15.4 Virulence factors of eukaryotic pathogens  (Page 2/4)

Protozoan virulence

Protozoan pathogens are unicellular eukaryotic parasites that have virulence factors and pathogenic mechanisms analogous to prokaryotic and viral pathogens, including adhesins, toxins, antigenic variation, and the ability to survive inside phagocytic vesicles.

Protozoans often have unique features for attaching to host cells. The protozoan Giardia lamblia , which causes the intestinal disease giardiasis, uses a large adhesive disc composed of microtubules to attach to the intestinal mucosa. During adhesion, the flagella of G. lamblia move in a manner that draws fluid out from under the disc, resulting in an area of lower pressure that facilitates adhesion to epithelial cells. Giardia does not invade the intestinal cells but rather causes inflammation (possibly through the release of cytopathic substances that cause damage to the cells) and shortens the intestinal villi, inhibiting absorption of nutrients.

Some protozoans are capable of antigenic variation . The obligate intracellular pathogen Plasmodium falciparum (one of the causative agents of malaria ) resides inside red blood cells, where it produces an adhesin membrane protein known as PfEMP1. This protein is expressed on the surface of the infected erythrocytes, causing blood cells to stick to each other and to the walls of blood vessels. This process impedes blood flow, sometimes leading to organ failure, anemia, jaundice (yellowing of skin and sclera of the eyes due to buildup of bilirubin from lysed red blood cells), and, subsequently, death. Although PfEMP1 can be recognized by the host’s immune system, antigenic variations in the structure of the protein over time prevent it from being easily recognized and eliminated. This allows malaria to persist as a chronic infection in many individuals.

The virulence factors of Trypanosoma brucei , the causative agent of African sleeping sickness , include the abilities to form capsules and undergo antigenic variation . T. brucei evades phagocytosis by producing a dense glycoprotein coat that resembles a bacterial capsule. Over time, host antibodies are produced that recognize this coat, but T. brucei is able to alter the structure of the glycoprotein to evade recognition.

Helminth virulence

Helminths, or parasitic worms, are multicellular eukaryotic parasites that depend heavily on virulence factors that allow them to gain entry to host tissues. For example, the aquatic larval form of Schistosoma mansoni , which causes schistosomiasis , penetrates intact skin with the aid of proteases that degrade skin proteins, including elastin.

To survive within the host long enough to perpetuate their often-complex life cycles, helminths need to evade the immune system. Some helminths are so large that the immune system is ineffective against them. Others, such as adult roundworms (which cause trichinosis , ascariasis , and other diseases), are protected by a tough outer cuticle.

Over the course of their life cycles, the surface characteristics of the parasites vary, which may help prevent an effective immune response. Some helminths express polysaccharides called glycans on their external surface; because these glycans resemble molecules produced by host cells, the immune system fails to recognize and attack the helminth as a foreign body. This “ glycan gimmickry ,” as it has been called, serves as a protective cloak that allows the helminth to escape detection by the immune system. I. van Die, R.D. Cummings. “Glycan Gimmickry by Parasitic Helminths: A Strategy for Modulating the Host Immune Response?” Glycobiology 20 no. 1 (2010):2–12.

In addition to evading host defenses, helminths can actively suppress the immune system. S. mansoni , for example, degrades host antibodies with proteases . Helminths produce many other substances that suppress elements of both innate nonspecific and adaptive specific host defenses. They also release large amounts of material into the host that may locally overwhelm the immune system or cause it to respond inappropriately.

Key concepts and summary

• Fungal and parasitic pathogens use pathogenic mechanisms and virulence factors that are similar to those of bacterial pathogens
• Fungi initiate infections through the interaction of adhesins with receptors on host cells. Some fungi produce toxins and exoenzymes involved in disease production and capsules that provide protection of phagocytosis.
• Protozoa adhere to target cells through complex mechanisms and can cause cellular damage through release of cytopathic substances. Some protozoa avoid the immune system through antigenic variation and production of capsules.
• Helminthic worms are able to avoid the immune system by coating their exteriors with glycan molecules that make them look like host cells or by suppressing the immune system.

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