"In addition to physical defenses, the innate nonspecific immune system uses a number of chemical mediators that inhibit microbial invaders. The term chemical mediators encompasses a wide array of substances found in various body fluids and tissues throughout the body. Chemical mediators may work alone or in conjunction with each other to inhibit microbial colonization and infection. Some chemical mediators are endogenously produced, meaning they are produced by human body cells; others are produced exogenously, meaning that they are produced by certain microbes that are part of the microbiome. Some mediators are produced continually, bathing the area in the antimicrobial substance; others are produced or activated primarily in response to some stimulus, such as the presence of microbes. Sebaceous glands in the dermis secrete an oil called sebum that is released onto the skin surface through hair follicles. This sebum is an endogenous mediator, providing an additional layer of defense by helping seal off the pore of the hair follicle. This supplemental defense layer prevents bacteria on the skin’s surface from invading sweat glands and surrounding tissue. Certain members of the microbiome, such as the bacterium Propionibacterium acnes and the fungus Malassezia, can use lipase enzymes to degrade sebum, using it as a food source. This produces oleic acid, which creates a mildly acidic environment on the surface of the skin that is inhospitable to many pathogenic microbes. Oleic acid is an example of an exogenously produced mediator because it is produced by resident microbes and not directly by body cells. Environmental factors that affect the microbiota of the skin can have a direct impact on the production of chemical mediators. Low humidity or decreased sebum production, for example, could make the skin less habitable for microbes that produce oleic acid, thus making the skin more susceptible to pathogens normally inhibited by the skin’s low pH. Many skin moisturizers are formulated to counter such effects by restoring moisture and essential oils to the skin. The digestive tract also produces a large number of chemical mediators that inhibit or kill microbes. In the oral cavity, saliva contains mediators such as lactoperoxidase enzymes, and mucus secreted by the esophagus contains the antibacterial enzyme lysozyme. In the stomach, highly acidic gastric fluid kills most microbes. In the lower digestive tract, the intestines have pancreatic and intestinal enzymes, antibacterial peptides called cryptins, bile produced from the liver, and specialized Paneth cells that produce lysozyme. Together, these mediators are able to eliminate most pathogens that manage to survive the acidic environment of the stomach. In the urinary tract, urine flushes microbes out of the body during urination. Furthermore, the slight acidity of urine, with an average pH of about 6, inhibits the growth of many microbes and potential pathogens in the urinary tract. The female reproductive system employs lactate, an exogenously produced chemical mediator, to inhibit microbial growth. The cells and tissue layers composing the vagina produce glycogen, a branched and more complex polymer of glucose. Lactobacilli in the area ferment glycogen to produce lactate, lowering the pH in the vagina and thereby inhibiting transient microbiota, opportunistic pathogens like Candida, and other pathogens responsible for sexually transmitted diseases. In the eyes, tears contain the chemical mediators lysozyme and lactoferrin, both of which are capable of eliminating microbes that have found their way to the surface of the eyes. Lysozyme cleaves the bond between NAG and NAM in peptidoglycan, a component of the cell wall in bacteria. It is more effective against gram-positive bacteria, which lack the protective outer membrane associated with gram-negative bacteria. Lactoferrin inhibits microbial growth by chemically binding and sequestering iron. This effectively starves many microbes that require iron for growth. In the ears, cerumen, or earwax, exhibits antimicrobial properties due to the presence of fatty acids, which lower the pH to between 3 and 5. The respiratory tract uses various chemical mediators in the nasal passages, trachea, and lungs. The mucus produced in the nasal passages contains a mix of antimicrobial molecules similar to those found in tears and saliva, such as lysozyme, lactoferrin, and lactoperoxidase. Secretions in the trachea and lungs also contain lysozyme and lactoferrin, as well as a diverse group of additional chemical mediators, such as the lipoprotein complex called surfactant, which has antibacterial properties."