Immune Surveillance And Susceptibility To Infection

Respiratory infections are recognized as the fifth leading cause of death for individuals over age 65 (National Vital Statistics, 2001). There are many factors that make the elderly more susceptible to lung infections. These include declining immune function, impaired oral and mucociliary clearance, neurologic disorders, malnutrition, chronic organ dysfunction syndromes, and the presence of parenchymal lung disease (Meyer, 2004). Although various aspects of systemic immunity decline with advancing age, there is considerable variation among individuals. Fairly robust immune responses can be identified in centenarians (Franceschi et al., 1995), and many other factors such as the presence of a swallowing disorder and aspiration can cause pneumonia in the elderly despite intact immune responses.

Both T and B lymphocyte responses tend to gradually wane with advancing age, and antibody responses to vaccines are less robust in the elderly than in younger individuals (Meyer, 2001). Although the effect of advancing age on acquired immune responses has been studied fairly extensively, relatively little is known about the effect of age on compartmentalized innate immune responses in the lung. Important components of innate immunity that may play a critical role in defense against infection include the ability of epithelia or other resident lung cell populations to produce antibacterial peptides such as the defensins (Huttner and Bevins, 1999) or collectins (Sano and Kuroki, 2005). Because the innate immune system is a key component of respiratory host defense that provides constant surveillance and immediate protection against invading pathogens (Meyer, 2001), age-associated decline in various components of innate immunity may play a key role in susceptibility to pulmonary infections.

One host defense mechanism that has been shown to decline gradually with advancing age in both animal models and human subjects is mucociliary clearance. Tracheal mucus velocity gradually declines in beagle dogs beginning at approximately age four (Mauderly and Hahn, 1982), and aged rats have diminished clearance of bacteria compared to young animals (Antonini et al., 2001). Mucociliary clearance has been shown to decline in humans with advancing age (Puchelle et al., 1979), and microtubular abnormalities in cilia have been associated with depressed nasociliary clearance time and lower ciliary beat frequency (Ho et al., 2001). Although not proven, age-associated ciliary dysfunction may significantly increase susceptibility to respiratory infection for elderly individuals and may also increase susceptibility to irritation and damage to airway mucosae by inhaled particulates that are deposited on airspace surfaces and not rapidly cleared.

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