The host can adopt three strategies to deal with the threat posed by microbes: avoidance, resistance, and tolerance. Avoidance mechanisms prevent exposure to microbes, and include both anatomic barriers and behavior modifications. If an infection is established, resistance is aimed at reducing or eliminating pathogens. To defend against the great variety of microbes, the immune system has numerous molecular and cellular functions, collectively called mediators, or effector mechanisms, suited to resist different categories of pathogens. Their description is a major aspect of this book. Finally, tolerance involves responses that enhance a tissue’s capacity to resist damage induced by microbes. This meaning of the term ‘tolerance’ has been used extensively in the context of disease susceptibility in plants rather than animal immunity. For example, increasing growth by activating dormant meristems, the undifferentiated cells that generate new parts of the plant, is a common tolerance mechanism in response to damage. This should be distinguished from the term immunological tolerance, which refers to mechanisms that prevent an immune response from being mounted against the host’s own tissues.
Anatomic and chemical barriers are the initial defenses against infection (Fig. 1.5). The skin and mucosal surfaces represent a kind of avoidance strategy that prevents exposure of internal tissues to microbes. At most anatomic barriers, additional resistance mechanisms further strengthen host defenses. For example, mucosal surfaces produce a variety of antimicrobial proteins that act as natural antibiotics to prevent microbes from entering the body.
If these barriers are breached or evaded, other components of the innate immune system can immediately come into play. We mentioned earlier the discovery by Jules Bordet of complement, which acts with antibodies to lyse bacteria. Complement is a group of around 30 different plasma proteins that act together and are one of the most important effector mechanisms in serum and interstitial tissues. Complement not only acts in conjunction with antibodies, but can also target foreign organisms in the absence of a specific antibody; thus it contributes to both innate and adaptive responses. We will examine anatomic barriers, the antimicrobial proteins, and complement in greater detail in Chapter 2.
the first is the anatomic barrier provided by the body’s epithelial surfaces. Second, various chemical and enzymatic systems, including complement, act as an immediate antimicrobial barrier near these epithelia. If epithelia are breached, nearby various innate lymphoid cells can coordinate a rapid cell-mediated defense. If the pathogen overcomes these barriers, the slower-acting defenses of the adaptive immune system are brought to bear.
Target tissues Production of antimicrobial proteins Induction of intracellular antiviral proteins Killing of infected cells Mediators Cytokines, cytotoxicity In˜ammatory inducers Bacterial lipopolysaccharides, ATP, urate crystals Sensor cells Macrophages, neutrophils, dendritic cells
Fig. 1.6 Cell-mediated immunity proceeds in a series of steps.
Inflammatory inducers are chemical structures that indicate the presence of invading microbes or the cellular damage produced by them. Sensor cells detect these inducers by expressing various innate recognition receptors, and in response produce a variety of mediators that act directly in defense or that further propagate the immune response. mediators include many cytokines, and they act on various target tissues, such as epithelial cells, to induce antimicrobial proteins and resist intracellular viral growth; or on other immune cells, such as IlCs that produce other cytokines that amplify the immune response.
1-3 The immune system is activated by inflammatory inducers that indicate the presence of pathogens or tissue damage.