Cell-mediated immunity is the type of host defense that is mediated by T lymphocytes, and it serves as the defense mechanism against microbes that survive and replicate inside phagocytes and nonphagocytic cells. Historically, immunologists have divided adaptive immunity into humoral immunity, which can be adoptively transferred from an immunized donor to a naive host by antibodies in the absence of cells, and cell-mediated immunity, which can be adoptively transferred only by viable T lymphocytes. The effector phase of humoral immunity is triggered by the recognition of antigen by secreted antibodies; therefore, humoral immunity neutralizes and eliminates extracellular microbes and toxins that are accessible to antibodies, but it is not effective against microbes inside cells. In contrast, in cell-mediated immunity, the effector phase is initiated by the recognition of antigens by T cells. T lymphocytes recognize protein antigens of microbes that are displayed on the surfaces of infected cells as peptides bound to self major histocompatibility complex (MHC) molecules. Therefore, cell-mediated immunity is specific for cell-associated microbes. Defects in cell-mediated immunity result in increased susceptibility to infection by viruses and intracellular bacteria as well as some extracellular bacteria and fungi that are ingested by phagocytes. T cell-mediated reactions are also important in allograft rejection (see Chapter 16), anti-tumor immunity (see Chapter 17), and immune-mediated inflammatory diseases (see Chapter 18). In Chapter 9, we described the activation of T lymphocytes and the differentiation of naive T cells into effector and memory cells. In this chapter, we discuss the reactions of effector T cells in cell-mediated immunity.

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