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Figure 2-2. Intestinal epithelial cells showing tight, junctional, and adherens junctions, and desmosomes. JAM, junctional adhesion molecules.
In contrast, the cells that line the surfaces of the interior of the body (the endothelium), such as blood vessels or lymphatic vessels, are not tightly bound to each other in order to allow the cells of the immune defense system to move freely from blood to tissues. Unfortunately, this feature also allows bacteria to move into and out of blood and lymphatic vessels by moving between the endothelial cells. Thus, once bacteria gain entry into the body at one site, it is possible for them to readily gain access to other parts of the body. Because of this vulnerability, it is imperative that the epithelia of skin and mucosal surfaces function as barriers against foreign invaders.
The membrane surface of an epithelial cell that faces toward the interior tissues of the body and is attached to other cells or to connective tissues (basolateral surface) has a different protein composition from the membrane surface that faces outward (apical surface). Cells with this asymmetrical surface property are said to be polarized cells. A feature of epithelial cells is that they are attached to a thin sheet of connective tissue called the basement membrane (basal lamina). The basal lamina covers regions of loose connective tissue (Figure 2-3), comprised of extracellular matrix (ECM) secreted by elongated fibroblast cells. The ECM composition varies with tissue type, but primarily contains a network of interlocking gels of polysaccharides called glycosaminoglycans (such as chondroitin sulfate, hyaluronan, keratan sulfate, and heparan sulfate) attached to fibrous collagens, the most abundant protein type in the ECM. Collagens bind to adhesion glycoproteins called fibronectins, which in turn bind collagens to transmembrane cell surface proteins called integrins that mediate cell-cell and cell-ECM interactions and cytoskeletal responses. Other ECM proteins called laminins bind to collagens and other ECM components to form fibrous networks that resist tensile forces in the basal lamina. There are numerous examples of pathogenic bacteria that attach to components of the ECM and manipulate or mimic ECM components during the course of infection.
Figure 2-3. Different types of epithelial cells and their relationships to underlying tissue. Shown are (A) simple squamous epithelium; (B) simple cuboidal epithelium; (C) stratified squamous epithelium (upper layers of cells are dead, typical of skin); (D) simple columnar epithelium; (E) ciliated columnar epithelium showing goblet cells, which secrete mucus (mucin); and (F) typical structure of connective tissue under an epithelial cell layer. Panel F modified from Cooper GM, Hausman RE. 2007. The Cell—A Molecular Approach, 4th ed. ASM Press, Washington, DC.
Epithelial cells in different body sites vary in shape, size, and number of layers (Figure 2-3), as well as in functional properties. Epithelial layers that cover surfaces where absorption or secretion is taking place (e.g., in the intestinal tract) usually consist of a single layer of epithelial cells (simple epithelium). Other surfaces, such as the female cervix or the skin, are composed of many layers of epithelial cells (stratified epithelium). Some have a flattened shape (squamous epithelium) and form the lining of cavities (such as the mouth, heart, and lungs) and the outer layers of the skin. Some are cube-shaped (cuboidal epithelium) and form the lining of kidney tubules and gland ducts and constitute the germinal epithelium that develops into egg and sperm cells. Others are tall and thin (columnar epithelium) and form the lining of the stomach and intestine.
Most of the surfaces that are exposed directly to the environment (e.g., the skin and mouth) are covered by stratified epithelia, whereas simple epithelia are found in internal areas, such as the intestinal tract or the lungs. Simple epithelia are more vulnerable to bacterial invasion than stratified epithelia because invading bacteria only have to pass through one layer of cells to gain access to the tissue underneath. We will use the terms mucosa epithelia, epithelial cells, mucosal layer, or mucosal cells to denote the simple epithelia of these internal areas.
Epithelia are protected by an array of innate and adaptive defenses. Some of these defenses are listed in Table 2-1 for the skin and Table 2-2 for mucosal surfaces. Other defenses, listed in Table 2-3, are more specific to certain areas of the body, such as the eyes and the respiratory, gastrointestinal, and urogenital tracts. For example, tears contain an enzyme (lysozyme) that degrades bacterial cell walls. Tears also provide a washing action that removes particles and bacteria from the eyes. Entry to the respiratory tract is protected by mucus and by specialized ciliated cells that propel bacteria-laden blobs of mucus out of the lungs. The urinary tract epithelium is protected by a sphincter at the end of the urethra, the tube that leads up to the bladder. This barrier makes it difficult for bacteria to enter the tube that leads to the bladder. Also, the washing action of urine during urination flushes out any bacteria that may have gained access to the bladder and urethra.
Table 2-1. Defenses of the skin
Table 2-2. Defenses of mucosal surfaces
Table 2-3. Special defenses of specific sites
Normal Microbiota of the Skin and Mucosa
The defenses of the skin do not completely prevent bacterial growth, as is evident from the fact that there are some bacteria capable of colonizing skin and mucosal surfaces. Immediately after birth, a wide range of microbes colonize humans, particularly on the skin and in the oronasopharyngeal, gastrointestinal, and urogenital tracts. The members of a bacterial population that are found residing at a particular body site without causing disease are called the resident (or commensal) microbiota of that site.
The skin microbiota, consisting primarily of the Gram-positive bacteria Staphylococcus epidermidis and Propionibacterium acnes, help protect against pathogenic bacteria by occupying sites that might be colonized by pathogenic bacteria. They also compete with incoming pathogens for essential nutrients. Some resident bacteria also produce antagonistic bactericidal compounds (e.g., pore-forming toxins such as bacteriocins or growth inhibitors, which target other bacteria). The commensal microbiota does not completely prevent colonization of skin by potential pathogens, but hampers it enough that colonization by pathogenic bacteria is usually transient.
In the case of P. acnes, this anaerobic bacterium colonizes sebaceous (fat) glands and digests the oily sebum, composed of triglycerides, waxy esters, squalene, and free fatty acids, to help generate a low pH environment that is protective against other bacteria. Sebum production and secretion by sebaceous glands is increased by testosterone. During puberty, testosterone levels increase, particularly in males, and cause overgrowth of P. acnes in response to the abundance of sebum production. Air-oxidized sebum plugs the hair follicle or gland duct and gives rise to a clogged follicle (called a comedo) that is open (also known as a blackhead) (Figure 2-4). Dried sebum causes dead skin cells to adhere at the opening of the fat gland, which gives rise to a comedo that is closed and accumulates sebum (also known as a whitehead). The resulting anaerobic environment further enhances bacterial growth, causing infection and inflammation that manifests as acne (i.e., pimples or zits), or in severe cases as cysts or boils. Treatment with antibiotics and benzoyl peroxides found in most acne medications work against P. acnes. Washing with warm water and soap can also help reduce acne by keeping the pores open and free of dried sebum.
