ALLERGY

From Big Medical Encyclopedia

Allergy (Greek allos — another and ergon — action) — the hypersensitivity of an organism to various substances connected with change of its reactivity. The term was offered by the Austrian pediatricians the Tuberculine test and Chic (S. to Pirquet, V. Schick, 1906) for an explanation of the phenomena of a serum disease observed by them at children at infectious diseases.

Hypersensitivity of an organism at the Allergy is specific, i.e. it raises to that antigen (or to other factor), about the Crimea: already earlier there was a contact and which caused a condition of a sensitization. Clinical manifestations of this hypersensitivity designate usually as allergic reactions. The allergic reactions arising at people or animals at primary contact with allergens call nonspecific. One of options of a nonspecific allergy is the paraallergy. Paraallergy call the allergic reaction caused by any allergen in an organism, sensibilized other allergen (e.g., positive skin reaction to tuberculine at the child after an inoculation to it smallpox). The valuable contribution to the doctrine about an infectious paraallergip was made by P.F. Zdrodovsky's works. An example of such paraallergy is the phenomenon of generalized allergic reaction to endotoxin of a cholera vibrio (see. Sanarelli — Zdrodovsky a phenomenon ). Resuming of specific allergic reaction after introduction of a nonspecific irritant is called a metallergy (e.g., resuming of tuberkulinovy reaction at the TB patient after introduction to it a typroid vaccine).

Classification of allergic reactions

Allergic reactions divide into two big groups: reactions immediate and reactions slowed down types. The concept about allergic reactions of the immediate and slowed-down types for the first time resulted from clinical observations: Distinguished a tuberculine test (1906) immediate (accelerated) and slowed down (stretched) forms of a serum disease, Tsinsser (N. Zinsser, 1921) — bystry anaphylactic and slow (tuberkulinovy) forms of skin allergic reactions.

Reactions of immediate type Cook (R. A. Cooke, 1947) called the skin and system allergic reactions (respiratory, digestive and other systems) arising in 15 — 20 min. after impact on the patient of offending allergen. Such reactions are a skin blister, the bronchospasm, disorder of function went. - kish. path, etc. Treat reactions of immediate type: acute anaphylaxis (see), Ouveri's phenomenon (see. Skin anaphylaxis ), allergic small tortoiseshell (see), serum disease (see), noninfectious and allergic forms bronchial asthma (see), hay fever (see. Pollinosis ), a Quincke's disease (see. Quincke hypostasis ), acute glomerulonephritis (see), etc.

Reactions of the slowed-down type, unlike reactions of immediate type, develop within many hours and sometimes days. They arise at tuberculosis, diphtheria, a brucellosis; are caused by a hemolitic streptococcus, a pneumococcus, a virus of a vaccine, etc. Allergic reaction of the slowed-down type in the form of damage of a cornea is described at streptococcal, pneumococcal, tubercular and other infections. At allergic encephalomyelitis reaction proceeds also as the slowed-down Allergy. Also reactions on vegetable (a primrose, an ivy, etc.), industrial (ursols), medicinal (penicillin, etc.) allergens belong to reactions of the slowed-down type at so-called contact dermatitis (see).

Allergic reactions of immediate type differ from the slowed-down allergic reactions on a number of signs.

1. Immediate allergic reactions develop in 15 — 20 min. after contact of allergen with sensibilized fabric which are slowed down — in 24 — 48 hours

2. Immediate allergic reactions are characterized by existence in blood of the circulating antibodies. At the slowed-down reactions of an antibody in blood, as a rule, are absent.

3. At reactions of immediate type passive transfer of hypersensitivity to a healthy organism with blood serum of the patient is possible. At the slowed-down allergic reactions such transfer is possible, but not with blood serum, and with leukocytes, cells of lymphoid bodies, cells of exudate.

4. Reactions of the slowed-down type are characterized by cytotoxic or lytic effect of allergen on sensibilized leukocytes. This phenomenon is not characteristic of immediate allergic reactions.

5. Toxic effect of allergen on culture of fabric is characteristic of reactions of the slowed-down type that is not typical for immediate reactions.

Partly the intermediate position between reactions of the immediate and slowed-down type occupies Artyus's phenomenon (see. Artyusa phenomenon ), which in initial stages of development costs closer to reactions of immediate type.

Evolution of allergic reactions and their manifestation in ontogenesis and phylogeny were in detail studied by N. N. Sirotinin and his pupils. It is established that in the embryonal period anaphylaxis (see) it is impossible to cause in an animal. In the period of a neonatality the anaphylaxis develops only at zrelorozhdayushchikhsya animal, such as Guinea pigs, goats, and still in weaker form, than at mature animals.

Emergence of allergic reactions in the course of evolution is connected with emergence in an organism of ability to develop antibodies. At invertebrates ability to develop specific antibodies is almost absent. Most this property is developed at the highest hematothermal animals and especially at the person therefore at the person allergic reactions are observed especially often and their manifestations are various.

Recently there was a term « immunopathology » (see). Refer demyelinating defeats of nervous tissue to immunopathological processes (postvaccinal encephalomyelitis, multiple sclerosis, etc.), various a nephropathy, some forms of an inflammation of a thyroid gland, testicles; the same processes are adjoined by extensive group of the diseases of blood (a hemolitic Werlhof's disease, anemias, leukopenias) combined in the section immunohematology (see).

The analysis of the actual material on studying of a pathogeny of various allergic diseases of morphological, immunological and pathophysiological methods shows that at the heart of all diseases combined in group of immunopathological allergic reactions lie and that immunopathological processes have no fundamental differences from the allergic reactions caused by various allergens.

Mechanisms of development of allergic reactions

Allergic reactions of immediate type

the Mechanism of development of allergic reactions of immediate type can be divided into three stages which are closely connected with each other (according to A. D. Ado): immunological, patokhimichesky and pathophysiological.

Immunological stage represents interaction of allergens with allergic antibodies, i.e. reaction allergen — an antibody. The antibodies causing allergic reactions at connection with allergen in some cases have precipitant properties, i.e. are capable to be besieged at reaction with allergen, e.g. at an anaphylaxis, a serum disease, Artyus's phenomenon. Anaphylactic reaction can be caused in an animal not only by an active or passive sensitization, but also introduction to blood of a cell-bound immune complex allergen — an antibody, prepared in a test tube. In pathogenic action of the formed complex the large role is played by a complement which is fixed by a cell-bound immune complex and is activated.

At other group of diseases (hay fever, atonic bronchial asthma, etc.) antibodies have no property to be besieged at reaction with allergen (monovalent antibodies).

Allergic antibodies (reagins) at atonic diseases at the person (see. Atopy ) do not form with the corresponding allergen of insoluble cell-bound immune complexes. Obviously, they do not fix a complement, and pathogenic action is carried out without its participation. A condition of emergence of allergic reaction in these cases is fixing of allergic antibodies on cells. Existence of allergic antibodies in blood of patients with atonic allergic diseases can be determined by Prausnitts's reaction — Kyustnera (see. Prausnittsa — Kyustnera reaction ), edges are proved by a possibility of passive transfer of hypersensitivity with blood serum from the patient on skin of the healthy person.

Patokhimichesky stage. An effect of reaction antigen — an antibody at allergic reactions of immediate type are profound changes in biochemism of cells and fabrics. Activity of a number of the fermental systems necessary for normal life activity of cells is sharply broken. A number of biologically active agents is as a result released. The most important source of biologically active agents are the mast cells of connecting fabric allocating histamine (see), serotonin (see) and heparin (see). Process of release of these substances of granules of mast cells proceeds in several stages. In the beginning there is «an active degranulation» to energy consumption and activation of enzymes, then release of a histamine and other substances and exchange of ions between a cell and the environment. Release of a histamine comes also from leukocytes (basophiles) of blood that can be used in vitro for diagnosis of the Allergy. The histamine is formed by decarboxylation of amino acid of a histidine and can contain in an organism in two types: unsteadily connected with fabric proteins (e.g., in mast cells and bazofpla, in the form of fragile communication with heparin) and free, physiologically active. Serotonin (5-gidroksitriptamin) in a large number contains in thrombocytes, in tissues of a digestive tract of N of a nervous system, at a number of animals in mast cells. Biologically active agent playing an important role in allergic reactions is also slowly operating substance, the chemical nature a cut is not opened finally. There are data that it represents mix of glucosides neuraminic to - you. During an acute anaphylaxis also bradikinin is released. It concerns group of kinin of plasma and is formed of a bradikininogen of plasma, collapses enzymes (kininaza), forming inactive peptides (see. Mediators of allergic reactions ). Except a histamine, serotonin, bradikinin, slowly operating substance, at allergic reactions such substances as are released acetylcholine (see), sincaline (see), noradrenaline (see), etc. Mast cells throw out preferential a histamine and heparin; in a liver heparin, a histamine are formed; in adrenal glands — adrenaline, noradrenaline; in thrombocytes — serotonin; in nervous tissue — serotonin, atsetplkholin; in lungs — slowly operating substance, a histamine; in plasma — bradikinin etc.

Pathophysiological stage it is characterized by the functional disturbances in an organism developing owing to reaction allergen — an antibody (or allergen — reagin) and releases of biologically active agents. Is the reason of these changes as immediate effect of immunological reaction to cells of an organism, and numerous biochemical intermediaries. E.g., the histamine at an intradermal injection is capable to cause the so-called «triple answer of Lewis» (an itch on site introductions, an erythema, a blister) which is characteristic of skin allergic reaction of immediate type; the histamine causes reduction of smooth muscles, serotonin — change of blood pressure (rise or falling, depending on a reference state), reduction of smooth muscles of bronchioles and a digestive tract, narrowing of larger blood vessels and expansion of small vessels and capillaries; bradikinin is capable to cause reduction of unstriated muscles, a vazodilatation, a positive chemotaxis of leukocytes; muscles of bronchioles are especially sensitive to influence of slowly operating substance (at the person).

Functional changes in an organism, their combination also make a clinical picture of an allergic disease.

These or those forms of an allergic inflammation with various localization (skin, a mucous membrane, a respiratory, digestive tract, nervous tissue, limf, glands, joints etc.), disturbance of a hemodynamics (very often are the cornerstone of a pathogeny of allergic diseases at an acute anaphylaxis), a spasm of smooth muscles (a bronchospasm at bronchial asthma).

Allergic reactions of the slowed-down type

the Slowed-down Allergy develops at vaccination and various infections: bacterial, virus and fungal. A classical example of such Allergy is tuberkulinovy hypersensitivity (see. Tuberkulinovaya allergy ). The role of the slowed-down Allergy in a pathogeny of infectious diseases is most demonstrative at tuberculosis. At local introduction of tubercular bacteria strong cellular reaction with caseous disintegration and formation of cavities — Koch's phenomenon arises a primed animal. Many forms of tuberculosis can be considered as Koch's phenomenon on site of superinfection of an aerogenic or hematogenous origin.

One of types of the slowed-down Allergy is contact dermatitis. It is caused by various low-molecular vegetable matters, industrial chemicals, varnishes, paints, epoxies, washing drugs, metals and metalloids, cosmetics, drugs, etc. In an experiment most often apply a sensitization of animals to receiving contact dermatitis applications on skin 2,4 dinitrobenzene chlorides and 2,4 dinitrofluobenzenes.

The general sign combining all types of contactants is their ability to connect to protein. Such connection happens probably through a covalent bond to free amino and sulphhydryl groups of proteins.

In development of allergic reactions of the slowed-down type it is also possible to allocate three stages.

Immunological stage. Not immune lymphocytes after contact with allergen (e.g., in skin) on circulatory and limf, to vessels are transferred in limf, nodes where are transformed to rich RNA a cell — a blast. Blasts, breeding, turn into the lymphocytes capable «to learn» the allergen at repeated contact again. Some of specifically «trained» lymphocytes are transported in a thymus. The contact of such specifically sensibilized lymphocyte with the corresponding allergen activates a lymphocyte and causes release of a number of biologically active agents.

Modern data on two clones of lymphocytes of blood (In - and T lymphocytes) allow to present in a new way their role in mechanisms of allergic reactions. For reaction of the slowed-down type, in particular at contact dermatitis, T lymphocytes (timuszavisimy lymphocytes) are necessary. All influences reducing the maintenance of T lymphocytes at animals sharply suppress hypersensitivity of the slowed-down type. V-lymphocytes as the cells capable to turn into the immunocompetent cells developing antibodies are necessary for reaction of immediate type.

There are data on a role of the hormonal influences of a thymus which are taking part in process of «training» of lymphocytes.

Patokhimichesky stage it is characterized by release by sensibilized lymphocytes of a number of biologically active agents of proteinaceous and polypeptide character. Treat them: a transfer factor, the factor inhibiting migration of macrophages, limfotsitotoksin, a blastogenic factor, the factor strengthening phagocytosis; a factor of a chemotaxis and, at last, the factor protecting macrophages from the damaging action of microorganisms.

Reactions of the slowed-down type do not slow down antihistamines. They are oppressed by cortisol and adrenocorticotropic hormone, given passively only by mononuclear cells (lymphocytes). The immune responsiveness is implemented in large part by these cells. In the light of these data there is clear the known fact of increase in maintenance of lymphocytes in blood at different types of a bacterial Allergy long ago.

Pathophysiological stage it is characterized by changes in fabrics which develop under the influence of the mediators stated above, and also in connection with direct cytotoxic and cytolytic action of sensibilized lymphocytes. The most important manifestation of this stage is development of different types of an inflammation.

The physical allergy

Allergic reaction can develop in response to influence not only a chemical, but also physical irritant (heat, cold, light, mechanical or beam factors). Since the physical irritation in itself does not cause antibody formation, various working hypotheses are made.

1. The speech can go about the substances arising in an organism under the influence of physical irritation, i.e. about the secondary, endogenous autoallergens undertaking a role of the sensibilizing allergen.

2. Antibody formation begins under the influence of physical irritation. High-molecular substances and polysaccharides can induce enzymatic processes in an organism. Perhaps, they stimulate antibody formation (approach of a sensitization), first of all (reagins) sensibilizing skin which under the influence of specific physical irritations become more active, and these activated antibodies like enzyme or the catalyst (as strong liberator of a histamine and other biologically active agents) cause release of fabric substances.

Close to this concept there is Cook's hypothesis, according to a cut the spontaneous factor sensibilizing skin is an enzimopodobny factor, the prosthetic group forms it with serum protein a fragile complex.

3. According to the clonal and selection theory of Burnett it is supposed that physical irritations in the same way as chemical, can cause proliferation of a «forbidden» clone of cells or a mutation of an immuno-lotcheska of competent cells.

Fabric changes at an allergy of the immediate and slowed-down type

the Morphology of the Allergy of the immediate and slowed-down type reflects various humoral and cellular immunologic mechanisms.

For the allergic reactions of immediate type arising at impact on fabric of complexes antigen — an antibody, the morphology of a giperergichesky inflammation is characteristic, speed of development, dominance of alterativny and vascular and exudative changes, drift of proliferative and reparative processes are inherent to Krom.

It is established that alterativny changes at the Imediate-type allergy are connected with gistopatogenny effect of a complement of cell-bound immune complexes, and vascular and exudative — with emission of vasoactive amines (mediators of an inflammation), first of all a histamine and kinin, and also with hemotaksichesky (leykotaksichesky) and degranulating (concerning mast cells) action of a complement. Alterativny changes preferential concern walls of vessels, paraplastic substance and fibrous structures of connecting fabric. They are presented by plasmatic treatment, mucoid swelling and fibrinoid transformation; extreme expression of alteration is the fibrinoid necrosis, characteristic of allergic reactions of immediate type. Emergence in a zone of an immune inflammation of coarse-dispersion proteins, fibrinogen (fibrin), the polymorphonuclear leukocytes «digesting» cell-bound immune complexes and erythrocytes is connected with pronounced plazmorragichesky and vascular and exudative reactions. Therefore fibrinous or fibrinous and hemorrhagic exudate is most characteristic of such reactions. Proliferative and reparative reactions at the Imediate-type allergy are delayed and expressed poorly. They are presented by proliferation of cells of an endothelium and a periteliya (adventitias) of vessels and synchronize emergence of mononuklearno-histiocytic macrophagic elements that reflects elimination of cell-bound immune complexes and the beginning of immunoreparative processes. Most typically dynamics of morphological changes at the Imediate-type allergy is presented at Artyus's phenomenon (see. Artyusa phenomenon ) and Ouveri's reactions (see. Skin anaphylaxis ).

Fig. 1. Allergic reaction of immediate type. Fibrinoid necrosis of a renal ball (system lupus erythematosus)

Allergic reactions of immediate type which proceed with dominance of alterativny or vascular and exudative changes are the cornerstone of many allergic diseases of the person. E.g., vascular changes (a fibrinoid necrosis) at a system lupus erythematosus (fig. 1), a glomerulonephritis, a nodular periarteritis, etc.; vascular and exudative manifestations at a serum disease, a small tortoiseshell, a Quincke's edema, hay fever, a lung fever, and also polyserosites, arthritises at rheumatism, tuberculosis, a brucellosis, etc.

Fig. 2. Allergic reaction of immediate type. Fixing of Ig of γ-globulin of the circulating cell-bound immune complexes in sites of a fibrinoid necrosis of a renal ball at a system lupus erythematosus (a direct method of Koons)
The mechanism and morphology of hypersensitivity considerably are defined by the nature and quantity of an antigenic irritant, duration of its circulation in blood, situation in fabrics, and also character of cell-bound immune complexes (the circulating or fixed complex, heterological or autologous, educated locally due to connection of antibodies with structural antigen of fabric). Therefore assessment of morphological changes at And. immediate type, their belonging to an immune response demand proofs by means of an immunohistochemical method (fig. 2) which allows not only to speak about the immune nature of process, but also to identify components of a cell-bound immune complex (antigen, an antibody, a complement) and to establish their quality.

For And. the slowed-down type reaction of sensibilized (immune) lymphocytes is of great importance. The mechanism of their action considerably gipotetichen though the fact of the gistopatogenny effect caused by immune lymphocytes in culture of fabrics or in allotransplant does not raise doubts. Believe that the lymphocyte comes into contact with a target cell (antigen) by means of the antitelopodobny receptors which are available on its surface. Activation of lysosomes of a target cell at its interaction with an immune lymphocyte and «transfer» is shown them to target cell H3-timidinovoy of a tag of DNA. However merge of membranes of these cells even at deep implementation of lymphocytes in a target cell does not happen that is convincingly proved by means of microcinema and elektronnomikroskopichesky methods.

Fig. 3. Allergic reaction of the slowed-down type. Cytoplasmatic bridges between a lymphocyte and a macrophage (the scanning supermicroscope of Stereoskan)

In addition to sensibilized lymphocytes, macrophages (histiocytes) which enter specific reaction with antigen by means of the cytophilic antibodies adsorbed on their surface participate in allergic reactions of the slowed-down type. Relationship of an immune lymphocyte and a macrophage are not found out. Only close contacts of these two cells in the form of so-called cytoplasmatic bridges (fig. 3) which come to light at an elektronnomikroskopichesky research are come. Perhaps, cytoplasmatic bridges serve for transfer as a macrophage of information on antigen (in the form of RNA or the RNA complexes — antigen); perhaps, the lymphocyte in return stimulates activity of a macrophage or shows in relation to it cytopathic action.

Consider that allergic reaction of the slowed-down type takes place at anything hron. an inflammation owing to release of autoantigens from the breaking-up cells and fabrics. Morphologically between And. the slowed-down type and a chronic (interstitial) inflammation much in common. However similarity of these processes — limfogistiotsitarny infiltration of fabric in combination with a vascular plazmorragicheskimi and parenchymatous and dystrophic processes — does not identify them. Proofs of participation of cells of infiltrate in sensibilized lymphocytes can be found at gistofermentokhimichesky and elektronnomikroskopichesky researches: at allergic reactions of the slowed-down type increase in activity of an acid foyefataza and dehydrogenases in lymphocytes, increase in volume of their kernels and kernels, increase in quantity by the policy, a hypertrophy of the device of Golgi is established.

Opposition of morphological manifestations of humoral and cellular immunity in immunopathological processes is not justified therefore combinations of morphological manifestations And. the immediate and slowed-down type are quite natural.

An allergy at radiation injury

Problem A. at radiation injury has two aspects: action of radiation on hypersensitivity reactions and a role of an autoallergy in a pathogeny of a radial illness.

Action of radiation on reaction of immediate hypersensitivity is most in details investigated on the example of an anaphylaxis. In the first weeks after the radiation which is carried out some days before the sensibilizing injection of antigen along with a sensitization or in the first days after it, hypersensitivity disease is weakened or does not develop absolutely. If the allowing injection of antigen is carried out to later period after recovery of an antibody response, then the acute anaphylaxis develops. The radiation which is carried out in several days or weeks after a sensitization and on antiserum capacities in blood does not influence a condition of a sensibilizirovannost. Action of radiation on cellular reactions of hypersensitivity of the slowed-down type (e.g., allergy tests with tuberculine, tularin, brucellin etc.) is characterized by the same patterns, however these reactions several more radiorezistentna.

At radial illness (see) manifestation of an acute anaphylaxis can be strengthened, weakened or changed depending on the period of a disease and clinical symptomatology. In a pathogeny of a radial illness a part is played by allergic reactions of the irradiated organism in relation to exogenous and endogenous antigens (autoantigens). Therefore the desensibilizing therapy is useful at treatment of both acute, and chronic forms of radiation injuries.

A role of endocrine and nervous systems in development of an allergy

Studying of a role of closed glands in development And. carried out by their removal at animals, administration of various hormones, studying of allergenic properties of hormones.

A hypophysis — adrenal glands

Data on influence of hormones of a hypophysis and adrenal glands on And. are contradictory. However the majority of the facts says that allergic processes proceed more hard against the background of the adrenal insufficiency caused a hypophysis - or an adrenalectomy. Glucocorticoid hormones and AKTG, as a rule, do not slow down development of allergic reactions of immediate type, and only their long introduction or use of high doses in a varying degree oppresses their development. Allergic reactions of the slowed-down type well are suppressed with glucocorticoids and AKTG.

Antiallergenic action of glucocorticoids is connected with braking of products of antibodies, phagocytosis, development of inflammatory reaction, decrease in fabric permeability.

Obviously, allocation of biologically active mediators also decreases and sensitivity of fabrics to them decreases. Allergic processes are followed by such exchange and functional changes (hypotension, a hypoglycemia, sensitization to insulin, an eosinophilia, a lymphocytosis, increase in ion concentration of potassium in a blood plasma and decrease in ion concentration of sodium) which demonstrate existence of glucocorticoid insufficiency. It is established, however, that at the same time insufficiency of bark of adrenal glands not always comes to light. On the basis of these these V. I. Pytsky (1968) made a hypothesis of extraadrenal mechanisms of the glucocorticoid insufficiency caused by increase in binding of cortisol proteins of a blood plasma, an anesthesia of cells to cortisol or strengthening of metabolism of cortisol in fabrics that leads to decrease in them efficiency concentration of hormone.

A thyroid gland

Consider that normal function of a thyroid gland is one of the main conditions of development of a sensitization. Tireopdektomirovanny animals it is possible to sensibilize only passively. The thyroidectomy weakens a sensitization and an acute anaphylaxis. The its influence on intensity of shock less time between the allowing administration of antigen and a thyroidectomy, the less. The thyroidectomy before a sensitization slows down emergence of pretsipitpn. If in parallel with a sensitization to give hormones of a thyroid gland, then antibody formation increases. There are data that hormones of a thyroid gland strengthen tuberkulinovy reaction.

The thymus

the Role of a thymus in the mechanism of allergic reactions is studied in connection with new data on a role of this gland in an immunogenesis. It is known that a pitchfork-point gland plays a large role in the organization limf, systems. It promotes settling limf, glands lymphocytes and regenerations limf, the device after its various damages. Thymus (see) plays an essential role in formation And. the immediate and slowed-down type and first of all at newborns. At rats, timektomirovanny at once after the birth, Artyus's phenomenon to the subsequent injections of a bull seralbumin does not develop though the nonspecific local inflammation caused, e.g., by turpentine under the influence of a thymectomy does not change. Adult rats after simultaneous removal of a thymus and a spleen have a braking of immediate allergic reactions. At such animals, sensibilized horse serum, observes clear braking of an acute anaphylaxis on intravenous administration of the allowing dose of antigen. It is established also that introduction to mice of extract of a thymus of an embryo of a pig causes hypo - and an agammaglobulinemia.

Early removal of a thymus causes also braking of development of all allergic reactions of the slowed-down type. At mice and rats after a neonatal thymectomy it is not possible to receive the local slowed-down reactions to the purified proteinaceous antigens. The similar effect is rendered by repeated injections of anti-thymic serum. Newborn rats have after removal of a thymus and a sensitization the killed tubercular mycobacteria a tuberkulinovy reaction on 10 — the 20th day of life of an animal is less expressed, than at the control not operated animals. The early thymectomy at chickens considerably extends the period of rejection of a gomotransplantat. The same impact is exerted by a thymectomy on newborn rabbits and mice. Change of a thymus or cells limf, nodes recovers immunological competence of lymphoid cells of the recipient.

Many authors connect development of autoimmune reactions with dysfunction of a thymus. Really, at timektomirovanny mice with the thymic glands replaced from donors with spontaneous hemolitic anemia autoimmune frustration are observed.

Gonads

About influence of gonads on the Allergy there are many hypotheses. According to one data, castration causes hyperfunction of a front share of a hypophysis. Hormones of a front share of a hypophysis reduce intensity of allergic processes. It is known also that hyperfunction of a front share of a hypophysis leads to stimulation of the function of adrenal glands which is a proximate cause of increase in resistance to an acute anaphylaxis after castration. Other hypothesis assumes that castration causes a lack of sex hormones of blood that also reduces intensity of allergic processes. Pregnancy, as well as are oestrogenic, can suppress skin reaction of the slowed-down type at tuberculosis. Estrogen slows down development of an experimental autoimmune thyroiditis and polyarthritis at rats. Similar action cannot be received, applying progesterone, testosterone.

The provided data speak about undoubted influence of hormones on development and the course of allergic reactions. Influence it is not isolated and is implemented in the form of complex action of all hemadens, and also various parts of the nervous system.

The nervous system

the Nervous system is directly involved in each of stages of development of allergic reactions. Besides, nervous tissue itself can be a source of allergens in an organism after impact on it of various damaging agents, in it allergic reaction of antigen with an antibody can be developed.

Local putting antigen on motor area of bark of big hemispheres of sensibilized dogs caused a hypomyotonia, and sometimes increase in a tone and spontaneous reductions of muscles on the party opposite to application. Impact of antigen on a myelencephalon caused lowering of arterial pressure, disturbance of respiratory movements, a leukopenia, a hyperglycemia. Putting antigen on area of a gray hillock of a hypothalamus led to a considerable hyperglobulia, a leukocytosis, a hyperglycemia. The entered initially heterogeneous serum has exciting effect on bark of big cerebral hemispheres and subcrustal educations. In the period of a sensibilized condition of an organism force of exciting process is weakened, process of active braking is weakened: mobility of nervous processes worsens, the limit of operability of nervous cells decreases.

Development of reaction of an acute anaphylaxis is followed by considerable changes of electric activity of a cerebral cortex, subcrustal gangliyev and formations of a diencephalon. Changes of electric activity arise from first seconds of administration of alien serum and further have phase character.

Participation autonomic nervous system (see) in the mechanism of an acute anaphylaxis and various allergic reactions many researchers at experimental studying of the phenomena assumed And. Further observations in the mechanism of allergic reactions were made by also many clinical physicians in connection with studying of a pathogeny of bronchial asthma, an allergic dermatosis and other diseases of the allergic nature about a role of the autonomic nervous system. So, researches of a pathogeny of a serum disease showed essential value of disturbances of the autonomic nervous system in the mechanism of this disease, in particular essential value of a vagus-phase (lowering of blood pressure, sharply positive symptom of Ashner, a leukopenia, an eosinophilia) in a pathogeny of a serum disease at children. Development of the doctrine about mediators of transfer of excitement in neurons of the autonomic nervous system and in various neuroeffector synapses also found reflection in the doctrine about And. and significantly advanced a question of a role of the autonomic nervous system in the mechanism of some allergic reactions. Along with the known histamine hypothesis of the mechanism of allergic reactions also other theories of the mechanism of allergic reactions appeared cholinergic, dystonic.

During the studying of allergic reaction of a small intestine of a rabbit transition of significant amounts of acetylcholine from the connected state in free was found. Relationship of mediators of the autonomic nervous system (acetylcholine, sympathin) with a histamine in process of allergic reactions are not found out.

There are data on a role of both sympathetic, and parasympathetic department of the autonomic nervous system in the mechanism of development of allergic reactions. On a nek-eye to data, the condition of an allergic sensitization is expressed in the beginning as dominance of a tone of a sympathetic nervous system which then is replaced by a parasympathotonia. Influence of sympathetic department of the autonomic nervous system on development of allergic reactions was studied by both surgical, and pharmacological methods. A. D. Ado and T. B. Tolpegina's researches (1952) showed that at serumal, and also at bacterial And. in a sympathetic nervous system increase in excitability to a specific antigen is observed; impact of antigen on heart according to sensibilized Guinea pigs causes release of sympathin. In the conditions of experiences with the isolated and perfuzirusmy upper cervical sympathetic node at cats, sensibilized horse serum, introduction of a specific antigen to current of perfusion causes excitement of a node and respectively reduction of the third century. Excitability of a node to electric irritation and to acetylcholine after a proteinaceous sensitization increases, and after influence of the allowing dose of antigen falls.

Change of a functional condition of a sympathetic nervous system is one of the earliest expressions of a condition of an allergic sensitization of animals.

Increase in excitability of parasympathetic nerves at a proteinaceous sensitization was established by many researchers. It is established that anaphylotoxin excites the terminations of parasympathetic nerves of smooth muscles. Sensitivity of a parasympathetic nervous system and the bodies innervated by it to sincaline and acetylcholine in development of an allergic sensitization increases. On Danpelopolu's hypothesis (D. Danielopolu, 1944), anaphylactic (parafilaktichesky) shock is considered as a condition of increase in a tone of all autonomic nervous system (an amphotonia on Daniyelopola) with increase in release of adrenaline (sympathin) and acetylcholine in blood. In a condition of a sensitization development both acetylcholine, and sympathin increases. Anaphylactogen causes nonspecific influence — release in bodies of acetylcholine (prekholin) and specific action — products of antibodies. Accumulation of antibodies causes a specific filaksiya, and accumulation of acetylcholine (prekholin) causes a nonspecific anaphylaxis, or a parafilaksiya. The acute anaphylaxis is considered as «gipokholinesterazny» diathesis.

Daniyelopolu's hypothesis in general is not accepted. However there are numerous facts about close connection between development of a condition of an allergic sensitization and change of a functional condition of the autonomic nervous system, e.g. sharp increase in excitability of cholinergic innervatsionny devices of heart, intestines, uterus and other bodies to sincaline and acetylcholine.

On And. D. Ado, allergic reactions of cholinergic type at which the leading process are reactions of cholinergic structures, reactions of gistaminergnchesky type at which the histamine plays the leading role, reactions of simpatergichesky type (presumably) where the leading mediator is sympathies, and, at last, various reactions of the mixed type distinguish. The possibility of existence and such allergic reactions in which mechanism the leading place will be occupied by other biologically active products, in particular slowly reacting substance is not excluded.

The role of heredity in development of an allergy

Allergic reactivity considerably is defined by hereditary features of an organism. Against the background of genetic predisposition to And. in an organism under the influence of the environment the condition of the allergic constitution, or allergic diathesis forms. Ekssudatpvny diathesis, eosinophilic diathesis, etc. are close to it. Allergic eczema at children and exudative diathesis often precede development of bronchial asthma and other allergic diseases. The medicinal allergy arises three times more often at patients with allergic reactivity (a small tortoiseshell, a pollinosis, eczema, bronchial asthma, etc.).

Studying hereditary otyagoshchennostn at patients with various allergic diseases showed that about 50% from them have in a lineage of relatives with these or those displays of the Allergy. 50,7% of children with allergic diseases also have a hereditary burdeness concerning A. U of healthy faces the Allergy in the hereditary anamnesis is noted no more than in 3 — 7%.

It is necessary to emphasize that not allergic disease per se, but only predisposition to the most various allergic diseases is inherited and if the inspected patient has, e.g., a small tortoiseshell, then at his relatives in various generations the Allergy can be expressed in the form of bronchial asthma, migraine, a Quincke's edema, rhinitis etc. Attempts to find patterns of inheritance of predisposition to allergic diseases showed that it is inherited as a recessive character according to Mendel.

Influence of hereditary predisposition on emergence of allergic reactions is clearly demonstrated on the example of studying of an allergy at enzygotic twins. Numerous cases of absolutely identical manifestations are described And. at enzygotic twins to the same set of allergens. At titration of allergens on skin tests absolutely identical credits of skin reactions, and also the identical maintenance of allergic antibodies (reagins) to the allergens causing a disease are found in enzygotic twins. These data show that hereditary conditionality of allergic states represents an important factor of formation of the allergic constitution.

During the studying of age features of allergic reactivity two raising of number of allergic diseases are noted. The first — at the earliest children's age — up to 4 — 5 years. It is defined by genetic predisposition to an allergic disease and is shown in relation to food-borne, household, microbic allergens. The second rise is observed p reflects completion of formation of the allergic constitution under the influence of a factor of heredity (genotype) in the period of puberty and the environment.



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V. A. Ado; R. V. Petrov (I am glad.). V. V. Serov (stalemate. An.).

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