Lung defense against infection.

The human lung has an exquisitely effective and complex defense against infections. Mucus prevents attachment of bacteria to the epithelium, and those bacteria that cannot cross the mucus are cleared by exhalation or by the mucus-ciliary escalator. Alveolar macrophages dispatch microbes that reach the peripheral barriers of the lung. The pulmonary phagocytic system immobilizes, kills, and walls off invading bacteria. The phagocytic system, developed in bone marrow, includes alveolar macrophages, granulocytes, and monocytes. The phagocytic system is amplified by humoral factors, including inflammatory mediators, acute-phase reactants, and opsonins that allow rapid engulfment and killing of microbes. Highly mobile polymorphonuclear granulocytes reinforce the macrophages when invading organisms reach tissue. Sterility of the lower respiratory tract in the normal host is evidence that the defense systems of the lung are highly effective and potently bactericidal. The oxidative and nonoxidative microbicidal mechanisms of alveolar macrophages and granulocytes are lethal for most ordinary microbes. However, certain pathogens have means of preventing phagocytosis, and obligate intracellular species have evolved mechanisms of intracellular survival. Successful biologic détente between microbe and host is the usual situation in the normal human lung, but the relationship is unfortunately short-lived in patients with cystic fibrosis. Mucus is not an adequate barrier in these patients. Bacterial pathogens colonize respiratory tissue and, as a consequence, compromise lung function. Better understanding of local defenses in normal human lungs and of the defects in lung defenses in patients with cystic fibrosis should lead to methods that will provide these patients with successful defense against invading microbes.