Transplant rejection is a process where the recipient’s immune system recognizes and attacks the transplanted organ or tissue as foreign, leading to organ failure. There are two types of rejection: hyperacute rejection, which occurs within minutes of transplantation, and acute rejection, which occurs within days to weeks after transplantation. Chronic rejection is a slower process that occurs over months to years.
Tolerance, on the other hand, is a state of immunological unresponsiveness to a particular antigen, such as a transplanted organ. Tolerance can be achieved through several mechanisms, including central tolerance, peripheral tolerance, and immune suppression.
Central tolerance occurs during the development of immune cells in the thymus and bone marrow, where self-reactive cells are eliminated before they can mature and leave these organs. Peripheral tolerance mechanisms, including regulatory T cells and anergy, function to suppress or inactivate self-reactive immune cells that have escaped central tolerance.
Immunosuppressive drugs, such as calcineurin inhibitors, glucocorticoids, and antimetabolites, are used to prevent or treat transplant rejection by suppressing the recipient’s immune response. However, these drugs can also increase the risk of infections and other complications.
Newer approaches to achieving transplantation tolerance include the use of co-stimulatory blockers, which interfere with the signals that activate immune cells, and chimeric antigen receptor (CAR) T cells, which are genetically engineered immune cells that can specifically target and eliminate immune cells that recognize transplanted tissue as foreign.
Transplantation of cells, tissues, or organs from one individual to another is a promising therapy for a variety of diseases. However, transplant rejection remains a major obstacle to successful transplantation. The immune system recognizes transplanted tissues as foreign and mounts an immune response, leading to rejection of the transplant. This response involves both innate and adaptive immune mechanisms.
The major histocompatibility complex (MHC) molecules play a critical role in transplant rejection. MHC molecules are highly polymorphic, and their presentation of foreign antigens to T cells is critical for inducing an immune response. The recognition of foreign MHC molecules by T cells leads to the activation of effector T cells that attack the transplanted tissue.
To prevent transplant rejection, immunosuppressive drugs are used to dampen the immune response. However, long-term immunosuppression can have adverse effects and increase the risk of infections and cancer. Thus, alternative strategies such as inducing immune tolerance to the transplanted tissue are being explored. Tolerance can be induced by various methods, including the use of regulatory T cells, chimeric antigen receptor (CAR) T cells, and co-stimulatory blockade.