A variety of factors determine whether an infection is a surface or a systemic infection

What prevents surface infections from spreading more deeply? Why do the microbes that cause systemic infections leave the relatively safe haven of the body surface to spread through the body, where they will bear the full onslaught of host defences? These are important questions. For instance, what are the factors that persuade meningococci residing harmlessly on the nasal mucosa to invade deeper tissues, reach the blood and meninges, and cause meningitis (see Ch. 24)? The answer is not known.

Temperature is one factor that can restrict microbes to body surfaces. Rhinovirus infections, for instance, are restricted to the upper respiratory tract because they are temperature sensitive, replicating efficiently at 33°C, but not at the temperatures encountered in the lower respiratory tract (37°C). Mycobacterium leprae is also temperature sensitive, which accounts for its replication being more or less limited to nasal mucosa, skin and superficial nerves.

The site of budding is a factor that can restrict viruses to body surfaces. Influenza and parainfluenza viruses invade surface epithelial cells of the lung, but are liberated by budding from the free (external) surface of the epithelial cell, not from the basal layer from where they could spread to deeper tissues (Fig. 15.2).

Figure 15.2 Topography of virus release from epithelial surfaces can determine the pattern of infection.

Many microorganisms are obliged to spread systemically because they fail to spread and multiply at the site of initial infection, the body surface. In the case of measles or typhoid, there is, for unknown reasons, next to no replication at the site of initial respiratory or intestinal infection. Only after spreading through the body systemically are large numbers of microorganisms delivered back to the same surfaces, where they multiply and are shed to the exterior. Other microorganisms need to spread systemically because they have committed themselves to infection by one route, while major replication and shedding occurs at a different site. The microbe must reach the replication site, and there is then no need for extensive replication at the site of initial infection. For instance, mumps and hepatitis A viruses infect via the respiratory and alimentary routes, respectively, but must spread through the body to invade and multiply in salivary glands (mumps) and liver (hepatitis A).

In systemic infections, there is a stepwise invasion of different tissues of the body

This stepwise invasion is illustrated in Figure 15.3, and such infections include measles (Fig. 15.4) and typhoid (Fig. 15.5). Although the final sites of multiplication may be essential for microbial shedding and transmission (e.g. measles), they are sometimes completely unnecessary from this point of view (e.g. meningococcal meningitis, paralytic poliomyelitis). These microbes are not shed to the exterior after multiplying in the meninges or spinal cord.

Figure 15.3 The spread of infection throughout the body. Bone marrow and muscle are possible sources for secondary parasitaemia in addition to blood vessels, liver and spleen. ^†In dengue, malaria and typhus, multiplication occurs in blood cells or vascular endothelium. ^††Poliovirus invades the brain and spinal cord from the blood, but is not shed from these sites, whereas rabies invades and later travels from brain to salivary glands via peripheral nerves.

Figure 15.4 The pathogenesis of measles. Virus invades body surfaces from the blood, traversing blood vessels to reach surface epithelium first in the respiratory tract where there are only 1–2 layers of epithelial cells and then in mucosae (Koplik’s spots) and finally in the skin (rash).

Figure 15.5 The pathogenesis of typhoid fever.

For the microbe, systemic spread is fraught with obstacles, and a major encounter with immune and other defences is inevitable. Microorganisms have therefore been forced to develop strategies for bypassing or countering these defences (see Ch. 16).

Rapid replication is essential for surface infections

The rate of replication of the infecting microorganism is of central importance, and doubling times vary from 20    min to several days (Table 15.1). Hit-and-run (surface) infections need to replicate rapidly, whereas a microorganism that divides every few days (e.g. Mycobacterium tuberculosis) is likely to cause a slowly evolving disease with a long incubation period. Microorganisms nearly always multiply faster in vitro than they do in the intact host, as might be expected if host defences are performing a useful function. In the host, microorganisms are phagocytosed and killed and the supply of nutrients may be limited. The net increase in numbers is slower than in laboratory cultures where microbes are not only free from attack by host defences, but also every effort has been made to supply them with optimal nutrients, susceptible cells, and so on.

Table 15.1 Replication rates of different microorganisms

a But some viruses show greatly delayed replication or delayed spread from cell to cell.

b But cannot be cultivated in vitro.

Invading microbes encounter a variety of defences on entering the body

After traversing the epithelium and its basement membrane at the body surface, invading microbes face the following defences:

Figure 15.6 Microbial invasion and spread to lymph and blood. Microbes (or other particles) beneath surface epithelium readily enter local lymphatics.

The infection may be halted at any stage, but by multiplying locally or in lymph nodes and by evading phagocytosis, the microorganism can ultimately reach the bloodstream. Therefore, a minor injury to the skin, followed by a red streak (inflamed lymphatic) and a tender, swollen local lymph node are classic signs of streptococcal invasion. Most bacteria cause a great deal of inflammation when they invade in this way. In the early stages, lymph flow increases, but eventually, if there is enough inflammation and tissue damage in the node itself, the flow of the lymph may cease. In contrast, viruses and other intracellular microorganisms often invade lymph and blood silently and asymptomatically during the incubation period; this is facilitated when they infect monocytes or lymphocytes without initially damaging them.

The fate of microorganisms in the blood depends upon whether they are free or associated with circulating cells

Viruses or small numbers of bacteria can enter the blood without causing a general body disturbance. For instance, transient bacteraemia are fairly common in normal individuals (e.g. they may occur after defecation or brushing teeth), but the bacteria are usually filtered out and destroyed in macrophages lining the liver and spleen sinusoids. Under certain circumstances, the same bacteria have a chance to localize in less well-defended sites, such as congenitally abnormal heart valves in the case of viridans streptococci causing infective endocarditis, or in the ends of growing bones in the case of Staphylococcus aureus osteomyelitis.

If microorganisms are free in the blood, they are exposed to body defences such as antibodies and phagocytes. However, if they are associated with circulating cells, these cells can protect them from host defences and carry them around the body. For example, many viruses, such as Epstein–Barr virus (EBV) and rubella, and intracellular bacteria (Listeria, Brucella) are present in lymphocytes or monocytes and, if not damaged or destroyed, these ‘carrying cells’ protect and transport them. Malaria infects erythrocytes.

On entering the blood, microorganisms are exposed to macrophages of the reticuloendothelial system (see Ch. 9). Here, in the sinusoids, where blood flows slowly, they are often phagocytosed and destroyed. But certain microorganisms survive and multiply in these cells (Salmonella typhi, Leishmania donovani, yellow fever virus). The microorganism may then:

Stay updated, free articles. Join our Telegram channel

Join