Research Project
2019983
DESCRIPTION: (Adapted from applicant's abstract) The objective of the proposed research is to develop a model system for studying interaction between the immune and nervous systems. Such interactions normally helps maintain both the physiological and behavioral components of homeostasis throughout the body. Previous studies in avian species indicated that parasympathetic and sympathetic nerve fibers serve a role in modulation of lymphocyte activity and consequently influence the secretory immune system. Whether manipulation of the immune system exerts reciprocal modulatory effects on the nervous system is currently unknown. This investigation aims to establish whether changes introduced through the immune system influence the parasympathetic division of the autonomic nervous system (ANS) with the eye of mouse as the experimental model. Preliminary studies indicate that modulation of cholinergic enzyme activity is induced primarily by T cell-dependent antigens. This may be due to the mobilization of T and/or accessory cells elaborating cytokines in the process. Subsequent experiments will explore effects of T cell- independent antigens on immunity and cholinergic neural activity. Mice will be immunized with antigen applied either topically on the eye or intraperitoneally. Thus, localized changes in the lacrimal gland and conjunctiva will be examined by immunohistochemistry to detect antibody production and lymphoid cell migration in conjunction with changes in acetylcholinesterase (AChE, EC 3.1.1.7) and choline acetyltransferase (ChAT, EC 2.3.1.6). B cells secreting specific antibody will be localized in mouse ocular tissues by plaque forming cell assay. The role of T and accessory cells will be evaluated un in vitro conditions by assessing the actions of cytokines on tissue cholinergic enzymes. Antibody production in circulation is assessed in individual mice by enzyme-linked immunosorbent assays. AChE and ChAT will be determined by radiometric assays. Brain and spleen serve as controls for ocular tissues, to distinguish the overall physiological changes that may accompany regional antigen application. This study will lend support to the hypothesis that secretory immunity and the ANS communicate bi- directionally to prevent host infections and maintain homeostasis.
