Introduction To Crohn's Disease

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We certify that this thesis was prepared under our supervision at the College of Medicine, Al-Nahrain University as a partial requirement for degree of Philosophy of Doctorate in medical microbiology.

In view of the available recommendation, forward this thesis for debate by the examining committee.

Crohn’s disease results from a complex interaction between susceptibility genes, immune system and microbes that can trigger disease pathology. This study aims to determine the significance of ATG16L1 T300A genetic variant on host immunological status, clinical phenotype and presentation as well as the risk of microbial (Norovirus and/or
) acquisition
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Although, most of these are safely killed by lysosomal degradation enzymes, many intracellular pathogens have evolved the ability to escape killing mechanism, allowing them to either proliferate inside the vesicular compartment or to escape into the cytosol. In an attempt to prevent infection, cells deploy macroautophagy and LC3-associated phagocytosis (LAP; discussed in detail later) to capture bacteria, followed by delivery into lysosomes for destruction. In contrast to LAP, which modifies the limiting membrane of pathogen-containing vesicles, macroautophagy engulfs pathogens with additional autophagosome- derived membranes. The principal targets of antibacterial autophagy are bacteria-containing vesicles, bacteria associated with remnants of damaged vesicles, and bacteria that have already escaped into the cytosol. Once caught safely inside an autophagosome, the autophagosomal double membrane restricts pathogen dispersal and provides an additional barrier against potential attempts of pathogens to manipulate cellular processes. The autophagosomal membranes separate pathogens from cytosolic resources and promote their lysosomal delivery.

Studies provides evidences as to how xenophagy accomplished, by utilizing adaptor protein molecules that act as bridges between ubiquitin- tagged cargoes and the autophagic machinery. In addition, these adaptor molecules may also serve as scaffolds for assembling not only the autophagic machinery to integrate the innate immune response.
The linkage between autophagy and bacterial invasion became evident in GFP–LC3-expressing mammalian cells, when GFP–LC3 signals surrounded invading intracellular bacterial infections
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