As noted already, mechanical and chemical defenses form the first line of host defense against pathogens (see Figure 23-1). Mechanical defenses, which operate continuously, include skin, epithelia, and arthropod exoskeletons, all barriers that can be breached only by mechanical damage or through specific enzymatic attack. Chemical defenses include the low pH found in gastric secretions as well as enzymes such as lysozyme, found in tears and in intestinal secretions, that can attack microbes directly.

The essential nature of mechanical defenses is immediately obvious in the case of burn victims. When the integrity of the skin (epidermis and dermis) is compromised, the rich source of nutrients in the underlying tissues is exposed, and airborne bacteria or otherwise harmless commensal bacteria found on the skin can multiply unchecked, ultimately overwhelming the host. Viruses and bacteria have evolved strategies to breach the integrity of these physical barriers. Enveloped viruses such as HIV, rabies virus, and influenza virus possess membrane proteins endowed with fusogenic properties. Following adhesion of a virion to the surface of the cell to be infected, direct fusion of the viral membrane with the host cell’s plasma membrane results in delivery of the viral genetic material into the host cytoplasm, where it is now available for transcription, translation, and replication (see Figures 5-46 and 5-48). Certain pathogenic bacteria (such as “flesh-eating bacteria,” which are highly pathogenic strains of Streptococcus) secrete collagenases that compromise the integrity of connective tissue and so facilitate access of the bacteria to underlying tissue.

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