The State Education Institution of Higher Professional Training

The State Education Institution of Higher Professional Training The First Sechenov Moscow State Medical University under Ministry of Health of the Russian Federation Department of Pathophysiology of the immune-surveillance system Lecture presentation Professor Pirozhkov S. V. 2014 -2015 education year

GENERAL ORGANIZATION OF THE IMMUNE-SURVEILANCE SYSTEM IMMUNE –SURVEILLANCE SYSTEM FACTORS OF THE INNATE IMMUNITY Nonspecific defense reactions FACTORS OF THE ADAPTIVE IMMUNITY Specific defense reactions (immune response)

TYPICAL FORMS OF DISORDER OF THE IMMUNE SURVEILLANCE SYSTEM ■ Immune deficiency states ■ Pathologic tolerance ■ Graft-versus-host disease ■ Allergies

Immune deficiency state is the result of a decrease of the immune response to various antigens or deficiency of factors of the innate immunity

CLASSIFICATION OF THE IMMUNE DEFICIENCY STATES I. Based on the subset of the immune surveillance system that is mainly affected: ● T-system-dependent ● B-system-dependent ● A-system-dependent ● complement-dependent ● due to deficiency of innate immunity (e. g. neutropenia) II. Based on the origin of disorder: ■ Primary (congenital) ■ Secondary (acquired) III. Based on the mechanism of disorder: ► Hyporegenetory ► Disfunctional ► Destructive (cytolytic)

Manifestations of the immune deficiency states ► High frequency of infectious diseases ► Unusual severity of infection ► Prolonged duration of infection ► Infection with unusual complications

T-dependent immunodeficiency state Di. George syndrome (thymic hypoplasia) Cause: deletion in chromosome 22 q 11 (or 10 p in some patients) Mechanism: hypoplasia of the thymus and parathyroid gland Manifestations: ● peripheral blood T-cell levels are reduced; B-cell levels - normal ● paracortical areas of the lymph nodes, periarteriolar sheaths of the spleen are depleted ● serum immunoglobulin concentrations are frequently normal, but Ab responses, particularly of Ig. G and Ig. A isotypes, are impaired ● hypocalcemic tetany ● facial abnormalities – abnormal ears, micrognathia (short maxilla), hypertelorism (e. g. increased distance between eyes) ● congenital cardiac defects

B-dependent immunodeficiency state X-linked agammaglobulinemia of Bruton Cause: mutation of gene for cytoplasmic tyrosine kinase in the long arm of the X-chromosome Mechanism: block of maturation of B lymphocytes at the pre-B stage Manifestations: ● B-cells are absent or remarkably reduced ● in the circulation levels of all classes of Ig are depressed ● plasma cells are absent throughout the body ● precursors of B cells (CD 19+, Ig-) are found in normal numbers in the bone marrow ● germinal centers of lymph nodes, Peyer’s patches, the appendix and tonsils are underdeveloped ● T-cell-mediated reactions are normal ● Recurrent bacterial infections of the respiratory tract, high susceptibility to enteroviruses and Giardia lamblia

Manifestations of the acute graft-versus-host disease ► Immune deficiency state (cytomegalovirus pneumonitis particularly important) ► Generalized rash leading to desquamation ► Jaundice ► Mucosal ulceration of the gut (bloody diarrhea)

ALLERGY is a pathologic process characterized by a specific increase in reactivity (hypersensitivity) to repeatedly administered allergen and manifested by more or less pronounced damage to the tissues of the body

TYPES OF ALLERGENES Heterologous (pollen, horse serum) Homologous (erythrocyte mass) Autologous (self-antigens) Exogenous Endogenous

TYPES OF ALLERGIES (P. Gell, R. Coombs, 1963) TYPE I : the immune response releases vasoactive and spasmogenic substances that act on vessels and smooth muscle and proinflammatory cytokins that recruit inflammatory cells TYPE II : humoral antibodies participate directly in injuring cells by predisposing them to phagocytosis or lysis. TYPE III : immune complex diseases in which humoral antibodies bind antigen and activate complement; the fractions of complement then attract neutrophils, which produce tissue damage. TYPE IV : sensitized T-lymphocytes are the cause of the cellular and tissue injury.

Type II allergy (cytotoxic) • Features of antigen: - present on the surface of cells or other tissue components - may be intrinsic to the cell membrane, or may take the form of an exogenous antigen • Features of reaction: - results from the binding of antibodies to (Ig. G or Ig. M) to normal or altered cell-surface antigens

TYPE III ALLERGY (IMMUNE COMPLEX MEDIATED) ● Features of antigen - exogenous: foreign protein, bacterium, virus - endogenous: antigenic component in cells and tissues ● Features of reaction: - it is initiated when Ag combines with Ab or at extravascular sites where Ag may have been deposited - complexes formed in the circulation produce damage when they are localize within blood vessel walls or when they are trapped in filtering structures (renal glomerulus)

TYPE IV ALLERGY (T-CELL MEDIATED) ● Features of antigen - intracellular microbiologic agents: Mycobacterium tuberculosum, viruses, fungi, protozoa, parasites - chemical agents - graft antigens ● Features of reaction: - delayed-type hypersensitivity - it is initiated by CD 4 T-cells and involves the direct cell cytotoxicity mediated by CD 8 T-cells