Mucosal immune system (MALT) MALT (Mucous Associated Lymphoid Tissue) •GALT (Gut Associated Lymphod tissue) •BALT (Bronchi Associated Lymphoid Tissue) •Immune tissues of the urinary tract, genital tract, conjunctiva, middle ear… •Includes also brest gland! Anatomy of MALT •Diffuse tissue containing lymphocytes and other cells of the immune system in submucosa. •Specialized organs: –Waldeyer´s ring –Payer´s patches –Appnedix EXPRESION • enzymes • HLA antigens • adhesion molecules • receptorsyfor: mikrobes cytokines polymeric Ig PRODUCTION • cytokines pro-inflammatory growth factors chemotactic • antibiotic peptides • various other mediators INTERACTION WITH SPECIFIC IMMUNE SYSTEM Epitelial cells are intergal part of the immune system of mucous membranes Antimicrobial nechanisms on mucous membranes Factor Mechanismus Comensal bacteria competition with pathogens production of antiinflammatory mediators Tight epitelial junctions protect from bacterial invasion into tissues Cilia bind and remove microbes Mucin bind microbes Lysozyme killing G+ bacteria Laktoferin iron binding (inhibition o microbial growth) Antibiotic peptides killing microbes (mainly b defensins) Secretory Ig Microbial adhesion blocade Mucosal immune system (MALT) •Antigenic stimulation in one part of MALT leads to immune response also in other compartments of MALT. •IgA is a predominant immunoglobulin secreted by the epitelial cells. •Oral administration of antigens frequently leads to induction of immune tolerance. •Intraepitelial lymphocytes - CD8+, restricted antigenic specificity. schema4-var2-01.png Mucous- asccociated lymphoid tissue Nasopharynx Lungs Mammary gland Gastrointestinal tract Genitourinary tract Vena cava Ductus thoracicus Intestine TL-zena1 Common immune system of mucous membranes Homing of Lymphocytes •The directed migration of subsets of circulating lymphocytes into particular tissue sites. •Regulated by selective expression of adhesion molecules called homing receptors on lymphocytes. •Tissue speciphic endothelial ligands are called addressins. High Endotelial Venules •Specialized venules. The site where lymphpocytes leave the blood stream and migrate into lymph nodes, spleen, organs of MALT. •Adhesion molecules enable selective attachment of various types of lymphocytes. S0241X-001-f017 Downloaded from: StudentConsult (on 15 July 2006 09:09 AM) © 2005 Elsevier top_logo Circulation of lymphocytes S0241X-008-f009 Downloaded from: StudentConsult (on 20 July 2006 11:29 AM) © 2005 Elsevier top_logo Secretory IgA formation Intraepitelial T-lymphocytes •TCR ab or gd •Extrathymic differentiation •First line of specific immune response •Predominantly CD8+ •Low antigenic specificity of TCR M-cells •Specialized enterocytes responsible for transport of antigens from the gut towards the immunocompetent cells inside the Payer´s patches. •Transport in mediated by transcytosis. Lymphocyte circulation in GALT 267_mehandru_saurabh_fig1_680 www.prn.org/.../hiv_1_gastrointestinal_galt_267 Oral tolerance •Stimulation of the GALT frequently leads to induction of immune tolerance to the stimulating antigen. •This occurs mainly if the gut is in „normal, non-inflammatory“ conditions. •Induction of Th3 cell is the main mechanism. •The tolerance is important to avoid unnecessary reactions to non-pathogenic antigens. Comensal (normal) mikroflóra (of GIT) •~ 1014 microbial cells, ~ 1000 microbial species •~ 50% non cultivated •Complex ecosystem •Included in innate immunity of GIT •Mutual interactions of microorganisms: • competition, symbiosis.. •Interaction with macroorganism: symbiosis, commensalism, important in metabolic processes (production of vitamins etc.) •Immune system modulation •