Resolution of an infection typically involves complete clearance of the pathogen, and thus the source of antigens, over the course of days to weeks, following which most effector lymphocytes die—a stage known as clonal contraction (see Section 11-16). What remain are long-lived antibody-producing plasma cells that sustain circulating antibodies for months to years, and small numbers of memory B and T cells that may also persist for years, poised for an accelerated adaptive response in the event of future encounters with the same pathogen. Thus, in addition to clearing the infectious agent, an effective adaptive immune response prevents reinfection. For some infectious agents, this protection is essentially absolute, whereas for others infection is only reduced or attenuated on reexposure to the pathogen.
It is not known how many infections are dealt with solely by the nonadaptive mechanisms of innate immunity, because such infections are eliminated early and produce little in the way of symptoms or pathology. Innate immunity does, however, seem to be essential for effective host defense, as shown by the progression of infection in mice that lack components of innate immunity but have an intact adaptive immune system (Fig. 11.4). Conversely, many infections can be curbed—but not cleared—in the absence of adaptive immunity.
After many types of infection, little or no residual pathology follows an effective primary adaptive response. In some cases, however, the infection itself, or the response it induces, causes significant tissue damage. In yet other cases, such as infection with cytomegalovirus or Mycobacterium tuberculosis, the pathogen is contained but not eliminated, and can persist in a latent form. If the adaptive immune response is later weakened, as it is in acquired immune deficiency syndrome (AIDS), these pathogens may resurface to cause virulent systemic infections. We will focus on the strategies used by certain pathogens to evade or subvert adaptive immunity, and thereby establish a persistent, or chronic, infection, in Chapter 13.
11-2 The effector mechanisms that are recruited to clear an infection depend on the infectious agent.
Most infections ultimately engage both Tand B-cell-mediated adaptive immunity, and in many cases both are helpful in clearing or containing the pathogen and setting up protective immunity. However, the relative importance of the different effector mechanisms, and the effective classes of antibody involved, vary with different pathogens. An emerging concept is that there are different types of immune responses that are focused on the activation of distinct immune effector modules (see Section 1-19). In each type of immune response, a specific collection of innate and adaptive mechanisms act together
Duration of infection
Fig. 11.4 The time course of infection in normal and immunodeficient mice and humans. The red curve shows the rapid growth of microorganisms in the absence of innate immunity, when macrophages (MAC) and polymorphonuclear leukocytes (PMN) are lacking. The green curve shows the course of infection in mice and humans that have innate immunity but have no T or B lymphocytes and so lack adaptive immunity. The yellow curve shows the normal course of an infection in immunocompetent mice or humans.
to eliminate a specific type of pathogen. Each effector module includes subsets of innate sensor cells, ILCs, effector T cells, and antibody isotypes, which coordinate with subsets of circulating or tissue-resident myelomonocytic cells whose microbicidal functions they recruit and enhance (Fig. 11.5). Circulating myelomonocytic cells are important innate effector cells that are targeted for heightened functions by ILCs, effector T cells, and antibodies following their recruitment into sites of infection. In their order of abundance in circulating blood, these include neutrophils, monocytes (which enter inflamed tissues and differentiate into activated macrophages), eosinophils, and basophils. Tissue-resident mast cells, which share many functions with basophils, are also targeted for heightened function.