Rejection of transplants

1. Basis of rejection

Recipient and donor (graft) carry different MHC molecules. Dying graft cells are processed inside the recipient, so donor antigens are seen as foreign, triggering an immune response.

2. Mechanisms

• T-cell mediated cytotoxicity (direct pathway) — recipient CD8⁺ T cells recognize donor MHC-I → differentiate into CTLs → kill graft cells.
• Antibody-mediated rejection (indirect pathway) — recipient APCs take up shed donor antigen → present on MHC-II to CD4⁺ T cells → IL-4/IL-5 → B cells → plasma cells → anti-graft antibodies.
• Delayed-type hypersensitivity — donor MHC-II recognized by CD4⁺ → Th1 → TNF + IFN-γ.

3. Rejection types

Type	Timing	Mechanism	Pathology
Hyperacute	Minutes–hours	Preformed anti-donor antibodies (ABO/HLA)	Acute arteritis, thrombosis, fibrinoid necrosis → cyanotic, flaccid graft
Acute	Days–weeks	Cellular (T-cell) ± humoral (antibody)	Tubulitis / endotheliitis; necrotizing vasculitis
Chronic	Months–years	Low-grade immune injury, cytokines	Intimal SMC proliferation, graft arteriosclerosis, fibrosis/atrophy

• Hyperacute — preformed antibodies (prior transfusion/transplant/pregnancy) → complement → widespread thrombosis & ischemic necrosis; graft fails on the table.
• Acute — cellular: CD4/CD8 infiltration, tubulitis, interstitial edema; humoral: anti-donor antibody → necrotizing vasculitis, endothelial necrosis, fibrin. Responds to ↑ immunosuppression.
• Chronic — ↑ serum creatinine (kidney); vascular-dominated: intimal proliferation, narrowed lumen → ischemia; ends in renal/tubular atrophy, glomerular hyalinization.

4. Improving graft survival

• HLA matching & crossmatch (best when both MHC-I and -II match; greatest impact in kidney).
• Immunosuppression — corticosteroids, calcineurin inhibitors (cyclosporine/tacrolimus), antimetabolites (MMF); all recipients except identical twins. Risk: ↑ viral-driven malignancy (EBV lymphoma, HPV SCC, HHV8 Kaposi).
• Anti-CD3 (T-cell suppression); co-stimulation blockade (B7–CD28) → anergy/apoptosis.

5. Bone-marrow transplantation

• Autologous — patient’s own harvested stem cells reinfused after chemo/irradiation (no rejection).
• Allogeneic — donor cells → rejection risk (host T/NK cells) and two key complications:
  • GVHD — graft T cells attack host (DTH + CTL): acute (skin rash, bile-duct necrosis → jaundice, GI ulceration → bloody diarrhea); chronic (sclerosis-like skin, autoimmune-like features).
  • Immunodeficiency — slow immune reconstitution → prolonged susceptibility to viral infection.

💡 High-yield: Hyperacute = preformed antibodies, minutes, thrombosis (ABO/HLA mismatch). Acute = T-cell (tubulitis) ± antibody, days–weeks, treatable. Chronic = graft arteriosclerosis + fibrosis, months–years, irreversible. Allogeneic BMT → GVHD (donor T cells attack host skin/liver/gut).