C.R. Wira

Innate and adaptive immunity at mucosal surfaces of the female reproductive tract: stratification and integration of immune protection against the transmission of sexually transmitted infections

This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract.

Endocrine control of mucosal immunity in the female reproductive tract: impact of environmental disruptors.

The complexity of the human female reproductive tract (FRT) with its multiple levels of hormonally controlled immune protection has only begun to be understood. Dissecting the functions and roles of the immune system in the FRT is complicated by the differential hormonal regulation of its distinct anatomical structures that vary throughout the menstrual cycle. Although many fundamental mechanisms of steroid regulation of reproductive tract immune function have been determined, the effects of exogenous synthetic steroids or endocrine disruptors on immune function and disease susceptibility in the FRT have yet to be evaluated in detail. There is increasing evidence that environmental or synthetic molecules can alter normal immune function. This review provides an overview of the innate and adaptive immune systems, the current status of immune function in the FRT and the potential risks of environmental or pharmacological molecules that may perturb this system.

Glucocorticoid Receptors in Rat Thymus Cells

Summary Studies of binding of glucocorticoids to rat thymus cells in vitro demonstrate two forms of binding: (a) Specific binding, which is well correlated with glucocorticoid activity, saturates at high physiological concentrations, and is characterized by slow association and dissociation. Specific binding appears to represent association with glucocorticoid receptors. With cortisol no metabolic transformation precedes this association. (b) Non-specific binding, which correlates with nonpolarity and interfacial activity, does not saturate, and is characterized by rapid association and dissociation. With all steroids tested this is the major fraction. It is distributed throughout the cell including the nucleus, accounting for the well-known nonspecific effects of steroids in vitro. ATP or some related substance may be necessary for specific binding in whole cells. A competitor for specific glucocorticoid binding, cortexolone, blocks the hormonal activity of cortisol. If cells are disrupted by hypotonic shock in 1.5 mM MgCl2 after incubation with cortisol at 20 °C or 37 °C most of the specifically bound hormone sediments with nuclei. But after incubation at 3 °C the hormone is mainly in the supernatant. For convenience the supernatant fraction is referred to as “cytoplasmic”. Cortisol in both the nuclear and “cytoplasmic” fractions is bound to macromolecules. These “receptors” are in part proteins. The binding properties – specificity, saturation, dissociation rates – of the isolated receptors, both of which can be extracted from cells that have not been preexposed to cortisol, are similar to those characteristic of specific binding to cells at 37 °C, showing that specific binding to cells at 37 °C displays the intrinsic properties of the receptor complexes. Cortisol bound to “cytoplasmic” receptors is rapidly transferred to the nucleus even in the presence of excess unlabelled cortisol, indicating that formation of the cytoplasmic complex is an obligatory step. The receptors do not appear to be ‘carriers’ since the cells are freely permeable to glucocorticoids. It is suggested that the hormone directs the cytoplasmic receptor to the nuclear site by increasing its affinity for the nuclear site and/or by releasing it from some initial site. To initiate metabolic activity the receptor probably has to have attached an active hormone molecule, since with cortexolone a nuclear steroid-receptor complex appears to be formed but activity is not initiated.

The secretory immune system in the uterus of the pregnant rat: production of secretory component by uterine tissues

Secretory component (SC) was measured in amniotic fluid, fetal serum, and maternal serum and compared with SC production during in vitro culture of uterine tissue segments from pregnant rats. The concentrations of SC in amniotic fluid did not change between days 14 and 20 of pregnancy. Similarly, there was no change in maternal or fetal serum during pregnancy, although, the levels of SC in sera were consistently higher than those in amniotic fluid. When uterine segments were incubated in vitro, release of SC was greater in the absence of cycloheximide than in the presence of cycloheximide at all stages of pregnancy. In contrast to SC values in amniotic fluid, however, SC production by uterine tissue changed markedly during pregnancy. SC levels were low during early pregnancy (day 7 post coitus) and increased to levels found in non-pregnant diestrous rats just prior to parturition (day 20). The findings suggest that the endocrine balance during pregnancy may play a central role in regulation of the uterus immune system. The pattern of SC release may reflect a need both to ensure protection of the fetus from the IgA immune system in early pregnancy and to prevent maternal infection during parturition by reactivation of this system.

1142280946 Effect of estradiol and PAMPs on class II mediated antigen presentation and immunomodulatory molecule expression in the mouse female reproductive tract

Problem:  Antigen presenting cells (APC) in the female reproductive tract play important roles in innate immune defense and activation of the adaptive immune responses. The objective of this study was to examine the effects of estradiol and PAMP on antigen presentation in the female reproductive tract.