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Mechanisms of immune injury of the glomerulus

Pierre Ronco, MD, PhD
Section Editors
Richard J Glassock, MD, MACP
Fernando C Fervenza, MD, PhD
Deputy Editor
Albert Q Lam, MD


A large body of clinical, immunopathologic, and experimental data support the hypothesis that most forms of human glomerulonephritis (GN) result from immunologic mechanisms [1-6]. The etiologic agents in human GN are largely unknown with the exception of infection-related forms of disease, such as beta-hemolytic streptococci in poststreptococcal GN and hepatitis C virus in cryoglobulinemic membranoproliferative GN. (See "Group A streptococcus: Virulence factors and pathogenic mechanisms" and "Clinical manifestations and diagnosis of the mixed cryoglobulinemia syndrome (essential mixed cryoglobulinemia)", section on 'Etiology' and "Clinical manifestations and diagnosis of the mixed cryoglobulinemia syndrome (essential mixed cryoglobulinemia)", section on 'Renal disease'.)

It is likely that most precipitating factors, such as infections and drug and toxin exposures, initiate similar immune responses that result in GN via shared common pathways. The nature of the immune responses which lead to GN and the individuals who develop them are strongly influenced by immunogenetic phenotypes [7].

Glomerular injury of immune origin is mediated by the actions of multiple elements of both the innate and adaptive immune systems, resulting in diverse clinical and pathologic manifestations [2,3,8]. In addition, elements of the complement cascade and the complement regulatory systems can be involved in both the production and mediation of many glomerular diseases. A schematic depiction of the relationship among immune events, effector cells, mediator release, and eventual glomerular injury is shown in the figure (figure 1).

This topic will review the immune events that occur after antigen exposure and that lead to immune complex formation in glomeruli, T cell-mediated glomerular injury, and the glomerular response to immune injury and the mediators that are involved.


The nephritogenic immune response includes both humoral and cellular components. The humoral, T helper cell 2 (Th2)-regulated immune response leads to B cell activation, immunoglobulin deposition, and complement activation in glomeruli. The cellular, T helper cell 1(Th1)-regulated immune response contributes to both the infiltration of circulating mononuclear inflammatory cells (including lymphocytes and macrophages) into glomeruli and to crescent formation. (See "T helper subsets: Differentiation and role in disease" and "Mechanisms of glomerular crescent formation", section on 'T cells'.)


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