Tissue Transplantation antigens

The monoclonal antibodies used as immunosuppressive agents in tissue transplantation include muromonoab-CD3, daclizumab and basiliximab. Muromonoab-CD3 binds to a specific site on CD3 receptors and interferes with the ability of the TCR to bind the antigen and also inhibits CD3 receptor-dependent signal transduction mechanisms, all of which result in immune suppression. Both daclizumab and basiliximab are monoclonal antibodies directed against IL-2 receptors and consequently inhibit IL-2-dependent responses after tissue transplantation, resulting in immune suppression. The monoclonal antibodies used as immunosuppressive agents are described in detail in Chapter 5. 

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)...

Proteins are the most abundant and diverse class of antigens to which the immune system can respond. This class includes toxins, allergens, products of infectious organisms, and transplantation antigens. Also included in this class are proteins that are of particular interest to archaeologists, such as blood and tissue proteins, which may be soluble or found on the cell surface, secreted or nonsecreted. 

Hypersensitivity can be defined as an exaggerated response of the immune system leading to host tissue damage. However, some of the immune responses described in the hypersensitivity classification below are, in some circumstances, appropriate responses to invading antigen. For example, a component in what is an appropriate immune response to tissue transplant rejection can be defined as a type II hypersensitivity reaction. 

Organ transplants and cellular and free tissue transplants are subject to cellular rejection. In allotransplantation, cellular rejection is controlled by conventional immunosuppressive therapy, but there is concern that, for several reasons, cellular rejection may be especially severe in xenotransplants. First, the great variety of antigenic proteins in a xenograft may lead to recruitment of a diverse set of xenoreactive T-cells. Second, the... 

Future studies are needed to determine the CMV gene products mediating these processes and the precise molecular mechanisms for these effects. These gene products will undoubtedly be unique tools for studying JAK/STAT signal transduction, MHC expression and antigen presentation, T lymphocyte function, and tissue transplantation. 

The significant participation of certain of these nutritional factors in the production of circulating antibodies to a variety of antigens and the manifestation of delayed hypersensitivity reactions, including the rejection of tissue transplants, have been described. 

General Considerations - The spectrum of potential clinical uses for an effective compound In this area Is continuing to broaden. During the past year a number of reports have appeared which tend to substantiate the role of FA In the hyperacute rejection of tissue transplants. It has been known for some time that antigen-antibody complexes are capable of aggre-... 

To detect HLA antigens and consequently to type tissues for transplantation. 

These T cells recognize peptide antigens bound to Class 1 MHC molecules on the surface of the target cell. During viral infections, viral peptides bind to selfMHCl molecules and are subsequently expressed on the cell surface. The MHCl molecules of transplanted tissues are themselves recognized by the Tc cells. 

The Major Histocompatibility Complex. The molecules making up the major histocompatibility complex (MHC) were first discovered through their ability to provoke rejection response when tissues from one individual were transplanted to another individual of the same species. Quite apart from the MHC s contribution to the difficulties of transplant surgery, in recent years it has become abundantly clear that the MHC plays a major role in the operation of T cell immunity, particularly in its function of presenting antigen to the T cell receptor. 

Petersdorf EW, Anasetti C, Martin PJ, Hansen JA. Tissue typing in support of unrelated hematopoietic cell transplantation. Tissue Antigens. 2003 Jan 61(l) l-ll. 

Treatment for transplant rejection is a very important application of glucocorticoids. The efficacy of these agents is based on their ability to reduce antigen expression from the grafted tissue, delay revascularization, and interfere with the sensitization of cytotoxic T lymphocytes and the generation of primary antibody-forming cells. 

---