The past four decades have observed the evolution of liver transplantation research procedures, and as they had witnessed a high mortality and morbidity they now serve as a successful therapeutic measure for end-stage liver disease.At the present time, one year and five years survival for elective cases are often in excess of 85%-88% and 70%-75% and with an excellent quality of life. Compared with other solid-organ transplants, liver allografts have long been considered to be immunologically privileged, as manifest by an absence of hyperacute rejection despite a positive T cell cross-match, a low incidence of graft loss due to chronic rejection. Despite this special status, the liver can display destructive immunologic processes, since acute liver allograft rejection occurs in approximately 50% to 75% of liver transplant recipients.Immunosuppressive drugs produce significant toxic effects that increase patient morbidity and mortality.Moreover the current immunosuppressive regimens do not prevent the development of chronic rejection, which is a major cause of graft loss.

Allograft Rejection and Immunology

Related to liver transplantation, grafts mostly originate from different members of the human species. The genetically encoded immunologically mediated barrier to transplantation was recognised and defined over the course of the last century. The immunological study of transplantation has played an extremely important role in the development of clinical transplantation. The rejection mechanism is very complex and has been shown to be caused by transplantation antigens,including minor histocompatibility antigens, major histocompatibility antigens and other alloantigens .

a. Allografts and cell-mediated rejection
Antibody-mediated, hyperacute vasculitic rejection can take place in individuals with preformed antibodies against the donor’s MHC class I antigens after liver transplantation.Under most other circumstances, acute allograft rejection is launched by the large number of recipient T cells that recognise donor alloantigens.Tcell-dependent pathway to rejection,graft alloantigens are processed by specialised antigen presenting cells (APCs). Acute cellular rejection is the best-characterised graft-specific form of immune rejection.

b. Allografts and humoral-mediated rejection
The production of anti-donor MHC antibodies is related with acute and chronic graft damage, usually in the form of graft vasculopathy.Donor specific antibodies can damage the graft by activating complement and mononuclear cells with Fc receptors that recognise the heavy chain of antibodies. Anti-donor antibodies can also directly inhibit signalling cascades within endothelial cells. Humoral mediated rejection of allografts is often perceive following kidney, heart and lung transplantation, but liver allografts appear to recover in relation to the development of humoral-mediated rejection.

c. Allografts and memory T cell mediated rejection
With regard to organ transplantation, upon re-exposure to donor antigens donor-reactive memory T cells are more sensitive to antigens, function more rapidly, produce effector cytokines, survive longer than naïve T cells and directly or indirectly produce cytolytic effects on the transplanted tissue.

d. Co-stimulatory pathways
T cells must receive two distinct but coordinated signals in order to achieve optimal activation. The first signal is provided by the TCR engagement with recognition of peptide/ MHC I or II on APCs, and the second signal is achieved by the interaction of costimulatory molecules on the T cells and their ligands on APCs. There are two co-stimulatory pathways that are important in the generation of a complete T cell response are CD28/B7 and CD40/CD154 in the co-stimulatory field.

The graft rejection has been divided into three groups;hyperacute ,acute and chronic rejection.Allograft rejection principal involves host-versus-graft reaction in liver transplantation,which is the rejection of the transplant by the recipient’s body.

Prevention of allograft rejection
Allograft rejection is prevented by graft selection before transplantation, such as ABO blood group and HLA matching. The majority of liver transplant centres regard blood group compatibility as the primarily immunological selection criterion. A liver from a donor with a compatible ABO and Rh blood group is easy and feasible, with well-documented reports of this being performed inurgent situations. In recent years, many transplantation centres have also carried out the operation with ABO-incompatible grafts, and the outcomes of ABO-incompatible liver transplantations have been similar to that of blood-type-matched transplantations in some centres. Retrospective data has not shown any clear survival advantages associated with good HLA matching. Interestingly, some studies suggest that there is a clear disadvantage with certain aspects of HLA-matching.Generaly,The immunological system of liver transplantation is very complex.

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