**5. Minimizing rejection**

Rejection is the consequence of the recipient's alloimmune response to the nonself antigens expressed in donor tissues. Although rejection cannot be completely prevented, a degree of immune tolerance to the transplant can develop. Several concepts have been postulated to explain the development of partial tolerance. They include clonal deletion, the development of anergy in donor-specific lymphocytes, development of suppressor lymphocytes, and the production of factors that down-regulate the immune response against the graft. Other hypotheses include the persistence of donor-derived dendritic cells in the recipient that promote an immunologically mediated chimeric state between the recipient and the transplanted organ.

Tissue typing or crossmatching is performed prior to transplantation to assess donorrecipient compatibility for human leukocyte antigen (HLA) and ABO blood group.

The ABO blood group compatibility is tested first because incompatibility between the blood groups leads to rapid rejection. In the lymphocytotoxicity assay, patient sera are tested for reactivity with donor lymphocytes. A positive crossmatch is a contraindication for transplantation because of the risk of hyperacute rejection. The lymphocytotoxicity assay is used mainly for kidney transplantation.

The panel-reactive antibody (PRA) test screens the serum of a patient for lymphocytic antibodies against a random cell panel. Patients with prior transfusions, transplants, or pregnancies may have a high degree of sensitization and are less likely to have a negative crossmatch with a donor. A reduced risk of sensitization at the time of a second transplant has been observed when a more potent immunosuppression therapy comprised of rabbit anti-thymocyte globulin, tacrolimus, and mycophenolate mofetil/sodium is utilized for nonsensitized primary kidney or kidney/pancreas transplant patients. Mixed lymphocyte reactions (MLR) can be used to assess the degree of major histocompatibility complex (MHC) class I and class II compatibility. However, this test is not rapid and can be used only in cases involving living related donors. Therefore, this test is rarely used at present.

The primary aim of immunosuppression has been to control acute rejection by allowing tissue repair to develop. Immunosuppressive drugs are used in 2 phases: the initial induction phase, which requires much higher doses of these drugs, and the later maintenance phase.

Immunosuppression can be achieved by several mechanisms that affect lymphocytes including lymphocyte depletion, diversion of lymphocyte traffic, or blocking lymphocyte response pathways[14, 15].

Most combination therapies block T-cell activation by providing intense immunosuppression during the immediate posttransplantation period (induction phase). Immunosuppressive agents exert their effects through the following mechanisms.

• Regulators of gene expression: The classic examples are glucocorticoids; others include vitamin D analogs and deoxyspergualin. However, recent studies have shown that glucocorticoids affect inflammation by other nongenomic mechanisms.

graft and may play a major role in resistance to tolerance induction. The development of methods to blunt innate immune responses, which has potential implications for a wide

Rejection is the consequence of the recipient's alloimmune response to the nonself antigens expressed in donor tissues. Although rejection cannot be completely prevented, a degree of immune tolerance to the transplant can develop. Several concepts have been postulated to explain the development of partial tolerance. They include clonal deletion, the development of anergy in donor-specific lymphocytes, development of suppressor lymphocytes, and the production of factors that down-regulate the immune response against the graft. Other hypotheses include the persistence of donor-derived dendritic cells in the recipient that promote an immunologically mediated chimeric state between the recipient and the

Tissue typing or crossmatching is performed prior to transplantation to assess donor-

The ABO blood group compatibility is tested first because incompatibility between the blood groups leads to rapid rejection. In the lymphocytotoxicity assay, patient sera are tested for reactivity with donor lymphocytes. A positive crossmatch is a contraindication for transplantation because of the risk of hyperacute rejection. The lymphocytotoxicity assay is

The panel-reactive antibody (PRA) test screens the serum of a patient for lymphocytic antibodies against a random cell panel. Patients with prior transfusions, transplants, or pregnancies may have a high degree of sensitization and are less likely to have a negative crossmatch with a donor. A reduced risk of sensitization at the time of a second transplant has been observed when a more potent immunosuppression therapy comprised of rabbit anti-thymocyte globulin, tacrolimus, and mycophenolate mofetil/sodium is utilized for nonsensitized primary kidney or kidney/pancreas transplant patients. Mixed lymphocyte reactions (MLR) can be used to assess the degree of major histocompatibility complex (MHC) class I and class II compatibility. However, this test is not rapid and can be used only

in cases involving living related donors. Therefore, this test is rarely used at present.

The primary aim of immunosuppression has been to control acute rejection by allowing tissue repair to develop. Immunosuppressive drugs are used in 2 phases: the initial induction phase, which requires much higher doses of these drugs, and the later maintenance phase. Immunosuppression can be achieved by several mechanisms that affect lymphocytes including lymphocyte depletion, diversion of lymphocyte traffic, or blocking lymphocyte

Most combination therapies block T-cell activation by providing intense immunosuppression

• Regulators of gene expression: The classic examples are glucocorticoids; others include vitamin D analogs and deoxyspergualin. However, recent studies have shown that

Immunosuppressive agents exert their effects through the following mechanisms.

glucocorticoids affect inflammation by other nongenomic mechanisms.

during the immediate posttransplantation period (induction phase).

recipient compatibility for human leukocyte antigen (HLA) and ABO blood group.

variety of diseases, is likely to have a significant impact on transplantation as well.

**5. Minimizing rejection** 

transplanted organ.

used mainly for kidney transplantation.

response pathways[14, 15].

