Hyperacute rejection occurs immediately after transplantation, typically within minutes to hours. It is due to the presence of preformed antibodies in the recipient’s serum which are either directed against donor HLA antigens (referred to as DSAs) or ABO blood group antigens located on the graft endothelium {Chan:2000ui, Howell:2010fg, Overviewoftranspla:2013ty, ImmunologicAspects:2002tn}. Following anastomosis and blood flow into the graft, the antibodies bind to their respective antigens on the vascular endothelium activating the complement cascade and also the clotting cascade. This leads to the accumulation of granulocytes and platelets in the graft, and ultimately the formation of thrombi. The thrombi block the …show more content…
It is mediated by a de novo response against non-self HLA molecules expressed on the graft. This response is mediated by a combination of cellular and antibody-mediated mechanisms . Firstly, CD8+ and CD4+ T cells recognise non-concordant HLA class I and class II molecules respectively, initiating a cellular response against the graft {Chan:2000ui, Howell:2010fg, Overviewoftranspla:2013ty, ImmunologicAspects:2002tn}. According to Ali et al., T cell activation in acute rejection is mediated by direct allorecognition i.e. recognition of intact donor HLA molecules either class I or class II on the surface of donor APCs {Ali:2013hc}. However, there is only a finite number of donor APCs present in the graft at the time of transplantation, thus the role of direct allorecognition in graft rejection will diminish over time. In contrast, indirect allorecognition can continue throughout the lifetime of the graft, thus is likely to be more important in driving chronic rejection {Ali:2013hc}. The activation of CD4+ T cells is a necessary step in the development of de novo antibodies targeted against mismatched HLA molecules as they drive B cell activation and differentiation into antibody producing cells. These generated antibodies then contribute to graft failure {Chan:2000ui, Howell:2010fg, Overviewoftranspla:2013ty, ImmunologicAspects:2002tn, Supon:2001tg}. In fact, several reports have demonstrated a strong correlation between the production of de novo DSAs post-transplantation and graft failure {Worthington:2003jq}. Due to its antibody and cellular-mediated aspects, acute rejection can be characterised by cellular infiltration and antibody deposition in the graft {Chan:2000ui, Howell:2010fg, Overviewoftranspla:2013ty,