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BRS Phase 1B Gastroenterology Crashcourse- GI Cancers and Infections

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Summary

Dive into the intricacies of gastrointestinal immunology and the association with cancers in this comprehensive session with Aiden. Key topics that will be discussed include gut microbiology, immunology of the gut, various cells residing in the gut, and disorders linked to it. Understand the importance of the gut's reaction to pathogens, learn about symbiotic and pathogenic bacteria, and explore dysbiosis - a state of altered gut composition leading to diseases. Additionally, the course will cover anatomical and chemical barriers in the gut, turnover cycles of gut lining, implications of radiation on turnover cycles, mucosal associated lymphoid tissue (MALT), and gut-associated lymphoid tissue (GALT). Sign up for this unique exploration of the evolution and complexities of the gut's immune system and its relationship with cancer.

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Description

9am - Upper GI

10am- Malnutrition, Appetite and Abdo. pain

11am- GI Cancers and Infections

12pm- GI surgery

Learning objectives

  1. Understand the basic elements of gastrointestinal (GI) immunology and how it relates to health and disease.
  2. Become familiar with the concept of gut microbiome, its role in health and disease, and the factors that can lead to dysbiosis.
  3. Understand the role, structure, and function of cells in the gut, including enterocytes and goblet cells and the different lines of defense in the gut, both physical and immunological.
  4. Understand the concept and function of mucosal associated lymphoid tissue (MALT) and gut-associated lymphoid tissue (GALT), and their roles in immune response in the GI tract.
  5. Gain knowledge about intestinal disorders, their links to gut immunology, and the role that both dietary and pathogenic antigens play in these disorders.
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Computer generated transcript

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The following transcript was generated automatically from the content and has not been checked or corrected manually.

Hi. Hi, everyone. Can everyone hear me? Ok. Um I don't know how many there are. Hello. Um uh just getting at the slides now. Um ok, here we are. Ok. Um um, and then I share this. Can everyone see the powerpoint? Um ok. Um, actually if I do uh it's quite difficult without any feedback. Ok. Um If, uh actually if I do this and then can every, can everyone see? Um, great. Ok. Um So, hi, I'm Aiden. Um I'm going to be presenting on gi immunology and cancers. So it's a bit of a broad topic, but I think it's really important to get the, get the kind of the basics in. I think that's probably what they're gonna be testing you on. So, um as a timeline I'm gonna go through the immunology section first and then the cancer section. Um three out. Um I'll just get my notes up on the side. Ok, great. So these are the Tylo's. Um we've got, um so we're gonna cover the immunology of the gut, then the cells in the gut and then also some of the intestinal disorders linked to that. And these are sort of your broad gastroenterology Tylo. So, obviously, with the Tylers, it's difficult to take away exactly what you need to know, but just focus on what they teach you in the lecture really. So, um in the gut microbiome, you've in the gut, at least you've got a very large antigen load, um containing bacteria, dietary and pathogenic antigens. And so the gut needs to be in the state of restrained activation where it's tolerant to the food antigens and to commensal bacteria, but it's reactive to pathogens. There's this idea that we have like symbiotic um and um pathogens and commensal bacteria in our, in our gut. And so the symbiotic bacteria, it means living with um and um and dysbiosis can occur when you've got an altered microbiota compos composition, which can then lead to disease. So, um some of some of the symbio, some, some of the symbion are called commensal. And these commensal are really useful because they provide the essential um they provide lots of essential metabolism. So things like metabolizing indigestible compounds as well as actually providing a defense against, against the colonization of of patho pathogens or patho bions and a patho which you've already mentioned before. These are the bacteria that usually live healthily in your bowel, but opportunistically can cause an infection in certain situations such as when you're taking antibiotics. Um There's a lot of factors which can cause dysbiosis, including infection, diet, drugs, um hygiene, and then genetics. Um the first line epithelial defense in the gut, um has uh has a, a wide array of physical barriers, some of which are anatomical and some of which are chemicals, these include the epithelial barrier and peristalsis as an anatomical barriers. Um And then as chemical barriers, you've got lots of enzymes in the gut and then you've also got an acidic and basic ph we'll also talk a bit more about some of the more complex um immune related barriers. Um enterocytes and goblet cells which line the enteric epithelium have quite a quick life turnover of around 36 hours. So this means that any damage that the epithelium sustains from toxins and the like are short lived and radiotherapy and ra radiation sickness, for example, can impair that turnover cycle leading to um severe intestinal dysfunction and diarrhea as the gut lining will accumulate more damage because it can't replace itself as well. Um In terms of the like anatomy, so to speak, or the structure of the epithelium, you've got on the top a mucous layer which is secreted by the goblet cells. And then you've got an epithelial monolayer which has your um er which has your vili and um and the epithelium itself is connected with all these tight junctions. So really nothing sh like no bacter, it's gonna be difficult for bacteria to get through that. Um So that's how they've, how um how that works. And then in the small intestine, you've also got these types of cells called panis cells. And these exist within the bases of the crypts of Lieberkuhn. Um And they secrete antimicrobial peptides incl including defensins and lysozyme. Some of the more complex immunology in the gut is is this is is malt, which is your mucosal associated lymphoid tissue. And malt is found in the submucosa just below the epithelium. Um and a specific type of malt which we'll tend to focus on is called organized malt. And these, this is structure is like these kind of lymphoid masses which contain lymphoid follicles. So, it's a, you know, I think you can think about it a bit like having like lymph nodes in your mucosa. It's a bit like that. This organized malt um and GALT which we'll talk about later. So, gut associated lymphoid tissue is present in the er specifically within the, within the, within the gut rather than in the um rather than, for example, in the oral cavity, et cetera um within the um within the um the lymphoid masses which are present in these organized malts. Um There exist these things called um lymphoid follicles and they're surrounded by lots of um high endothelial venules, which are these postcapillary venules which allow passage of lots of lymphocytes. Um So you're getting a lot of good immune supply basically to that area. So immune cells can quickly respond to what's going on. Um There are lots of examples of mold tissue. So as I was talking about before GALT, but you've also got in the oral cavity in particular, which is relevant for the gi you've got your palatine tonsils, lingual tonsils, and your pharyngeal tonsils also known as your adenoids. Um So, obviously, those can inflame um during active infection within the oral cavity. Um GALT, which is the main, which is what we'll focus on in the next slide is dot associated lymphoid tissue and it's a type of malt and it exists in the um within these vili um in the gut, you know, with the enterocytes and it's separated into two types and non organized, which makes about 1/5 of the intestinal epithelium in terms of cell count. And then you've got your organized GALT, which is this concentrated immunological tissue like the malt present in the oral cavity. So things like Hayer patches, which includes lots of follicles, et cetera. You can see a diagram of this um on the side. So you've got your T cells, macrophages, um B cells, uh dendritic cells, et cetera, which all form up the non organized go. Um So non organized gault in the gut, it exists intraepithelially and then also within the lamina propria. And remember the lamina propria is the layer between the epithelium and muscularis mucosa. Um And these um cells contain lots of different types, including T cells, B cells, macrophages, dendritic cells, as I was saying before. And um so basically there, there's lots of cells which can very quickly respond to what's going on inside the gut lumen um within the large intestine. Um You've actually got lower numbers of lymphocytes. Um and you've got more goblet cells and this is because in the lower large intestine, um you don't need as strong of an immune system because actually the um commensal and symbion um uh provide a lot of the protection from colonization of other bacteria. Um and the infections which are, which, you know, before things like antibiotics which were more dangerous, tended to be infections in the upper parts. So like your stomach, et cetera. Um.