Basic science of the innate immune system and the lung

SummaryInfections of the lung are prevented first by denial of access, mediated by humoral and cellular systems that obscure the pathogen’s target, simultaneously acting to kill and clear the pathogen. Where pathogens penetrate these initial defence systems, rapid detection of their presence is achieved by their engagement with a large family of pattern recognition receptors, including Toll-like receptors, retinoic-acid-inducible gene-like helicases and Nod-like receptors. Activation of a coordinated inflammatory response is achieved by cooperative signalling between sentinel leucocytes such as alveolar macrophages and lung tissue, following which a profound pro-inflammatory response mobilizes phagocytes such as neutrophils and monocytes to the lung. Resolution of the innate immune response, largely dependent upon neutrophil apoptosis, results in restoration of normal tissue architecture. In chronic disease, dysregulated inflammation maintains these systems in a state of constant activation, potentially resulting in tissue damage and progressive disease.