Skin. The intact surface of the healthy epidermis seems to be rarely if ever penetrated by bacteria. If the integrity of the epidermis is broken (by the bite of an insect, needle stick, abrasion, cut, etc.) invasive microbes may enter. The normal flora of the skin, which metabolize substances secreted onto the skin, produce end products (e.g. fatty acids) that discourage the colonization of skin by potential pathogens. Perspiration contains lysozyme and other antimicrobial substances.

Mucous membranes. Many are heavily colonized with bacteria in whose moist secretions they survive. These normal flora are restricted from entry and usually occupy any attachment sites that might otherwise be used by pathogens. The normal flora established on mucous membranes may antagonize non-indigenous species by other means, as well. Typically, mucus contains a number of types of anti-microbial compounds, including lysozyme and secretory antibodies (IgA). Sometimes phagocytes patrol mucosal surfaces (e.g. in the lower respiratory tract). Nonetheless, most infectious agents impinge on the skin or mucous membranes of the oral cavity, respiratory tract, GI tract or urogenital tract, and from these sites most infections occur. Damage to the epithelial cells caused by toxic products of these bacteria may play a role.

Respiratory tract. Fine hairs and baffles of the nares (nasal membranes) entrap bacteria which are inhaled. Those which pass may stick to mucosal surfaces of the trachea or be swept upward by the ciliated epithelium of the lower respiratory tract. Coughing and sneezing also eliminate bacteria. The lower respiratory tract (lung) is well protected by mucus, lysozyme, secretory antibody, and phagocytosis.

Mouth, stomach and intestinal tract. Microorganisms entering by the oral route, more than any other, have to compete with the well-adapted normal flora of the mouth and intestine. Most organisms that are swallowed are destroyed by acid and various secretions of the stomach. Alkaline pH of the lower intestine can discourage other organisms. The peristaltic action of the intestine ultimately flushes out organisms which have not succeeded in colonization. Bile salts and lysozyme are present, which kill or inhibit many types of bacteria.

Urogenital Tract. The flushing mechanisms of sterile urine and the acidity of urine maintain the bladder and most of the urethra free of microorganisms. The vaginal epithelium of the female maintains a high population of Doderlein's bacillus (Lactobacillus acidophilus) whose acidic end products of metabolism (lactic acid) prevent colonization by most other types of microorganisms including potentially-pathogenic yeast (Candida albicans).

Eyes (Conjunctiva). The conjunctiva of the eye is remarkably free of most microorganisms. Blinking mechanically removes microbes, the lavaging action of tears washes the surface of the eye, and lachrymal secretions (tears) contain relatively large amounts of lysozyme.

Competition with non-indigenous species for binding (colonization) sites. The normal flora are highly-adapted to the tissues of their host. That is why they are there.

Specific antagonism against non-indigenous species. Members of the normal flora may produce very specific proteins called bacteriocins which kill or inhibit other (usually closely-related) species of bacteria.

Nonspecific antagonism against non-indigenous species. The normal flora produce a variety of metabolites and end products that inhibit other microorganisms. These include fatty acids (lactate, propionate, etc.), peroxides and antibiotics.

Figure 4. Enterococcus faecalis, also classified as Streptococcus faecalis. Occasionally there is invasion of the host by the normal flora, as evidenced by this blood culture. Enterococcus faecalis, blood culture. © Gloria J. Delisle and Lewis Tomalty, Queens University Kingston, Ontario, Canada. Licensed for use by ASM Microbe Library http://www.microbelibrary.org.

Complement is an enzymatic system of serum proteins made up of nine major components (C1 - C9) that are sequentially activated during two pathways, the classical pathway and the alternative pathway, resulting in a variety of antibacterial defenses. Complement components play a part in phagocytic chemotaxis, opsonization and the inflammatory response, and may be involved in the lysis of certain bacteria, some viruses, and other microorganisms. 

Complement is activated in the classical pathway by reactions between antibodies and antigens on the surface of a microbe. Some Immunoglobulins (i.e., IgG and IgM) can "fix complement" because they have a complement binding site on the Fc portion of the molecule. The reaction between IgG and Ag activates the complement and initiates a "cascade reaction" on the surface of the microbe that results in the principal effects of complement which are:

1. Generation of inflammatory factors, C3a and C5a, which focus antimicrobial serum factors and leukocytes into the site of infection.

2. Attraction of phagocytes. Chemotactic factors C3a and C5a attract phagocytes to the site.

3. Enhancement of phagocytic engulfment. C3b component on Ag - Ab complex attaches to C3b receptors on phagocytes and promotes opsonization of Ab-coated cells. C3b-opsonization is important when Ab is IgM because phagocytes have receptors for Fc of IgM only when it is associated with C3b.