External Barriers Against Infection
As mentioned above, the simplest way to avoid infection is to prevent the microorganisms from gaining access to the body (Figure 1.6). When intact, the skin is impermeable to most infectious agents; when there is skin loss, as for example in burns, infection becomes a major problem. Additionally, most bacteria fail to survive for long on the skin because of the direct inhibitory effects of lactic acid and fatty acids in sweat and sebaceous secretions and the low pH that they generate. An exception is Staphylococcus aureus, which often infects the relatively vulnerable hair follicles and glands.
Mucus, secreted by the membranes lining the inner surfaces of the body, acts as a protective barrier to block the adherence of bacteria to epithelial cells. Microbial and other foreign particles trapped within the adhesive mucus are removed by mechanical stratagems such as ciliary movement, coughing, and sneezing. Among other mechanical factors that help protect the epithelial surfaces, one should also include the washing action of tears, saliva, and urine. Many of the secreted body fluids contain bactericidal components, such as acid in gastric juice, spermine and zinc in semen, lactoperoxidase in milk, and lysozyme in tears, nasal secretions, and saliva.
A totally different mechanism is that of microbial antagonism associated with the normal bacterial flora of the body (i.e., commensal bacteria). This suppresses the growth of many potentially pathogenic bacteria and fungi at superficial sites by competition for essential nutrients or by production of inhibitory substances. To give one example, pathogen invasion is limited by lactic acid produced by particular species of commensal bacteria that metabolize glycogen secreted by the vaginal epithelium. When protective commensals are disturbed by antibiotics, susceptibility to opportunistic infections by Candida and Clostridium difficile is increased. Gut commensals may also produce colicins, a class of bactericidins that bind to the negatively charged surface of susceptible bacteria and insert a hydrophobic helical hairpin into the membrane; the molecule then undergoes a “Jekyll and Hyde” transformation to become completely hydrophobic and forms a voltage‐dependent channel in the membrane that kills by destroying the cell’s energy potential. Even at this level, survival is a tough game.
If microorganisms do penetrate the body, the innate immune system comes into play. Innate immunity involves two main defensive strategies to deal with a nascent infection: the destructive effect of soluble factors such as bactericidal enzymes and the mechanism of phagocytosis – literally “eating” by the cell (see Milestone 1.1). Before we discuss these strategies in more detail, let us first consider the major cellular players in the immune system.