【正文】 rather, it must recognize antigen in the context of peptide (613 amino acids in length)/MHC plexes on the surface of APCs. Associated with the TCR is the CD3 molecule. Together they constitute the TCR plex. Figure 162 Overview of intracellular signaling events during Tcell activation. Immediately after the Tcell receptor (TCR) binds antigen on an antigenpresenting cell (APC), several protein tyrosine kinases are activated, and these enzymes phosphorylate substrates, which leads to activation of guanosine triphosphate (GTP)–binding proteins such as Ras and activation of enzymes that break down membrane phospholipids. 13 Most TCRs are heterodimers, consisting of two transmembrane polypeptide chains designated α and β, which are bonded covalently. All TCRs have a variable region that confers antigen specificity. The αβTCR is noncovalently associated with CD3. This highly conserved plex of proteins is responsible for providing the signaling ponents to the antigenbinding TCR heterodimer, which binds the antigen. Binding of a foreign antigen results in the conformational change in the plex. The associated CD3 molecules transduce the intracellular signals after antigen binding occurs. The development of monoclonal antibodies directed against CD3, such as OKT3, which interfere with Tcell function by altering or inhibiting the intracellular signaling, have played a significant clinical role in an transplantation. Both MHC molecules and αβTCR are expressed on resting T cells。 NK, natural killer。 IL, interleukin。 CD18 (LFA1), cellcell adhesion CD105 Endothelial cells, activated macrophages Binds TGFβ, modulates cell response to TGFβ ADCC, antibodydependent cellular cytotoxicity。 binds to fibrinogen MISCELLANEOUS 7 TABLE 162 Summary of Cell Surface CD Markers Marker Main Cellular Expression Function CD25 Activated T cells and B cells Complexes with IL2R, highaffinity IL2 receptor CD34 Precursors of hematopoietic cells Ligand for Lselectin。 ligand for CD28 and CD152 (CTLA4) MYELOIDCELL ASSOCIATED CD11a Leukocytes Adhesion, binds to CD54 (ICAM1), CD102 (ICAM2), CD50 (ICAM3) CD11b Granulocytes, monocytes, NK cells Adhesion。 EBV receptor CD40 B cells, macrophages, dendritic cells, endothelial cells, epithelial cells Role in Bcell activation by Tcell contact。 primary receptor for HIV retroviruses CD5 T cells, Bcell subset Ligand for CD72 CD8 Class I restricted T cells, thymocyte subsets Adhesion molecule, binds to class I MHC。 NK, natural killer. Adapted from Abbas AK, Lichtman AH, Pober JS: Cellular and Molecular Immunology, 4th ed. Philadelphia, WB Saunders, 2020. TABLE 162 Summary of Cell Surface CD Markers Marker Main Cellular Expression Function TCELL ASSOCIATED CD3 T cells, thymocytes Cell surface expression and signal transduction with TCR。 macrophage activator。 antiviral。 activates macrophages and endothelial cells。 induces Bcell proliferation。 inhibits adipogenesis Interleukin12 IL12 Mononuclear phagocytes。 T cells Bcell activation/differentiation。 Tcell activation。 mast cells Bcell activation/differentiation。 endothelial cell activation。 fibroblasts。 1 Chapter 16 Transplantation Immunology and Immunosuppression Transplantation of solid ans has bee the treatment of choice for endstage renal, hepatic, cardiac, and pulmonary disease. The field has progressed rapidly in the past 5 decades, primarily because of the development of safer and more effective immunosuppressive agents. Continued improvements in the control of rejection at both the cellular and molecular levels have been possible, owing to increased understanding of the plexity of the immune system and of the events that constitute the rejection process. Because outes may vary with the type of graft and the patient’s clinical history, the choice of immunosuppression depends on a plete understanding of the interrelationship between host and graft. In the past decade a diverse armamentarium of immunosuppressive agents targeting various aspects of the immune system has emerged. CONCEPTUAL APPROACHES TO IMMUNOSUPPRESSIVE THERAPY The rejection reaction begins when T lymphocytes recognize foreign histopatibility antigens on cells of the transplanted tissue. The foreign antigen is thought to be presented directly to host lymphocytes by antigenpresenting cells (APCs), most notably dendritic cells and macrophages, which phagocytose and then display the processed antigenic epitope on their surface. Whatever the APC, the ability to differentiate self from nonself resides with the lymphocytes. A lymphocyte, therefore, can recognize only one or a few closely related antigens. The range of possible antigen configurations is matched by a panoply of 2 lymphocyte clones arrayed against them. Immune specificity is acquired during early development, and it is postulated that fully petent clones of small resting lymphocytes await immunologic stimulation by foreign tissue antigens. Among the vast variety of antigens that can be recognized are the foreign antigens, which are governed by the major histopatibility plex (MHC). Stimulation of a resting lymphocyte by the antigen for which it is specific causes it to transform into a large active cell that secretes cytokines. These are soluble proteins or glycoproteins ( Table 16–1 ) that are effective across short distances and that, in turn, amplify the response and activate other cells. For the transplant patient, the encounter of the APC and the T lymphocyte is generally considered to be the first point of possible immunosuppressive attack. Once the lymphocyte has responded to foreign antigen and bee activated, immunosuppressive therapy is less effective. Specific effectors, such as preformed antibodies and activated killer (cytotoxic) lymphocytes as well as nonspecific