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INTRODUCTION

Innate immunity (see Chapter 58) and antibodies (see Chapter 61) are important mechanisms for preventing infections from taking hold, but in many infectious diseases, it is primarily the T cells that orchestrate resistance and recovery. Furthermore, T cells are important in the immune system’s surveillance for cancer, and they are responsible for most autoimmune diseases and rejection of organ transplants. The strongest evidence for the importance of T cells comes from the increase in infections and cancers that occurs when T-cell function is reduced by immunosuppressive drugs, by acquired diseases such as human immunodeficiency virus (HIV), or in congenital (primary) immunodeficiency syndromes.

The constituents of the T-cell–mediated immune system include several cell types: (1) macrophages and dendritic cells, which phagocytize microbes and present antigens to T cells (see Chapter 58); (2) effector/helper CD4-positive T cells, which use antigen receptors to recognize antigen and make cytokines that enhance or suppress immune functions; (3) cytotoxic CD8-positive T cells, which use antigen receptors to detect and kill infected cells; and (4) natural killer (NK) cells, which detect and kill infected cells using innate receptors.

The major defining feature of cell-mediated immunity, covered in detail in this chapter, is that it is critically dependent on cytokines produced by these cells. Although the interactions between various cells are complex, the result is relatively simple: opportunistic microbes only cause disease when T-cell–mediated immunity is compromised.

ACTIVATION OF T CELLS

As discussed in previous chapters, lymphocyte precursors develop into mature B cells and T cells in the bone marrow and thymus, respectively, and these are therefore called primary lymphoid organs (see Chapter 59). The result is an enormous diversity of adaptive immune cell “clones,” and each clone has a unique and specific antigen receptor, which is either a B-cell receptor (BCR) or a T-cell receptor (TCR). At this stage, a lymphocyte is considered mature, because it has a functional antigen receptor, but naïve, because it has not yet encountered a foreign antigen that can strongly bind to its TCR or BCR. Note that only a few lymphocyte clones might be specific for any given antigen.

How do lymphocyte clones survey our entire barrier, bloodstream, and organs for microbial antigens? Secondary lymphoid organs concentrate and filter antigenic material so that immune cells can sample it and remove it if necessary. After lymphocytes complete their maturation (see Chapter 59), they exit to circulate through the secondary lymphoid organs via blood and lymphatic vessels (Figure 60-1).

FIGURE 60–1

Schematic of the circulation through secondary lymphoid organs. (1) The spleen has arterial (red) and venous (blue) circulation. The “red pulp” filters and clears the blood of damaged red blood cells and circulating microbes, and the “white pulp” contains T and B lymphocytes that survey the blood for antigens. ...

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