allergyЕn.pptx
- 1. Allergy The plan 1. Allergy, definition, etiology. Exo- and endogenous allergens, their characteristic. 2. Classification of allergic reactions. 3. Pathogenesis of allergic reactions. Sensitization, concept, types, pathogenesis. 4. Allergic reactions of reagenic type, etiology, pathogenesis.
- 2. 6. Allergic reactions of cytotoxic type, etiology, pathogenesis. 7. Allergic reactions of immune complex mediated type, etiology, pathogenesis. 8. Allergic reactions of cellular - mediated type, etiology, pathogenesis. 9. Hyposensitization, types, pathogenesis. 10.Pseudo-allergic reactions, concept, pathogenesis. Pictures are from Robbins Pathologic basis of disease. V. Kumar, A.K. Abbas, S.N. Fausto, 7th , 8th edition, 2007, 2010; prof. O.I. Urasova’s lectures and internet resources
- 4. Органы иммунной системы Центральные органы лимфопоэза ТИМУС КОСТНЫЙ МОЗГ КРОВЬ ЛИМФА ТКАНИ лимфоидные ЛИМФОУЗЛЫ СЕЛЕЗЕНКА Периферические органы лимфопоэза
- 5. NAIVE (immunologically inexperienced) lymphocytes - are mature lymphocytes that have not encountered the antigen for which they are specific. EFFECTOR CELLS differentiated lymphocytes after activation by antigens, perform the function of eliminating microbes MEMORY CELLS which live in a state of heightened awareness and are better able to combat the microbe in case it returns.
- 6. T- (thymus-derived) lymphocytes – 60% of blood lymphocytes CD4 and CD8 serve as “coreceptors” in T-cell activation CD4 is expressed on approximately 60% of mature CD3+ T cells, which function as cytokine-secreting helper cells that help macrophages and B lymphocytes to combat infections CD8 is expressed on about 30% of T cells, which function as cytotoxic (killer) T lymphocytes (CTLs) to destroy host cells harboring microbes.
- 7. The B-cell receptor complex is composed of membrane immunoglobulin M (IgM; or IgD, not shown), which recognize antigens, and the associated signaling proteins Igα and Igβ. CD21 is a receptor for a complement component that also promotes B-cell activation B - (bone-marrow- derived) lymphocytes
- 8. FIGURE 6-1 The principal classes of lymphocytes and their functions in adaptive immunity.
- 9. Dendritic cells. A, Cultured dendritic cells showing the prominent surface projections. B, The location of dendritic cells (Langerhans cells) in the epidermis (stained blue using an immunohistochemical method). (Courtesy of Dr. Y-J. Liu, M.D. Anderson Cancer Center, Houston, TX.)
- 10. Macrophages . Process the antigens and present peptide fragments to T cells. Thus, macrophages function as APCs in T-cell activation Are key effector cells in certain forms of cell- mediated immunity, the reaction that serves to eliminate intracellular microbes. In this type of response, T cells activate macrophages and enhance their ability to kill ingested microbes. Participate in the effector phase of humoral immunity, efficiently phagocytose and destroy microbes that are opsonized (coated) by IgG or C3b.
- 11. NK cells kill a variety of infected and tumor cells, without prior exposure to or activation by these microbes or tumors.
- 12. Migration of naive and effector T lymphocytes. Naive T lymphocytes home to lymph nodes via high endothelial venules (HEVs). Activated T lymphocytes, including effector and memory cells, home to sites of infection in peripheral tissues, and this migration is mediated by E- selectin and P-selectin, integrins, and chemokines secreted at inflammatory sites that are recognized by chemokine receptors that are expressed on activated T cells. APC, antigen-presenting cell; ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion molecule 1.
- 13. Antigen processing and display by MHC molecules. A, In the class I MHC pathway, peptides are produced from proteins in the cytosol and transported to the endoplasmic reticulum (ER), where they bind to class I MHC molecules. The peptide-MHC complexes are transported to the cell surface and displayed for recognition by CD8+ T cells. B, In the class II MHC pathway, proteins are ingested into vesicles and degraded into peptides, which bind to class II MHC molecules being transported in the same vesicles. The class II–peptide complexes are expressed on the cell surface and recognized by CD4+ T cells.
- 15. Humoral immunity. Naive B lymphocytes recognize antigens, and under the influence of TH cells and other stimuli, the B cells are activated to proliferate and to differentiate into antibody-secreting plasma cells. Some of the activated B cells undergo heavy-chain class switching and affinity maturation, and some become long-lived memory cells. Antibodies of different heavy-chain classes (isotypes) perform different effector functions, shown on the right.
- 17. ALLERGY is immune response accompanied by damage to the tissues of the body (V.I.Pytsky) The causes of allergy are allergens Classification of allergens (by A.D.Ado) Exoallergens: Household Dust mites cockroaches
- 18. Food
- 19. Medications Layel Syndrome Stevens – Johnson Syndrome
- 20. Animal origin dandruff and hair of animals Bee, wasp venom Fodder, feathers
- 21. Plants
- 22. plants
- 24. • Industrial • Microbial • Fungal mould
- 25. ENDOALLERGENS AUTOALLERGENS • NATURAL (PRIMARY) • AQUIRED (SECONDARY) Primary endoallergens Normal tissue proteins, which didn’t have a contact with lymphocytes during embryogenesis. Organism doesn’t have immune tolerance for these proteins
- 26. NATURAL OR PRIMARY ENDOALLERGENS • Nervous tissue • lens (crystalline)
- 27. • Thyroid colloid • Testis
- 28. Aquired or secondary endoallergens Proteins with changed structure: • Infectious • Non infectious
- 29. THE CONDITIONS PROMOTING DEVELOPMENT OF ALLERGY Social factors vaccination, environmental polution, widespread chemical substances, uncontrolled administration of medications. Organism’s peculiarities • hereditary predisposition • high permeability of biobarriers • insufficiency to inactivate mediators of allergy
- 30. CLASSIFICATION OF ALLERGIC REACTIONS: According to the rapidity and duration of the immune response (by Kook,1930 ) I. Immediate type. Allergen sets in motion immediate (second to minutes) immune response, mediated by humoral antibodies. II. Delayed type in which the reaction is slower in onset and develops within 24-48 hours and the effect is prolonged. Immune response is mediated by T- lymphocytes.
- 31. According to the pathogenesis (P. Gell and R. Coombs’s classification) • Type I – anaphylactic, reagenic type • Type II – cytotoxic type • Type III – immune complex mediated type • Type IV – cell-mediated type
- 32. PATHOGENESIS OF ALLERGIC REACTIONS 1. Immunological stage (a stage of immune reactions) 2. Pathochemical stage (a stage of biochemical reactions) 3. Pathophysiological stage (a stage of clinical symptoms)
- 33. • Formation of antibodies or sensitized Т-lymphocytes (s-ТL) at primary contact with allergen (sensitization) • Formation of complexes allergen+antibody or allergen + s-ТL at secondary contact with allergen Immunological stage
- 34. PATHOCHEMICAL STAGE Releasing, activation, synthesis of biologically active substances - mediators of allergy.
- 35. III. Pathophysiological stage (a stage of clinical symptoms) • structural and functional disorders of organs and tissues
- 36. SENSITIZATION is formation of the high sensitivity of an organism to certain allergen It is characterized by formation of specific antibodies or sensitized Т- lymphocytes (s-ТL) to the certain allergen.
- 37. SENSITIZATION ACTIVE Develops in 10-14 days after primary contact with allergen Organism immune system actively participates in process of specific antibodies or s-TL formation PASSIVE Develops after infusion of serum containing antibodies, or a cellular suspension with s-TL Organism immune system does not participate in formation of antibodies and s-TL
- 38. TYPE I ALLERGIC REACTIONS type I hypersensitivity reagenic or anaphylactic type ALLERGEN • pollen of plants, animal and vegetative proteins • medications
- 39. Allergen Macrophage Т-lymphocyte В- lymphocyte Transformation of B-lymphocytes into plasma cells IgE, G4 synthesis IgE, IgG4 fixation on mast cells, basophils Sensitization
- 40. Гуморальный (Th2) иммунный ответ CD4+ Т- клетка В- клет ка В В В В В В Плазмоцит Плазмоцит Плазмоцит Плазмоцит Антитела АПК Клональная пролиферация В-клеток Негативная селекция Тh1-клеток IL- 10 IL-4,5,6,13 В- клетки памяти CD4+ Th0 CD4+ Th2 IL-4
- 41. Re-exposure of allergen (repeated contact with allergen Formation of complexes Allergen + antibody on a surface of mast cells (labrocytes) or basophils
- 43. Pathochemical stage • Mast cells degranulation and releasing of: • histamine, proteases, heparin, chemotactic factors for eosinophils and neutrophils • Formation of leukotrienes B4C4D4 and prostaglandins D2 from membrane phospholipids.
- 44. • Migration to the zone of allergic reaction eosinophils, neutrophils and releasing secondary mediators: histaminase, proteases, phospholipases etc.
- 45. Pathophysiological stage • vasodilation • increased vascular permeability • edema • smooth muscles contraction •bronchospasm •Bronchial hypersecretion of mucus • cell injury
- 47. Clinical symptoms • Anaphilactic shock • Pollinosis (Hay fever) • Atopic bronchial asthma • Urticaria (hives) • Quincke’s edema • Gastroenterocolitis
- 49. Type II Allergic reactions (cytotoxic type) Allergens (endoallergens) Either normal or altered components of cellular membranes, glomerular basement membrane collagen etc. Chemical substances, including drugs, fixed on a cellular membrane (Au, Ni, Zn, Cu, antibiotics)
- 50. Allergen Macrophage Т-lymphocyte В-lymphocyte Transformation of B-lymphocytes into plasma cells IgG1, 2,3, IgM synthesis Secondary contact with allergen
- 51. Basal membrane of Renal glomeruli
- 52. • Formation of complexes allergen+antibody on a surface of target cells
- 53. • Activation of complement components • liberation of lisosomal enzymes (DNA-ase, RNA-ase, elastase) • free radicals (О-, ОН., Н2О2) during phagocytosis Lysis of target cells, destruction of basement membranes
- 54. Complement-mediated cytolysis activation of complement components: С3а, С3в, С5а (opsonization) phagocytosis Complex С5 - С9 formation of channels in cellular membranes osmotic lysis of cells
- 55. Complement-independent (antibody- dependent) cytotoxicity • а) cells coated with antibodies (IgG) are susceptible to phagocytosis (opsonization) • б) cells coated with antibodies activate NK-cells (killers) having on the surface receptors to a Fc- fragment of antibodies NK-cell
- 56. Antibody-mediated cellular dysfunction antibodies directed against cell surface receptors (myasthenia gravis) antibody mediated stimulation of cell function (Grave’s disease). IgG acts as Thyrotropin
- 57. Clinical examples Autoimmune: hemolytic anemia thrombocytopenia Goodpasture syndrome agranulocytosis
- 58. TYPE III ALLERGIC REACTIONS (immune complex mediated ) ALLERGENS BACTERIA, VIRUSES, DNA, DRUGS, ANTISERA, SOLUBLE PROTEINS
- 59. Allergen Macrophage Т-lymphocyte В-lymphocyte Transformation B-lymphocytes into plasma cells IgG, M synthesis Secondary contact with allergen
- 60. Formation of soluble allergen+antibody complexes (the complexes are of intermediate size and there is antigen excess • Circulation of immune complexes in blood and lymph • Deposition of the immune complexes in vascular basement membranes
- 61. Mediators • Activation of complement components, phagocytosis activation, release of lysosomal enzymes and free oxygen radicals • Degranulation of mast cells and release of histamine, serotonin, heparin, chemotactic factors, formation of LT and PG, PAF • Kinin and clotting systems activation
- 62. Pathophysiological stage • Increased vascular permeability • Damage of cells • thrombosis • Inflammation
- 63. • Vasculitis • Serum sickness • Glomerulonephritis • Rheumatic heart disease • Farmer’s lung • Arthus reaction – localized area of tissue necrosis
- 65. TYPE IV ALLERGIC REACTIONS (cell - mediated) ALLERGEN mycobacterium tuberculosis fungi parasites viruses tissue proteins of low molecular weight and low immunogenity
- 66. Recognition of allergen, Cooperation Macrophages and lymphocytes differentiation ThoTh1 Formation of sensitized T-L (CD4+) At secondary contact with allergen activation of T- lymphocytes and production of lymphokines
- 67. Formation and secretion lymphokines by s-TL • activators of macrophages (IFN-) and granulocytes (chemotactic factors) • activators of lymphocytes (IL-2, IL-12) • Lymphokines which damage tissues (TNF-) • Antiinflammatory IL-10, TGFβ
- 68. Tissue damage due to: • lymphokines • CD8 – T-killers (with the help of perforin, which drill holes in the target cells, thus causing osmotic lysis; and by inducing apoptosis) • Lysosomal enzymes
- 70. • Tuberculin test (positive Mantoux reaction). After intracutaneous injection of tuberculin, a protein- lipopolysaccharide component of the tubercle bacillus, a local area of erythema and induration begins to appear at 8 to 12 hours, reaches a peak (1-2 cm in diameter) in 2 to7 days and there after slowly subsides.
- 71. Examples • Tuberculin test (positive Mantoux reaction). After intracutaneous injection of tuberculin, a protein-lipopolysaccharide component of the tubercle bacillus, a local area of erythema and induration begins to appear at 8 to 12 hours, reaches a peak (1-2 cm in diameter) in 2 to7 days and there after slowly subsides. • Brucellosis • Candidosis • Transplant rejection • Contact Dermatitis
- 72. Hyposensitization is decreased sensitivity to allergen • Specific • Nonspecific
- 73. Specific hyposensitization (it is effective for type I hypersensitivity) • Is decreased sensitivity to the same allergen that caused allergy (Injection of serum using Bezredka’s method: firstly the small amount of allergen, then the rest). Pathogenesis • Formation of blocking antibodies • Decreased synthesis of reagens • Decreased amount of mediators
- 74. Nonspecific hyposensitization is used when specific can’t be performed. It restores the immune reactivity. It can be achieved by using of antimediators, membrane stabilizators, antioxidants, glucocorticoids.
- 75. PSEUDO-ALLERGIC REACTIONS • Group of reactions, similar to allergy by clinical symptoms, but without immunological stage. • Develop under the action of factors causing mast cells degranulation and liberation of biologically active substances.
- 76. Pathogenesis 1. Due to high Histamine level Mast cells degranulation Impaired histamine breakdown Increased reception with food (certain cheeses, smoked sausages) Dysbacteriosis
- 77. 2. Disorders of the complement system activation Excessive activation of complement system Deficiency of inhibitors of complement components 3. Disorders of arachidonic acid metabolism Impaired balance between prostaglandins and leukotrienes (aspirin administration )