PATHOGENESIS OF RESPIRATORY TRACT INFECTION



Development of pulmonary infection reflects a victory for microbial load and virulence over the lung’s defense system found throughout the air­ways from the nose to the alveoli. An understand­ing of the various abnormalities of lung defense expected in different clinical situations often helps point toward the correct etiological agent . Organisms may enter the lung by direct extension from an adjacent infected site, hematogenous transfer, inhalation of aerosolized particles, or, most commonly, aspiration of oro­pharyngeal secretions following colonization of the upper airways. The factors determining microbial adherence to the buccal mucosa remain unclear, but it is known that colonization with gram-negative bacilli (GNB) is seen only in 2 to 18 per cent of healthy subjects, whereas it is uni­versally observed in some patients in intensive care units (ICU).

When an organism breaches the anatomic and cough defenses, the mucociliary system aids in its removal by trapping it in the mucous layer and the cilia propel it cephalad. Abnormalities of mu­cociliary clearance may be aquired as a result of viral infections that denude the epithelium or may be inherited, as with defects in ciliary microtu-bular structure (immotile cilia syndrome) and cys­tic fibrosis, in which tenacious airway secretions impair ciliary beating.

In the distal respiratory tract, organisms en­counter a dual phagocytic system, pulmonary al­veolar macrophages and polymorphonuclear neu­trophils. The macrophages are vital for protection against intracellular organisms such as mycobac­teria and some other bacteria, fungi, and viruses. Macrophage function may be disrupted by viral infection or immunosuppressive therapy. Neutro­philic recruitment may be the most important component of the host’s defense once the inflam­matory response has commenced and, in con­junction with antibodies and complement, pro­vides important protection against pyogenic bacterial infection. In addition, neutrophils pro­tect against invasive and systemic infection with opportunistic fungi such as Candida, Aspergillus, and Mucor, which rarely, if ever, produce infec­tion in healthy subjects.

Humoral and cellular responses depend on the host’s previous exposure to the organism. Anti­body in secretions interferes with local spread of preventing spread to distant sites by maximizing phagocytosis (opsonization). Antibody also causes direct bacterial killing in conjunction with complement. Actively sensitized T lymphocytes release lymphokines that attract and activate mac­rophages to enhance their phagocytic function. This cell-mediated immunity is particularly im­portant in protection against viruses, facultative intracellular bacteria such as mycobacteria, Le­gionella, Brucella, and Listeria, and most sys­temic fungi. Both the classic and alternate path­ways of complement activation help with opsonization and direct microbial killing and lysis.