Innate Immune Responses to Transplants

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Presentation transcript:

Innate Immune Responses to Transplants William M. Baldwin, Christian P. Larsen, Robert L. Fairchild Immunity Volume 14, Issue 4, Pages 369-376 (April 2001) DOI: 10.1016/S1074-7613(01)00117-0

Figure 1 The Complement Cascade Can Be Activated through Three Different Initial Pathways: The Classical (C1, C4, and C2), Alternative (Factor B), and Mannose Binding Lectin (MBL) Pathways All three pathways converge in the activation of C3. Activation of C3 and C5 occurs by enzymatic cleavage into two biologically active fragments. The small fragments (C3a and C5a) mediate chemotaxis and activation through separate receptors (C3aR and C5aR) on leukocytes. Activation of monocytes through their C5a receptor causes production of proinflammatory cytokines, such as IL-1, IL-6, IL-8, and TNFα. The large fragment of C3 can bind covalently to proteins or carbohydrates. Deposition of C3b can be increased through an amplification loop with factor B of the alternative pathway. The terminal components of complement (C5b-C9) form a tubular structure, the membrane attack complex (MAC) Immunity 2001 14, 369-376DOI: (10.1016/S1074-7613(01)00117-0)

Figure 2 CRP Is Composed of Five Identical Subunits Arranged in a Planar Ring Structure CRP binds to phosphatidylcholine and sphingomyelin that are exposed on plasma membranes of injured cells. After CRP complexes with a tissue ligand on one surface, it can activate the classical pathway of complement by binding to the collagen-like region of C1q. CRP binds factor H in addition to C1q and thereby truncates complement activation at C3. CRP also interacts with the high- and low-affinity receptors for IgG, FcγRI, and FcγRII, respectively Immunity 2001 14, 369-376DOI: (10.1016/S1074-7613(01)00117-0)

Figure 3 C3 Is Activated by Enzymatic Cleavage into C3a and C3b that Can Bind Covalently to Proteins or Carbohydrates through a Thioester Bond C3b is cleaved successively by factor I leaving first iC3b and then C3dg bound to the membrane. CR1 or factor H serve as cofactors to Factor I. C3b, iC3b, and C3d stimulate cells with complement receptors CR1, CR3, and CR2, respectively Immunity 2001 14, 369-376DOI: (10.1016/S1074-7613(01)00117-0)