2. Microorganism

One of the characteristics of the pathogen that influences its clinical manifestations is whether it grows inside host cells (is an intracellular parasite) or in the hosts body fluids and tissue spaces (extracellular parasite). Many of the body's defenses are directed against extracellular invaders. Even though they do not invade the interior of cells, most extracellular parasites attach to cells when colonizing specific tissues and frequently damage the cells to which they attach.

Intracellular parasites face a different series of challenges for survival. They must adhere to the host cells in which they will reproduce before they can invade them. Some pathogens are engulfed by phagocytic cells, survive destruction, and make themselves at home in the otherwise hostile phagocyte (incomplete phagocytosis).

The interior of a host cell protects the intracellular parasites against destruction by the body's defense mechanisms. Intracellular infections are poorly controlled by chemotherapeutic agents that either fail to penetrate the infected host cells or are ineffective in its cytoplasm. Because they are difficult to eradicate, intracellular parasites often produce chronic diseases with less rapid onsets, much longer recovery times (even with chemotherapy), and a greater likelihood of clinical relapse.

To initiate infection, pathogens must enter the body through a portal of entry that allows them access to tissues displaying the appropriated surface receptors.

The affinity most pathogens exhibit for a limited number of preferential tissues is called tissue tropism. Tissue tropism determines not only the location of the primary site of colonization (the first habitat infected, sometimes with little or no damage to the area), but also the predilection for specific secondary sites of infection once the initial lines of defense have been breached.

NOTE: Tissues that lack surface receptors complementary to the microbes attachment sites usually remain uninfected, although they may still be damaged by extracellular toxins or cytocidal substances released either from the microbe or from neighboring injured tissues.

Based on their relationship to hosts, microbes can be classified as:

• Saprophytes (sapros= decayed, phyton= plant). They are free-living microbes that subsist on dead or decaying organic matter. They are found in soil and water and play an important role in the degradation of organic materials in nature. They usually produce no disease in the healthy host, but occasionally can be harmful for immunocompromized host.

• Pathogenic microbes (pathos= suffering, gen= produce). These are disease producing microbes, usually parasites, which can establish themselves and multiply in the living hosts.

• Facultative pathogens, or opportunistic microbes. They are usually commensals that can live in complete harmony with the host without causing any damage to it (for example, microbes of the normal flora). In case of lowering the host defense, these microbes can produce the infectious process.

The term “pathogenicity” refers to as the potential ability of a microbial species to produce disease or tissue injury.

The term “virulence” is applied to the same property in a strain of the microbe and characterizes the degree of pathogenicity. The virulence of a strain is not constant and may undergo spontaneous or induced variation. Reduction of virulence is known as attenuation and can be achieved by passage through unfavorable conditions. These avirulent attenuated strains of pathogenic microbes are applied as vaccine strains. (See LESSON 15).

Virulence is quantified by determining the pathogens lethal dose, the number of microorganisms required to cause the death of infected animals. The greater the pathogens virulence, the fewer microbes are required to cause disease symptoms. The result is expressed as LD₅₀, the number of microbes required to cause disease and death in 50 percent of the laboratory animals experimentally infected with the pathogen.

For virulence tests, the commonly used laboratory animals are guinea pigs, rabbits, rats, and mice. The routes used for animal infecting may be subcutaneous, intramuscular, intraperitoneal, intracerebral, or intravenous. The oral route and nasal spray can also be used.