TRANSPLANTATION: IMMUNOLOGICAL OBSTACLES

 

Although the short-term survival rates of organ transplants continue to improve, it is long established that survival rates do decrease with time. The reason for this is still not fully understood but can be attributed to the phenomenon of rejection.

Whether a vascularized donor graft comes from a donor of the same species (allograft) or a different species (xenograft), the recipient will express an immunological response. In the case of the latter, three types of immune response exist:

hyperacute rejection - immediate immune response

delayed xenograft rejection - occurring within some days

chronic rejection - occurring much later (months or years)

Acute rejection can occur when the transplanted graft stimulates the activation of T-cells that kill foreign cells directly (cytotoxic T-cells) or aid other cells in this task (helper T-cells).

The body possesses over 20 antibody proteins that, when activated, attack and destroy foreign antigens (complement reaction). To prevent self-harm, the body has also been equipped with a way of distinguishing the native and foreign cells. Complement-regulating proteins on the surfaces of the bodily cells prevent activation of the complement proteins. Among the most important of these are the decay-accelerating factor (DAF), CD59, and the membrane cofactor protein (MCP).

 

 Source: Duke University

 

When a graft is transplanted, antibodies bind to the antigens in the endothelial cells of its blood vessels. Such binding may lead to immediate (hyperacute) organ failure or may initiate more long-term (delayed xenograft or chronic) failure (Xenotransplants, 1999).

There are generally two methods employed by doctors to suppress the rejection complex. The first is to try and achieve high computability between the donor and recipient antigens (histocompatibility). Yet, such an option remains unfeasible expect in the case of transplants between identical twins or other close relatives. Furthermore, it is completely unfeasible in the case of xenografts.

The second technique is to suppress the recipient's immune system with immunosuppressive drugs. Generally accepted as the most effective of these agents is cyclosporine A, which has demonstrated great success in inhibiting T-cell activity. Within the past decade, numerous other immunosuppressive drugs with distinct functions have been introduced into the market (Xenotransplants, 1999).

Although applicable to a greater range of patients, immunosuppressive drugs are not without their own problems. The greatest issue is that suppression of the patient's immune system also makes that person more susceptible to possibly fatal infections. The results of an experiment conducted by one liver study group indicate that infections could occur in as many as 39 percent of immunosuppressed patients (Xenotransplants, 1999).