By I. Lim Jennifer
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Additional info for Age-Related Macular Degeneration, 2nd Edition
Direct deposition of circulating antibodies targeted at antigens uniformly expressed within the glomerular matrix is a welldeﬁned but rare form of glomerulonephritis, especially in Goodpasture’s syndrome. Deposition of preformed circulating antigen/antibody complexes in the blood has been proposed as another major mechanism in many types of glomerulonephritis associated with deposit formation. Nevertheless, it is unlikely that deposition of either anti-basement membrane antibodies or circulating ICs plays an important role in AMD.
Experimental data suggest that reparative macrophages release mediators that induce mesangial cell proliferation, amplify the accumulation of extracellular matrix and might induce killing of endothelial cells. Antigen-Specific Immunity in Glomerular Diseases Antigen-speciﬁc immunity contributes signiﬁcantly to inﬂammatory glomerular disorders. Lymphocytemediated immunity clearly contributes to glomerulonephritis, especially in renal allograft rejection (161). However, the relevance of this mechanism to AMD is probably minimal.
Three pathways have been identiﬁed to activate the complement cascade: classical pathway, alternative pathway, and the lectin pathway (Fig. 1). Antigen-speciﬁc immunity typically activates complement via the classical pathway with antigen/ antibody (immune) complexes, especially those formed by IgM, IgG1, and IgG3 (7–9). , implanted medical devices) (10). , amyloid P), or apoptotic cells can also trigger the 2: IMMUNOLOGY OF AGE-RELATED MACULAR DEGENERATION Classical Pathway (Immune Complexes (IgM, IgG), DNA, RNA, Apoptotic Cell, Memebrane Blebs, Amyloid P, etc) (+) C1q Alternative Pathway (Activating Surfaces, Biomaterials, LPS) (+) 13 Letin Pathway (Cell Surface Carbohydrates, Oxidative Stress) (+) Mannose Binding Lectin (MBL) C3b +C4 +C4 +C2 +C2 C3 +C3b +C3b C3a C3a Enhanced Phagocytosis C3 C5 C5b C5b-9 MAC C6, C7, C8, C9 Figure 1 Schematic of the components and fragments of the complement cascade indicating three primary sources of activation via the classical, alternative, or lectin pathway.
Age-Related Macular Degeneration, 2nd Edition by I. Lim Jennifer