Effector T cells differ from their naive precursors in ways that equip them to respond quickly and efficiently when they encounter specific antigen on target cells. Among the changes that occur are alterations in the expression of surface molecules that alter the patterns of migration of effector T cells, directing them to exit the secondary lymphoid tissues and move to sites of inflammation where pathogens have entered, or to B-cell zones within secondary lymphoid tissues, where they help generate pathogen-specific antibodies. The interactions with target cells in these sites are mediated both by direct T-cell–target cell contact and the release of cytokines, which can act locally on target cells; and at a distance to orchestrate the clearance of antigen. Some of the effector functions of T cells will be considered in this chapter; others will be discussed in Chapters 10 and 11 in the context of T-cell help for B cells and heightened activation of effector cells of the innate immune system.
The activation and clonal expansion of a naive T cell on its initial encounter with antigen is often called priming, to distinguish this process from the responses of effector T cells to antigen on their target cells and the responses of primed memory T cells. The initiation of adaptive immunity is one of the most compelling narratives in immunology. As we will learn, the activation of naive T cells is controlled by a variety of signals. The primary signal that a naive T cell must recognize is antigen in the form of a peptide:MHC complex on the surface of a specialized antigen-presenting cell, as discussed in Chapter 6. Activation of the naive T cell also requires that it recognize co-stimulatory molecules that are displayed by antigen-presenting cells. Finally, cytokines that control differentiation into different types of effector cells are delivered to the activated naive T cell. All these events are set in motion by earlier signals that arise from the initial detection of the pathogens by the innate immune system. Microbe-derived signals are delivered to cells of the innate immune system by receptors such as the Toll-like receptors (TLRs), which recognize microbe-associated molecular patterns, or MAMPs, that signify the presence of nonself (see Chapters 2 and 3). As we will see in this chapter, these signals are essential to activate antigen-presenting cells so that they are able, in turn, to activate naive T cells.
By far the most important antigen-presenting cells in the activation of naive T cells are dendritic cells, whose major function is to ingest and present antigen. Tissue dendritic cells take up antigen at sites of infection and are activated as part of the innate immune response. This induces their migration to local lymphoid tissue and their maturation into cells that are highly effective at presenting antigen to recirculating naive T cells. In the first part of this chapter we will consider the development and organization of secondary lymphoid tissues and discuss how naive T cells and dendritic cells meet in these sites to initiate adaptive immunity.
Development and function of secondary lymphoid organs—sites for the initiation of adaptive immune responses.