Transplant Immunology
Grafts
🅱️Acute → Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
🅰️Hyperacute → Widespread thrombosis of graft vessels (arrows within glomerulus)
Definition
- Acute graft rejection:
- ↑ Serum creatinine by >10% from baseline.
- Acute graft dysfunction:
- Either
- ↑ Serum creatinine
- >10% from baseline
- Or ≥20 µmol/L absolute rise
Causes of Early Graft Dysfunction
- Acute rejection
- Antibody-mediated
- T-cell-mediated
- Calcineurin inhibitor toxicity
- Dehydration
- UTI or pyelonephritis
- Sepsis
- Renal vein or renal artery thrombosis
- Ureteric obstruction
- Urine leak
Graft Rejection Types:
Rejection Type | Timeframe | Note | Pathology |
Hyperacute Mnemonic: 2 days → Type 2 → too many pregnancies and transfusions → 2 necrosis | Within 48 hours Dusky kidney on table Type 2 | preformed anti-HLA antibodies in recipient (e.g., multiparous women, multiple transfusions). Graft must be removed | Coagulative necrosis (solid organs like kidney), Fibrinoid necrosis (blood vessels). Cyanotic and mottled graft with pale white areas Neutrophil accumulation Intravascular thrombosis |
Acute | Weeks to months Type 2 (humoral) & Type 4 (cellular) | 90% 5-year graft survival Prevent/reverse with immunosuppressants | Humoral: - C4d deposition in blood vessels (rejection vasculitis). Cellular: - Endothelitis (blood vessels), - Tubulitis (tubules). |
Chronic | Months to years Type 4 (primarily) | Most common rejection type. 6 months post-transplant HPE: Glomerular sclerosis | Kidney pathology GOATI - Glomerular BM → duplication, - Tubules → Atrophy - Blood vessels → obliterate - Interstitium → Fibrosis Organ-specific examples: - Chronic allograft nephropathy - Bronchiolitis obliterans - Accelerated atherosclerosis (heart) → Most important long-term → allograft arteriopathy, also known as cardiac allograft vasculopathy (CAV) - Vanishing bile duct syndrome |
Category | Acute humoral rejection | Acute cellular rejection |
Mediated by | Newly synthesized antibodies | CD4 & CD8 T cells |
Type of hypersensitivity | Type II | Type IV |
Pathogenesis | Immune complex formation → Complement activation | Donor APC's present Ag to recipient's CD4 & CD T cells |
H&E | Deposition of C4d in capillaries Fibrinoid necrosis in vessels → Rejection vasculitis | Tubulitis, Endothelitis |
marker | C4d (Complement breakdown product) | - |
Response to immunosuppressants | No response to increasing dose | Responsive |
Swyer James Mcleod syndrome
- Post bronchiolitis obliterans.
- decreased vessel markings
- Mnemonic: Mcleod syndrome → Makkalkk varunna syndrome
Graft Versus Host Disease (GVHD):
- Occurs when:
- Graft (immunocompetent) attacks recipient (immunocompromised).
- Timeline (definitive):
- Acute GVHD:
- < 100 days.
- Chronic GVHD:
- > 100 days.
- Mnemonic:
- Graft → Greeshma → Kashayam Greeshma
- 100 days of love (Kidney is love)
- After that → Try to kill him with poison ()
- Diarrhea
- Rash
- Jaundice
- Organs Attacked:
- Skin (rash), Intestine (diarrhea), Liver/Hepatobiliary (jaundice).
- Mnemonic: SIL
Prevention
- Irradiation of blood products, including RBCs, is done.
Purpose of Irradiation:
- Damages donor lymphocyte DNA.
- Prevents lymphocyte proliferation.
- Prevents immune response by inactivating donor lymphocytes.
Which organ has the highest chances of Graft rejection response?
A. Cornea
B. Gut
C. Liver
D. Skin
A. Cornea
B. Gut
C. Liver
D. Skin
Most important HLA:
- HLA DR
HLA matching is not required in
- Cornea
- Lung
- Heart
- Testis/seminiferous tubules
- Brain
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