Mechanisms of Eukaryotic Pathogenesis

Pathogenesis of eukaryotic cells including fungi and protozoa include the same basic scheme as that of bacterial pathogens— colonization, evasion of host defenses, and damage to the host. The mechanisms, however, are generally not well understood.

Fungi

Most fungi, such as yeasts and molds, are saprophytes, meaning that they acquire nutrients from dead and dying material;

those that can cause disease are generally opportunists, although notable exceptions exist.

A group of fungi referred to as dermatophytes can cause superficial infections of hair, skin, and nails but do not invade deeper tissues. These fungi have keratinase enzymes that break down the keratin in superficial tissues for use by the fungi, resulting in diseases such as ringworm and athlete's foot.

Fungi in the normal flora, especially the yeast Candida albicans, can cause disease in immunocompromised hosts. Generally this leads to infection of the mucous membranes, causing thrush, an infection of the throat and mouth, or vaginitis. Factors that may lead to excessive growth of C. albicans include disruption of normal flora due to hormonal influences or antibiotic treatment, AIDS, uncontrolled diabetes, and severe burns.

The most serious fungal infections are caused by a group of fungi that are dimorphic; they occur as molds in the environment, but they assume other forms, usually yeasts, when they invade tissues. Infection occurs when the small airborne spores of the molds are inhaled, lodging deep within the lungs. Within the lung the fungi undergo a morphological change and take up residence in macrophages. These infections are generally controlled by the immune system and do not cause serious disease unless there is an overwhelming infection or if the person is immunocompromised. When the disease does progress, granulomatous damage to the lung and sometimes to other organs occurs.

Some fungi produce toxins, collectively referred to as mycotoxins, which can cause disease. For example, Aspergillus flavus, a fungus that grows on certain grains and nuts, including peanuts, produces aflatoxin. If this toxin is ingested it can damage the liver, perhaps leading to cancer. The spores and other fungal elements can cause hypersensitivities in some people.

Eukaryotic Parasites

Most eukaryotic parasites either live within the intestinal tract or enter the body via the bite of an arthropod. Schistosoma species, however, can enter the skin directly (see Perspective 15.1).

Like bacteria and viruses, eukaryotic parasites attach to host cells via specific receptors. For example, Plasmodium vivax, one of the two most common causes of malaria, attaches to the Duffy blood group antigen on red blood cells. Most people of West African ancestry lack this antigen and are therefore resistant to infection by this species. Giardia lamblia uses a disc that functions as a suction cup to attach to the intestine; it appears that it also has an adhesin associated with the disc that facilitates the initial attachment.

Eukaryotic parasites use a variety of mechanisms to avoid antibodies. Some hide within cells, thus avoiding exposure to antibodies as well as certain other defenses. For example, malarial parasites produce enzymes that allow them to penetrate red blood cells. These host cells do not present antigen to T-cytotoxic cells, enabling the parasite to also escape the cellular immune defenses as well. Leishmania species are able to survive and multiply within macrophages when phagocytized. Parasites such as the African trypanosomes, the cause of sleeping sickness, escape from the effects of antibody by routinely varying their surface antigens, repeatedly activating different genes. Schistosoma species coat themselves with host proteins, effectively disguising themselves. Some parasites appear to suppress immune responses in general.

The extent and type of damage caused by parasites varies tremendously. In some cases, the parasites compete for nutrients in the intestinal tract, contributing to malnutrition of the host. Helminths may accumulate in high enough numbers or grow long enough to cause blockage of the intestines or other organs. Some parasites can produce enzymes that digest host tissue, causing direct damage. In other cases, damage is due to the immune response; high fevers that characterize malaria, and the granulomatous response to schistosoma eggs are examples.

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