Transplants and rejections
A transplant consists of replacing a diseased organ with another that is working properly. An organ (or tissue and sometimes cells) is removed from a healthy individual (donor), and placed in the body of the same or another organism (recipient) in which it is not working properly. In the case of transplants of vital organs, the donor has to be in a state of “brain death”.
Transplants and their classes
Normally, the immune system of the recipient person recognizes the molecules of the graft and transplanted organ as foreign to the body and acts against them, producing a rejection against the transplanted organ.
Depending on the relationship between donor and recipient, transplants can be:
- Autotransplantation, if the transplanted organ or tissue comes from the same individual.
- Isotransplantation, if the donor is an individual genetically identical to the recipient. This occurs only between univitelline twins.
- Allotransplantation, when the donor is a genetically different individual from the donor.
- Xenotransplantation, if the donor and recipient belong to different species.
Naturally, the immune responses will be lower in autologous transplants, and higher in xenografts, since the donor and recipient tissues are less compatible. For this reason, autologous and isotransplants are safer than allogeneic or xenograft transplants, which have a higher risk of rejection.
The chances of rejection increase as the relationship between donor and recipient decreases. The xenotransplantation in humans, for example, derived from pork, the species which gives less problems, and there are even transgenic pigs expressing in its cells some human proteins.
Although the medical techniques for transplantation are very advanced, the biggest problems are the availability of organs and the possibility of immune rejection by the recipient.
However, corneal transplantation does not usually cause rejection, since the cornea does not have lymphatic or blood circulation and, therefore, lymphocytes do not easily access it.
The rejection mechanism occurs as a response of the recipient's immune system to the donor tissue or organ with a certain surface antigen on the cells, which their T lymphocytes do not recognize as their own. This causes a large number of cytotoxic lymphocytes and macrophages to go to the transplanted organ, producing necrosis of the transplanted tissue or organ.
The cytotoxic lymphocytes activated the macrophages and also thanks to the interferon (interleukin) the NK cells that secrete perforins that attack cell membranes of transplantation and destroy them.
The neutrophils also phagocytose cells with opsonins and form platelet thrombi. The production of antibodies in response to MHC antigens activates the complement system that causes cell lysis.
Rejection is greater if the donor's surface antigens (MHC proteins) are different from those of the recipient. If the donor and recipient autoantigens do not match, rejection occurs, beginning with the attack of TC lymphocytes, causing lysis of cells in transplanted tissues. If the MHC autoantigens are identical, rejection does not occur, but this rarely occurs. For this reason, before transplanting an organ, it is necessary to test that the autoantigens of the donor and recipient cells are very similar.
In rejection, in addition to the action of TC lymphocytes, the specific humoral response (antibodies) and the nonspecific response (macrophages, complement activation) also intervene .
Depending on the moment in which the rejection occurs, these types are distinguished:
- The acute rejection occurs within 24 to 48 hours after transplantation, and is mainly due to the action of antibodies that bind to antigens of foreign cells causing their destruction.
- The delayed or chronic rejection several weeks or months after transplantation appears. It is caused by the development of memory T lymphocytes which, in the presence of antigens from the transplanted organ, activate TC lymphocytes and macrophages that go to the affected area and act against the transplanted organ.
The rejection depends on the genetic relationship between donor and recipient, and occurs because the proteins of the major histocompatibility complex (HLA in the human species) that lymphocytes have in their membrane and the vast majority of cells that each person has, are recognized by their immune system. MHC proteins in transplanted tissue cells act as foreign antigens and cause rejection.
If the donor and recipient have the same histocompatibility systems, there is no problem of rejection, but only univitelline twins are genetically the same. In cases of autologous transplants, such as skin, for example, there is no rejection. There is also no problem of rejection in tissue transplants that do not have blood supply or it is very scarce, as in the case of corneal transplantation, since it does not produce any immune reaction.
In the rest of the transplants, to minimize rejection, it is a question of having the maximum degree of histocompatibility between donor and recipient, looking for the most compatible according to their blood group and the HLA type of their cells. The recipient has to undergo immunosuppressant treatments to decrease the activity of the immune system and not recognize the transplanted tissue as foreign, which can cause them to have some infection problems due to their weakened immune system.