Fig. 2.4 Pathogens can damage tissues in a variety of different ways. The mechanisms of damage, representative infectious agents, and the common names of the diseases associated with each are shown. Exotoxins are released by microorganisms and act at the surface of host cells, for example, by binding to receptors. Endotoxins, which are intrinsic components of microbial structure, trigger phagocytes to release cytokines that produce local or systemic symptoms. Many pathogens are cytopathic, directly damaging the cells they infect. Finally, an adaptive immune response to the pathogen can generate antigen:antibody complexes that activate neutrophils and macrophages, antibodies that can cross-react with host tissues, or T cells that kill infected cells. All of these have some potential to damage the host’s tissues. In addition, neutrophils, the most abundant cells early in infection, release many proteins and small-molecule inflammatory mediators that both control infection and cause tissue damage.
and highly specific antibodies produced by the adaptive immune system are required to neutralize their action (see Fig. 1.28). The damage caused by a particular infectious agent also depends on where it grows; Streptococcus pneumoniae in the lung causes pneumonia, for example, whereas in the blood it causes a potentially fatal systemic illness, pneumococcal sepsis. In contrast, nonsecreted constituents of bacterial structure that trigger phagocytes to release cytokines with local and systemic effects are called endotoxins. An endotoxin of major medical importance is the lipopolysaccharide (LPS) of the outer cell membrane of Gram-negative bacteria, such as Salmonella. Many of the clinical symptoms of infection by such bacteria—including fever, pain, rash, hemorrhage, septic shock—are due largely to LPS.
Most pathogenic microorganisms can overcome innate immune responses and continue to grow, making us ill. An adaptive immune response is required to eliminate them and to prevent subsequent reinfection. Certain pathogens are never entirely eliminated by the immune system, and persist in the body for years. But most pathogens are not universally lethal. Those that have lived for thousands of years in the human population are highly evolved to exploit their human hosts; they cannot alter their pathogenicity without upsetting the compromise they have achieved with the human immune system. Rapidly killing every host it infects is no better for the long-term survival of a pathogen than being wiped out by the immune response before the microbe has had time to infect someone else. In short, we have adapted to live with many microbes, and they with us. Nevertheless, the recent concern about highly pathogenic strains of avian influenza and the episode in 2002–2003 of SARS (severe acute respiratory syndrome), a severe pneumonia in humans that is caused by a coronavirus from bats, remind us that new and deadly infections can transfer from animal reservoirs to humans. Such transmission appears responsible for the Ebola virus epidemic in West Africa in 2014–2015. These are known as zoonotic infections—and we must be on the alert at all times for the emergence of new pathogens and new threats to health. The human immunodeficiency virus that causes AIDS (discussed in Chapter 13) serves as a warning that we remain constantly vulnerable.
2-2 Epithelial surfaces of the body provide the first barrier against infection.
Our body surfaces are defended by epithelia, which impose a physical barrier between the internal milieu and the external world that contains pathogens. Epithelia comprise the skin and the linings of the body’s tubular structures— the respiratory, urogenital, and gastrointestinal tracts. Epithelia in these locations are specialized for their particular functions and possess unique innate defense strategies against the microbes they typically encounter (Fig. 2.5 and Fig. 2.6).