Immune Pathology Immune system functions reactivity to tolerance nonshared Ag to self-Ag reduction pErVeRsIoN malfunction immunodeficiency hypersensitivity autoimmune diseases Hypersensitivity Hypersensitivity - excessive or inadequate manifestation adaptive immune of reactions Can manifest as local and systemic reactions Hypersensitivity Type Synonym Immunological mechanisms I IgE-mediated, anaphylactic, IgE-mediated degranulation of mast reaginic, HIS (blood cells dyscrasia) II antibody-dependent Cytotoxic antibodies activate cytotoxicity complement, which leads to cell lysis III immune complex Immune complexes activate leukocytes IV cell-mediated, delayed-type Cytokine production by hypersensitivity macrophages and lymphocytes V antibody-dependent Antibodies alter functional state of functional changes cells by interacting with its receptor Type I hypersensitivity • Speed ​​of reaction - seconds or minutes • IgE-mediated • Chemical mediators of damage - vasoactive products of mast cells / basophils (histamine, arachidonic acid derivatives) • Mechanism - accumulation of of neutrophils, unstriated muscle spasm Type I hypersensitivity • bronchial asthma (some forms) • anaphylactic shock • Urticaria • Quincke's edema • dietary allergy • nasal allergy • allergic conjunctivitis Mast cell Аг Synthesis and secretion: leukotrienes (LTC4, LTB4), prostaglandins (PGD2), degranulation: IL-3, 4,5,6 histamine Platelet-activating factor serotonin (PAF) eotoxin Type I hypersensitivity Morphological manifestations IHS: • exudative alterative inflammation (many eosinophils infiltrate) • dilation of blood vessels, increased vascular permeability • unstriated muscle spasm Type II hypersensitivity • Speed ​​of reaction – hours or days • Mediated by IgG, IgM • Chemical mediators of damage – complement • Mechanism - phagocytosis, lysis of target Type II hypersensitivity Types: • Cytotoxicity, complement-mediated • Antibody-dependent damage to connective tissue Type II hypersensitivity Mechanisms of complement-mediated cytotoxicity: 1. Lysis 2. Opsonization phagocytosis Example: some hemolytic anemia (blood transfusion of differ group, hemolytic disease of fetus and newborn) Membrane attack complex Ат Аг Osmotic lysis Complement Opsonization С3b-R Fc-receptor Macrophage Phagocytosis Type II hypersensitivity Antibody-dependent damage to the connective tissue • Circulating antibodies are fixed on connective tissue Ag and thus stimulate inflammation Examples: Goodpasture's syndrome, bullous pemphigoid Type III hypersensitivity • Speed ​​of reaction – hours or days • Mediated by IgG, IgM, IgA as part of immune complexes • Chemical mediators of damage - complement and its fractions • Mechanism - accumulation of of neutrophils, macrophages, release of lysosomal enzymes Type III hypersensitivity • most of glomerulonephritis • Systemic lupus erythematosus (SLE) (vasculitis and nephritis) • Rheumatoid arthritis (RA) • some vasculitides • Arthus reaction (experimental vasculitis) Type III hypersensitivity Morphological manifestations: • vascular injuries (vasculitis with large numbers of neutrophils, edema and hemorrhage into surrounding tissue) • Mesenchymal dysproteinosis (mucoid swelling, fibrinoid swelling, fibrinoid necrosis) Deposition of IC Complement IC activation basal membrane endotheliocyte Blood vessel neutrophil proteases proteolysis of BM 4 Secretion of proteases Chemotaxis and and active O2 neutrophils activation tissue damage Type IV hypersensitivity • Speed ​​of reactions – days • Mediated by T-and NK-cells • Chemical mediators of damage - lymphokines, monokines • Mechanism - the action of lymphocytes and macrophages, granulomas formation Type IV hypersensitivity • diseases associated with formation of granulomas (tuberculosis, syphilis, leprosy, sarcoidosis, Crohn's disease, etc.) • contact dermatitis (poison ivy) • transplant rejection reaction • autoimmune thyroiditis (Hashimoto) • insulin-dependent diabetes mellitus Type IV hypersensitivity Morphological manifestations of DTHS (delayed-type hypersensitivity): • productive inflammation, often with formation of granulomas. In infiltrate dominated lymphocytes, monocytes, macrophages Type V hypersensitivity Antibody-dependent functional changes: • The antibodies attach to the receptors and, thus, or block them (miastenia gravis), or stimulate (Graves' disease) • does not occur death of cell-target Examples: Ab acetylcholine receptor - miastenia gravis, Ab to thyroid-stimulating hormone receptor - Graves' disease (diffuse thyrotoxicosis). acetylcholine Ab to acetylcholine receptor acetylcholine receptor Immunodeficiency states Immunodeficiency states - a group of diverse syndromes caused by isolated or multiple defects of the immune system. Characterized by increased susceptibility to infections, leading to severe, acute and chronic diseases. Immunodeficiency states Primary immunodeficiency – genetically determined disease Secondary immunodeficiency – immunodeficiency which arose as a result of an illness of previously healthy person Primary immunodeficiency Depending on the affected section are divided onto groups: 1. B-cell deficiency 2. T-cell deficiency 3. combined ID 4. phagocyte defects 5. complement defects Primary immunodeficiency Epidemiology overall incidence of symptomatic PIDS - 1:10 000 Predominant pathology of B cells - 50% PIDS (frequency of IgA deficit - 1:400) pathology of T-cells - 30% phagocyte defects - 18% complement deficiency - 2% About 80% of patients younger than 20 years 70% - affected males (X-linked). B-cell deficiency Main manifestation - Ab deficiency and consequently increased sensitivity to bacterial infections • X-linked agammaglobulinemia (Bruton's syndrome) • common variable immunodeficiency • IgA deficiency • IgG subclass deficiency • etc. X-linked agammaglobulinemia (Bruton's syndrome) Panhypogammaglobulinemia of boys, characterized by low IgG, low or lack of other Ig-s, unchanged cellular immunity and outbreaks of infections in the age of 6 months, when mother’s Ab-s disappear X-linked agammaglobulinemia (Bruton's syndrome) Genetic defect associated with the inability to differentiate B- cells from pre-B cells. Hypersensitivity to pyogenic infections High risk of vaccinal poliomyelitis Autoimmunity: RA, SLE, etc. morphologically : • No germinal centers in lymph nodes and spleen • No plasma cells • Poorly developed palatine tonsils Selective IgA deficiency Absence or abrupt decrease of serum IgA at normal level of other Ig and intact cellular immunity The most common and lightest ID (up to 1:400) In the majority are asymptomatic IgA in secretions also not detected, its deficiency can be compensated by other Ig May occur recurrent respiratory infections, chronic diarrhea, allergic or autoimmune diseases T-cell deficiency The main manifestation - deficiency of cellular immunity and, consequently, increased sensitivity to viral and fungal infections • syndrome Dee Georgie • chronic mucocutaneous candidiasis • etc. Dee Georgie syndrome Synonyms: thymic hypoplasia, syndrome of 3rd and 4th pharyngeal recess Congenital ID, which is characterized by: • hypocalcemic tetany • congenital disorders of the heart and great vessels • specific face shape • increased susceptibility to infections • hypoplasia of the thymus and parathyroid glands • partial or total T-cells ID • normal B-cells immunity Dee Georgie syndrome Low-set ears, cleavage at the middle of face, jaw hypoplasia, hypertelorism and a shorter longitudinal groove between the nose and upper lip. Microscopically: None thymus-dependent area of lymph nodes and spleen Tetany begins to manifest in 1-2 days after birth Etiology: • disruption of normal development of derivatives pharyngeal recess on the eighth week of gestation. • deletion of chromosome 22 The degree of ID for different patients varies, can occur spontaneous function improvement of T-cells. Combined ID Group of diseases with congenital and often hereditary defect of T-and B-cell systems, aplasia of lymphoid tissue and dysplasia of thymus. • severe combined ID (SCID) • Swiss agammaglobulinemia • dysgenesis of reticulum • Combined ID with preservation of Ig (Nezelof syndrome) • etc. Combined ID • at an early age (up to 3 months) appear thrush, pneumonia, diarrhea, which untreated progresses to death before the age of 2 • pronounced deficiency of B-cells, Ig, T-cells • lymphopenia • common opportunistic infections • absence of radiologically detectable thymus lymph nodes aplasia Secondary immunodeficiency Causes: • severe infectious diseases • malabsorption • aging • malnutrition • treatment with immunosuppressive drugs (corticosteroids, cytotoxic drugs) • radiation therapy • AIDS • autoimmune diseases • malignant tumors • etc. AIDS HIV CD4 Proviral DNA T-helper AIDS Lymphoid Lymphoid hyperplasia depletion Morphology of immunity organs at secondary immunodeficiencies Thymus - is formed atrophy corresponding IV-V phase ATMT. In peripheral immune organs - devastation (delymphonyzation) of structural-functional areas. Autoimmune diseases Autoimmune disease - a group of diseases, which are based on development of immune responses in body's self-Ag Autoimmune diseases I. Organ-specific II. Organo-nonspecific • Hashimoto's thyroiditis • systemic lupus • autoimmune encephalomyelitis erythematosus • insulin-dependent DM • rheumatoid arthritis • Graves' disease • Sjögren's sicca [Mikulicz- • miastenia gravis Sjögren] syndrome • autoimmune pernicious anemia • Scleroderma systematica • autoimmune orchitis • inflammatory myopathies • autoimmune Addison's