Immunology L5: Transplantation

Question 1

Hyperacute Rejection

Answer 1

• Occurs minutes to hours post transplant; Type II H
• Mechanism: binding of preformed antibodies to graft antigens (HLA, ABO, other), followed by complement fixation, attraction of neutrophils, and tissue damage
• Site of attack: vascular endothelium (kidney and heart)
• Histology: hemorrhage,edema,vascular necrosis, acute inflammation (neutrophils), Ig in vessel wall, fibrin- platelet thrombi

Question 2

Acute Rejection

Answer 2

• Occurs early: weeks after transplantation; Type IV H
• Mechanism: recognition of graft antigens (especially HLA antigens) by allo- specific T cells, followed by cytotoxicity (CD8 T cells) or release of inflammatory lymphokines (CD4 T cells)
• Site of attack: variable, depending on organ
  
  • Kidney: tubules, interstitum
  • Liver: venous endothelium, bile ducts Heart: myocytes,
  • Lung: arterioles
• Histology: infiltration of mononuclear leukocytes (lymphocytes, macrophages), hemorrhage and necrosis

Question 3

Chronic Rejection

Answer 3

• Occurs months to years post transplant; Type I to IV H
• Mechanism: Recent evidence suggests specific components of the rejection phenotype can be linked to cell-mediated (Type IV), antibody- mediated (Type II), immune complex-mediated (Type III), and even immediate (Type I) hypersensitivity processes.
• Site of attack: variable, depending on organ
  
  • Kidney: vasculature (especially arteries), tubules, interstitium
  • Liver: bile ducts (“vanishing bile duct syndrome”) Heart: vasculature
  • Lung: bronchioles
• Histology: fibrosis, atrophy, vascular thickening (especially intimal)

Question 4

Acute Graft vs. Host Disease

Answer 4

• Occurs days – wks post-transplant – Rash
  
  • – Destruction of bile ducts (jaundice)
  • – Gut mucosal ulceration (bloody diarrhea)
• Lesions are pauci-cellular
• CTLs and cytokines are effectors.

Question 5

Chronic GVHD

Answer 5

• Cutaneous fibrosis and destruction of skin appendages
• Cholestatic jaundice
• Espohageal and GI strictures
• Lymphodepletion
• Autoimmunity possible

Prevention

• Molecular typing of HLA alleles
• Depletion of donor T cells in graft
• – Decreased engraftment
• – Loss of graft-vs-leukemia effect