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MUCOSAL IMMUNITY

MUCOSAL IMMUNITY. MUCOSAL IMMUNITY - CHARACTERISTICS. skin and mucosa are interfaces between immune system and environment estimated area of mucosal surfaces is several hundreds of m 2 musosa is the largest organ of the immune system complex protection is mediated by both

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MUCOSAL IMMUNITY

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  1. MUCOSAL IMMUNITY

  2. MUCOSAL IMMUNITY - CHARACTERISTICS skin and mucosa are interfaces between immune system and environment estimated area of mucosal surfaces is several hundreds of m2 musosa is the largest organ of the immune system complex protection is mediated by both non-immunological and immunological mechanisms immune reaction is concentrated predominantly on the surface of mucosa

  3. PHYSIOLOGICAL BARRIERS: histological architecture of mucosa, tight junctions rapid turnover of epithelium from epithelial stem cells presence of mucus, glycocalyx ciliated surfaces (movement) optimal pH presence of physiological microflora

  4. IMMUNOLOGICAL MECHANISMS: MALT: mucosa-associated lymphoid tissues complex set of lymphoid tissues, immune cells and macromolecules, contribution of epithelial cells mucosal systém of eyes NALT: nose-associated lymphoid tissue BALT: bronchus-associated lymphoid tissue GALT: gut-associated lymphoid tissue mucosal systém of breast urogenital mucosal system

  5.  Krejsek, 2004

  6. Y Y BASIC CHARACTERISTICS OF MUCOSAL IMUNITY sIgA microbe adhesines blockage M U C U S MOVEMENT OF CILIA GUT MOVEMENT EPITHELIAL REPARATION TIGHT JUNCTIONS TS/C intraepithelial lymphocytes CD8+ (suppressor) IEL

  7. INDUCTION OF MUCOSAL IMMUNITY mucosa of gut is the central part of mucosal immunity intraepithelial lymphocytes are CD8+ suppressor cytotoxic T-cells: - down regulation of immune response - cytotoxic activity penetration of foreign compounds is through specialised mucosal M-cells of Payer’s plaques antigens are translocated into lamina propria via M-cells antigens are processed by lamina propriamacrophages antigenic peptides are presented to T-cells in context of HLA molecules

  8. INDUCTION OF MUCOSAL IMMUNITY helper inducer T-cells are dominant lymphocyte population in lamina propria T and B-cells in lamina propria are activated and clonally expanded activated T-cells leave gut mucosa and migrate into mucosa of other organs (lung, urogenital tract, breasts) and back to gut migration of T-cells is non-random (homing), regulated by specific interactions between surface molecules of T-cells and addressins on high endothelial venules

  9. Y Y plazmocyt B Y Y Y Y TH MUCOSAL IMMUNITY INDUCTION Ag sIgA2 penetration transport TS/C IEL M- cell transcytosis Y B7 CD28 IL- 6 vein IL-2,4 diferentiation HLA II. TcR clonal expansion TH directed migration APC TH 7 B 4 HEV homing molecule IL-12 TH INF- addressins (MAdCAM)

  10. SECRETORY IgA IMMUNOGLOBULINS: dimers of IgA molecules joined by J-chain produced by plasma cell dimers are transported through epithelia into lumen by transcytosis transcytosis is mediated by IgA receptors of epithelial cells part of this receptors remain bound to IgA dimers

  11. sIgA J - chain  Krejsek, 2004

  12. SECRETORY IgA IMMUNOGLOBULINS: part of IgA receptor is retained on IgA dimer as a secretory component secretory component prevents secretory IgA (sIgA) against proteolytic digestion IgA2 subclass of IgA is predominated in mucosal immune systeme all components of innate immunity including both complement system and phagocytosis are the integral part of mucosal immunity

  13. Y T B B Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y SECRETORY IgA SYNTHESIS VEIN LAMINA PROPRIA EPITHELIUM LUMEN MUCUS TH cytokines costimulation TH plasma cell IgA dimer Y Y IgG Ag Y Y IgG complement TS/C Y complement complement act.

  14. Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y TRANSCYTOSIS OF SECRETORY IgA LAMINA PROPRIA EPITHELIUM LUMEN IgA receptor secretory component Golgi apparatus plasma cell endoplasmic reticulum J - chain IgA dimer endosome endosome endocytosis

  15. ROLE OF MUCOSAL IMMUNITY IN THE ONTOGENESIS OF IMMUNE REACTIVITY newborn’s mucosa is germ-free colonisation of mucosa by microbial microflora has to be succesive maternal strains of microbes predominate in breast-fed kids actions of transplacentally transfered maternal IgG specific antibodies are complemented by sIgA in maternal milk (breast feeding) generation of immune reactivity is induced through mucosal immune systeme

  16. MODULATION OF MUCOSAL IMMUNITY active immunisation via mucosa has many advantages in prevention of food or water born infectious diseases oral tolerisation is induction of down-modulating immune mechanisms by the feeding of antigens (MBP)

  17. MUCOSAL TOLERISATION Ag pinocytosis penetration transportation TS/C HLA II. M-cell IEL CD4 CD28 absence of costimulation TH CD28 HLA II. cytokines (TGF) TcR APC TH CD4 ANERGY DELETION

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