Integration of the innate and adaptive immune responses is required for effective protection of the host against pathogenic microorganisms. The responses of the innate immune system act early to restrain pathogens while simultaneously helping to initiate the adaptive immune response, which takes a longer time to fully develop. Different types of pathogens cause the activation of different patterns of cytokine production by innate sensor cells. This, in turn, promotes the activation of different patterns of innate lymphoid cells (ILCs), which recruit innate effector cells to sites of infection and contribute to the differentiation of parallel programs of CD4 T-cell differentiation. Coordination of the induction of different immune effector modules that are composed of related subsets of ILCs, innate effector cells, CD4 effector T cells, and class-switched antibodies underlies the different types of immunity directed against different types of pathogens.
Effector T cells augment the effector functions of innate immune cells.
In Chapter 9 we described how dendritic cells loaded with their antigen cargo migrate away from the infected tissue through the lymphatics to enter secondary lymphoid tissues, where they initiate the adaptive immune response. We discussed how CD8 T cells are primed to become cytotoxic effectors that are specialized for killing infected target cells that express MHC class I molecules. We also saw how transcription factor networks activated by specific cytokines direct the differentiation of naive CD4 T cells into distinct classes of CD4 effector T cells—TH1, TH2, and TH17 (see Fig. 9.31). In Chapter 10 we discussed the specialized role of TFH cells, which engage antigen-bearing B cells to control antibody class switching and B-cell maturation in germinal centers in the context of type 1, type 2, and type 3 responses. We now turn our attention to the specialized roles of subsets of effector CD4 T cells that emigrate from secondary lymphoid tissues after their differentiation to orchestrate the functions of innate immune cells at sites of infection.
As discussed in the preceding sections, the pattern of cytokines produced by the innate immune response during the early course of infection is determined by how the microorganism influences the behavior of innate sensor cells and the different subsets of ILCs they engage. The local inflammatory conditions produced by these interactions have a major impact on how T cells differentiate during their initial contact with dendritic cells, thus determining the subsets of effector T cells that are generated (see Chapter 9). In turn, the recruitment of effector T cells to sites of infection sustains and amplifies innate effector cell responses initiated by ILCs through effector mechanisms that require antigen-specific recognition, whether through cell–cell contact between CD4 or CD8 T cells and cell targets bearing their cognate antigens, or via pathogen-specific antibodies. In this part of the chapter, we will discuss how the differentiation of effector CD4 T cells generated during the adaptive immune response alters their expression of surface receptors and causes them to leave secondary lymphoid tissues and home to sites of infection. We will then consider how TH1, TH2, and TH17 cells interact with innate immune cells at sites of infection to bring about the clearance of the specific pathogens that elicit their development and recruitment. Finally, we will consider how the primary effector response is terminated as the pathogen is eliminated.
11-3 Effector T cells are guided to specific tissues and sites of infection by changes in their expression of adhesion molecules and chemokine receptors.