The goal is to define the way in which sex hormones regulate the secretory immune system in the female genital tract. The approach presented builds on recent observations by the applicant that estradiol and progesterone, depending on the site involved (uterus, cervix or vagina), has either stimulatory or inhibitory effects on the presence of immunoglobulin A (IgA) and G (IgG) and secretory component (SC) in the genital tract secretions of the rat. Our immediate objective is to identify the endocrine condition and routes of immunization that result in a maximal genital tract immune response to specific antigens including group B streptococcus 1a antigen and gonococcus pili. These studies may define effective protocols for the treatment of and protection against venereal diseases which at present are at epidemic levels in this country. To increase our understanding of the mechanisms through which hormones control the secretory immune system, we propose to examine both the transfer of immunoglobulins into genital tract secretions and the cellular aspects of mucosal immunity. Movement of IgA and IgG into the genital tract in response to hormones will be examined using isotope tracer (biochemical) and colloidal gold-tagged (microscopic) immunoglobulins to identify the way in which the sex hormones exert their effects both during the reproductive cycle and during pregnancy. In addition, the female genital tract transiently plays host to most immunologically important cell types. Our objective will be to examine the role of the sex hormones in the migration of lymphocytes, eosinophils, neutrophils and monocytes into the female genital tract and to characterize the sites(s) at which these effects take place. Since sex hormones and glucocorticoids have a marked effect on SC production by rat hepatocytes, we will test the hypothesis that in vivo hormonal changes may reduce liver clearance of IgA from blood and simultaneously promote its uptake at mucosal sites such as the female genital tract. We also propose to examine the role of the female sex hormones in the regulation of the secretory immune system in the uteri of women. Through in vitro studies we will attempt to determine whether estradiol and/or progesterone are responsible for the cyclic pattern of SC levels in uterine secretions during the menstrual cycle. These studies are an attempt to understand more fully the role of the sex hormones in regulating mucosal immunity in the human.
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