sandwiches allergic component (allergic phase A. A. Koltypin), and diseases of infectious-allergic (collagenosis, etc.). Substances that can cause allergies in humans and animals, are called allergens. At present we know of many diseases, which are based on allergic reactions (asthma, urticaria, medicinal allergies, rheumatism, contact dermatitis, reaction "to the transplant rejection" and others). Various quantitative and qualitative changes in the condition of Allergy designate special terms. Those forms of allergic reactions, which are developing most rapidly and are characterized by high intensity of the damaging action on the tissues, called hyperergy. Giperergicakie inflammation is called, for example, artusa phenomenon (see). The decrease of allergic reactivity of organism is sometimes called geirgia. The complete absence of reactivity of the organism, for example to tuberculin, called anergy. Positive energies called lower reactivity of the organism to infectious agent on the background of recovery, such as tuberculosis. Negative energies are the lack of reactivity of the organism of a patient to the pathogen on the background of severe intoxication and wasting of the body from infections (tuberculosis, pneumonia). Paraplegia call a state of an Allergy caused by one allergen to another (for example, a positive skin reaction to tuberculin in a child after smallpox vaccinations). Metallurgia called the resumption of specific allergic reactions after exposure to non-specific stimulus (for example, renewal of tuberculin reaction in the TB patient after introducing him bruchkomitsky vaccines).
Allergic person may have in relation to many groups of allergens (pollen, food, dust and other). So, when allergic rhinitis (see hay fever) often there is increased sensitivity to pollen of plants of many kinds. The allergen pollen meadow grasses are proteins with mol. weighing less than 10 000 closely connected with pigment - carbohydrate complex. One of the reasons paraallergii with allergic rhinitis - the presence in the pollen of plants of many kinds of common antigens. Polivalentes allergic reactions is also due to hereditary constitutional predisposition of some individuals to allergic diseases, i.e. the so-called allergic to the Constitution, or allergic diathesis. Predisposition to allergic bronchial asthma, urticaria and other allergic diseases is inherited as a recessive trait defined several pairs of alleles (see Hereditary diseases). Allergic diathesis is conditioned, first, by a sharp increase in the permeability of blood capillaries and generally histo-hematic barriers, and therefore allergens can easily penetrate the respiratory system, the digestive tract and other ways in the blood and tissues of the patient; secondly, the fact that the proteins in the blood and tissues of the patient are easily attach different chemical substances (drugs, antibiotics, and others) with the formation in the body of complex compounds with antigenic properties; finally, in allergic diathesis there is a high reactivity apparatus that produce antibodies: "immunologically competent cells of the patient is able in a large number of to produce specific antibodies against different allergens. All these features together generate in a patient with allergic diatesom [exudative catarrhal, on mobiles (A. Czerny)] a predisposition to various allergic diseases (bronchial asthma, urticaria, allergic rhinitis, and others), often combined in the same patient.
The clinical picture and many aspects of the pathogenesis of the diseases associated with these or other allergic reactions are completely different, but each of them is damaging effect on the fabric 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. Allergic reactions immediate type) skin blister, bronhospazm, the disorder of the functions of the gastrointestinal tract, etc. is a reaction of the skin, respiratory, digestive and other devices arising in a few minutes or hours after exposure to specific allergen. Allergic reactions delayed type cook offered to name those that occur only after many hours and even days after exposure to the allergen, such as tuberculin reactions, skin reactions if you are allergic to poison ivy, some forms of eczema and urticaria caused by food (chocolate, milk, fish) or drugs (potassium iodide) substances. To allergies delayed type was allocated and bacterial Allergy.
Allergens can be a variety of substances, ranging from the simple, such as iodine, bromine, to complex protein (whey Allergy, allergic rhinitis), protein-lipid (bacterial, fungal allergies) and other Allergens can also be complex compounds of non-protein nature. These include many polysaccharides, connection of polysaccharides with lipids or with other substances (Allergy to various kinds of dust, bacterial, allergic). A large group of substances with allergenic properties are of different colouring matter, many compounds used in medicine for therapeutic purposes.
So, it is established that penicillin, streptomycin, chlormycetin, terramycin and other antibiotics can cause a variety of allergic reactions, anaphylactic shock, serum sickness, contact dermatitis, bronchial asthma, urticaria and other allergic Skin reaction to penicillin are accompanied by the appearance in the blood of antibodies and can be passively transferred from person to person. These reactions attributable to medical illnesses pose a serious complications. An allergic reaction can cause a variety of medicinal substance: acetylsalicylic acid (aspirin), cinchophen (atavan), atropine, barbiturates, chloral hydrate, digitalis, iodides, morphine, quinine, pantopon, sulfanilamida, insulin and other
In experimental conditions allergens can be obtained by artificial accession different chemicals to proteins. Allergens that enter the body from external environment, called "actualarray" and is divided into the following main groups.
1. Actuallity of infectious origin: a) consumer (home dust and other); b) the epidermal (wool, hair and dandruff" animals); C) pollen (pollen herbaceous and woody plants); d) medicines (antibiotics, sulfanilamides, drugs arsenic, barbiturates, and other); d) chemical substances (gasoline, benzene, bleach, Ural and others); (e) food, subdivided on animal allergens (meat, fish and vegetable (vegetables, fruits) origin.
2. Actuallity infectious origin: a) bacterial (pathogenic and non-pathogenic bacteria and products of their activity); b) fungal (various kinds of non-pathogenic fungi) and C) viral (different types of viruses and their interaction with tissues).
Recently started studying the allergenic properties of the products denaturation of different tissues or products connections animal tissues with bacterial antigens, toxins or components of the bacterial cell. These allergens are sometimes called autoallergy, though this name is inaccurate, as the true Autoallergy are only a few tissues of humans and animals (lens, myelin nerve tissue, the tissue of the thyroid gland and testicles). Such autoallergy are the fabric of the heart in myocardial infarction (with the allergen are as nekrotizirovanne fabric and fabric morphologically unchanged infarction), the fabric of the kidneys in the nefrosonefrit, fabric the liver, with the hepatitis etc.
Antiallergenic divided into the following main groups.
I. Antiallergenic natural, primary (normal tissue lens, nervous tissue, and others).
II. Antiallergenic acquired secondary (abnormal tissue):
1) non-infectious (burns, radiation, cold); 2) infectious: a) intermediate antigenic products (tissue damage pathogenic microbes and viruses); b) antigenic complex products (cloth, and microbe, fabric and toxin).
The existence of several types of antibodies, participating in formation of allergic reactions (present in the blood, lymph and tissue fluid in the free state and fixed tissues). Antibodies type precipitin participate in the mechanism, only a small group of allergic reactions that will otkazat phenomenon artusa rabbit, allergic reaction to eggs, epidermis horses and some other antigens. Passive transfer of anaphylaxis among pigs is possible with the help of antibodies, not having the properties of precipitin. These neprezimlilsa antibodies produced sensitization among pigs even more than precipitin, quantity, called the centre o (J. R. Marrack) "an incomplete antibody". In this group, turned on and detected allergic antibodies type reagin, or topanov. Electrophoretic analysis of proteins containing sensitizing skin antibodies, have shown that they are in the factions ' - or 2 M, or β2А-globulin human blood. The reagents termolabilnyh. Specificity sensitizing skin antibodies relative. People who are sensitive to many allergens include sensitizing skin antibodies that can connect to multiple allergens from the set to which this sensitive people. In addition to sensitizing skin antibodies, also highlighted "blocking antibodies"that can connect to the corresponding allergen, causing skin sensitization to allergens to which they connect. Blocking antibodies are monospecific and, consequently, against the reagents more or less full antibodies. They are in the faction " - or β2A-globulin human blood. Relationships of various kinds of allergic antibodies can be presented in the following chart:
In the basis of the pathogenesis of allergic reactions immediate type lies the damaging effect of reaction allergen - antibody on the surface of cells sensitized by the body. This reaction develops in the fat cells of loose connective tissue, blood and blood platelets, endothelial cells of blood capillaries. The antibody type of Regina attached one part to the cell, another active group records the allergen. This reaction accession allergen - antibody cause allergic injury (alteration) cells. Such alteration fat cells leads to the disintegration and destruction of pellets, resulting from the cell are exempt biologically active substances (gistamina and other Histamine in turn causes dilation of blood capillaries, smooth muscle contraction, increased secretion of mucus mucous membranes, excitation of nerve cells. For example, in bronchial asthma reduction of bronchial smooth muscle and increases the secretion of mucous membrane bronchi leads to seizure of suffocation. Ventilation of the lungs makes it difficult at this, and hypertrophy of the mucous membrane of small and medium-sized bronchi. According to current data, the reaction itself allergen - antibody (in addition to histamine) can cause expansion of blood capillaries and increase their permeability. This leads to the fact that on the skin and the mucosa of patients under the influence of the allergen are easily formed blisters. Valdyma reaction is widely used today to determine the status of allergies in humans in relation to a particular allergen (see Allergic diagnostic test). Valdyma reaction may develop on the mucous membranes of the internal organs (the gastrointestinal tract, urinary tract), brain membranes and cause secondary severe neurological disorders. From a morphological point of view, allergic reactions immediate type cause damage to the vascular and capillary system, the basic substance and collagen fibers of the connective tissue. In vascular and capillary network observed the expansion of capillaries, increases the permeability, exudation and emigration of neutrophils, eosinophils, basophils, lymphocytes; typical accumulation in the tissues of eosinophils. Abundant exudation to the deposition of fibrin and other proteins ('-globulin and others) in the glomeruli of the kidney characterized picture of allergic glomerulonephritis. By the fluorescence analysis in the composition of proteins found in areas of allergic inflammation of the immediate type (glomerulonephritis, lymphadenitis, neuritis and mn. others), shows the presence of soluble and loose sediments complexes allergen - antibody. Assume that these complexes in some cases (the phenomenon artusa and others) are formed in the blood or other liquid fabric environments and in the future again have a damaging effect on blood capillaries and cell affected tissue. Great value specified complexes are given in the pathogenesis of autoimmune lesion of various organs (autoimmune gastritis, jade, thyroiditis, orchitis, and others).
In the loose connective tissue, lymph nodes allergic reactions immediate type are accompanied by characteristic changes of the basic substance and connective tissue fibers. The essence of such a "disruption" is "Mokoena" the swelling of basic substances and fibrous structures, rolling in the future "fibrinoidnogo" swelling and "fibrinoid necrosis. When Mokoena swelling appears basophilic grainy protein weight (globulins blood and immune complexes, caught in the fabric of the blood). In addition, based muhidnova swelling is a change in the properties of mucopolysaccharides and glycoproteins basic substance and collagen fibers, which increases the hydrophilicity of the connective tissue (A. I. Strukov). Fibrinoidnogo swelling is formed on the surface of collagen fibers and between them fibrin blood of connection products of fibrin with alfanumeriske connective tissue and possibly decay products DNA. In the future, under the influence of the enzyme collagenase be the destruction of the collagen fibers, further disorganization of connective tissue and its necrosis ("fibrinovy"). The most vivid of these changes under influence of protein allergens on sensitised skin tissue (see artusa phenomenon), blood vessels, kidneys and other organs. Some allergic reactions following the described changes in the connective tissue arise proliferation gestionhotelera cells with the formation of granulomas, and further sclerotic processes (see Collagenoses).
Allergic reaction of the delayed type depending on the type causing them allergens can be divided into five major groups [Waxman (Century Waksman)]: 1) allergic reaction tuberculin type; 2) allergic reaction contact type (contact dermatitis); 3) experimental autoimmune (encephalomyelitis, thyroiditis, orchitis, and others) reaction; 4) allergic reaction to purified proteins; 5) allergic reactions "to the transplant rejection". These groups have both common and distinctive features. When serviceregistration the study of the phenomenon artusa and tuberculin reactions of Jelle distinguishes three main pathogenetic components: 1) "perivascular islet reaction" - perivascular limfo-gisti-macrophage infiltration of connective tissue; 2) "vascular necrotic reaction" - non-specific connective tissue necrosis and partly parenchymatous skin elements, in many cases accompanied by swelling, bleeding and fibrinous exudation; 3) "the transformation of plasma cells" - gestionhotelera elements hearth allergic reaction delayed type metaplasia in immature and Mature pyroninophilia plasma cells. Waxman is a Discerner of the fourth component of morphological changes in allergic reactions delayed-type - "invasive and destructive reaction", closely associated with perivascular islet reaction of Jelle. When the reactions of the type of contact dermatitis in humans perivascular islet reaction and invasive-destructive component essentially determine histological picture of this type of inflammation. The point is that the reaction is expressed by the thickening of the skin and erythema, microscopically - vacuolization and desquamation of the epidermis. When autoimmune reactions of the two specified component often also determine fully histological picture. Often determines picture of defeat one "invasive and destructive" process, for example when demyelination of nerve agents, the destruction of follicles in the thyroid gland, etc., In some agencies, for example in the eye, leading component can be "perivascular-islet reaction", accompanied by the accumulation of mononuclear cells. When tuberculin skin reactions and allergic reactions delayed type caused by the introduction of proteins (globulin the blood of the bull), histological changes consist almost exclusively of perivascular-islet reaction of mononuclear cells, macroscopically expressed in the compaction and redness. Vascular-necrotic reaction is here only as a complication, such as necrosis of cavities in the lungs of patients with tuberculosis. The reaction of the plasma cells in small doses or tuberculin purified protein antigen u appropriately sensitized animal can be almost absent. In cases of rejection reactions primary gomotransplantatov perivascular-islet and invasive and destructive reactions define the entire picture of the process. The result is a light swelling and blackening of transplant. Reaction from the plasma cells is missing. Most typically, this picture is observed in Guinea pigs.
Allergic skin reactions delayed-type are passed from one person to another with the help of the cells of the lymphoid series (cells of the lymph nodes, blood lymphocytes). So, manages to convey passively allergies delayed type to tuberculin, pyrrhotite, experimental allergic encephalomyelitis, graft skin. Contact sensitivity managed to move also with the cells of the spleen, thymus, thoracic lymphatic duct. Clinical observations of people with different forms of failure lymphoid system (for example, when sarcode Beck, chlamydia, some lymphomas) showed that in these cases allergies delayed type is not developing. In favor of the importance of lymphoid elements in the mechanism of Allergy delayed type say and the fact that the accumulation of cells of the lymphoid series in each focus inflammatory reaction, which develops in these cases, and observations of impact impacts, reduce the content of lymphocytes in the body, on the development of this type of allergic reactions.
So, irradiation of animals of x-rays caused suppression of tuberculin and contact allergies experimental allergic encephalomyelitis. Introduction of cortisone in doses, reduce the content of lymphocytes, also inhibited the development of the above reactions are delayed type. Thus, the cells of the lymphoid series Allergy delayed-type function are as sensitization, and forming a picture of allergic inflammation and General allergic reaction of a sick person or sensitized animal. In the process of sensitization Allergy delayed type, probably participate mononuclear cells of the skin. Schild (N. Schild) suggests that these cells after exposure to sensitizing agent produce bioactive substances that cause inflammation. Mononuclear cells, apparently, can cause metaplasia sensitised cells of the epidermis, participating in the reaction of the delayed type (for example, contact dermatitis). Cm. also Anaphylaxis, Idiosyncrasy, Serum sickness.
Allergy is the sensitivity of the organism, arising under the influence of some factors of external and internal environment, called allergens.
In most cases allergens enter the body from external environment, sometimes they are formed in the organism (see Autoallergy). Allergens can enter the body through the respiratory tract (pollen, household dust, dry food for fish and other), organs of digestion (food allergens egg white, milk, tomato, chocolate, strawberry, crabs and others, some medications - acetylsalicylic acid, amidopyrine, antibiotics and others), through the skin and mucous membranes with medical procedures (injections of sera, vaccines, antibiotics, topical application of drugs on the wound surface). Allergens can be also bacteria and viruses.
The re-entering of allergen sensitization occurs - the acquisition of the body's sensitivity to the allergen. The time between the first hit in the body of the allergen and the emergence of allergic diseases is called the period of sensitization. It can vary from a few days (when serum sickness) to several months and even years (when drug Allergy). In the process of sensitization are produced in the body and accumulate antibodies (allergic antibodies man called reagents). Chemical composition antibodies are modified globulins in the blood serum. The most important is their property and immunological specificity, that is, the ability to connect with the allergen, which caused their education.
The sensitization of clinical manifestations is not. Allergic reactions occur only after the second, so-called permissive, contact of the body with the same allergen. Allergens, re-established already sensitised organism, connected with specific antibodies, or fixed on the cells or circulating in the blood. On the surface of cells are formed complexes of allergens and antibodies. It causes damage to the surface of cell membranes, and then the internal structures of the cell. The result of an allergic damage of cells go ions potassium and biologically active substances (gistamina and other), which are in liquid environments of an organism (blood, lymph and act on various systems of the body (smooth muscles bronchi, capillary walls, end of nerve fibers, and so on), disrupting their normal function. The result is a General and local manifestations allergic reaction (bronhospazm, inflammation, swelling, skin rashes, itching, the fall of vascular tone - anaphylactic shock and other).
Stated mechanism characteristic Allergy immediate type; it includes anaphylaxis (see), serum sickness (see), hay fever (see), urticaria (see), Kwinke swelling (see), bronchial asthma and other Common symptom of allergies immediate type is speed of development of the reaction. So, allergic skin reaction in these cases, you may receive a few minutes after intradermal injection of the allergen. Skin reaction after many hours (24 to 72) after exposure to the allergen characteristic Allergy delayed type. Such reactions can be observed with sensitization to bacteria (such as tuberculosis, brucellosis, Sapa, tularemia and other), contact dermatitis in workers of the chemical industry, pharmacists, and medical staff. Modify the reactivity of the organism after transplantation alien tissues and organs, as expressed in their rejection, also represents an allergic reaction delayed type.
In the pathogenesis of allergic delayed-type antibodies and biologically active substances are of little value. A crucial role is played by the so-called cell antibodies, are strongly associated with sensitised lymphocytes that come from lymphoid organs in the blood, and participate in the General and local manifestations of Allergy delayed type.
The Allergy is of great importance genetic predisposition. In family members with hereditary predisposition to allergic diseases occur more often, although direct transfer of a specific disease from parents to offspring is missing. In such families is more likely to occur and the so-called parallele.
Paraplegia is a state of increased sensitivity to the body not only to the main specific allergen, but also to some other nonspecific factors, only sometimes have similarities with the major allergen on the chemical structure. For example, if sensitization to penicillin person may have increased sensitivity to other antibiotics, and sometimes quite a large number of different drugs. Often there is increased sensitivity to physical factors (heat, cold). Parallele usually held at elimination of sensitization to the main allergen, that is, with desensitization.
The desensitization is the decrease or removal of the state of sensitization. In the experiment the animals it occurs after anaphylactic shock (see Anaphylaxis) or as a result of repeated injections of small doses of specific allergen (specific desensitization). The introduction of the allergen start with a very low dose, gradually increase the dose. As a result, the body produces special blocking antibodies that can overcome the illness. Perhaps they are connected with the reagents, modified in reaction to the allergen. In the prevented damage to the cells and removes the sensitization. In addition to the specific treatment of allergies, there are non-specific, few reduce allergic reactions,- the use of antihistamines (diphenhydramine and others), chloride calcium (10% solution), calcium gluconate, vitamins, corticosteroids (prednisone and others).
In the section on modern level described the mechanism of allergic reactions delayed and immediate type, the most common allergens. Considered some of the phenomena important for understanding allergic processes. Lit the question of the relationship of allergic reactions immediate and delayed type, and the problem of immunological tolerance and specific immunospecificity, very important at this time in connection with the transplantation of organs. Describes the etiology, mechanisms and principles of treatment of the most common diseases as bronchial asthma, urticaria and angioedema, contact dermatitis, eczema. A special Chapter is devoted to autoimmune diseases with a description of some of the experimental data and immunological reactions that help make a diagnosis in the clinic. Describes the principles and results of specific giposencibilization and lit immunological mechanism and prospects of this method of treatment.
Designed for immunologists, physicians, allergists, dermatologists.
Famous French scientist Bernard Alpern member of the French Academy of Sciences, immunologist wide profile. He is the Creator of many of antihistamines.
In his laboratory studies have been conducted to study the mechanisms of anaphylaxis gladkomyshechnykh bodies and the role of the reticuloendothelial system in reactivity of organism.
The book B. Alpern "Allergy" is devoted to an actual problem of modern medicine. It at a high scientific level and quite popular outlined various issues of Allergy and its relationship with the immune system.
The author provides modern classification of allergic reactions, comments immunological aspects allergies immediate and delayed type, tissue changes, characteristic of allergic reactions, experimental models of allergic reactions, stopped on the important issue of immunological tolerance, the role of the different biologically active substances in allergic reactions.
The book describes a number of allergic diseases (atopic diseases - a bronchial asthma, allergic rhinitis, urticaria, and serum sickness, contact dermatitis, the various manifestations of drug Allergy and their immunological mechanism), given immunological aspects of autoallergy lit important for practical medicine principles specific diagnosis and therapy of some of allergic diseases outlined prospects of development of Allergy.
The book is of great interest for doctors of various specialties.
Academician of AMS of the USSR, Professor A. D. ADO