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Transcript
Clinical immunology • Allergy is an immune response, which is accompanied damage of own tissues. • Allergic diseases are widely spread among people. It is considered that they occupy about 10 % of earth population. In different countries these figures change from 1 to 50 % and more. • The cause of allergic disease is an allergen. • Allergen – is the substance that causes development of an allergic response. • Allergens have all properties of antigen (macromolecularity, mainly protein nature, foreign for particular organism). • However allergic reactions can be caused by substances not only antigen nature, but also substances, not possessing these properties. To this group belong many officinal preparations, bacterial products, polysaccharides, simple chemical substances (bromine, iodine, chrome, nickel). These substances are called haptens. They become antigens (allergens) only after binding with tissues proteins. Classification of allergens • Exogenous allergens • Endogenous allergens (autoallergens). • Exogenous allergens penetrate the organism from outside • Endoallergens are formed in the organism Classification of allergens a) uninfectious allergens: Home dust Epidermal Pollen Food Industrial Officinal b) infectious allergens: Bacterial Fungous Viral Food allergens • Domestic allergens. Main role among them domestic dust plays, which includes particles, bed-clothes, furniture, bacteria. Epidermal allergens. To this group refer: scurf, wool, birds, fur, fish, scales. Professional sensitization by epidermal allergen is observed in sheepmen, horsemen, poultry farms workers, hairdressers. Officinal allergens. Any officinal preparation with a little exception causes the development of officinal allergy. Medicines or their metabolites are, as usual, haptens. In case of sensitization of the organism to one preparation, allergic reactions to other medicines, having alike chemical structure can arise. Pollen allergens. Allergic diseases are caused by shallow plants, pollen. It is called pollinosis. The diverse types of pollen can have the general allergens, therefore in people, sensitive to one type of pollen, a reaction on its other kinds is possible. Food allergens. Many food products can be by allergens. It is usually fish, wheat, beans, tomatoes, milk, eggs. Chemical substances added to food products (dyestuffs, antioxidants, aromatic and other substances) may also be allergens. Industrial allergens. The industrial allergens for the most are haptens. In each industrial production a particular admission of chemical matters is used. These are: resin, glue and covering materials, plastics, dye-stuffs, metals and their salts, wood products, latex, perfumer substances, washing means, synthetic cloths and others. Pollen allergens Domestic allergens Infectious allergens Allergens of infectious origin. All the different causative agents of infectious diseases and products of their life activity cause the development of allergic processes. Those infectious diseases, in pathogenesis of which allergy plays leading role, were named infectious allergic. These are all the chronic infections (tuberculosis, lepra, brucellosis, syphilis, rheumatism, chronic candidosis etc.). The widespread allergens are the fungi. Many nonpathogenic fungi while entering the organism cause sensitization and development of diverse allergic diseases (bronchial asthma). Such fungi are contained in atmospheric air, dwellings, domestic dust, food products. With biotechnological development possibility of sensitization on enterprises on production of stern squire, vitamins, antibiotics, enzymes arises. Classification of endogenous allergens Natural Ecquired (brain,eye,sexuel 1.Infectious and thyroid glands) a) simplex b) complex 2.Uninfectious Pathogenesis of allergy reactions Classification of allergic reactions by R.A.Cooke • Allergy of immediate type • Allergy of delayed-type or hypersensitization of delayedtype Classification of allergy by R.A.Cooke • 1.Allergy of immediate type 1.1. Anaphylaxis 1.2. Serum disease 1.3. Atopic disease a) pollinosis (hay fever,rhinitis,conjunctivitis) b) bronchial asthma c) nettle-rash (urticaria,hives) d) Quincke’s edema Atopic Rhinites Classification of allergy by R.A.Cooke • 2. Allergy reactions of delayed-type 2.1. Contact dermatosis 2.2. Infectious allergy 2.3. Autoallergy 2.4. Reaction of graft rejection Classification of allergy by P.Gell, R.Coombs • • • • • Anaphylaxic Cytotoxic Immune-complex Delayed hypersensitivity Stimulating It is based on pathogenic principle. The peculiarities of immune mechanisms lay in its base. Formation of hypersensitivity • Immunological mechanisms lie in base of allergic processes development. • Central cell of immune system is a lymphocyte. • Lymphocytes are heterogenic according to their functions, markers, receptors. • They develop from a stem cell. After that a lymphoid stem cell is formed, from which T- and B-lymphocytes develop. • The T-lymphocytes acquire the specific antigen receptors, by means of which they identify an antigen and other markers. Immune mechanisms There are 3 types of T-cells: T-helper T-suppressors T-effectors • The last ones form sensitized lymphocytes or killers, which participate in realization of allergic reaction of delayed-type and realize cytotoxic action on cell-target. B-lymphocytes produce 5 classes of immunoglobulins IgG, IgM, IgA, IgE, IgD. • These cells during ripening acquire the receptors for antigen on their membranes. During binding of such B-cells with proper allergens and after the signal, received from Thelper, they become activated, and proliferation and differentiation into antibody producing cells starts. Mechanisms of allergy development Immune mechanisms • The correlation between two groups of subpopulations of T-helpers (Th-1 and Th-2) plays an important role in the development of immune reaction. • They are both formed of Th-0 and differ form each other by the set of secreted lymphokines and quantity of Fc-receptors for immune globulins on their surface. • On Th-2 there are many receptors for immune globulins A, M, E, and on Th-1 there are a few of them or they are absent. Mechanisms of allergy development Anaphylactic type of allergy Anaphylactic type includes the next atopic diseases: Atopic bronchial asthma Pollinosis Atopic dermatitis Nettle-rash (urticaria, havis) Food and officinal allergy Immunological stage • IgE and IgG4 are formed as an answer to penetrated allergen into the organism. • They get fixed on the mast cells and basophiles of blood. These cells have on their surface Fc receptors for immune globulin. The state of sensitization of the organism appears. • If the same allergen again gets into the organism or it still stays in the organism after the first penetration, connection of antigen with IgE-antibodies occurs. • The same thing is observed with IgG4. They bind with their receptors on basophiles, macrophages, eosinophiles, thrombocytes. • Depending on the quantity of IgE-antibodies connected to antigen, quantity of antigen can observe either inhibition of the cell activity or its activation and transfer to the pathochemical stage. Cellular mechanisms of allergy • Degranulation of mast cell Histamine • Histamine is localized in ready form in granules of the mast cells and basophile leucocytes. • In the blood of healthy people histamine almost totally stays in basophile leucocytes. • Histamine acts on the tissues cells through the receptors of two types – H1 and H2. • Their correlation and spreading on the cells of different cells is different. Stimulation of H1 promotes to contraction of smooth muscles, endothelial cells and postcapillary part of microcirculation. This leads to increasing of permeability of vessels, development of edema and inflammation. • Stimulation of H2 causes the opposite effects. Heparin • Heparin is activated after releasing out of the mast cells. • It possesses an antithrombine and anticomplementar activity. • Thrombocyte (platelet)activating factor (PAF) is secreted by basophiles, lymphocytes, thrombocytes and endothelial cells. Pathophysiological stage • Under influence of mediators permeability of vessels and chemotaxis of neutrophiles and eosinophiles are increased, that leads to development of inflammatory reaction. • The increase of permeability of vessels promotes the exit of fluid, immunoglobulins and complement into tissues. • By means of mediators and also through the IgEantibodies, the cytotoxic effect of macrophages is activated, secretion of enzymes, prostaglandins and leukotriens, thrombocyte activating factor is stimulated. • The released mediators cause also damaging action onto cells and connective tissue structures. • Bronchospasm develops in respiratory organs. • These effects clinically are manifested by attacks of bronchial asthma , rhinitis, conjunctivitis, nettle-rash, skin itch, diarrhea. Medicated allergy Anaphylactic shock • Anaphylactic shock develops as severe complication. • Spasm of smooth muscles of internal organs with clinical manifestation of bronchospasm (cough, expiratory dyspnea), spasm of gastro-intestinal tract muscles (spastic pain in the whole abdomen, nausea, vomiting, diarrhea), spasm of uterus in women (pain below abdomen) are observed. • Spastic phenomena are worsened by edemas of mucous covers of internal organs, during the edema of larynx the picture of asphyxia may develop. • The arterial pressure sharply is decreased, the heart insufficiency, ischemia of brain, paralysis develop danger for the life of the patient appears. • Pathochemical stage. The main mediator of cytotoxicity is the activated enzymes of complement. Phagocytes release some lyzosome enzymes and generate superoxide anion-radical. • Pathophysiological stage. The damage of the cell with antigen properties may be caused by three factors: • a) due to activation of complement, the components of which damage the cell membrane; • b) due to activation of phagocytosis of the cells with fixed antibodies; • c) due to activation of T-lymphocytes, natural killers, K-lymphocytes. Immune complex type • Pathophysiological stage. Usually immune complexes are placed on vessels of cannalicular apparatus of kidneys, inflammation with alteration, exudation and proliferation (glomerulonephritis) develops, in case if the complexes are placed in the lungs alveolitis appears, in skin – dermatitis. The inflammation may lead to formation of ulcers, hemorrhages, thrombosis is possible in the vessels. This type of allergic reactions is main in development of serum sick, some cases of officinal and food allergy, some autoallergic diseases (rheumatoid arthritis, systemic red lupus erythematosus). In case of activation of complement anaphylactic shock, bronchial asthma may develop. Immunological mechanisms • The foreign antigen is phagocyted by macrophages and get to T-helpers. At the same time macrophages secrete IL-1, which stimulates T-helpers. The latest excrete the growth factor pro-Tlymphocytes – IL-2, which activates and supports proliferation of T-cells. This process leads to formation of sensitized lymphocytes.They belong toT-lymphocytes and in the cell membrane they have receptors of the antibody type, which are able to connect with the antigen. In case of repeated penetration of the allergen into the organism it binds with the sensitized lymphocytes. Mechanisms of delayed type allergy Cellular mechanisms of delayed type allergy Allergic inflammation Pseudoallergic reactions • Pseudoallergy is pathological process, which is clinically similar to allergy but doesn’t have an immune stage of its development. The rest two stages – releasing of mediators (pathochemical) and pathophysiological (stage of clinical manifestations) take place. • For pseudoallergic reactions are characterized only processes in the development of which the leading role play mediators, which are formed also in pathochemical stage of true allergic reactions. Skin reaction onto allergen • 2. Specific desensitization by Bezredka. Desensitization is provided by little doses of the antigen, which do not cause severe reactions. The doses are introduced repeatedly after certain intervals of time, during which produced mediators get inactivated in the organism. The main dose of the antigen is introduced after antibodies binding. This method is effective in introduction of foreign medical vaccines. • 3. Inactivation of biological active substances. For this purpose antihistamine preparations, inhibitors of proteolytic enzymes etc. • 4. Protection of the cells from the influence of biological active substance and also normalizing of functional disorders in organs and systems (narcotic, spasmolytic substances, receptor blockers etc.).