Microorganisms gaining entry via the skin may cause a skin infection or infection elsewhere

Microorganisms which infect or enter the body via the skin are listed in Table 13.1. On the skin, microorganisms other than residents of the normal flora (see Ch. 8) are soon inactivated, especially by fatty acids (skin pH is about 5.5), and probably by substances secreted by sebaceous and other glands, and certain peptides formed locally by keratinocytes protect against invasion by group A streptococci. Materials produced by the normal flora of the skin also protect against infection. Skin bacteria may enter hair follicles or sebaceous glands to cause styes and boils, or teat canals to cause staphylococcal mastitis.

Table 13.1 Microorganisms that infect via the skin

Several types of fungi (the dermatophytes) infect the non-living keratinous structures (stratum corneum, hair, nails) produced by the skin. Infection is established as long as the parasites’ rate of downward growth into the keratin exceeds the rate of shedding of the keratinous product. When the latter is very slow, as in the case of nails, the infection is more likely to become chronic.

Wounds, abrasions or burns are more common sites of infection. Even a small break in the skin can be a portal of entry if virulent microorganisms such as streptococci, water-borne leptospira or blood-borne hepatitis B virus are present at the site. A few microbes, such as leptospira or the larvae of Ancylostoma and Schistosoma, are able to traverse the unbroken skin by their own activity.

Biting arthropods

Biting arthropods such as mosquitoes, ticks, fleas and sandflies (see Ch. 27) penetrate the skin during feeding and can thus introduce infectious agents or parasites into the body. The arthropod transmits the infection and is an essential part of the life cycle of the microorganism. Sometimes the transmission is mechanical, the microorganism contaminating the mouth parts without multiplying in the arthropod. In most cases, however, the infectious agent multiplies in the arthropod and, as a result of millions of years of adaptation, causes little or no damage to that host. After an incubation period, it appears in the saliva or faeces and is transmitted during a blood feed. The mosquito, for instance, injects saliva directly into host tissues as an anticoagulant, whereas the human body louse defecates as it feeds, and Rickettsia rickettsii, which is present in the faeces, is introduced into the bite wound when the host scratches the affected area.

The conjunctiva

The conjunctiva can be regarded as a specialized area of skin. It is kept clean by the continuous flushing action of tears, aided every few seconds by the windscreen wiper action of the eyelids. Therefore, the microorganisms that infect the normal conjunctiva (chlamydia, gonococci) must have efficient attachment mechanisms (see Ch. 25). Interference with local defences due to decreased lacrimal gland secretion or conjunctival or eyelid damage allows even non-specialist microorganisms to establish themselves. Contaminated fingers, flies, or towels carry infectious material to the conjunctiva, examples including herpes simplex virus infections leading to keratoconjunctivitis or chlamydial infection resulting in trachoma. Antimicrobial substances in tears, including lysozyme, an enzyme, and certain peptides have a defensive role.

Some microorganisms can overcome the respiratory tract’s cleansing mechanisms

Air normally contains suspended particles, including smoke, dust and microorganisms. Efficient cleansing mechanisms (see Chs 18 and 19) deal with these constantly inhaled particles. With about 500–1000 microorganisms/m³ inside buildings, and a ventilation rate of 6    l/min at rest, as many as 10 000 microorganisms/day are introduced into the lungs. In the upper or lower respiratory tract, inhaled microorganisms, like other particles, will be trapped in mucus, carried to the back of the throat by ciliary action, and swallowed. Those that invade the normal healthy respiratory tract have developed specific mechanisms to avoid this fate.

Interfering with cleansing mechanisms

The ideal strategy is to attach firmly to the surfaces of cells forming the mucociliary sheet. Specific molecules on the organism (often called adhesins) bind to receptor molecules on the susceptible cell (Fig. 13.2). Examples of such respiratory infections are given in Table 13.2.

Figure 13.2 Influenza virus attachment to ciliated epithelium. Influenza virus particles (V) attached to cilia (C) and microvilli (M). Electron micrograph of thin section from organ culture of guinea pig trachea 1    h after addition of the virus.

(Courtesy of R.E. Dourmashkin.)

Table 13.2 Microbial attachment in the respiratory tract

Inhibiting ciliary activity is another way of interfering with cleansing mechanisms. This helps invading microorganisms establish themselves in the respiratory tract. B. pertussis, for instance, not only attaches to respiratory epithelial cells, but also interferes with ciliary activity, while other bacteria (Table 13.3) produce various ciliostatic substances of generally unknown nature.

Table 13.3 Interference with ciliary activity in respiratory infections

Avoiding destruction by alveolar macrophages

Inhaled microorganisms reaching the alveoli encounter alveolar macrophages, which remove foreign particles and keep the air spaces clean. Most microorganisms are destroyed by these macrophages, but one or two pathogens have learnt either to avoid phagocytosis or to avoid destruction after phagocytosis. Tubercle bacilli, for instance, survive in the macrophages, and respiratory tuberculosis is thought to be initiated in this way. Inhalation of as few as 5–10 bacilli is enough. The vital role of macrophages in antimicrobial defences is dealt with more thoroughly in Chapter 14. Alveolar macrophages are damaged following inhalation of toxic asbestos particles and certain dusts, and this leads to increased susceptibility to respiratory tuberculosis.

Some microorganisms can survive the intestine’s defences of acid, mucus and enzymes

Apart from the general flow of intestinal contents, there are no particular cleansing mechanisms in the intestinal tract, except insofar as diarrhea and vomiting can be included in this category. Under normal circumstances, multiplication of resident bacteria is counterbalanced by their continuous passage to the exterior with the rest of the intestinal contents. Ingestion of a small number of non-pathogenic bacteria, followed by growth in the lumen of the alimentary canal, produces only relatively small numbers within 12–18    h, the normal intestinal transit time.

Infecting bacteria must attach themselves to the intestinal epithelium (Table 13.4) if they are to establish themselves and multiply in large numbers. They will then avoid being carried straight down the alimentary canal to be excreted with the rest of the intestinal contents. The concentration of microorganisms in faeces depends on the balance between the production and removal of bacteria in the intestine. Vibrio cholerae (Figs 13.3, 13.4) and rotaviruses both establish specific binding to receptors on the surface of intestinal epithelial cells. For V. cholerae, establishment in surface mucus may be sufficient for infection and pathogenicity. The fact that certain microbes infect mainly the large bowel (Shigella spp.) or small intestine (most salmonellae, rotaviruses) indicates the presence of specific receptor molecules on mucosal cells in these sections of the alimentary canal.

Table 13.4 Microbial attachment in the intestinal tract

Figure 13.3 Attachment of Vibrio cholerae to brush border of rabbit villus. Thin section electron micrograph (×    10 000).

(Courtesy of E.T. Nelson.)

Figure 13.4 Adherence of Vibrio cholerae to M cells in human ileal mucosa.

(Courtesy of T. Yamamoto.)

Infection sometimes involves more than mere adhesion to the luminal surface of intestinal epithelial cells. Shigella flexneri, for example, can only enter these cells from the basal surface. Initial entry occurs after uptake by M cells, and the bacteria then invade local macrophages. This gives rise to an inflammatory response with an influx of polymorphs, which in turn causes some disruption of the epithelial barrier. Bacteria can now enter on a larger scale from the intestinal lumen and invade epithelial cells from below. The bacteria enhance their entry by exploiting the host’s inflammatory response.

Crude mechanical devices for attachment

Crude mechanical devices are used for the attachment and entry of certain parasitic protozoans and worms. Giardia lamblia, for example, has specific molecules for adhesion to the microvilli of epithelial cells, but also has its own microvillar sucking disk. Hookworms attach to the intestinal mucosa by means of a large mouth capsule containing hooked teeth or cutting plates. Other worms (e.g. Ascaris) maintain their position by ‘bracing’ themselves against peristalsis, while tapeworms adhere closely to the mucus covering the intestinal wall, the anterior hooks and sucker playing a relatively minor role for the largest worms. A number of worms actively penetrate into the mucosa as adults (Trichinella, Trichuris) or traverse the gut wall to enter deeper tissues (e.g. the embryos of Trichinella released from the female worm and the larvae of Echinococcus hatched from ingested eggs).

Mechanisms to counteract mucus, acids, enzymes and bile

Microbial exotoxin, endotoxin and protein absorption

Microbial exotoxins, endotoxins and proteins can be absorbed from the intestine on a small scale. Diarrhea generally promotes the uptake of protein, and absorption of protein also takes place more readily in the infant, which in some species needs to absorb antibodies from milk. As well as large molecules, particles the size of viruses can also be taken up from the intestinal lumen. This occurs in certain sites in particular, such as those where Peyer’s patches occur. Peyer’s patches are isolated collections of lymphoid tissue lying immediately below the intestinal epithelium, which in this region is highly specialized, consisting of so-called M cells (see Fig. 13.4). M cells take up particles and foreign proteins and deliver them to underlying immune cells with which they are intimately associated by cytoplasmic processes.

Microorganisms gaining entry via the urogenital tract can spread easily from one part of the tract to another

The urogenital tract is a continuum, so microorganisms can spread easily from one part to another, and the distinction between vaginitis and urethritis, or between urethritis and cystitis, is not always easy or necessary (see Chs 20 and 21).

Vaginal defences

The vagina has no particular cleansing mechanisms, and repeated introductions of a contaminated, sometimes pathogen-bearing foreign object (the penis), makes the vagina particularly vulnerable to infection, forming the basis for sexually transmitted diseases (see Ch. 21). Nature has responded by providing additional defences. During reproductive life, the vaginal epithelium contains glycogen due to the action of circulating estrogens, and certain lactobacilli colonize the vagina, metabolizing the glycogen to produce lactic acid. As a result, the normal vaginal pH is about 5.0, which inhibits colonization by all except the lactobacilli and certain other streptococci and diphtheroids. Normal vaginal secretions contain up to 10⁸/mL of these commensal bacteria. If other microorganisms are to colonize and invade they must either have specific mechanisms for attaching to vaginal or cervical mucosa or take advantage of minute local injuries during coitus (genital warts, syphilis) or impaired defences (presence of tampons, estrogen imbalance). These are the microorganisms responsible for sexually transmitted diseases.