W+天然免疫教程分析.ppt

* * In this model, phagocytosed microorganisms, including bacteria, release ligands that are recognized by NOD proteins and peptides that associate with MHC classs II molecules. Recognition of intracellular ligands by NOD proteins and extracellular ligands by Toll-like receptors (TLRs) mediates the activation of signalling pathways including those downstream of nuclear factor- B (NF- B). These intracellular events induce the secretion of cytokines by the antigen-presenting cell (APC), as well as the expression of co-stimulatory molecules (for example, CD80 and CD86) on the surface of the APC. Signalling through the T-cell receptor (TCR) and co-stimulatory receptors, such as CD28, leads to the development of antigen-specific effector T cells. CIITA, MHC class II transactivator; NOD, nucleotide-binding oligomerization domain. Function is not defined in humans but possibly these proteins play an important role in innate immunity and function as intracellular receptors for pathogens Structurally similar to family of resistance gene products in plants Activate NFkB and MAP kinases signaling pathways Some NOD family proteins implicated in pathogenesis of inflammatory diseases (NOD2/Crohn’s Dis.) Figure 2-21 Binds to antibody:antigen complex C1q binds to antibody:antigen complexes, thus it recruits complement to antigen tagged by antibody Figure 7.30 Figure 2-22 For MB lectin MASP1/2 cleave C4 The rest is the same Complement activation is a proteolytic cascade, in which one protease activates by proteolysis the next protease Zymogen= inactive enzyme that is activated by proteolysis Components of mannose-binding lectin (MBL) pathway C4 MBL C2 MASP1 MASP2 MASP2: mannan-binding lectin serine peptidase 2 Figure 2-24 Mannose binding lectin is an innate recognition molecule that recruits complement Mannose-binding lectin pathway C4 MBL C4b C4a C4b C2 C2b C2a C2a C4b2a is C3 convertase; it will lead to the generation of C5 convertase MASP1 MASP2 Components of thealternat