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Epithelial Barriers

Epithelial Barriers
Physical, mechanical, and biochemical barriers against microbial invasion are found in all common portals of entry into the body, including the skin and respiratory, gastrointestinal, and urogenital tracts. The intact skin is by far the most formidable physical barrier available to infection because of its design. It is comprised of closely packed cells that are organized in multiple layers that are continuously shed. In addition, a protective layer of protein, known as keratin, covers the skin. The skin has simple chemicals that create a nonspecific, salty, acidic environment and antibacterial proteins, such as the enzyme lysozyme, that inhibit the colonization of microorganisms and aid in their destruction. The complexity of the skin becomes evident in cases of contact dermatitis where increased susceptibility to cutaneous infection occurs as the result of abnormalities of the innate immune response including defects in the epithelial layer itself and defects in both signaling and or expression of innate responses.

Sheets of tightly packed epithelial cells line and protect the gastrointestinal, respiratory, and urogenital tracts and physically prevent microorganisms from entering the body. These cells destroy the invading organisms by secreting anti-microbial enzymes, proteins, and peptides. Specialized cells in these linings, such as the goblet cells in the gastrointestinal tract, secrete a viscous material comprised of high molecular weight glycoproteins known as mucins, which when hydrated form mucus. The mucins bind to pathogens, thereby trapping them and washing away potential invaders. In the lower respiratory tract, hairlike, mobile structures called cilia protrude through the epithelial cells and move microbes trapped in the mucus up the tracheobronchial tree and toward the throat. The physiologic responses of coughing and sneezing further aid in their removal from the body.
Microorganisms that are trapped by mucus are then subjected to various chemical defenses present throughout the body. Lysozyme is a hydrolytic enzyme found in tears, saliva, and human milk, which is capable of cleaving the walls of bacterial cells by hydrolyzing the 1,4 beta-linkages between residues in peptidoglycan. The complement system is found in the blood and is essential for the activity of antibodies. It is comprised of 20 different proteins, many of which act as precursors of enzymes. An antigen–antibody complex initiates this system. Activation of the complement system increases bacteria aggregation, which renders them more susceptible to phagocytosis through activation of mast cells and basophils and through the direct release of lytic complexes that rupture cell membranes of invading organisms (Fig. 13.1). In addition, recent research has shown that complement plays a key role in bridging the innate–adaptive immune responses through the release of C3 and C5 from DCs. In the stomach and intestines, death of microbes results from the action of digestive enzymes, acidic conditions, and secretions of defensins, small cationic peptides that kill within minutes both gram-positive and gram-negative microorganisms by disrupting the microbial membrane.
Phagocytosis. (A) A phagocytic white blood cell moves through a capillary that is in an infected area and engulfs the bacteria. (B) The lysosome digests the bacteria that was in a vesicle

When pathogens overcome the epithelial defenses, the innate immune response is initiated by the body’s leukocytes by the recognition of common surface receptors present on the invading microorganisms.