Defense Systems

Abstract

The lung is the anatomical site not only for gaseous exchange, but also for high-turnover sampling of pathogens and other antigenic and allergenic material. It constitutes a vast mucosal surface area, constantly exposed to inhaled substances that, allowed free ingress, would cause substantial damage or death. Any defense mechanism must accommodate the fact that the respiratory tract is made up of delicate tissues required for gas exchange. The lung, therefore, requires a multilayered system of protection that allows a fast, efficient, and effective response able to deal with infectious pathogens and other foreign particles without damaging the lung itself in the process. This encompasses physical barriers, innate immune mechanisms, and the cellular and antibody adaptive immune response. The price of excessive or inappropriate inflammatory responses can be high and may lead to lung damage. The first line of defense against entry to the lung is from physical barriers such as mucus and cilia, followed by the innate immune response that includes a battery of mediators such as lactoferrin, lysozyme, collectins, and defensins. Release of these molecules leads directly to lysis of pathogens, or destruction through opsonization or the recruitment of inflammatory cells. Rapid activation of the innate immune response also comes through the triggering of Toll-like receptors (TLRs) and the chemotactic recruitment and activation of neutrophils. Natural killer (NK) cells provide a fast and effective immune surveillance response against infectious pathogens. Type I interferons exert a direct antiviral effect. The adaptive immune response contributes by making neutralizing antibodies and T lymphocytes orchestrate antigen-specific immune responses through their ability to differentiate self from nonself and provide memory. T lymphocyte populations of different cytokine phenotypes—so-called T-helper-1 (Th1), T-helper-2 (Th2) and T-helper-17 (Th17)—dramatically alter the balance between pathogen clearance and tissue damage.