Signal transduction mechanisms in the immune system. Potential implication in immunosenescence.
The essence of the immune system is the recognition of environmental agents foreign to the host. This recognition is accomplished at the cellular level through specific membrane receptors, which when bound by appropriate ligands trigger a complex response that results in the activation of immunocompetent cells. The receptor-mediated processes that activate resting lymphocytes involve transmembrane signaling mechanisms, which have been characterized in other cell systems and are currently being investigated in B and T lymphocytes. Lymphocyte activation, proliferation, and differentiation require a sequence of cellular reactions initiated by both antigen-receptor and growth factor-receptor interactions. Signals induced by antigens or mitogens initiate responses, including gene activation for the production of hormone-like lymphocytic growth factors and their specific receptors. The physiologic mitogenesis of lymphocytes is then regulated by interactions of these specific growth factors with receptors that transmit another set of signals across the cell membrane to induce a proliferative response. As a result of this complexity, there are discrepancies with regard to the nature of the signals required for lymphocytes to acquire the ability to proliferate, as distinguished from signals inducing proliferation. Deficiencies in the transmission of any of the multiple signals essential in lymphocyte immunobiology would be expressed in vivo as an immunodeficiency of the host. Investigations of the signaling mechanisms regulating lymphocyte function may therefore provide an understanding of the age-associated reduction in the functional capacity of the immune system.
Nordin
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AA
Gerontology Research Center, National Institute on Aging, Baltimore, Maryland.
Proust
J J
JJ
D000375:Aging / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D007109:Immunity; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008564:Membrane Potentials; D010716:Phosphatidylinositols / Q000378:metabolism; D011519:Proto-Oncogenes; D017923:Sodium-Hydrogen Exchangers; D010738:Type C Phospholipases / Q000378:metabolism
D002147:Calmodulin; D002352:Carrier Proteins; D005231:Fatty Acids, Unsaturated; D010716:Phosphatidylinositols; D017923:Sodium-Hydrogen Exchangers; D000242:Cyclic AMP; D010738:Type C Phospholipases; D006152:Cyclic GMP; D002118:Calcium