Fig. 2.7 Ciliated respiratory epithelium propels the overlying mucus layer for clearance of environmental microbes.
Top panel: The ciliated respiratory epithelium in the airways of the lung is covered by a layer of mucus. The cilia propel the mucus outward and help prevent colonization of the airways by bacteria. Bottom panel: Section of a lung from a patient with cystic fibrosis. The dehydrated mucus layer impairs the ability of cilia to propel it, leading to frequent bacterial colonization and resulting inflammation of the airway. Courtesy of J. Ritter.
antimicrobial peptides. When commensal microorganisms are killed by antibiotic treatment, pathogens frequently replace them and cause disease (see Fig. 12.20). Under some circumstances commensal microbes themselves can cause disease if their growth is not kept in check or if the immune system is compromised. In Chapter 12, we will further discuss how commensal microorganisms play an important role in the setting of normal immunity, particularly in the intestine; and in Chapter 15, we will see how these normally nonpathogenic organisms can cause disease in the context of inherited immunodeficiencies.
2-3 Infectious agents must overcome innate host defenses to establish a focus of infection.
Our bodies are constantly exposed to microorganisms present in our environment, including infectious agents that have been shed by other individuals. Contact with these microorganisms may occur through external or internal epithelial surfaces. In order to establish an infection, a microorganism must first invade the body by binding to or crossing an epithelium (Fig. 2.8). With the epithelial damage that is common due to wounds, burns, or loss of the integrity of the body’s internal epithelia, infection is a major cause of mortality and morbidity. The body rapidly repairs damaged epithelial surfaces, but even without epithelial damage, pathogens may establish infection by specifically adhering to and colonizing epithelial surfaces, using the attachment to avoid being dislodged by the flow of air or fluid across the surface.
Disease occurs when a microorganism succeeds in evading or overwhelming innate host defenses to establish a local site of infection, and then replicates there to allow its further transmission within our bodies. The epithelium lining the respiratory tract provides a route of entry into tissues for airborne microorganisms, and the lining of the gastrointestinal tract does the same for microorganisms ingested in food and water. The intestinal pathogens Salmonella typhi, which causes typhoid fever, and Vibrio cholerae, which causes cholera, are spread through fecally contaminated food and water, respectively. Insect bites and wounds allow microorganisms to penetrate the skin, and direct contact between individuals offers opportunities for infection through the skin, the gut, and the reproductive tract (see Fig. 2.2).
In spite of this exposure, infectious disease is fortunately quite infrequent. Most of the microorganisms that succeed in crossing an epithelial surface are efficiently removed by innate immune mechanisms that function in the underlying tissues, preventing infection from becoming established. It is difficult to know how many infections are repelled in this way, because they cause no symptoms and pass undetected.
In general, pathogenic microorganisms are distinguished from the mass of microorganisms in the environment by having special adaptations that evade the immune system. In some cases, such as the fungal disease athlete’s foot, the initial infection remains local and does not cause significant pathology. In other cases, such as tetanus, the bacterium (Clostridium tetani in this case) secretes a powerful neurotoxin, and the infection causes serious illness as it spreads through the lymphatics or the bloodstream, invades and destroys tissues, and disrupts the body’s workings.