The long-term objectives of this project are to define the key events in the inductive and effector pathways leading to ocular mucosal- associated immune responses. The hypotheses to be tested are: that nasal-associated lymphoid tissue is the primary mucosal inductive site for eliciting tear IgA antibodies following topical antigen administration to the conjunctiva; that a specific lymphocyte receptor mediates the localization of lymphoid populations within lacrimal gland tissues; and that the lymphocyte receptor interacts with an adhesion (or ligand) molecule produced by acinar epithelial cells located within the lacrimal gland.
The specific aims are: 1. To define the mucosal inductive pathway(s) that leads to the expression of IgA antibodies in tears.
this aim will compare the uptake and distribution of antigen following ocular topical and nasal-associated lymphoid tissue delivery and determine the effects of mucosal signal delivery on trafficking of antibody forming cells to lacrimal glands. 2. To isolate and characterize the lymphocyte receptor that mediates the localization of lymphoid populations within lacrimal gland tissues.
This aim will determine the structure of the isolated lymphocyte receptor at the molecular level and assess receptor distribution and function. 3. To isolate and characterize the acinar epithelial cell adhesion (or ligand) molecule that mediates lymphocyte retention with lacrimal gland tissues.
this aim will determine the structure of the isolated lacrimal gland epithelial cell adhesion (or ligand) molecular and define the mechanism by which it functions to mediate lymphocyte retention with the lacrimal gland interstitium. Investigations in the rat model will utilize biochemical, immunological and molecular approaches together with cell and tissue culture systems, adherence and motility assays and flow cytometry. these investigations will provide new information applicable to the design of clinically relevant mucosal immunization strategies to protect external ocular surfaces.
| Ridley Lathers, D M; Gill, R F; Montgomery, P C (1998) Inductive pathways leading to rat tear IgA antibody responses. Invest Ophthalmol Vis Sci 39:1005-11 |
| Masinick, S A; Montgomery, C P; Montgomery, P C et al. (1997) Secretory IgA inhibits Pseudomonas aeruginosa binding to cornea and protects against keratitis. Invest Ophthalmol Vis Sci 38:910-8 |
| Carr, R M; Lolachi, C M; Albaran, R G et al. (1996) Nasal-associated lymphoid tissue is an inductive site for rat tear IgA antibody responses. Immunol Invest 25:387-96 |
