The treatment of organ rejection with immunosuppressive medication: a discussion

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Since the pioneering experiments of allograft heart transplantation by Christiaan Barnard in 1967, there have been significant advances in the development of human organ transplantation. Indeed, over 35,000 patients in both the US and Europe benefit annually from organ transplantation (Hampton, 2005). Through the transplantation and engraftment of these organs, not only can biological function of organs be restored, but also the quality of life of recipients can be greatly increased. As a result the number of transplantation operations carried out each year has increase exponentially over the past decades. Despite improvements in surgical techniques, the hurdle of immunological rejection by the host of transplanted organs still remains a current obstacle. This represents a challenge both scientifically and clinically and, as a result, is a focus of both the medical and scientific communities. Over the past 60 years, there has been an exponential increase in the development of immunosuppressive drugs in order to treat organ rejection, as well as autoimmune diseases (Gummert et al. 1999). These drugs seek to suppress various components of the immune system in order to prevent rejection in the context of organ transplantation. This essay seeks to examine the broad immunology of transplantation as well as the different classes of immunosuppressive drugs and their associated benefits and side effects. Transplantation is broadly defined as the act of transferring cells, tissues, or organs from one site to another. In the context of organ transplantation, this is generally from one person to another, with transplantation classed as either from a living donor or cadaveric. Although less common, there has been some attempt to transplant organs from other animals, known as xenografts. This was initially attempted given the lack of availability of human donor organs. However, as transplantation occurs between two immunologically distinct persons, a degree of immunological mismatch occurs. Due to this mismatch, the host immune system recognises the donor organ as ‘foreign’ and, as a result, activates various arms of the immune system. Several types of immune rejection can occur in individuals undergoing organ transplantation. Hyperacute rejection occurs when pre-existing antibodies within the host against donor antigens attack the graft and result in rapid rejection of the graft, typically within a few hours (Murphy et al. 2010). This results in rapid declining function of the graft and is often non-reversible, thereby causing the recipient to lose the graft. In contrast, acute rejection occurs within six months following transplantation and is the result of activated T cells against donor antigens (Murphy et al. 2010). The third type of rejection is known as chronic rejection and, as the name suggests, occurs years after transplantation and is mediated by both antibodies and T cells. In order to encourage graft survival, and prevent the aforementioned from occurring, effective regimes in order to suppress these immune responses have been developed, although as outlined, they often come with significant side effects. Glucocorticoids, such as prednisone, are commonly used in immunosuppressive regimes. These drugs seek to prevent rejection by suppressing various arms of the immune system including T cells,

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