8536d_ch01_001-0238/1/02 4: 25 PM Page 10 mac79 Mac 79: 45_BW: Godsby et al. / Immunology 5e (a)B cell (b)TH cell (c)Tc cell TCR FIGURE 1-5 Distinctive membrane molecules on lymphocytes. (a) antigen associated with class I MHC molecules. In general, CD4* B cells have about 105 molecules of membrane-bound antibody per cells act as helper cells and CD8* cells act as cytotoxic cells.Both cell. All the antibody molecules on a given B cell have the same anti. types of T cells express about 105 identical molecules of the antigen- genic specificity and can interact directly with antigen.()T cells binding T-cell receptor(TCR) per cell, all with the same antigenic bearing CD4(CD4* cells)recognize only antigen bound to class ll specificity. MHC molecules. (c)T cells bearing CD8 (CD8 cells) recognize only LYMPHOCYTES an important role in activating B cells, Tc cells, macrophages, Tlymphocytes also arise in the bone marrow. Unlike B cells, and various other cells that participate in the immune re- which mature within the bone marrow, T cells migrate to the sponse. Differences in the pattern of cytokines produced by thymus gland to matt uring its maturation within the activated TH cells result in different types of immune thymus, the T cell comes to express a unique antigen-binding esp Inder the influence of TH-derived cytokines, a Tc cell membrane-bound antibodies on B cells, which can recognize that recognizes an antigen-MHC class I molecule complex antigen alone, T-cell receptors can recognize only antigen proliferates and differentiates into an effector cell called a cy- that is bound to cell-membrane proteins called major histo- totoxic T lymphocyte( CTL). In contrast to the Tccell,the compatibility complex(MHC)molecules. MHC molecules CTL generally does not secrete many cytokines and instead that function in this recognition event, which is termed "anti- exhibits cell-killing or cytotoxic activity. The Ctl has a vital gen presentation,"are polymorphic (genetically diverse)gly- function in monitoring the cells of the body and eliminating coproteins found on cell membranes(see Chapter 7). There any that display antigen, such as virus-infected cells,tumor are two major types of MHC molecules: Class I MHC mole- lls, and cells of a foreign tissue graft. Cells that display for cules, which are expressed by nearly all nucleated cells of ver- eign antigen complexed with a class I MHC molecule are tebrate species, consist of a heavy chain linked to a small called altered self-cells these are targets of CTls. invariant protein called B2-microglobulin. Class II MHC olecules, which consist of an alpha and a beta glycoprote ANTIGEN-PRESENTING CELLS chain, are expressed only by antigen-presenting cells. When a Activation of both the humoral and cell-mediated branches naive T cell encounters antigen combined with a MHC mol- of the immune system requires cytokines produced by Th ecule on a cell, the T cell proliferates and differentiates into cells. It is essential that activation of TH cells themselves be memory T cells and various effector T cells carefully regulated, because an inappropriate T-cell response There are two well-defined subpopulations of T cells: t to self-components can have fatal autoimmune conse- helper(TH)and T cytotoxic(Tc)cells. Although a third type quences. To ensure carefully regulated activation of TH cells, of T cell, called a T suppressor(Ts)cell, has been postulated, they can recognize only antigen that is displayed together recent evidence suggests that it may not be distinct from TH with class MHC II molecules on the surface of antigen-pre nd Tc subpopulations. T helper and T cytotoxic cells can be senting cells(APCs). These specialized cells, which include distinguished from one another by the presence of either macrophages, B lymphocytes, and dendritic cells, are distin- CD4 or CD8 membrane glycoproteins on their surfaces (Fig- guished by two properties: (1) they express class II MHC ure 1-5b, c). T cells displaying CD4 generally function as TH molecules on their membranes, and(2) they are able to lls, whereas those displaying CD8 generally function as Tc deliver a co-stimulatory signal that is necessary for TH-cell cells(see Chapter 2) ctIvation After a TH cell recognizes and interacts with an anti Antigen-presenting cells first internalize antigen, either by gen-MHC class II molecule complex, the cell is activated -it phagocytosis or by endocytosis, and then display a part of becomes an effector cell that secretes various growth factors that antigen on their membrane bound to a class II mHC known collectively as cytokines. The secreted cytokines play molecule. The TH cell recognizes and interacts with theT LYMPHOCYTES T lymphocytes also arise in the bone marrow. Unlike B cells, which mature within the bone marrow, T cells migrate to the thymus gland to mature. During its maturation within the thymus, the T cell comes to express a unique antigen-binding molecule, called the T-cell receptor, on its membrane. Unlike membrane-bound antibodies on B cells, which can recognize antigen alone, T-cell receptors can recognize only antigen that is bound to cell-membrane proteins called major histo￾compatibility complex (MHC) molecules. MHC molecules that function in this recognition event, which is termed “anti￾gen presentation,” are polymorphic (genetically diverse) gly￾coproteins found on cell membranes (see Chapter 7). There are two major types of MHC molecules: Class I MHC mole￾cules, which are expressed by nearly all nucleated cells of ver￾tebrate species, consist of a heavy chain linked to a small invariant protein called 2-microglobulin. Class II MHC molecules, which consist of an alpha and a beta glycoprotein chain, are expressed only by antigen-presenting cells. When a naive T cell encounters antigen combined with a MHC mol￾ecule on a cell, the T cell proliferates and differentiates into memory T cells and various effector T cells. There are two well-defined subpopulations of T cells: T helper (TH) and T cytotoxic (TC) cells.Although a third type of T cell, called a T suppressor (TS) cell, has been postulated, recent evidence suggests that it may not be distinct from TH and TC subpopulations. T helper and T cytotoxic cells can be distinguished from one another by the presence of either CD4 or CD8 membrane glycoproteins on their surfaces (Fig￾ure 1-5b,c). T cells displaying CD4 generally function as TH cells, whereas those displaying CD8 generally function as TC cells (see Chapter 2). After a TH cell recognizes and interacts with an anti￾gen–MHC class II molecule complex, the cell is activated—it becomes an effector cell that secretes various growth factors known collectively as cytokines. The secreted cytokines play an important role in activating B cells, TC cells, macrophages, and various other cells that participate in the immune re￾sponse. Differences in the pattern of cytokines produced by activated TH cells result in different types of immune response. Under the influence of TH-derived cytokines, a TC cell that recognizes an antigen–MHC class I molecule complex proliferates and differentiates into an effector cell called a cy￾totoxic T lymphocyte (CTL). In contrast to the TC cell, the CTL generally does not secrete many cytokines and instead exhibits cell-killing or cytotoxic activity. The CTL has a vital function in monitoring the cells of the body and eliminating any that display antigen, such as virus-infected cells, tumor cells, and cells of a foreign tissue graft. Cells that display for￾eign antigen complexed with a class I MHC molecule are called altered self-cells; these are targets of CTLs. ANTIGEN-PRESENTING CELLS Activation of both the humoral and cell-mediated branches of the immune system requires cytokines produced by TH cells. It is essential that activation of TH cells themselves be carefully regulated, because an inappropriate T-cell response to self-components can have fatal autoimmune conse￾quences. To ensure carefully regulated activation of TH cells, they can recognize only antigen that is displayed together with class MHC II molecules on the surface of antigen-pre￾senting cells (APCs). These specialized cells, which include macrophages, B lymphocytes, and dendritic cells, are distin￾guished by two properties: (1) they express class II MHC molecules on their membranes, and (2) they are able to deliver a co-stimulatory signal that is necessary for TH-cell activation. Antigen-presenting cells first internalize antigen, either by phagocytosis or by endocytosis, and then display a part of that antigen on their membrane bound to a class II MHC molecule. The TH cell recognizes and interacts with the 10 PART I Introduction (a) B cell Antigen￾binding receptor (antibody) (b) TH cell (c) TC cell CD4 TCR CD8 TCR FIGURE 1-5 Distinctive membrane molecules on lymphocytes. (a) B cells have about 105 molecules of membrane-bound antibody per cell. All the antibody molecules on a given B cell have the same anti￾genic specificity and can interact directly with antigen. (b) T cells bearing CD4 (CD4+ cells) recognize only antigen bound to class II MHC molecules. (c) T cells bearing CD8 (CD8+ cells) recognize only antigen associated with class I MHC molecules. In general, CD4+ cells act as helper cells and CD8+ cells act as cytotoxic cells. Both types of T cells express about 105 identical molecules of the antigen￾binding T-cell receptor (TCR) per cell, all with the same antigenic specificity. 8536d_ch01_001-023 8/1/02 4:25 PM Page 10 mac79 Mac 79:45_BW:Goldsby et al. / Immunology 5e: