粘膜免疫系统(英文)资料.pptVIP

* MUCOSAL IMMUNE SYSTEM October 31, 2008 Deborah A. Lebman, PhD dlebman@vcu.edu Goodwin Research Lab Rm 290 Reading: Janeway’s Immunobiology, Chapter 11 ORGANIZATION OF THE MUCOSAL IMMUNE SYSTEM Mucosal sites represent a large surface area exposed to the environment The vast majority of infections invade via mucosal surfaces Microorganisms that live in mucosal tissues are essential to our health The mucosa is exposes to a variety of antigens, e.g., food. An immune response to these antigens would do more harm than good FEATURES OF THE MUCOSAL IMMUNE SYSTEM THE MUCOSAL IMMUNE SYSTEM IS THE LARGEST SEGMENT OF THE BODIES IMMUNE DEFENSE MECHANISMS THE MUCOSAL IMMUNE SYSTEM: GALT THE MUCOSAL IMMUNE SYSTEM: NALT ANTIGEN ENTRY INTO MUCOSAL SITES THE EPITHELIUM OF PP CONTAINS SPECIALIZED CELLS M cells are distinguished by membrane ruffles/microvilli M CELLS ARE RESPONSIBLE FOR ANTIGEN UPTAKE M cells facilitate antigen entry. THEY ARE NOT APC M cell “hands” off intact antigen to lymphocyte or dendritic cell Enteric pathogens know how to exploit M cells DENDRITIC CELLS FACILITATE ANTIGEN UPTAKE You can come home again!!! LYMPHOCYTE CIRCULATION Figure 10-20 A COMMON MUCOSAL IMMUNE SYSTEM Lymphocytes stimulated in mucosal sites traffic to mucosal sites LYMPHOCYTES ACTIVATED IN INTESTINAL TISSUES RETURN TO INTESTINAL TISSUE B cell homing/recirculation is similar to that of T cells B cells and T cells are activated in “inductive” sites (PP, SLN) and specifcally traffic to effector sites (intestinal lamina propria CHEMOKINES AND ADHESION MOLECULES DIRECT HOMING Integrin (a4b7):Addressin (MadCAM) Interactions Chemokine Receptor(CCR9/10): Chemokine (CCL25/28) Interactions MUCOSAL IMMUNE RESPONSES THE IgA RESPONSE Effective immunization against enteric pathogens is associated with an IgA response IgA2 vs IgA1: More resistant to proteases IgA vs IgM : Higher affinity, inability to bind C’ (less inflammatory) Most IgA is from the gi tract/PP EFFECTOR SITES: EPITHELIUM AND LA