Figure 1. Schematic depiction of the human lymphoid system. B lymphocytes develop in the bone marrow and T cells in the thymus. These cells then migrate to the peripheral (secondary) lymphoid organs, such as the lymph nodes, spleen and gut-associated lymphoid organs, which are the sites where they respond to antigens. The lymphatic vessels drain tissue fluids, including lymphocytes, into the lymph nodes and ultimately into a vessel called the thoracic duct, which joins the bloodstream at the left subclavian vein (not shown). Lymphocytes in the blood re-enter the lymphoid organs. The recirculation of lymphocytes therefore provides a mechanism whereby these cells can monitor most tissues in the body for the presence of antigens.

Figure 2. Structure of antibody molecules. (a) The basic structure of an antibody molecule, such as IgG, composed of two heavy (H) chains (in IgG called the chain) and two light (L) chains joined to each other by disulfide bridges. The N-terminal half of each L chain and the corresponding 25% of the H chain are variable in sequence (V regions, green) and together comprise the antigen-binding site of the molecule. The remainder of the H chain and L chain (C regions) are constant in sequence and, in the case of the H chain, are responsible for carrying out effector functions (such as opsonization) of the molecule once it has bound antigen. (b) The structure of a secreted IgM antibody. It is composed of a pentamer of the basic four-chain structure, in this case containing H chains, and again divided into V and C regions. Secretory IgM therefore contains 10 antigen-binding sites.

Figure 3. The clonal selection hypothesis. (1) During the development of T and B lymphocytes thousands of clones of cells bearing antigen receptors of differing specificities are generated in the central lymphoid organs. Any that bind to self antigens with sufficiently high affinity are deleted early in their development. The remainder colonize the secondary lymphoid organs and comprise the primary immune repertoire. (2) The introduction of a foreign antigen induces activation, proliferation and differentiation of those clones which are specific for that antigen. This leads to the emergence of a markedly expanded population of specific effector cells (shown here as plasma cells, secreting specific antibodies), which neutralize and eliminate the antigen. (3) At the same time, a proportion of these antigen-specific cells enter a distinct differentiation pathway, which also involves substantial cell proliferation. However, these cells then return to a quiescent state, when they are called memory cells. Memory cells are responsible for the capacity of immunized individuals to mount more rapid and effective immune responses following re-exposure to the same antigen (see Figure 8).

Figure 4. Antigen recognition by T and B cells. (a) The B-cell receptor (BCR) can recognize native components of pathogens (illustrated here schematically as a long-chain bacterial capsular polysaccharide). This type of antigen can crosslink a substantial number of receptors, leading to the delivery of activating signals across the cell membrane (arrows) and subsequent expansion of that clone of cells. Most protein antigens require additional signals from CD4 helper T cells to induce B-cell activation. T cells, in contrast, only recognize peptide fragments of foreign protein antigens, associated with MHC proteins on other cells. (b) CD4 T cells recognize peptides associated with class II MHC proteins (shown in green): these derive from proteins which have been taken up by antigen-presenting cells (such as a dendritic cell depicted here) and degraded intracellularly. (c) CD8 T cells also recognize peptides, but only those associated with class I MHC proteins (grey). In this case, the peptides are derived from components of intracellular pathogens (e.g. from a virus-infected cell).

Figure 5. Generation of the BCR during B-cell development by gene rearrangements. In all cells of the body except B cell, the genes encoding the V, J and D segments of the H chain and V and J of the L chain are separated from each other (germline configuration). During the development of B cells recombination leads to the deletion of intervening stretches of DNA, generating a complete V-region gene, consisting of fused VDJ segments in the case of the H chain and VJ in the case of the L chain. These become spliced to the C-region genes and then transcribed into the complete polypeptide chains, which form the surface IgM receptor.

Figure 6. Schematic structure of the thymus. The thymus is composed of lobules, each of which is divided into an outer (cortical) and inner (medullary) region. The cortex contains dense aggregates of immature developing T cells (thymocytes), interspersed with epithelial cells. The medulla consists of mature thymocytes, epithelial cells and dendritic cells.

Figure 7. T cell–B cell cooperation. CD4 T cells that have encountered antigen on dendritic cells (see Figure 4) become activated and express a protein called CD154. B cells bind and internalize protein antigens (dashed arrow) and present peptides on their class II MHC molecules (dark green). When these cells encounter T cells specific for that antigen, the two cells form conjugates. Signals delivered via the interaction of CD154 with CD40, in conjunction with cytokines produced by T cells, lead to B-cell activation.

Figure 8. Immunological memory. The graph illustrates the levels (titres) of antibodies elicited after primary and secondary (booster) immunization with a typical T-dependent antigen. The primary response is relatively slow in onset, composed initially of IgM antibodies, followed by low levels of IgG. Following secondary immunization, antibodies appear more rapidly and reach higher titres. They are principally of the IgG class and have higher affinity for the antigen than those produced in the primary response.