The main antigen-presenting cells, known as conventional DCs, are typically found in the submucosa of the lungs and other mucosal tissues. They start off in an immature state and act as sentinels, capturing and processing antigens. Once they mature, they migrate to the local draining lymph node (mediastinal node in the case of the lungs) where they present the antigen to T cells. This presentation triggers an adaptive immune response, which can either be proinflammatory or suppressive depending on the antigen and the type of DC involved. CD103+ DCs have been found to induce regulatory/suppressor T cells by producing and releasing TGF-β and indoleamine dioxygenase. Plasmacytoid DCs, on the other hand, are located in similar submucosal areas but have a more focused role in combating viral infections. When activated by a virus, they quickly release the antiviral cytokine IFN-γ. Macrophages and DCs share the ability to synthesize and secrete similar cytokines in response to specific stimuli. These 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 and CD4 T cells to become Th1 T cells), tumor necrosis factor α (which activates vascular endothelium and increases permeability), IL-8 (which recruits neutrophils, basophils, and T cells), and IFN-γ (which has antiviral effects).

NK cells originate in the bone marrow and develop through the common lymphoid progenitor lineage. They are distinct from both T and B cells. Mucosal sites and the lung interstitium house resident populations of functionally active NK cells and invariant natural killer T (iNKT) cells. NK cells play a crucial role in the body's innate immune defense against various pathogens such as herpesviruses, bacterial infections, and tumor cells. Interferons (IFN-α and IFN-β) and other cytokines produced by macrophages (IL-12 and IL-18) can activate NK cells, enhancing their ability to kill pathogens. NK cells eliminate target cells by releasing granular enzymes (granzymes, perforins, and serine esterases), which create pores in the target cell membranes, leading to cell death. Additionally, NK cells can produce IFN-γ, which inhibits viral infections and stimulates CD4 and CD8 T cell responses.

NK cells possess a complex set of receptors that enable them to recognize a wide range of infectious bacteria and viruses. Individuals lacking NK cells are highly susceptible to herpesvirus infections and frequently experience recurring infections. iNKT cells belong to the category of innate-like lymphocytes and are found alongside TCRγδ cells in mucosal tissues. Unlike adaptive immune cells, iNKT cells have antigen receptors with limited diversity. These cells are believed to act as a connection between innate and adaptive immunity. One critical aspect of this link is that iNKT cells can respond much faster than classical adaptive immune cells, limiting early damage until a stronger defense can be mobilized. Upon activation, iNKT cells with their invariant T cell receptor α chain secrete the regulatory cytokines IL-10 and IFN-γ.

Epithelial cells and commensal microbiota play a protective role in the airway lumen.
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