Immune mechanisms of glomerular injury
- Mechanism
Most glomerulonephritis is immune. Where the antibody meets its antigen decides where deposits sit, and that shapes the disease.
What it is
Antibodies can bind antigens that belong to the glomerulus or were planted there, forming complexes in place; they can attack the basement membrane itself; or complexes formed in the blood can lodge in the glomerulus. The deposits then switch on complement and draw in leukocytes, which release proteases, oxidants and cytokines. Uncontrolled activation of the alternative complement pathway and T cells can injure without antibodies, and podocyte injury is the common route to proteinuria.
Step by step
- Antigen and antibody meet: in place on the GBM or podocyte, or as complexes from the blood.
- Size and charge of the complex decide where it lodges: mesangium, under the endothelium or under the podocyte.
- Deposits activate complement; C5a draws neutrophils and monocytes, C5b-9 damages cell membranes.
- Leukocytes release proteases, oxidants and arachidonic acid products that damage the capillary wall.
- Mesangial cells, platelets and coagulation add growth factors and fibrin; severe breaks form crescents.
- Injured podocytes efface their foot processes, detach and leave bare basement membrane: protein leaks.
- Lost podocytes and scarred segments start a cycle that ends in sclerosis.
Where deposits sit and what they do
| Deposit site | Effect | Examples |
|---|---|---|
| Subepithelial (under podocytes) | Little inflammation; proteinuria | Membranous nephropathy; humps of postinfectious GN |
| Subendothelial | Strong inflammation, hematuria, crescents possible | Lupus class III–IV, MPGN |
| Mesangial | Mesangial proliferation, hematuria | IgA nephropathy, early lupus |
| Linear along the GBM (no complex deposit) | Necrosis and crescents | Anti-GBM disease (Goodpasture) |
Clinical notes
- Lowered serum complement suggests immune-complex or complement-driven disease (postinfectious, lupus, MPGN, C3 glomerulopathy).
Test yourself
Think of the answer, then tap the question to see it.
Why do subepithelial deposits cause proteinuria with little inflammation?
They lie on the urinary side of the basement membrane, out of reach of circulating leukocytes; injury comes mainly from complement attack on podocytes.
What is the target antigen in anti-GBM disease?
The noncollagenous (NC1) domain of the α3 chain of type IV collagen.
Which immunofluorescence pattern points to immune complexes?
Granular, lumpy deposits; a smooth linear pattern points to antibodies against the basement membrane.
Elsewhere in DurgiPedia
- Type II hypersensitivity (antibody against cells)
- Type III hypersensitivity (immune complexes)
- Complement: three pathways, MAC, regulators
- Glomerulus and the filtration barrier: podocytes, mesangium, JGA
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Glomerulonephritis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.