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Louisiana State University Health Sciences Center, New Orleans, Louisiana
Pulmonary host defenses against infection can be viewed as layers of protection from inhaled foreign material; in this case, a bolus of potentially infectious microorganisms deposited on the airways or the alveolar surface. The cells of the respiratory tract must recognize these microorganisms as foreign and then mount a cellular inflammatory response to clear the infectious particles. The first part of this inflammatory response, innate immunity, involves the recruitment of neutrophils from the vasculature and the elaboration of a variety of proinflammatory cytokines, which further serve to draw other cells into the lungs and to activate resident phagocytic cells. For certain pathogens, the adaptive immune system must be enlisted in which microbial antigens are presented to lymphocytes in hilar and mediastinal lymph nodes and effector lymphocytes are then recruited into lung tissue. An equally important part of adaptive immunity is the production of antibodies, which provide long-lasting protection against infection and are the basis for many of the current vaccines against respiratory infection.
Innate Immunity
T. R. Martin, C. W. Frevert
Innate immunity starts with recognition of certain pattern molecules on the microbial surface that engage specific receptors (including the Toll-like receptors) on phagocytes, leading to cellular activation and the elaboration of proinflammatory cytokines. Innate responses are very rapid and do not require participation of regional or systemic lymphoid tissues. Inflammation is normally suppressed at the alveolar level by surfactant lipids and proteins. During an acute inflammatory challenge, concentrations of these lipids fall, while concentrations of proteins enhancing lipopolysaccharide (LPS) responses rise. An emerging role for alveolar epithelial cells is appreciated both in terms of microbial recognition and in elaboration of chemokines and cytokines. Exciting new data in patients with acute respiratory distress syndrome and sepsis point to individual differences in responses to lipopolysaccharide which may have prognostic value.
Adaptive Immunity
J. L. Curtis
Adaptive immunity requires antigen presentation to lymphocytes in draining lymph nodes. In the lungs, immature dendritic cells (DC) carry antigen to hilar and mediastinal lymph nodes. The inflammatory environment as well as the presence of natural killer (NK) cells dictate how this antigen is presented and whether resultant lymphocyte responses fall into the Th1 or Th2 pathway. Secondary immune responses (in which the immune system is exposed to an antigen it has previously responded to) are accelerated because the tissues are populated with memory T-lymphocytes, which can respond to inhaled antigen independent of lymph nodes.
Humoral Immunity
H. L. Twigg
Humoral immunity is the production of antibodies. IgG is the most prevalent immunoglobulin in the lower respiratory tract, while IgA predominates in the upper respiratory tract. IgG-secreting B-lymphocytes are generated in lymph nodes and then circulate to lung tissue. In contrast, IgA-secreting B lymphocytes are produced locally in mucosa-associated lymphoid tissue. Systemic immunization results in vigorous IgG responses, while airway vaccination (nasal or inhaled) also results in IgA responses. Animal studies suggest that airway vaccination may provide more effective protection against pulmonary pathogens than systemic vaccination, but this concept is only now being tested in humans.
FOOTNOTES
Conflict of Interest Statement: J.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
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