For this year’s STEAM project, I decided to cover how eosinophils attack helminths and how it related back to the hygiene hypothesis.
Eosinophils are made in bone marrow and like basophils and neutrophils, they are a granulocyte with a segmented nucleus. They make up about 5 percent of WBC’s and have a few roles in the human body but are known for their ability to fight parasitic infections. They have receptors for multiple cytokines, chemokines, and adhesion molecules that allow them to participate in inflammatory responses and homeostasis. The thick granules of the eosinophil contain the cationic proteins, and when stimulated, they release. Some of these include MBP 1 and 2, ECP, EPX, EDN and cytosine. Granule proteins can be released in two different ways; piecemeal degranulation and eosinophil cytolytic mode of degranulation. Piecemeal degranulation occurs in two different ways. When either the cell wall ruptures and subsequently the proteins are released, or when specific granule proteins are released in cytoplasmic vesicles. Eosinophil cytolytic mode of degranulation happens when eosinophils release groups of whole granules along with CLC protein to create an extracellular trap or EET. These EET’s contain nuclear DNA fibers and they can also be made with eosinophil granule proteins and mitochondrial DNA.
During a parasitic infection, a Th-2 induced reaction that line up with the metabolic and physical interaction between host and worm occurs. Immune mediators like histamine and prostaglandins can displace or disrupt the environment, and or deprive the worms of nutrients. The type 2 cytokine IL- 5 and eotaxin start eosinophil activation and draws them to the site of infection. Once there, the eosinophils either bind to the parasite larva or close by degranulation, releasing reactive oxygen species, cationic peptides, or other granular proteins. These white blood cells are more effective in fighting parasites at the larvae stage than adult. In the event of an adult infestation, eosinophils can cause more damage than good. In failure to rid the host of parasites, eosinophils can cause tolerogenic responses that confine the helminth and hopefully stop parasitic damage to the body. High levels of eosinophils and they’re activity during a parasitic infection can cause eosinophil-mediated organ damage, such as severe dermal pathology, tissue fibrosis, and organomegaly. As well as the formation of granulomas to confine eggs that can cause a plethora of other issues especially if found in the GI tract.
Eosinophils are hardwired to fight and defeat parasites especially parasitic larvae. So, what happens when there’s nothing for them to fight? Since the birth of modern healthcare and improved hygiene, there’s been a significant rise in autoimmune diseases, especially in the GI tract. The hygiene hypothesis theorizes that with the increase in hygiene and access to health care has driven the rise in these disorders. Since eosinophils are made to fight these infections, when there is none, these cells essentially get bored. They’re made to fight and they can’t, so they begin to attack healthy systems. In third world countries where there’s less medical aid and where diseases are more rampant, there can be found significantly lower levels of autoimmune diseases like celiac disease and Crohn’s.
Sources:
- The Role of Eosinophils in Parasitic Helminth Infections: Insights from Genetically Modified Mice. The Role of Eosinophils in Parasitic Helminth Infections: Insights from Genetically Modified Mice – ScienceDirect
Eva’s project is how eosinophils attack helminths and how it relates back to the hygiene hypothesis. While reading her project I can summarize that Eosinophils are granulocytes produced in the bone marrow that have a segmented nucleus, similar to neutrophils and basophils. Even though they comprise only 5% of WBCs and provide a variety of functions in the human body, their ability to fight parasitic illnesses is what makes them most famous. They have receptors for a range of cytokines, chemokines, and adhesion molecules, which allows them to participate in both inflammation and homeostasis.
Granule proteins can be released by two different mechanisms: piecemeal degradation and the eosinophil cytolytic mode of degranulation. The eosinophil cytolytic method of degradation is the process by which eosinophils release aggregates of whole granules together with CLC protein to form an extracellular trap, or EET. In addition to nuclear DNA fibers, these EETs can also be produced using eosinophil granule proteins and mitochondrial DNA.
The physical and metabolic interaction that takes place during an infection between the parasitic worm and its host is accompanied by a Th-2 triggered response. Immune mediators such as histamine and prostaglandins have the potential to disturb or alter the environment and/or deprive the worms of food. The type 2 cytokines IL-5 and eotaxin, which also draw cells to the infection site, cause eosinophil activation. After arriving, the eosinophils bind to the parasite larva or degranulate near it to release cationic peptides, other granular proteins, or reactive oxygen species. These white blood cells are more effective against larval forms of parasites than adult versions when it comes to fighting them. Not all uses for eosinophils are beneficial. Eosinophils may cause tolerogenic reactions that limit the helminth and potentially stop the parasites’ detrimental effects on the body if they are unable to remove the parasites from the host. High eosinophil levels and their activity during a parasite infection can cause eosinophil-mediated organ damage, such as organomegaly, tissue fibrosis, and severe cutaneous disease. Furthermore, granulomas develop to hold eggs, which can lead to a number of other issues, especially if they are found in the gastrointestinal tract. The ability to fight and remove parasites, especially parasitic larvae, is encoded in the DNA of eosinophils.
The hygiene hypothesis states that improved access to healthcare and advancements in hygiene are to blame for the rise in these conditions. Eosinophils, cells made to fight infections, essentially get bored when there are none. They begin targeting systems supposed to be healthy because they are unable to fight. In third-world nations, where access to healthcare is scarce and disease prevalence is higher, autoimmune disorders like Crohn’s disease and celiac disease are significantly less frequent. Also her artwork/media is really well done, and really matches her written piece:)