Table 3.

Physiological barriers protecting the vagina.

Vaginal protective barrier/characteristic	Description	Function
Microbiota	It was previously thought that a healthy vagina was dominated by Lactobacillus spp.; however, in some healthy women, lactobacilli are absent and replaced by other lactic acid-producing bacteria, such as Atopobium vaginae, Megasphaera spp., and/or Leptotrichia spp. 3 The ability of lactobacilli to grow in biofilms has been demonstrated in vitro, suggesting that there may be a role for a physiological lactobacilli biofilm in the vagina83,84	Lactobacilli produce lactic acid, maintaining an acidic environment, and compete with exogenous pathogens to adhere to vaginal mucosa.3,78,85 Lactobacilli also produce H2O2 and bacteriocins, which suppress invasive bacteria3,85,86
pH	Vaginal pH in women of reproductive age is ⩽4.5; this is mediated by the high presence of lactobacilli.3,87 Vaginal pH rises during menstruation 88	Maintains vaginal eubiosis, 78 protects against sexually transmitted pathogens78,87 and inhibits the growth of anaerobic bacteria 86
Skin (epithelium)	Vaginal skin is covered with a non-keratinized epithelial lining which, with oestrogen presence, is thick, with folds kept moist by fluid secreted through the vaginal wall and mucus from cervical and vestibular glands 3	Provides a physical/mechanical biobarrier 82
Epithelial cells	The lower part of the female reproductive tract is lined with multiple layers of stratified squamous epithelial cells. A lack of tight junctions in the lower part of the female reproductive tract may permit transition of pathogens to the intra-epithelial region, allowing them to come into contact with immune cells 82	Provide a physical barrier against pathogens and microbial infections as well as secretions containing antimicrobial peptides, cytokines and chemokines which recruit and activate immune cells 82
Vaginal secretions/mucus	Composed primarily of 90% to 95% water, inorganic and organic salts, urea, carbohydrates, mucins (particularly mucin-1), fatty acids, albumins, immunoglobulins, iron chelator, lysozyme and other macromolecules, leukocyte and epithelial debris82,85	Prevents epithelial cells from direct contact with infectious agents 82
Immune system
NAPs	Includes defensin, elafin, cathelicidin, secretory leukocyte protease inhibitor, lysozyme, and lactoferrin; produced by epithelial cells and neutrophils 82	Destroy target microbial cells through abrogation of pH and ionic concentration gradients 82
Pattern recognition receptors (TLRs)	Expressed on immune cells, including neutrophils, macrophages, dendritic cells, dermal endothelial cells and mucosal epithelial cells 82	Detect microbial-associated molecular patterns and initiate intracellular signalling pathways in order to recruit the immune cells, secrete antimicrobial factors eradicating pathogens and facilitate adaptive immune responses 82
Immune response	Includes cytokines and chemokines (secreted from epithelial cells) and inflammatory immune cells (macrophages, dendritic cells, natural killer cells, neutrophils), as well as resident epithelial cells and stromal fibroblasts 82	Inflammatory immune cells that migrate into the genital tract, as well as resident epithelial cells and stromal fibroblasts, facilitating the immune response 82

NAP: natural antimicrobial peptide; spp.: species; TLR: toll-like receptor.