Question

Describe the innate and acquired immune functions that prevent bacteria from colonizing the lung

Answer 1

Innate immune system is the primordial system that has a primary role in lung antimicrobial defenses. Due to the constant exposure to environmental components containing potentially airborne pathogens, the pulmonary immune system plays an important role in protecting the host with this immediate contact. Large particles deposit in the nasopharynx and tonsillar regions when inertial forces carry them out of the bending airstream and against the posterior pharyngeal wall. Particles that are carried into the conducting airways sediment onto the mucociliary
surface of the airways under the influence of gravity, where they encounter soluble constituents in airway fluids and the upward propulsive force of the mucociliary system. Particles 1 um in size and smaller, the size of bacteria and viral particles, are carried to the alveolar surface where they interact with soluble components in alveolar fluids (e.g., IgG, complement, surfactant and surfactant-associated proteins) and alveolar macrophages. Through the integrated action of proinflammatory lipid, chemokine, complement, and cytokine mediators, different immune cell populations are sequentially recruited into the bronchoalveolar and lung parenchymal compartments. In an acute inflammatory reaction, neutrophils are attracted first and localize mainly in the bronchoalveolar space, followed by monocytes and lymphocytes for more sustained/chronic host defense functions. The defense functions of the airway epithelium and submucosa include regulation of barrier tightness, secretion of mucus and antimicrobials, and cooperation with various immune subsets via cytokine, chemokine, and growth factor production. At the root of innate defense in the lung, however, is the ability of the airway epithelium to sense pathogens via a variety of receptors (pattern recognition receptors (PRR) such as Toll-like receptors (TLR), RIG-I-like receptors (RLR), protease-activated receptors (PAR), Nod-like receptors (NLR), C-type lectin receptors, and the bitter- and sweet-taste receptors). Complement components bind to bacterial cell walls and facilitate bacterial uptake by leukocytes by the C3bi receptor. The complement component C5a is a potent chemotactic factor that interacts with a specific receptor on neutrophils to facilitate directed migration of neutrophils toward sites of inflammation.

Cell-mediated adaptive immune responses contribute to defense against all classes of pulmonary pathogens and are essential against viruses, mycobacteria, and fungi. Adaptive responses depend on sequential pairwise interactions between three cell types: T cells, natural killer (NK) cells, and dendritic cells (DC). Differential expression of specific adhesion molecules and chemokines regulates the location and timing of these interactions. Primary adaptive responses are triggered by immature myeloid DC, which carry antigen from the lungs to regional lymph nodes. Antigen presentation by these mature DC activates naive CD4 T cells, which are essential to generate polarized type 1 or type 2 effector responses and for robust immunologic memory. Inflammation recruits NK cells and DC that interact in a contact- and tumor necrosis factor alpha-dependent fashion within injured tissues to initiate immune response polarization. NK cells exposed to IL-12 favor survival of DC that prime for Th1 responses, whereas NK cells exposed to IL-4 do not exert DC selection, leading to tolerogenic or Th2 responses. Naive alpha and beta T cells, NK cells, and DC also amplify secondary adaptive responses to previously encountered pathogens. However, secondary responses are accelerated because memory T cells migrated directly to infected tissues where they are activated without strenuous costimulatory requirements. Additionally, previous pulmonary infections or immune responses increase numbers of lung DC and populate the lungs with clones of memory B cells and T cells that are immediately available to respond to infections.