Cell-mediated adaptive immune defense of the lungs.
Cell-mediated adaptive immune responses contribute to defense against all classes of pulmonary pathogens and are essential against viruses, mycobacteria, and fungi, including Pneumocystis carinii. 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 is required to activate 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 alphabeta T cells, NK cells, and DC also amplify secondary adaptive responses to previously encountered pathogens. However, secondary responses are accelerated because memory T cells can migrate directly to infected tissues where they can be 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.
Curtis
Jeffrey L
JL
Pulmonary and Critical Care Medicine Section (506/111G), Department of Veterans Affairs Health System, 2215 Fuller Road, Ann Arbor, MI 48105-2303, USA. jlcurtis@umich.edu
D000222:Adaptation, Physiological; D002450:Cell Communication / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007121:Immunocompetence / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology