Graft Rejection

Graft Rejection

Definition: Graft rejection is an immune response in which the recipient’s immune system recognizes transplanted tissue or organs (grafts) as foreign and mounts an attack against them. This process can lead to the failure of the transplant.

Types of Graft Rejection

• Hyperacute Rejection:

• Timing: Occurs within minutes to hours after transplantation.
• Mechanism: Mediated by pre-existing antibodies in the recipient against donor antigens, particularly blood group antigens and MHC molecules. This leads to rapid complement activation and thrombosis in the graft.

• Acute Rejection:

• Timing: Can occur days to weeks after transplantation.
• Mechanism: Primarily mediated by T cells (cell-mediated immunity) and antibodies (humoral immunity). The recipient’s T cells recognize foreign antigens on the graft, leading to inflammation and damage.

• Chronic Rejection:

• Timing: Develops over months to years.
• Mechanism: Characterized by gradual loss of graft function due to chronic inflammation and fibrosis. It involves both immune-mediated mechanisms and non-immune factors, such as chronic injury from ischemia or hypertension.

Mechanisms of Graft Rejection

• Cell-Mediated Immunity: T cells play a central role in recognizing foreign antigens presented by MHC molecules on donor cells, leading to their activation and proliferation.
• Humoral Immunity: B cells produce antibodies against donor antigens, which can lead to complement activation and further recruitment of immune cells.
• Inflammation: The immune response triggers inflammation, which can cause tissue damage and contribute to graft dysfunction.

Prevention of Graft Rejection

• Immunosuppressive Therapy:

• Patients are typically placed on immunosuppressive medications (e.g., corticosteroids, calcineurin inhibitors, mTOR inhibitors) to reduce the immune response against the graft.

• Matching Donor and Recipient:

• Careful matching of donor and recipient MHC antigens can minimize the risk of rejection. This includes blood type compatibility and HLA typing.

• Desensitization Protocols:

• For patients with pre-existing antibodies against donor antigens, desensitization protocols may be employed prior to transplantation.

Conclusion

Graft rejection is a complex immunological process that poses significant challenges in transplantation medicine. Understanding its mechanisms is crucial for developing effective strategies to prevent rejection and improve transplant outcomes.

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References

1. Opelz G, et al. “Influence of HLA matching on kidney transplant survival.” Transplantation Proceedings. 2007; 39(5): 1405-1409. DOI: 10.1016/j.transproceed.2007.04.016
2. Halloran PF, et al. “The importance of T cell-mediated immunity in renal transplantation.” Transplantation. 2004; 78(8): 1090-1096. DOI: 10.1097/01.TP.0000133363.36011.BC
3. Kauffman HM, et al. “The impact of pre-transplant sensitization on kidney transplant outcomes.” American Journal of Transplantation. 2004; 4(5): 682-688. DOI: 10.1111/j.1600-6143.2004.00418.x