Pathophysiology of Transplant Rejection
Transplant rejection is an immune-mediated injury to transplanted tissue (allograft), leading to its dysfunction or destruction.
Mainly involves recognition of alloantigens by the recipient’s immune system.
Types of Transplants
Autograft: same individual (no rejection).
Syngeneic graft: genetically identical individual (e.g., identical twins).
Allograft: same species but genetically different (common; risk of rejection).
Xenograft: different species (high rejection risk).
Key Antigens Involved
Major histocompatibility complex (MHC):
- HLA class I: present on most nucleated cells.
- HLA class II: on antigen- presenting cells (APCs).
Minor histocompatibility antigens: less immunogenic but can contribute.
Pathogenesis
- 1 Sensitization phase
Direct pathway:
- Donor APCs in graft present donor MHC to recipient’s T cells → strong acute response.
Indirect pathway:
- Recipient APCs process donor antigens → present on self-MHC → chronic response.
- 2 Effector phase
Cellular mechanisms:
- CD8+ cytotoxic T cells: kill graft cells directly.
- CD4+ helper T cells: secrete cytokines → recruit macrophages, induce delayed- type hypersensitivity.
Humoral mechanisms:
- Alloantibodies against donor HLA or endothelial antigens → complement activation, vascular injury, thrombosis.