Conventional DCs reside in the submucosa of lung and other mucosa tissues and are considered the major antigen-presenting cells. They are usually in a resting immature state in which they function as sentinels to capture and process antigen, after which they mature and migrate to the local draining lymph node (mediastinal node for the lungs). At this node, they present antigen to T cells, which initiates an adaptive immune response, either proinflammatory or suppressive, depending on the antigen and DC. CD103+ DCs have been shown to induce regulatory/suppressor T cells by means of their synthesis and secretion of TGF-β and indoleamine dioxygenase. Plasmacytoid DCs are located in similar submucosal areas but function more in an antiviral role, as opposed to antigen presentation; upon viral activation, they rapidly secrete the antiviral cytokine IFN-γ. Macrophages and DCs commonly synthesize and secrete many similar cytokines, depending on the stimulus; such cytokines include IL-1β (which activates vascular endothelium and lymphocytes), IL-6 (which activates lymphocytes and enhances antibody production), IL-12 (which activates NK cells, CD4 T cells to Th1 T cells), tumor necrosis factor α (which activates vascular endothelium and increases permeability), IL-8 (which recruits neutrophis, basophils, and T cells), and IFN-γ (which has antiviral effects).
NK cells originate in the bone marrow and differentiate through the common lymphoid progenitor lineage . They are neither T or B cells, and resident populations of functionally active NK and invariant natural killer T (iNKT) cells are present in mucosal sites and the lung interstitium. NK cells are a major component of the body’s innate immune system of defense against invading pathogens such as herpesviruses, various bacterial infections, and tumor cells. NK cells can be activated by interferons (IFN-α and IFN-β) and other macrophage-derived cytokines (IL-12 and IL-18), which enhances their killing capabilities. The mechanism of killing is through the release of granular enzymes (granzymes, perforins, and serine esterases), which create holes or pores within the target cell membranes and thereby cause cell death. In addition, NK cells can synthesize IFN-γ, which is capable of inhibiting viral infections and stimulating CD4 and CD8 T cell responses.
NK cells have a complicated set of receptors to recognize a wide array of infectious bacteria and viruses. Individuals who lack NK cells are very prone to herpesvirus infections and often have recurrent infection. The iNKT cells belong to a category of lymphoid cells termed innate-like lymphocytes, reside together with TCRγδ cells in mucosal tissues, and have antigen receptors with limited diversity, unlike the adaptive immune cells. These types of cells are thought to be links between innate and adaptive immunity. A critical aspect of the link is that these cells can respond must faster than cells of the classical adaptive immune response, limiting early damage until the adaptive response can mobilize a stronger defense. The iNKT cells have an invariant T cell receptor α chain and, on activation, secrete the regulatory cytokines IL-10 and IFN-γ.
Epithelial Cells and Commensal Microbiota Protect the Lumen of the Airways