The long term objective of the proposed research is to further our understanding of secretory immunity in the female genital tract. Such information is important for the development of immunocontraceptive methods and for immunization to protect the genital tract against infectious agents. Using the mouse as a model, we will study the afferent limb of the secretory immune system and explore the effectiveness of various adjuvants and routes of the afferent limb of the secretory immune system and explore the effectiveness of various adjuvants and routes of immunization in promoting secretory immunity.
The specific aims are to determine: 1) the occurrence of lymphatic vessels in the vagina and their changes during the estrous cycle using histological techniques, and the lymphatic drainage pathway of the vagina using Pontamine Blue and colloidal carbon as tracers; 2)the occurrence and distribution of cells involved in antigen recognition in the vagina and cervix during the estrous cycle by labeling Langerhans; cells, macrophages, T and B lymphocytes using immunohistological techniques. 3) the uptake and fate of intravaginally administered protein tracers during the estrous cycle using a variety of histological techniques: 4) the involvement of lymph nodes draining the vagina in the response to intravaginal (iv) immunization by localizing antigen-specific igA and igG lymphocytes in iliac lymph nodes from immunized mice using double immunofluorescent labeling: 5) the involvement of regional lymph nodes in the response to iv immunization by measuring ELISA titers of antiferritin Iga and IgG antibodies in vaginal fluids of immunized mice after removal of the iliac, caudal, or both nodes: 6) whether IgA and IgG in vaginal fluid are secreted across the wall of the vagina or enter the vagina from elsewhere in the tract by measuring ELISA titers of antiferritin IgA and IgG antibodies in vaginal fluids of hysterectomized or sham-treated mice immunized sc-iv: 7) whether paravaginal immunization elicits long-lasting secretory IgA responses in vaginal fluid by measuring ELISA titers of antiferritin IgA and IgG in vaginal fluid after immunization in 3 paravaginal sites with ferritin combined with several non-toxic, depot adjuvants. 8) whether an immunostimulating complex (ISCOM), consisting of membrane proteins incorporated into Quil A adjuvant micelles, can elicit a secretory immune response in the genital tract by measuring ELISA titers of specific IgA and IgG antibodies in vaginal fluid after immunization with a model ISCOM at several sites: 9) which routes of immunization are effective in stimulating immune responses in uterine fluid by measuring ELISA titers of antiferritin IgA and IgG in uterine fluid after immunization with ferritin at various sites.
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