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Review
. 2011 Mar;88(2):185-94.
doi: 10.1016/j.jri.2011.01.005. Epub 2011 Feb 26.

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

D K Hickey  1 , M V Patel, J V Fahey, C R Wira
Affiliations
Review

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

D K Hickey et al. J Reprod Immunol. 2011 Mar.

Abstract

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.

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Figures

Figure 1
Figure 1
Schematic of the major components of the mucosal innate immune system in the human female reproductive tract (female reproductive tract). Panel A: The upper female reproductive tract, consisting of the Fallopian tubes, uterine endometrium and endocervix is lined by a single layer of columnar epithelial cells linked by tight junctions. Overlying the cells is a protective mucus layer (Section 2). Secretion is generally preferential towards the apical/luminal compartment with a gradient across the epithelial layer from lumen to tissue. Underlying the epithelial cells are innate and adaptive immune cells (Section 3). Also shown are lymphoid aggregates (LA) that are unique to the uterus. Panel B: The lower female reproductive tract, consisting of the ectocervix and vagina is covered by a layer of stratified squamous epithelial cells (Sections 2 and 3). Similar to the upper female reproductive tract, epithelial cells are protected by a mucus layer. The lower female reproductive tract has a resident commensal bacterial population that produces lactic acid thus lowering vaginal pH (Section 2). Below the epithelial layer are innate and adaptive immune cells. Panel C: The innate immune response of upper female reproductive tract epithelial cells to an invading pathogen. Epithelial cells express a panel of Toll-like receptors (TLRs) and RIG-like receptors (RLRs) that allow them to recognize and respond to bacteria or viruses. The Type I Interferon (IFN) response (green arrows, middle section of panel C) is a potent defense system in female reproductive tract cells (Sections 4 and 5). Additionally, in response to pathogens and sex hormones, antimicrobials and cytokines/chemokines are secreted to confer broad spectrum protection.
Figure 2
Figure 2. The effector arm of adaptive (TH1: cell-mediated and TH2: humoral) immune responses
During infection, pathogen specific adaptive responses are driven by antigen presentation to T and B cells directly by dendritic cells, macrophages and epithelial cells in the mucosa or following activation by CD4+ T cell migration from circulation. Once activated through cytokine stimulation, T and B cells proliferate and differentiate. The cell-mediated response (left) is characterized by the production of IFNγ and the apoptosis of infected cells by cytotoxic CD8+ T cells. IFNγ also stimulates the production of intracellular antiviral genes that block viral replication. The humoral response (right) is mediated by B cell differentiation into antibody-secreting plasma cells. Both IgG and IgA are produced in the female reproductive tract and are secreted into the mucosa. Antibodies bind to pathogens, blocking infection by mediating phagocytosis or complement pathways.
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