G lomerulonephritis (GN) is not a single disease but shows a variety of histologic patterns, clinical features, and outcomes that indicate multiple pathogenic mechanisms. A pivotal role for adaptive immune responses in initiation of GN has been demonstrated in experimental models, but across the spectrum of human GN, direct evidence of immune pathogenesis is more variable. The strongest case that adaptive immune responses drive nephritogenic events in glomeruli in humans has been mounted in crescentic GN, and evidence for involvement of autoimmunity, either organspecific autoimmunity to glomerular antigens (e.g., anti-glomerular basement membrane [anti-GBM] GN) or systemic autoimmunity to nonglomerular antigens (e.g., ANCA-associated crescentic GN, lupus nephritis) now is emerging for many forms of human crescentic GN. CD4 ϩ T cells play a central role in adaptive immunity. T cell-independent responses are uncommon. They usually are associated with simple carbohydrate-rich antigens and do not show extensive Ig isotype switching or strong affinity maturation. The known antigens that drive crescentic GN show strong evidence of CD4 ϩ T cell dependence and do not have the characteristics of T-independent antigens. The evidence from glomerular pathology also suggests a prominent role for local CD4 ϩ T cell-driven Th1-type responses in crescentic GN with delayed-type hypersensitivity (DTH)-like cellular effectors (T cells and macrophages) as well as Th1 Ig isotypes in glomeruli.The relative contributions of cellular and humoral CD4 ϩ T cell-driven effectors, particularly in ANCA-associated GN, remains controversial, but it is clear that the nephritogenic immune responses are CD4 ϩ T cell-driven.