In glomerulonephritis, which mechanism represents a major component of both primary and secondary glomerular injury?

• A. Antigen-antibody complexes that deposit within the glomerulus
• B. T-cell mediated cytotoxicity
• C. Complement activation without immune complexes
• D. Ischemic injury due to vascular compromise

Answer: (A)

Immune complex deposition in the glomerulus is a central driver of injury in many forms of glomerulonephritis. Circulating antigen–antibody complexes lodge in the glomerular basement membrane and mesangium, where they activate the complement system. The classical pathway is typically triggered by these immune complexes, leading to generation of inflammatory mediators that recruit neutrophils and other immune cells. The ensuing inflammation damages the glomerular capillary walls and mesangial matrix, increasing permeability and producing the characteristic features of glomerulonephritis such as hematuria and proteinuria. This mechanism is seen in multiple primary GN diseases (like IgA nephropathy and membranous nephropathy) and in secondary GN (such as lupus nephritis and post-infectious GN).

T-cell–mediated cytotoxicity can contribute in some contexts, but it is not the predominant mechanism across most glomerular diseases. Complement activation can occur without immune complexes in other contexts (e.g., pauci-immune GN), but the major, broadly applicable pathogenic pathway in primary and many secondary forms is immune complex–driven injury. Ischemic injury from vascular problems is a different process and not the primary driver of glomerular damage in these GN scenarios.