LECTURE NOTES ON

SKIN AND MUCOUS MEMBRANE: FIRST LINE OF DEFENSE

PHYSICAL FACTORS
The intact skin is the human body’s largest organ in terms
of surface area and weight and is an extremely important
component of the first line of defense (see Figure 6.1). It consists
of two distinct portions: the dermis and the epidermis (Figure 6.2).
The dermis, the skin’s inner, thicker portion, is composed of
connective tissue. The epidermis, the outer, thinner portion, is in
direct contact with the external environment. The epidermis
consists of many layers of continuous sheets of tightly packed
epithelial cells with little or no material between the cells. The top
layer of epidermal cells is dead and contains a protective protein
called keratin. The periodic shedding of the top layer helps remove
microbes at the surface. In addition, the dryness of the skin is a
major factor in inhibiting microbial growth on the skin. Although
normal microbiota and other microbes are present on the entire
skin, they are most numerous on moist areas of the skin. When the
skin is moist, as in hot, humid climates, skin infections are quite
common, especially fungal infections such as athlete’s foot. These
fungi hydrolyze keratin when water is available. If we consider the
closely packed cells, continuous layering, the presence of keratin,
and the dryness and shedding of the skin, we can see why the intact
skin provides such a formidable barrier to the entrance of
microorganisms. Microorganisms rarely, if ever, penetrate the
intact surface of healthy epidermis. However, when the epithelial
surface is broken, a subcutaneous (below-the-skin) infection often
develops. The bacteria most likely to cause infection are the
staphylococci that normally inhabit the epidermis, hair follicles,
and sweat and oil glands of the skin. Infections of the skin and
underlying tissues frequently result from burns, cuts, stab wounds,
or other conditions that break the skin.
Figure 6.1. A section through human skin. The thin layers at the

Figure 6.2. An overview of the body’s

Epithelial cells called endothelial cells that line blood and lymphatic vessels are not closely packed like those of the
epidermis. Although this arrangement permits defensive cells to move from blood into tissues during inflammation, it also
permits microbes to move into and out of blood and lymph. Mucous
membranes also consist of an epithelial layer and an underlying connective
tissue layer. Mucous membranes are an important component of the first line
of defense (see Figure 6.1) and inhibit the entrance of many microorganisms.
Mucous membranes line the entire gastrointestinal, respiratory, and
genitourinary tracts. The epithelial layer of a mucous membrane secretes a
fluid called mucus; a slightly viscous (thick) glycoprotein produced by goblet
cells of a mucous membrane. Among other functions, mucus prevents the
tracts from drying out. Some pathogens that can thrive on the moist secretions
of a mucous membrane are able to penetrate the membrane if the
microorganism is present in sufficient numbers. Treponema pallidum is such
a pathogen. This penetration may be facilitated by toxic substances produced
by the microorganism, prior injury by viral infection, or mucosal irritation.
Figure 6.3 The lacrimal apparatus. The washing
action of the tears
Besides the physical barrier presented by the skin and mucous membranes,
several other physical factors help protect certain epithelial surfaces. One
such mechanism that protects the eyes is the lacrimal apparatus, a group of structures that manufactures and drains away
tears (Figure 6.3). The lacrimal glands, located toward the upper, outermost portion of each eye socket, produce the tears,
and pass them under the upper eyelid. From here, tears pass toward the corner of the eye near the nose and into two small
holes that lead through tubes (lacrimal canals) to the nose. The tears are spread over the surface of the eyeball by blinking.
Normally, the tears evaporate or pass into the nose as fast as they are produced. This continual washing action helps keep
microorganisms from settling on the surface of the eye. If an irritating substance or large numbers of microorgan isms meet
the eye, the lacrimal glands start to secrete heavily, and the tears accumulate more rapidly than they can be carried away.
This excessive production is a protective mechanism because the excess tears dilute and wash away the irritating substance
or microorganisms. In a cleansing action very similar to that of tears, saliva, produced by the salivary glands, helps dilute
the numbers of microorganisms and wash them from both the surface of the teeth and the mucous membrane of the mouth.
This helps prevent colonization by microbes. The respiratory and gastrointestinal tracts have many physical forms of
defense. Mucus traps many of the microorganisms that enter the respiratory and gastrointestinal tracts. The mucous
membrane of the nose also has mucus-coated hairs that filter inhaled air and trap microorganisms, dust, and pollutants. The
cells of the mucous membrane of the lower respiratory tract are covered with cilia. By moving synchronously, these cilia
propel inhaled dust and microorganisms that have become trapped in mucus upward toward the throat. This so-called ciliary
escalator (Figure 6.4) keeps the mucus blanket moving toward the throat at a rate of 1 to 3 cm per hour: coughing and
sneezing speed up the escalator. Some substances in cigarette smoke are toxic to cilia and can seriously impair the
functioning of the ciliary escalator by inhibiting or destroying the cilia. Mechanically ventilated patients are vulnerable to
respiratory tract infections because the ciliary escalator mechanism is inhibited. Microorganisms are also prevented from
entering the lower respiratory tract by a small lid of cartilage called the epiglottis, which covers the larynx (voicebox) during
swallowing. The external ear canal contains hairs and earwax (cerumen), which help prevent microbes, dust, insects, and
water from entering the ear. The cleansing of the urethra by the flow of urine is another physical factor that prevents
microbial colonization in the genitourinary tract. As you will see later, when infections or urinary catheters alter urine flow,
urinary tract infections may develop. Vaginal secretions likewise move microorganisms out of the fe male body. Peristalsis,
defecation, vomiting, and diarrhea also expel microbes. Peristalsis is a series of coordinated contractions that propel food
along the gastrointestinal tract. Mass peristalsis of large intestinal contents into the rectum results in defecation. In response
to microbial toxins, the muscles of the gastrointestinal tract contract vigorously, resulting in vomiting and/or diarrhea, which
may also rid the body of microbes.

Figure 6.4 The ciliary

CHEMICAL FACTORS
Physical factors alone do not account for the high degree of resistance of skin and mucous membranes to microbial
invasion. Certain chemical factors also play important roles. Sebaceous (oil) glands of the skin produce an oily substance
called sebum that prevents hair from drying and becoming brittle. Sebum also forms a protective film over the surface of
the skin. One of the components of sebum is unsaturated fatty acids, which inhibit the growth of certain pathogenic bacteria
and fungi. The low pH of the skin, between pH 3 and 5, is caused in part by the secretion of fatty acids and lactic acid. The
skin’s acidity probably discourages the growth of many other microorganisms. Bacteria that live commensally on the skin
decompose sloughed-off skin cells, and the resultant organic molecules and the end-products of their metabolism produce
body odor. Certain bacteria commonly found on the skin metabolize sebum, and this metabolism forms free fatty acids that
cause the inflammatory response associated with acne. Isotretinoin (Accutane), a derivative of vitamin A that prevents
sebum formation, is a treatment for a very severe type of acne called cystic acne. The sweat glands of the skin produce
perspiration, which helps maintain body temperature, eliminate certain wastes, and f lush microorganisms from the surface
of the skin. Perspiration also contains lysozyme, an enzyme capable of breaking down cell walls of gram-positive bacteria
and, to a lesser extent, gram negative bacteria. Specifically, lysozyme breaks chemical bonds on peptidoglycan, which
destroys the cell walls. Lysozyme is also found in tears, saliva, nasal secretions, tissue fluids, and urine, where it exhibits
its antimicrobial activity. Alexander Fleming was studying lysozyme in 1929 when he accidentally discovered the
antimicrobial effects of penicillin. Earwax, besides serving as a physical barrier, also functions as a chemical protectant. It
is a mixture of secretions from glands producing earwax as well as from the sebaceous glands, which produce sebum. The
secretions are rich in fatty acids, giving the ear canal a low pH, between 3 and 5, which inhibits the growth of many
pathogenic microbes. Earwax also contains many dead cells from the lining of the ear canal. Saliva contains not only an
enzyme (salivary amylase) that digests starch, but also several substances that inhibit microbial growth. These include
lysozyme, urea, and uric acid. The pH acid of saliva (6.55–6.85) also inhibits some microbes. Saliva also contains an
antibody (immunoglobulin A) that prevents attachment of microbes so that they cannot penetrate mucous membranes.
Gastric juice is produced by the glands of the stomach. It is a mixture of hydrochloric acid, enzymes, and mucus. The very
high acidity of gastric juice (pH 1.2–3.0) is sufficient to destroy bacteria and most bacterial toxins, except those of
Clostridium botulinum and Staphylococcus aureus. However, many enteric pathogens are protected by food particles and
can enter the intestines via the gastrointestinal tract. In contrast, the bacterium Helicobacter pylori neutralizes stomach acid,
thereby allowing the bacterium to grow in the stomach. Its growth initiates an immune response that results in gastritis and
ulcers. Vaginal secretions play a role in antibacterial activity in two ways. Glycogen produced by vaginal epithelial cells is
broken down into lactic acid by Lactobacillus acidophilus. This creates an acid pH (3–5) that inhibits microbes. Cervical
mucus also has some antimicrobial activity. Urine, in addition to containing lysozyme, has an acid pH (average 6) that
inhibits microbes.

NORMAL BIOTA AND INNATE IMMUNITY

Technically speaking, the normal microbiota is not usually considered part of the first line of defense of the innate immune
system, but they are discussed here because of the considerable protection they afford (see Figure 6. Some of these
relationships help prevent the overgrowth of pathogens and thus may be considered components of innate immunity. For
example, in microbial antagonism, the normal microbiota prevent pathogens from colonizing the host by competing with
them for nutrients (competitive exclusion), by producing substances that are harmful to the pathogens, and by altering
conditions that affect the survival of the pathogens, such as pH and oxygen availability. The presence of normal microbiota
in the vagina, for example, alters pH, thus preventing overpopulation by Candida albicans, a pathogenic yeast that causes
vaginitis. In the large intestine, E. coli bacteria produce bacteriocins that inhibit the growth of Salmonella and Shigella. In
commensalism, one organism uses the body of a larger organism as its physical environment and may make use of the body
to obtain nutrients. Thus in commensalism, one organism benefits while the other is unaffected. Most microbes that are part
of the commensal microbiota are found on the skin and in the gastrointestinal tract. The majority of such microbes are
bacteria that have highly specialized attachment mechanisms and precise environmental requirements for survival.
Normally, such microbes are harmless, but they may cause disease if their environmental conditions change. These
opportunistic pathogens include E. coli, Staphylococcus aureus, S. epidermi dis, Enterococcus faecalis, Pseudomonas
aeruginosa, and oral streptococci. Recent interest in the importance of bacteria to human health has led to the study of
probiotics. Probiotics (pro 5 for, bios 5 life) are live microbial cultures applied to or ingested that are intended to exert a
beneficial effect. Probiotics may be ad ministered with prebiotics, which are chemicals that selectively promote the growth
of beneficial bacteria. Several studies have shown that ingesting certain lactic acid bacteria (LAB) can al leviate diarrhea
and prevent colonization by Salmonella enterica during antibiotic therapy. If these LAB colonize the large intes tine, the
lactic acid and bacteriocins they produce can inhibit the growth of certain pathogens. Researchers are also testing the use of
LAB to prevent surgical wound infections caused by S. aureus and vaginal infections caused by E. coli. In a Stanford
University study, HIV infection was reduced in women treated with a LAB that was genetically modified to produce CD4
pro tein that binds to HIV. Probiotics may not work for all diseases, and studies on probiotics are ongoing. A Dutch medical
team, for example, reported increased deaths in pancreatitis patients treated with probiotics.