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The lung is constantly exposed to environmental nonpathogenic and pathogenic moieties in ambient air. These moieties include infectious agents or their products, allergens, irritants, and other inhaled antigens capable of eliciting an immune response. The first line of defense in the interactions between environmental exposures and the respiratory tract is a barrier composed of a mucus layer, airway surface liquid, cilia, and the airway epithelium. This barrier is supported by a complex network of immune defense mechanisms that are both innate and adaptive.1,2 The immune response must recognize and react to a wide variety of stimuli. It must also identify and eliminate unwanted pathogens to keep pulmonary structures free from infection. On the other hand, this response must be closely regulated to maximize pathogen clearance while minimizing excessive inflammation and tissue injury. An adequate balance between immune response and its resolution is essential to preserve normal pulmonary architecture, especially the highly vascular and fragile alveolar epithelial surface required for gas exchange. The disruption of these lung protective mechanisms contributes to the pathogenesis of many pulmonary diseases. Therefore, understanding innate and adaptive immune responses in the lung is important to understand the pathophysiology and to improve the management of respiratory diseases. These anatomic and immune defenses are reviewed below.


The lung’s extensive surface area creates an opportunity for frequent and numerous inhaled environmental challenges that include infectious agents, irritants, and fine particulate matter (Fig. 19-1). The alveolar and capillary membranes are critical for gas exchange and must be defended from the noxious effects of these challenges and the immune response they elicit. Unchecked, these exposures can cause excessive inflammation, tissue injury, and the propagation of infection. In turn, unchecked inflammation and tissue damage can lead to anatomic distortion, functional impairments, and abnormal fibrotic repair that compromise gas exchange. Air is inhaled through the nose or the mouth into the extrathoracic portion of the trachea before it enters the thorax. The air is filtered of large particulates by vibrissae (nasal hairs) in the nasal passages and subsequently warmed and humidified as it flows through the nasal turbinates. The nasal secretions lining the airway mucosa contain immunoglobulins (such as secretory immunoglobulin A, sIgA), mucins, and host defense peptides and proteins that facilitate mucociliary clearance, inactivate invading pathogens, and modulate innate immune responses. For example, sIgA accounts for 15% of the total protein in upper airway secretions and plays a significant role in neutralizing and preventing epithelial attachment of invading viruses and bacteria, while host defense proteins and peptides such as lysozyme, cathelicidins, and defensins perform antibacterial, antiviral, and immunomodulatory roles.3 The airway mucosa is coated, with viscous fluid and mucus secreted by Clara cells, goblet cells, and bronchial glands (Fig. 19-1). This fluid makes up an important airway surface lining that protects the bronchial epithelium and forms a barrier between the environment and the lung parenchyma.


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