Immune Pathology Immune system functions reactivity to tolerance nonshared Ag to self-Ag

reduction pErVeRsIoN malfunction

immunodeficiency

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 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

• 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 (some forms) • anaphylactic shock • Urticaria • Quincke's edema • dietary • nasal allergy • 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,

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

• Systemic erythematosus (SLE) (vasculitis and nephritis)

• (RA)

• some vasculitides

• (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) • 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 : 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 disease (dermatomyositis, (hypo(adreno)corticism) polymyositis) • autoimmune hemolytic anemia and thrombocytopenia • Transferred (sympathetic) ophtalmia Types of hypersensitivity reactions with various autoimmune diseases

Type Disease II Autoimmune thrombocytopenia, hemolytic anemia and agranulocytosis Goodpasture's syndrome (primary pulmonary hemosiderosis with glomerulonephritis) III systemic lupus erythematosus rheumatoid arthritis (Ankylosing spondylitis) Bechterew's disease Sjogren syndrome scleroderma Dermatomyositis IV Hashimoto's thyroiditis insulin-dependent diabetes mellitus V exophthalmic [toxic] goiter (Graves' [Basedow's] disease) Organ-specific autoimmune diseases

Possible reasons are: • violation of histohematogenous barriers (occurrence of autoimmune orchitis after injury) • as Ag becomes a protein expressed only by certain tissues (thyroid-stimulating hormone receptor at Graves' disease, Ag of erythrocytes at autoimmune hemolytic anemia)

Organ-nonspecific autoimmune diseases

• systemic lupus erythematosus • rheumatoid arthritis • Sjogren syndrome • Scleroderma systematica • inflammatory myopathies (dermatomyositis, polymyositis) • etc. Changes in thymus

1. Age involution 2. Accidental transformation of mature type (ATMT) 3. Accidental transformation of immature type (ATIT) 4. aplasia 5. hypoplasia 6. dysplasia 7. Hyperplasia (thymomegaly) Accidental transformation of mature thymus type (ATMT)

Observed more frequently in infants with infectious diseases, leukemia and malignant tumors. Differs from age involution of the thymus by diminution of thymocytes, leading to organ mass reduction, collapse of lobules