What causes hyperacute transplant rejection?

Hyperacute transplant rejection is primarily caused by the presence of preformed antibodies against donor antigens, specifically human leukocyte antigens (HLA) and ABO blood group antigens. When a transplanted organ is introduced into a recipient, if the recipient has antibodies that were formed in response to previous exposures to these antigens (through prior transplants, blood transfusions, or pregnancies), these antibodies can immediately recognize and bind to the foreign vascular endothelium of the transplanted organ.

This binding initiates a rapid immune response, leading to the activation of the complement system and recruitment of inflammatory cells, which causes thrombosis and quickly compromises blood flow to the transplant. This rejection process occurs within minutes to hours of transplantation, hence the term "hyperacute."

It's important to note that this type of rejection differs from other forms, such as delayed hypersensitivity, which involves a slower immune response mediated by T-cells, or chronic inflammation, which is a long-term, low-grade immune response. Cell-mediated immunity is also relevant in other types of rejection, but hyperacute rejection specifically involves antigen-antibody interactions that are preformed, leading to an immediate and devastating outcome for the transplanted organ.