Triggering of innate sensors on various cells—neutrophils, macrophages, and dendritic cells in particular—not only activates these cells’ individual effector functions, but also stimulates the release of pro-inflammatory chemokines and cytokines that act together to recruit more phagocytic cells to the site of infection. Especially prominent is the early recruitment of neutrophils and monocytes. Furthermore, cytokines released by tissue phagocytic cells can induce more systemic effects, including fever and the production of acute-phase response proteins, including mannose-binding lectin, C-reactive protein, fibrinogen, and pulmonary surfactant proteins, which add to a general state of augmented innate immunity. These cytokines also mobilize antigen-presenting cells that induce the adaptive immune response. The innate immune system has at its service several recently recognized subtypes of innate lymphoid cells which join the ranks of the long-recognized NK cells. ILCs exhibit specialized effector activity in response to different signals, and act to amplify the strength of the innate response. The production of interferons in response to viral infections serves to inhibit viral replication and to activate NK cells. These in turn can distinguish healthy cells from those that are infected by virus or that are transformed or stressed in some way, based on the expression of class I MHC molecules and MHC-related molecules that are ligands for some NK receptors. As we will see later in the book, cytokines, chemokines, phagocytic cells, and NK cells are all effector mechanisms that are also employed in the adaptive immune response, which uses variable receptors to target specific pathogen antigens.
Summary to Chapter 3.
Innate immunity uses a variety of effector mechanisms to detect infection and eliminate pathogens, or hold them in check until an adaptive immune response develops. These effector mechanisms are all regulated by germline-encoded receptors on many types of cells that can detect molecules of microbial origin or that sense signs of host cellular damage. The induced responses of the innate immune system are based on several distinct components. After the initial barriers—the body’s epithelia and the soluble antimicrobial molecules described in Chapter 2—have been breached, the most important innate defenses rely on tissue macrophages and other tissue-resident sensor cells, such as dendritic cells. Macrophages provide a double service: they mediate rapid cellular defense at the borders of infection through phagocytosis and antimicrobial actions, and they also use their various innate sensors to activate the process of inflammation, which involves recruiting additional cells to sites of infection. Innate sensors activate signaling pathways that lead to the production of pro-inflammatory and antiviral cytokines, which in turn stimulate innate effector responses while also helping to initiate an adaptive immune response. The uncovering of the pathogen-sensing mechanisms described in this chapter is still extremely active. It is providing new insights into human autoinflammatory conditions such as lupus, Crohn’s disease, and gout. Indeed, the induction of powerful effector mechanisms by innate immune recognition based on germline-encoded receptors clearly has some dangers. It is a double-edged sword, as is illustrated by the effects of the cytokine TNF-α—beneficial when released locally, but disastrous when produced systemically. This illustrates the evolutionary knife edge along which all innate mechanisms of host defense travel. The innate immune system can be viewed as a defense system that mainly frustrates the establishment of a focus of infection; however, even when it proves inadequate in fulfilling this function, it has already set in motion—by recruiting and activating dendritic cells—the initiation of the adaptive immune response, which forms an essential part of humans’ defenses against infection.
Having introduced immunology with a consideration of innate immune function, we next turn our attention to the adaptive immune response, beginning with an explanation of the structure and function of the antigen receptors expressed by lymphocytes.
Questions.