What does transplant rejection mean?
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Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant.
Transplant rejection
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Acute rejection occurs in 10–25% of people after transplant during the first 60 days. Rejection does not necessarily mean loss of the organ, but it may necessitate additional treatment and medication adjustments.
Kidney transplantation
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Transplant rejection is a primary concern, both immediately after the surgery and continuing throughout the patient's life. Because the transplanted lung or lungs come from another person, the recipient's immune system will see it as an invader and attempt to neutralize it. Transplant rejection is a serious condition and must be treated as soon as possible.
Lung transplantation
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Bone marrow transplant can replace the transplant recipient's immune system with the donor's, and the recipient accepts the new organ without rejection. The marrow's hematopoietic stem cells—the reservoir of stem cells replenishing exhausted blood cells including white blood cells forming the immune system—must be of the individual who donated the organ or of an identical twin or a clone. There is a risk of graft-versus-host disease (GVHD), however, whereby mature lymphocytes entering with marrow recognize the new host tissues as foreign and destroy them.
Transplant rejection
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Hyperacute rejection manifests severely and within minutes, and so treatment is immediate: removal of the tissue. Chronic rejection is generally considered irreversible and poorly amenable to treatment—only retransplant generally indicated if feasible—though inhaled ciclosporin is being investigated to delay or prevent chronic rejection of lung transplants. Acute rejection is treated with one or several of a few strategies. Despite treatment, rejection remains a major cause of transplant failure.
Transplant rejection
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Developing with formation of cellular immunity, "acute rejection" occurs to some degree in all transplants, except between identical twins, unless immunosuppression is achieved (usually through drugs). Acute rejection begins as early as one week after transplant, the risk being highest in the first three months, though it can occur months to years later. Highly vascular tissues such as kidney or liver often host the earliest signs—particularly at endothelial cells lining blood vessels—though it eventually occurs in roughly 10 to 30% of liver transplants, and 10 to 20% of kidney transplants. A single episode of acute rejection can be recognized and promptly treated, usually preventing organ failure, but recurrent episodes lead to "chronic rejection". It is believed that the process of acute rejection is mediated by the cell mediated pathway, specifically by mononuclear macrophages and T-lymphocytes.
Transplant rejection
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The term "chronic rejection" initially described long-term loss of function in transplanted organs via fibrosis of the transplanted tissue's blood vessels. This is now "chronic allograft vasculopathy", however, leaving "chronic rejection" referring to rejection due to more patent aspects of immunity.
Transplant rejection
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The discovery of the MHC and role of histocompatibility in transplantation was a combined effort of many scientists in the 20th century. A genetic basis for transplantation rejection was proposed in a 1914 Nature paper by C.C. Little and Ernest Tyyzer, which showed that tumors transplanted between genetically identical mice grew normally, but tumors transplanted between non-identical mice were rejected and failed to grow. The role of the immune system in transplant reject was proposed by Peter Medawar, whose skin graft transplants in world war two victims showed that skin transplants between individuals had much higher rejection rates then self-transplants within an individual, and that suppressing the immune system delayed skin transplant rejection. Medawar shared the 1960 Nobel Prize in part for this work.
Histocompatibility
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Organ rejection is the unfortunate circumstance of the host immune system recognizing the transplanted organ as foreign. This is the most notable complication facing transplant recipients. Through T-cell receptors, T-lymphocytes are able to distinguish between self and non-self by recognizing human leukocyte antigens (HLA) bound to the major histocompatibility complex (MHC) protein located on the surface of organ cells. Once identified as foreign, the immune system proceeds to destroy the transplanted tissue. The panel reactive antibody (PRA) test measures the proportion of the population to which a recipient will react via pre-existing antibodies to various HLA antigens; in other words, how likely a patient is to acutely reject their new transplant. Therefore, it is essential that HLA and PRA statuses are tested for and demonstrate low immunoreactivity of the patient to the graft. In some cases, a recipient may suffer from graft-versus-host disease, in which cells of the transplanted organ attack the recipient's cells.
Intestine transplantation
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Rejection is an adaptive immune response via cellular immunity (mediated by killer T cells inducing apoptosis of target cells) as well as humoral immunity (mediated by activated B cells secreting antibody molecules), though the action is joined by components of innate immune response (phagocytes and soluble immune proteins). Different types of transplanted tissues tend to favor different balances of rejection mechanisms.
Transplant rejection
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While kidneys can routinely be obtained from human donors, most organs are in short supply leading to consideration of xenotransplants from other species. Pigs are especially likely sources for xenotransplants, chosen for the anatomical and physiological characteristics they share with humans. However, the sugar galactose-alpha-1,3-galactose (αGal) has been implicated as a major factor in hyperacute rejection in xenotransplantation. Unlike virtually all other mammals, humans and other primates do not make αGal, and in fact recognize it as an antigen. During transplantation, xenoreactive natural antibodies recognize αGal on the graft endothelium as an antigen, and the resulting complement-mediated immune response leads to a rejection of the transplant.
Transplant rejection