Block D - inflammatory Bowel disease Flashcards
when does IBD occur ?
IBD happens when OT breaks down , this is when there is an immune response to food you eat or the microbiome.
11.2 million people worldwide affected by IBD , IBS is a completley different thing.
role of OT ?
Role of OT is to provide homeostatic regulation of intestinal inflammation directed at harmless or beneficial antigens such as gut flora or food
types of IBD ?
There are different type of IBD , there are Food sensitive enteropathies, a T cell mediated hypersensitivity response, examples include coeliac disease, cow’s milk allergies. No anaphylaxis , there is a dysfunction of the gut
what does IBD include ?
Inflammatory bowel diseases include ulcerative colitis and chron’s diseases , they are a breakdown in tolerance to own gut flora.
coeliac disease ?
Loss of tolerance to wheat gluten
cows milk allergy ?
Loss of tolerance to milk proteins
chrons disease and UC ?
OT breakdown for microbiome
describe IBD and chrons?
Bowel is the large intestine, not the small intestine. This is the area responsible for water absorption as the digestion process.
A healthy colon , will have healthy blood vessels and no inflammation. A person with ulcerative colitis will have a colon that is thickened, inflamed , red and ulcerations present in parts. In some cases of UC and Chron’s these ulcerations can perforate the bowel with severe consequences.
induciton of intestinal inflammation ?
Normal gut will have long villi and crypts, the epithelial cells proliferate at the bottom of the villi and move towards the top. There will be some form of inflammatory insult , this could be food or bacteria etc. , this will activate the immune response in the lamina propria to produce cytokines. These cytokines are the growth and differentiation factors required by epithelial cells to proliferate, the crypts then get longer. After proliferation there is a destructive phase where the inflammatory immune response is producing cytotoxic and cytolytic factors to induce apoptosis in epithelial cells, this is villus atrophy as the villi have been destroyed but the crypts get longer.
consequence of intestinal insult ?
Consequence is there is a loss to the absorptive surface and nutrients from digesting food from the small intestine cannot be utilised and proteins, minerals, vitamins and carbohydrates cannot be absorbed. If this occurs for a long time, they become malnourished, if a child suffers their growth can be stunted.
healthy specimen of intestinal slide ?
A healthy specimen, the villi are long, and crypts are of adequate size. The nuclei of the epithelial cells are seen and there is an appropriate number of immune cells. The holes are the goblet cells, which produce mucus and protect the gut. There is a large surface area
cryptoplasia and IBD ?
This sample has had an inflammatory insult, from a helminth, there is cryptypeoplasia as the crypts have increased in size and there is a lot more disorganisation. The villi are not long, and the epithelial cells have breaches in the smooth surface which allows the microbiome to come into contact with the immune system. Furthermore, the number of goblet cells have increased . The smooth muscle layer has thickened during infection – muscular hyperplasia and increased peristalsis occurs in the gut.
how can you confirm that IBD is T cell mediated ?
You can confirm that this is a T cell mediated response as knocking out the t cell response will allow the villi to return to normal length , crytotypoplasia has reduced and goblet cells are back to normal.
chrons vs UC ?
In Chron’s there are granuloma , normally in response to intracellular pathogens but in this cause to bodies own tissues. This destroys the intestinal architecture and tissue cannot function normally. These granuloma can turn into ulcers and perforate the gut.
In UC there are abscess in the crypts , with bacteria and immune cells .
description of chrons ?
an affect any part of the GI tract (from the mouth to the anus) , however, most often found in the large bowel. Inflammation may reach through the multiple layers of the walls of the GI tract leading to perforations. Th1/Th17 mediated and there is an infiltration of macrophages and neutrophils.
description of UC ?
Usually occurs in the large intestine (colon) and the rectum. Inflammation is continuous (not patchy in Chron’s) and only in the inner layer of the lining of the colon. Th2 mediated and this leads to activation and recruitment of mast cells and goblet cells. This Th2 mediation is proved by blocking IL-4Rα is protective and restores the disease
what drives IBD ?
complex disorder which involves 4 factors: environmental factor including pollution and smoking , presence of gut microbiome in gut , abnormal immune response , genetics.
factors inducing IBD - primary immune defect ?
Primary immune defect for instance lacking a cell for immune response regulation then develop IBD , a defect in T cells for example.
epithelial cell defect ?
Epithelial cell defect as lacking tight junctions increases permeability allowing microbiome into lamina propria then this will activate immune cells and activate the inflammatory cascade.
genetic succeptibility ?
Genetic susceptibility MHC and TNF gene. Shown as Identical twins are more likely to develop IBD than non-identical twins, this reveals genetics rather than environment
non immune defence mechanism ?
Non-immune defence mechanisms for example a deficiency for developing pancreatic enzymes or too much gastric acid in gut which disrupts epithelial cell permeability.
endogenous factors ?
Endogenous factors - gastric acid, proteolytic enzymes, anti-microbial molecules (defensins, cryptidins), trefoil peptides, neuroendocrine system, substance P. Defects in any one or more of these may alter the antigenicity of luminal antigens and/or increase intestinal permeability.
