Tissue transplantation graft rejection

Establishment of tolerance to tissue grafts. If a newborn X mouse is injected with Y cells when it is young, it is tolerant to Y tissue transplants when it becomes an adult. If the X mouse is not exposed to Y cells at an early age, it readily rejects the tissue graft. 

The above-mentioned observations were also described in humans by P.B. Medawar in the 1940s. Based on his observations in humans, and later in animal experiments, he concluded that the graft rejection was a result of immune response, which eventually led to the discovery of MHC. The development of acquired immune response to transplanted tissue results in the rejection of the tissue where cytotoxic T cells, inflammatory T cells and antibodies play a major role in the rejection process. 

Fig. 7.1 Phases of tissue transplant rejection. The transplanted tissue sheds antigens. These antigens undergo uptake, processing and presentation to the T cells in the secondary lymphoid tissue by APCs, which include macrophages, B cells, Langerhans cells or dendritic cells. This phase results in the production of antibodies and antigen-specific TH and Tc cells. The antibodies and effector cells then migrate to the grafted tissue where TH cells secrete cytokines and which in combination with the antibodies and Tc cells destroy the grafted tissue (see Color Insert)...

Bi-anti-Tac has been found also to be effective in eliminating selectively unwanted T cells thought to play a major role in the rejection of transplanted tissues without removal of the majority of T-cells which are not involved in graft rejection. 

Azathioprine, 6-(l-methyl-4-nitro-imidazole-5-yl)-thiopurine (see Figure 1), is an immunosuppressive agent [1,2], which is widely used in clinical treatment of autoimmune disorders as weU as in prevention of graft rejection or graft-versus-host disease in organ and tissue transplantation [3-10], Azathioprine acts on several activities in cellular immunity processes. It inhibits lymphocyte activation [11], lymphocyte differentiation [12], in-vitro lymphocyte stimulation [13,14], in-vitro mixed lymphocyte reaction [15] and it reduces the activity of natural killer lymphocytes [16,17],... 

Fig. 1. Various ways chemokines might accelerate transplant rejection. Release of chemokines from the transplanted organ and/or cells infiltrating the graft may result in shifting the TH-l/TH-2 cytokine balance and cell activation that lead to further chemokine release and continued cell reemitment. Collectively these changes lead to tissue damage, graft arteriosclerosis, and eventually graft dysfunction.

CVF has been used in the investigation of the role of complement in various immunologic reactions. The anticomplement action of the CVF has potential use in the prevention of transplanted organ rejection. CVF as an immunosuppressor has been investigated by a number of workers their results showed increased survival time of transplanted or grafted tissues. 

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