Chapter 20: Innate and Adaptive Immunity in the Lung

Introduction

The lung is constantly exposed to the environment. As a result, it is faced with the challenge of distinguishing nonpathogenic moieties in ambient air, from potentially pathogenic antigens derived from microorganisms. Here, we use the term “pathogens” to refer to infectious agents, allergens, toxins and other inhaled antigens unless stated otherwise. The lung protects itself using local tissue structures such as the mucus layer, airway surface liquid, cilia, and smooth muscles. It also employs complex immune defenses that are both innate and adaptive.^1,2 The immune responses need to be able to recognize, and to react to, a wide variety of stimuli. They must be able to identify, and to eliminate, unwanted pathogens to keep pulmonary structures free from infection. On the other hand, this response must not overreact to inhaled stimuli, which leads to excessive inflammation and lung injury. This need to control the intensity and duration of such responses is required to preserve normal lung structure, especially the highly vascularized and fragile alveolar epithelial surface that is required for gas exchange. Alterations of these lung protective mechanisms lead to many of the pulmonary diseases physicians face in their patients. Therefore, understanding the innate and adaptive immune responses in the lung is important in our attempts to understand the pathophysiology and to improve the management of many pulmonary diseases. The anatomic and immune defenses are reviewed below.

Anatomic Mechanisms

Given the lungs’ large surface area, it is exposed to many inhaled environmental challenges because the air we breathe contains infectious agents, toxic gases, and fine particulate matter (Fig. 20-1). The alveolar and capillary membrane barriers are important for gas exchange, and need to be defended from the injurious effects of incoming toxins and infectious pathogens. If the consequences of these exposures are not controlled, this can lead to excessive inflammation, lung edema, as well as propagation of infection. This can, in turn, lead to alveolar destruction, abnormal fibrotic repair, which results in compromised gas exchange. Air is inhaled through the nose or the mouth into the extrathoracic portion of the trachea before it enters the thorax. The nose filters and conditions the inhaled air for humidity and body temperature as it flows through the nasal turbinates. Nasal hairs also provide a barrier to trap larger particulates. The nasal secretions lining the airway mucosa contain many substances such as lysozyme, immunoglobulins [such as secretory immunoglobulin A (sIgA)], and antimicrobial peptides that bind to, and inactivate invading microbes. 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.³ The conducting airway mucosa is also coated with a viscous fluid and mucus secreted by Clara cells, goblet cells and bronchial glands (...