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The innate immune system is composed of physical barriers, cells, and circulating factors that are always active and ready to repel microbes. They form a boundary between you and the viruses, bacteria, and fungi that live on and inside you. Innate immune cells also clean up debris and dying cells. Advantages of the innate immune system are that it responds rapidly and targets molecular patterns widely shared among microbes.


An extremely important, but often overlooked, component of host defense is the barrier formed by skin and mucous membranes. The epithelia covering our skin, respiratory, gastrointestinal, and genitourinary tracts provide the first line of defense against invaders. The central mission of the barrier is to separate you from the outside world, allowing some microbes to survive in niches along the surface, but preventing any from gaining a foothold to cause disease.

Mechanical Barrier

The outermost layer of the barrier is the epithelial cells, connected to one another by tight junctions. The skin’s epidermis is covered by keratinized squamous cells that are continuously shed (“desquamated”). Similarly, nonskin barriers are called mucous membranes because they are coated by mucins, a sticky mixture of glycoproteins produced by secretory cells of the respiratory, gastrointestinal, and genitourinary tracts. Cells of the mucous membranes also rapidly divide, slough off, and are replaced continuously. Keratinized epidermis, cell sloughing, sweat secretion, and mucins all prevent microbes from attaching and invading.

The ciliated cells lining the respiratory tract, the gastrointestinal tract’s peristalsis, and the continuous flow of urine from the kidney through the bladder and urethra ensure that microbes cannot attach and invade these sites. Failure of any of these mechanisms is a common predisposing factor to infection by bacteria or fungi that otherwise colonize us harmlessly. In patients with severe skin burns, pulmonary ciliary cell disorders, or bowel or urinary obstruction, infection is the key cause of morbidity and mortality.

Chemical Barrier

Epithelial cells also produce a number of chemicals and proteins that inhibit microbes from growing or attaching. The skin and the stomach excrete concentrated hydrochloric acid that kills bacteria. Lysozyme is an enzyme in saliva and tears that makes holes in bacterial cell walls by breaking linkages in their peptidoglycan molecules. In addition, antimicrobial peptides, such as defensins, are produced throughout the skin and mucous membranes.

Defensins are highly positively charged peptides, primarily produced in the gastrointestinal and lower respiratory tracts, that create pores in lipid membranes of bacteria, fungi, and even some viruses. Neutrophils and Paneth cells in the intestinal crypts contain one type of defensin (α-defensins), which may have antiviral activity, whereas the respiratory tract produces different defensins called β-defensins, which are antibacterial. Surfactants are lipoproteins produced in the lung alveoli that bind to the surface of microbes, which can ...

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