Porth's Essentials of Pathophysiology, 4e

338

Infection and Immunity

U N I T 4

the B-cell receptor. The T-cell receptor is composed of two polypeptide chains that form a groove that recognizes the processed antigen peptide–MHC molecules (Fig. 15-12). Maturation of subpopulations of T cells (i.e., CD4 + and CD8 + ) also occurs in the thymus. Mature T cells migrate to the peripheral lymphoid tissues and, upon encoun- tering antigen, multiply and differentiate into memory T cells and various mature T-cell populations. The two main populations of mature T cells are CD4 + (helper) and CD8 + (cytotoxic) T cells. Helper T Cells The CD4 + helper T cell serves as a master regulator for the immune system. Activation of CD4 + helper T cells depends on the recognition of antigen in association with class II MHC molecules. Once activated, the helper T cells secrete cytokines that influence the function of nearly all other cells of the immune system. Differences in the types of cytokines made by the CD4 + helper T cell produce different types of immune responses. These cytokines activate and regulate B cells, cytotoxic T cells, NK cells, macrophages, and other immune cells. The activated CD4 + helper T cell can differenti- ate into distinct subpopulations of helper T cells (e.g., T H 1, T H 2, and T H 17) based on the cytokines secreted by the antigen-presenting cell at the site of activation. The cytokine IL-12 produced by macrophages and den- dritic cells directs the maturation of CD4 + helper T cells toward T H 1 cells. The cytokine IL-4 produced by mast cells and T cells induces differentiation toward T H 2 cells. The cytokines IL-6 and transforming growth factor-beta (TGF- β ), notably in the absence of either IL-4 or IL-12, will induce differentiation toward T H 17 cells. The distinct pattern of cytokines secreted by mature T H 1 and T H 2 cells defines these subpopulations of T cells and determines their functions. Activated T H 1 cells stimulate phagocyte-mediated ingestion and kill- ing of microbes. T H 1 cells produce the cytokine IFN- γ ,

Activated B cell

Activated B cell

Memory B cell

Naive B cell

Primary response

Secondary response

8

12

10

4

6

2

Weeks

Antigen

Antigen

FIGURE 15-11. Primary and secondary or memory phases of the humoral immune response to the same antigen.

receptors on CD4 + helper T cells recognize the antigenic peptide–class II MHC molecules, the T cells become acti- vated and produce cytokines to further stimulate and direct the immune system. In humoral immunity, acti- vated CD4 + helper T cells trigger B cells to proliferate and differentiate into a clone of plasma cells that produce antibody. This activation process takes 1 to 2 weeks, but once generated, detectable antibody continues to rise for several weeks. Recovery from many infectious diseases occurs during the primary response when the antibody concentration is reaching its peak. The secondary or memory response occurs on sec- ond or subsequent exposures to the antigen. During the primary response, a fraction of activated B cells does not differentiate into plasma cells but instead forms a pool of memory B cells. In a secondary response, the rise in antibody occurs sooner and reaches a higher level because of these available memory cells. The booster immunization given for some diseases, such as tetanus, makes use of the memory response. For a person who has been previously immunized, administration of a booster shot causes an almost immediate rise in anti- body to a level sufficient to prevent development of the disease. Activated T cells can also generate primary and secondary cell-mediated immune responses. T Lymphocytes and Cell-Mediated Immunity T lymphocytes function in the activation of other T cells and B cells, in the control of intracellular viral infections, in the rejection of foreign tissue grafts, and in delayed hypersensitivity reactions (see Chapter 16). Collectively, these immune responses are referred to as cell-mediated or cellular immunity. T lymphocytes arise from bone marrow stem cells, but unlike B cells, pre-T cells migrate to the thymus for their maturation. There the immature T lymphocytes undergo rearrangement of the genes needed for expression of a unique T-cell antigen receptor similar to but distinct from

Antigen-presenting cell

MHC molecule

CD4

Peptide

TCR

CD4 + T cell

FIGURE 15-12. TheT-cell receptor (TCR) on a CD4 + T cell and the interaction of the major histocompatibility complex (MHC) on the antigen-presenting cell. Note that theTCR recognizes the peptide fragment of antigen bound to the MHC class II molecule.The CD4 molecule binds to a portion of the MHC molecule, stabilizing the interaction.