An adaptive immune response is initiated when a pathogen overwhelms innate defense mechanisms. As the pathogen replicates and antigen accumulates, sensor cells of the innate immune system become activated to trigger the adaptive immune response. While some infections may be dealt with solely by innate immunity, as discussed in Chapters 2 and 3, host defense against most pathogens, almost by definition, requires recruitment of adaptive immunity. This is shown by the immunodeficiency syndromes that are associated with failure of particular parts of the adaptive immune response; these will be discussed in Chapter 13. In the next three chapters, we will learn how the adaptive immune response involving antigen-specific T cells and B cells is initiated and deployed. T-cell responses that lead to cellular immunity will be considered first, in this chapter; and B-cell responses that lead to antibody-mediated, or humoral, immunity will be considered in Chapter 10. In Chapter 11 we will consider the dynamics of T-cell and B-cell responses in the context of their integration with innate immunity and how this culminates in one of the most important features of adaptive immunity—immunological memory.
Once T cells have completed their primary development in the thymus, they enter the bloodstream. On reaching a secondary lymphoid organ, they leave the blood to migrate through the lymphoid tissue, returning via the lymphatics to the bloodstream to recirculate between blood and secondary lymphoid tissues. Mature recirculating T cells that have not yet encountered their specific antigens are known as naive T cells. To participate in an adaptive immune response, a naive T cell must meet its specific antigen, presented to it as a peptide:MHC complex on the surface of an antigen-presenting cell, and be induced to proliferate and differentiate into progeny with new activities that contribute to removal of antigen. These progeny cells are called effector T cells and, unlike naive T cells, perform their functions as soon as they encounter development and function of secondary lymphoid organs—sites for the initiation of adaptive immune responses.
priming of naive T cells by pathogen-activated dendritic cells.
General properties of effector T cells and their cytokines.
T-cell-mediated cytotoxicity.
their specific antigen on other cells—generally without requirement for further differentiation. Because of their requirement to recognize peptide antigens presented by MHC molecules, all effector T cells act on other host cells, not on the pathogen itself. The cells on which effector T cells act will be referred to as their target cells.
On recognizing antigen, naive T cells differentiate into several functional classes of effector T cells that are specialized for different activities. CD8 T cells recognize pathogen peptides presented by MHC class I molecules, and naive CD8 T cells differentiate into cytotoxic effector T cells that recognize and kill infected cells. CD4 T cells have a more flexible repertoire of effector activities. After recognizing pathogen peptides presented by MHC class II molecules, naive CD4 T cells can differentiate down distinct pathways that generate effector subsets with different immunological functions. The main CD4 effector subsets are TH1, TH2, TH17, and TFH, which activate their target cells; and regulatory T cells, or Treg cells, which inhibit the extent of immune activation.