Transplant Rejection: Mechanisms & Pathology
Transplant rejection is an immune-mediated process where the recipient’s immune system recognizes the donor organ as foreign (allogeneic). This is primarily driven by disparities in the Major Histocompatibility Complex (MHC/HLA).
1. Clinical Classification of Rejection
| Type | Timing | Mechanism & Pathology |
|---|---|---|
| Hyperacute | Minutes to Hours | Pre-existing antibodies in the recipient’s blood bind to donor antigens. Type II Hypersensitivity. Causes immediate widespread thrombosis and ischemia (organ turns blue/white). |
| Acute | Weeks to Months | T-cell mediated (Type IV). CD8+ T-cells attack donor parenchymal cells. Requires biopsy showing dense lymphocytic infiltrate. Treated with immunosuppressives. |
| Chronic | Months to Years | T-cell-mediated process causing intimal thickening and vascular fibrosis. Results in slow, irreversible organ failure. |
2. Graft-Versus-Host Disease (GVHD)
Clinical Core: GVHD occurs when donor T-cells (from bone marrow or blood) recognize the recipient’s tissues as foreign. This is a classic Type IV hypersensitivity reaction.
- Typical Scenario: Allogeneic bone marrow transplantation.
- Target Organs: Skin (maculopapular rash), Liver (cholestatic jaundice), and Gastrointestinal tract (severe watery diarrhea).
3. Exam Must-Knows
- Direct vs. Indirect Recognition:
• Direct: Recipient T-cells recognize intact MHC molecules on donor APCs.
• Indirect: Recipient T-cells recognize processed donor MHC peptides presented by the recipient’s own APCs.
- Clinical Hint: If a post-transplant patient develops sudden organ failure in the recovery room, think Hyperacute Rejection (Type II hypersensitivity).
- Prevention: Match HLA-DR, HLA-A, and HLA-B to reduce the risk of rejection, though this is primarily feasible for kidney and bone marrow transplants.