Please follow the link bellow and please be as detailed and as specific with a s
ID: 204674 • Letter: P
Question
Please follow the link bellow and please be as detailed and as specific with a short prograph.
https://www.nature.com/articles/mi201077
In the paper by PJ Sansonetti, three hypotheses are proposed to explain host immune system tolerance to microbial symbionts and immune reactivity to microbial pathogens.A) How do the three hypotheses apply to Giardia and Entamoeba histolytica infections? B) What molecules fromthe parasites trigger innate and adaptive immune responses like those found on microbial pathogens and symbionts resulting in the secretion of inflammatory cytokines? Be specific with full explanation with a small prograph
Explanation / Answer
Answer to A)
In the article provided, the three hypothesis which were described for explaining the host differentiating capacity between pathogenic and non pathogenic or commensal type of microbe are:
i. Hypothesis I: Chemical modification of Pathogen-associated molecular motifs (PAMPs) by symbiotic microbes which make them agonistic to Host-pathogen pattern recognition receptors (PRRs). The symbiotic microbes can now evade in stealth mode due to this modification.
Application of Hypothesis I to Giardia and Entamoeba histolytica: Giardia causes decreased expression of brush border enzymes in the intestine, induces morphological changes in microvilli, ultimately resulting programmed cell death of small intestinal epithelial cells. All these are antagonistic to PRRs making the host immune system comes into play to eradicate the Giardia
On the otherhand, Trophozoites of E. hystolytica contains lectin which binds to the epithelial cells in the intestine and forms pores in the intestines with the help of its enzymes like lipases, cysteine proteases. These enzymes enable the E. hystolytica to penetrate into the intestinal wall, blood vessels, liver and even other organs like brain when they gain access to systemic circulation. All these are anatagonistic to the host immune responses and help to discriminate E. hystolytica as pathogen
ii. Hypothesis II states that symbiotic microbes have special effectors that induce tolerogenic signals actively in the host and thus maintaining a favorable environment for their survival
Application of Hypothesis II to Giardia and Entamoeba histolytica: Damage to the intestinal barrier, increased permeability, down regulation of anti-apoptotic proteins by Giardia results in non-tolerogenic signals in the host which activates the immune system and enable it to recognise Giardia as a pathogen but not symbiont
On the other hand, E. histolytica induces a chain reaction of tissue destruction, and ulcer induction lead to non-tolerogenic signals which makes it recognised as Pathogen by host immune system
iii. Hypothesis III postulates that Pathogens have distinct PRRs which attracts the host responses and induce level of stress which is perceived as a signal of danger in the host. This sets up inflammatory responses and ultimately leads to microbial eradication
Application of Hypothesis III to Giardia and Entamoeba histolytica: Caspase dependent apoptosis and consumption of arginine which leads to arginine starvation of host cell and its death by Giardia explains the invoke of danger signals in host system
Trophozoite ingesting the cells and ulcer formations by E. histolytica serves as danger signals making them distinguishable as pathogens by the host
Answer to B)
Giardia: Polypeptides of Giardia serve as potential surface antigens which is targeted by the host immune system via Acquired immunity. The other molecules that trigger the immune responses in the host are Heat shock proteins on the surface membrane of trophozoites, surface membranes lectins. Giardia also has unique proteins called as Giardins which play a role in triggering first local innate immunity response. Giradia also has five variants of tubulins that may trigger the immune responses
E. histolytica: E. histolytica disrupts the innate immunity by being acid resistant in the first place. The first line of defence is bypassed by E. histolytica with the help of its enzymes Cysteine protease- A5 which degrades mucin and extracellular matrix of intestine
E. histolyitca has lectins which is a major surface adhesion molecule and serves as target for adaptive immunity. The heavy chain of lectin contains carbohydrate recognition domain which is responsible for binding.