FAHEY, J/V*; SCHAEFER, T/M; WIRA, C/R; Dartmouth Medical School; Dartmouth Medical School; Dartmouth Medical School: Innate and Adaptive Immunity in the Human Female Reproductive Tract: Regulation by Sex Hormones

Understanding the immune system in the human female reproductive tract (FRT) is vital because sexually transmitted infections are a major worldwide health problem. Innate and adaptive immune cells have evolved a variety of mechanisms to protect the host from pathogens, and are also participants in the cyclical reproductive process to prepare for the conceptus. For example, epithelial cells in the upper tract form an uninterrupted physical barrier, secrete natural microbicides into the lumen, produce cytokines and chemokines that attract and activate immune cells, express toll-like receptor molecules that recognize microbial pathogens, and participate in normal physiology of reproduction. The immune system in the FRT is precisely regulated by sex hormones. Estradiol and progesterone influence the number and character of immune cells in the FRT and regulate the ability of immune cells to recognize antigen and control the degree of response. Sex hormones also mediate the cell architecture and cooperation that exists between immune cells. For example, the size of lymphoid aggregates, which consists of a B cell core surrounded by T cells and encapsulated by macrophages, varies during the menstrual cycle. Largest aggregates are found during the secretory phase of the cycle. Among the immune responses regulated by sex hormones in the human FRT are immunoglobulin transport, chemotaxis of immune cells, secretion of microbicides, chemokines and cytokines, proliferation of T cells, and antigen presentation. The overall conclusion from these studies is that the immune system in the FRT has evolved to protect against potential microbial pathogens without compromising fetal survival. Supported by AI 51877, NIH.