Reference no: EM133368594
Assignment:
Antibody-mediated rejection (AMR) is the most common cause of immune-mediated graft failure after kidney transplantation. In AMR the patient/recipient has produced antibodies against antigens on the donor tissue/organ. When antibodies bind to antigens on the donated kidney they can activate immune responses that lead to injury of the kidney and eventually death of the transplanted organ.
One of the main categories of antibodies that can cause AMR are anti-HLA antibodies. HLAs are a category of highly polymorphic proteins found on human cells. That means while we all produce HLAs the 'version' or allele of an HLA we express may be different from the version someone else expresses (especially if they aren't related genetically).
Ideally the best way to reduce transplant rejection would be for the organ donor and the recipient to have the same HLA alleles across all HLA loci/genes. However, due to the level of polymorphism in the population, a complete genetic match is often not possible. Therefore, in most kidney transplants (where there are genetic mismatches at some HLA loci), the patient can produce antibodies that target donor HLA antigens (donor specific anti-HLA antibodies) raising the risk of AMR and death of the donated kidney.
Both C1 and C5 inhibitors have shown some success in lessening the impact of AMR, prolonging graft/organ survival even when anti-HLA antibodies are present. In other words, even when the transplant recipient produces antibodies that can bind to HLA antigens on the donated tissue in the presence of C1 or C5 inhibitors those antibodies are less likely to trigger responses that damage the donated kidney and therefore the kidney/graft survives longer.
Your lab is working on developing C3 inhibitors for prevention of AMR because you think C3 inhibitors will be better at preventing antibody-mediated damage to donated tissue better than C1 or C5 inhibitors.
Using your knowledge of the complement system explain why you think C3 inhibitors could prevent antibody-mediated damage to donated organs/tissue better than C1 or C5 inhibitors. Your explanation for why C3 inhibitors are better than C1 inhibitors may not be the same as why C3 inhibitors are better than C5 inhibitors.