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 non-immunological and immunological mechanisms immune reaction is concentrated predominantly on the surface of mucosa MUCOSAL IMMUNITY - CHARACTERISTICS
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 PHYSIOLOGICAL BARRIERS:
mucosa-associated lymphoid tissues complex set of lymphoid tissues, immune cells and macromolecules, contribution of epithelial cells IMMUNOLOGICAL MECHANISMS: MALT: 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
T S/C sIgA adhesines blockage GUT MOVEMENT M U C U S MOVEMENT OF CILIA EPITHELIAL REPARATION TIGHT JUNCTIONS intraepithelial lymphocytes CD8 + (suppressor) microbe IEL BASIC CHARACTERISTICS OF MUCOSAL IMUNITY Y Y
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 propria macrophages antigenic peptides are presented to T-cells in context of HLA molecules 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 INDUCTION OF MUCOSAL IMMUNITY
T S/C sIgA 2 Ag HLA II. TcR IL-12 INF- APC T H CD28 B7 clonal expansion Y diferentiation T H T H B IEL transport M- cell penetration transcytosis IL-2,4 IL- 6 4 7 HEV directed migration homing molecule addressins (MAdCAM) vein MUCOSAL IMMUNITY INDUCTION Y Y Y Y B T H plazmocyt Y Y
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 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 IgA 2 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 SECRETORY IgA IMMUNOGLOBULINS:
Y Y T S/C complement act. VEIN LAMINA PROPRIA EPITHELIUM MUCUS LUMEN T H cytokines costimulation Y complement complement IgA dimer Y Y T H plasma cell IgG IgG Ag SECRETORY IgA SYNTHESIS T B Y Y Y Y Y Y Y Y Y Y B Y Y Y Y Y Y Y Y Y Y Y Y
IgA dimer J - chain plasma cell IgA receptor LAMINA PROPRIA endocytosis endosome Golgi apparatus endoplasmic reticulum endosome secretory component EPITHELIUM LUMEN TRANSCYTOSIS OF SECRETORY IgA Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
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 ROLE OF MUCOSAL IMMUNITY IN THE ONTOGENESIS OF IMMUNE REACTIVITY
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) MODULATION OF MUCOSAL IMMUNITY
T S/C HLA II. TcR APC CD28 IEL M-cell ANERGY DELETION HLA II. CD28 CD4 pinocytosis penetration Ag cytokines (TGF ) transportation T H T H CD4 absence of costimulation MUCOSAL TOLERISATION
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