Throughout this book we have examined the separate ways in which the innate and the adaptive immune responses protect against invading pathogens. In this chapter, we consider how the cells and molecules of the immune system work as an integrated defense system to eliminate or control different types of infectious agents, and also how the adaptive immune system provides long-lasting protective immunity. In Chapters 2 and 3, we saw how innate immunity is brought into play in the earliest phases of an infection and is probably sufficient to prevent colonization of the body by most of the microorganisms encountered in the environment. We also introduced innate lymphoid cells (ILCs), which, although lacking antigen-specific receptors, share overlapping developmental and functional features with effector CD4 T-cell subsets and cytotoxic CD8 T cells and act early during infection to generate distinct types of immune responses that target specific types of pathogens. Unlike naive T and B cells, ILCs reside in barrier tissues, such as the intestinal and respiratory mucosae, where they are poised to respond rapidly to pathogens to impair or eliminate their spread.
However, most pathogens have developed strategies to evade innate immune defenses and establish a focus of infection. In these circumstances, the innate immune response sets the scene for the induction of an adaptive immune response, which is orchestrated by signals that emanate from innate sensor cells and is coordinated with innate effector cells to bring about pathogen clearance. In the primary immune response, which occurs against a pathogen encountered for the first time, ILCs respond to innate sensor cells to mount a rapid response over the first few hours to days of pathogen invasion. Concurrent with this response, clonal expansion and differentiation of naive lymphocytes into effector T cells and antibody-secreting B cells is initiated and guided by innate sensor cells and ILCs. However, the adaptive response requires several days to weeks to fully mature, largely due to the rarity of antigen-specific precursor cells. Following expansion and differentiation in the secondary lymphoid tissues, effector T cells migrate to sites of infection and, along with pathogen-specific antibodies, enhance the effector functions of innate immune cells, and, in most cases, effectively target the pathogen for elimination (Fig. 11.1).
4. Memory phase 3. Effector phase 1. Establishment of infection 2. Inductive phase
Level of microorganism
Threshold level of antigen to activate adaptive immune response
Duration of infection
Integration of innate and adaptive immunity in response to specific types of pathogens.
Effector T cells augment the effector functions of innate immune cells.
Immunological memory.
Fig. 11.1 The course of a typical acute infection that is cleared by an adaptive immune response. 1. The infectious agent colonizes and its numbers increase as it replicates. The innate response is initiated immediately following detection of the pathogen. 2. When numbers of the pathogen exceed the threshold dose of antigen required for an adaptive response, the response is initiated; the pathogen continues to grow, restrained by responses of the innate immune system. At this stage, immunological memory also starts to be induced. 3. After 4–7 days, effector cells and molecules of the adaptive response start to clear the infection. 4. When the infection has been cleared and the dose of antigen has fallen below the response threshold, the response ceases, but antibody, residual effector cells, and immunological memory provide lasting protection against reinfection in most cases.
During this period, specific immunological memory is also established by adaptive immune cells. This ensures a rapid reinduction of antigen-specific antibody and effector T cells on encounter with the same pathogen during a secondary immune response, thus providing long-lasting and often lifelong protection against the pathogen. Immunological memory is discussed in the last part of the chapter. Memory responses differ in several ways from primary responses. We discuss the reasons for this, and what is known about how immunological memory is maintained.
Integration of innate and adaptive immunity in response to specific types of pathogens.