SECRETORY IGA SYSTEM OF THE EYE

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The long-range objective os this grant application is to advance our understanding of mucosal immmunity in the eye. Proposed research focuses upon the response and function of the rat ocular secretory immune system, with emphasis placed upon the impact of aging and nutrition on immunological activity in the eye. Experimental methods include ELISAs. RlAs, ELISPOT assays, immunofluorescence, cell isolation and culture, hybridoma production, flow cytometry and autoradiography. Specific aims are: 1) To identify the sources of IgA-containing cells in the lacrimal gland; 2) To evaluate the ocular immune response to non-invasive soluble and particulate antigens. These studies involve examining: a) processing of topically applied antigen to the ocular surface; b) various routes of antigenic exposure for eliciting tear IgA and IgG; c) influence of antigen dosage on tear antibody responses; d) impact of parenteral priming or boosting with antigen on tear antibody levels; e) potential for immunological memory in the ocular secretory immune system; and f) comparison of the secretory immune response in the eye to that in other mucosal secretions. 3) To analyze the functional response of the ocular secretory immune system to viral infection. This research includes determining: a) impact of viral invasion in the lacrimal gland on tear IgA, IgG, secretory component (SC) and total protein levels; b) influence of viral infection on the density of Ig-containing cells and lymphoid aggregates in lacrimal tissue and the acinar cell expression of SC and la antigens; c) tear and cellular antibody response to viral infection; d) effect of viral invasion on ocular mucosal responses to non-invasive antigens; e) influence of immunization with live or inactivated virus on subsequent ocular response to viral challenge; and f) functional role of IgA antibodies to viral antigens in ocular defense. 4) To determine the effect of aging and nutrition on the ocular secretory immune system by assessing the a) influence of aging on the ocular secretory immune response to noninvasive and viral antigens; b) effect of severe protein malnutrition on tear levels of IgA, IgG and SC and lacrimal gland content of immunoglobulin-containing cells; and c) impact of protein malnutrition and senescence on the ocular immune response to non-invasive and viral antigens. These studies have health-relatedness for the eye: they address the functional role of the secretory immune system, which serves as the first line of defense to protect the ocular surface against bacterial colonization and viral invasion.