are deposited in the lower respiratory tract predominantly by inertial impaction at points of turbulent airflow (i.e., nasopharynx, trachea, and bronchi) and at airway bifurcations because their tendency to move in a straight direction prevents them from changing directions rapidly. In more distal areas, where airflow is slower, smaller particles (0.2 to 2 µm) are deposited on the surface by sedimentation as a result of gravity. For substances with elongated shapes (i.e., asbestos, silica), the mechanism of deposition is interception. The elongated particle’s center of gravity is compatible with the flow of air; however, when the distal tip of the particulate comes in contact with a cell or mucus layer, deposition is facilitated. Particles smaller than 0.2 µm are deposited in the smaller airways and alveoli and are influenced mainly by their diffusion coefficient and brownian motion. Unlike the deposition of larger particles in the upper airways, particle density does not influence diffusion of these smaller particles, and deposition is enhanced with decreased size. These smaller particles come in contact with the alveolar epithelium, where cilia and the mucociliary transport system do not exist; thus they are removed by the phagocytic activity of alveolar macrophages or absorption into the interstitium with subsequent clearance by lymphatic drainage. Although most alveolar macrophages are adjacent to the epithelium of the alveolus, some are located in the terminal airways and interstitial space.
In the conducting airways, the mucociliary clearance system transports deposited particles from the terminal bronchioles to the major airways, where they are coughed up and either expectorated or swallowed. Deposited particles can be removed in a matter of minutes to hours. In the trachea and main bronchi, the rate of particle clearance is 5 to 20 µm/minute, but it is slower in the bronchioles (0.5 to 1 µm/minute). In general, the longer an inhaled material remains in the airways, the greater is the probability that the material will cause lung damage. The region from the terminal bronchioles to the alveoli is devoid of ciliated cells and is considered the “Achilles heel” in what is otherwise a highly effective system. The relatively slow rate of particle clearance in this area, which is mediated by macrophages, renders it the most common location for many occupational lung diseases.
Insomelungdiseases—forexample,thosecausedbyinhalationofsilicaparticles(silicosis) orcoaldustparticles(pneumoconiosis, the“blacklung”diseaseofcoalminers)—alveolarmacrophagesphagocytizetheparticlesbutareunabletodestroythem,andthemacrophageseventuallydie.Alveolarmacrophageshavelocalizedandconcentratedtheparticlesinthe“Achillesheel”regionofthelung.Theseparticlesarenotremovedviamucociliaryclearanceandeventuallyenterthelunginterstitium.Theensuinginflammatoryresponseleadstoagranulomatouslikelesionwithfibrosis,arestrictivelungdisease.Silicosisandpneumoconiosisareclassicalexamplesofdiseasesoriginatingthroughenvironmentalworkplaceexposure.Increasedawarenessofthecauseofthesediseasesandimprovedworkplaceenvironmentshaveledtoreductionintheincidenceofthesetypesoflungdiseases.
Mucosal Immune System: Adaptive and Innate Immunity