Innate Immunity of Airway Epithelium and COPD

Abstract

The mammalian immune system consists of two branchesinnate and adaptive immune systems and together they provide protection against infection. Innate immunity is a first line of host defense and is responsible for immediate recognition of pathogens to prevent microbial invasion. In addition innate immune responses also stimulate adaptive immune system (Medzhitov and Janeway, 1997). Cellular components of innate immune system include mucosal epithelial cells, macrophages, neutrophils, natural killer cells, basophils, eosinophils and others. The airway mucosa represents the body’s largest mucosal surface and is the first point of contact for inhaled microorganisms, environmental pollutants, airborne allergens and cigarette smoke (Diamond et al., 2000). Airway mucosa provides protection against potentially hazardous inhaled factors by multiple mechanisms. For instance, mucus secreted by the airway epithelium covers the apical surface of airway epithelium and traps inhaled microorganisms, allergens and particulate material. The trapped material is then cleared by mucociliary escalator away from lungs and towards the pharynx. Tight junctions between the polarized airway epithelial cells restrict the paracellular movement of solutes and ions, and prevent pathogens from gaining access to the submucosal compartment. In addition to its role as a physical barrier between environmental factors and internal milieu, airway epithelial cells also play a critical role in bridging innate and adaptive immune defenses (Hammad and Lambrecht, 2011; Kato and Schleimer, 2007). Airway epithelial cells express number of innate immune receptors also known as pattern recognition molecules, which recognizes pathogen-associated molecular patterns (PAMPS) or danger-associated molecular patterns (DAMPS) to initiate appropriate innate defense mechanisms. This includes elaboration of antimicrobial molecules, proinflammatory cytokines and chemokines that recruits and activates other mucosal innate immune cells. The responses of activated innate immune cells lead to recruitment of immune cells into epithelium or airway lumen and initiate adaptive immune responses. Continuous exposure to environmental stimuli, such as cigarette smoke, noxious gases or other environmental hazards may lead to prolonged and aberrant activation of airway epithelial cells resulting in excessive expression of pro-inflammatory cytokines and chemokines that recruit large number of inflammatory cells into airway lumen. This in turn leads to persistent inflammation, airway damage and abnormal repair, impaired innate immune responses. There are reports suggesting that exposure to cigarette smoke also