Why Organ Transplants Fail
Causes Behind the Rejection of Grafts
Transplantation is the process by which healthy cells, tissue or organ are grafted from one site to another. Early in the twentieth century, largely through the path breaking work of Alexis Carrel, it was realised that an organ can perform the same kind of work when it is transplanted to another body. Similarly, grafting of cells and tissue can cure many diseases.
Since Carrel’s experiments on cats in 1908 where he interchanged both kidneys in a series of nine cats, surgical techniques have improved considerably and one impediment has been removed. But others remain. One is the extremely short supply of organs for transplantation. Organs like heart, lungs, and kidneys are provided by accident victims, and in some cases, living donors, but there are more patients requiring transplants than there are donors.
The Immune System Attacks Transplants
While the lack of sufficient numbers of organs for transplantation remains a barrier, the most formidable challenge for routine transplantation is posed by the immune system. This might sound ironic since the system which has evolved as protection from diseases is the one which destroys a transplanted organ recognizing it as foreign and a potential threat to the body.
The adaptive immunity is that branch of immune system which recognizes the foreign particle entering the body and gives a response accordingly. That is, the response of adaptive immunity to, say, tubercle bacillus would be different from that to dysentery bacillus. Adaptive immunity can distinguish between self and non-self components and it also possesses immunological memory. Thus it will never respond against its own body cells or tissue since they are “self” and it will possess a “memory” of a previous encounter with a foreign body.
So, when the immune system targets the transplanted tissue or organ and subsequently destroys it, it is merely fulfilling its primary function of obliterating anything that is “non-self.” (It should be noted that grafts from the same body or from the body of an identical twin are not recognized as foreign and may survive indefinitely in the body of the recipient.) So how does one make the grafted tissue or organ survive in the body of the recipient? One way is to use “immunosuppressive” drugs which lessen the powers of the immune system and do not let it act with full might to destroy the graft.
Immunosupression
Transplantation requires immunosuppression if the transplant is to survive. Most immunosuppressive methods used today make use of drugs which have the disadvantage of being nonspecific (that is, they result in generalized immunosuppression; suppression of immune responses to all foreign bodies, thus placing the recipient at increased risk of infections). Efforts are underway to develop more specific immunosuppressive agents which will suppress only those responses which try to attack the graft.
Nowadays, drugs like azathioprine (Imuran), cyclophosphamide, methotrexate, corticosteroids, cyclosporine A, tacrolimus and rapamycin are routinely used in combinations to achieve a safe level of immunosuppression. Although these drugs given before or after transplantation, or at both times, increase the survival time of the graft, it should be borne in mind that grafts do not survive indefinitely in the recipient’s body. This is because of the fact that it is not possible to completely suppress the activities of the immune system and at a much slower level, the immune system will keep on “eating away” at the graft until it finally destroys it completely.
Transplantation is a challenge for immunologists, physicians and molecular biologists and unless an effective specific immunosuppressive or tolerance-generating agent is not developed, the immune system will remain the most dreadful obstruction in routine transplantation, the miserable supply of organs for transplantation notwithstanding.
Reference : Reference : Immunology by Goldsby, Kindt, Osborne and Kuby (5th Ed.) W. H. Freeman, NY.
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