Immunology in the Gut Mucosa

the human guts can be the scene for devastating conditions such as inflammatory bowel disease which arises through an improperly controlled immune response the gut is often the body's first point of contact with microbes every mouthful of food is accompanied by a cargo of microorganisms that go on to encounter the mucosa the innermost layer of the gut most microbes are destroyed by the harsh acidic environment in the stomach but a hardy few make it through to the intestine the intestinal surface is covered with finger-like protrusions called villi whose primary function is the absorption of nutrients however these structures and the underlying tissues also host the body's largest population of immune cells scattered along the intestinal mucosa are dome-like structures called peyer's patches these are enriched in lymphoid tissue making them key sites for coordinating immune responses to pathogens whilst promoting tolerance to harmless microbes and food the villi contain a network of blood vessels to transport nutrients from food to the rest of the body lymphatics from both the peyer's patches and villi drain into the mesenteric lymph node within the villi is a network of loose connective tissue called the lamina propria and at the base of the villi are the crypts which host stem cells that replenish the epithelium finally the epithelium together with its thick overlying mucous forms an important barrier against microbial invasion embedded within the matrix of the payers patch is a mix of immune cells including T and B lymphocytes macrophages and dendritic cells a key function of the payers patch is the sampling of antigens in this case mostly bacteria and bits of food to facilitate this the payers patch has a much thinner mucous layer as well as specialized phagocytic cells called M cells which can transport material across the epithelial barrier via a process called transit ptosis finally dendritic cells are able to extend dendrites between epithelial cells to sample antigens that are then broken down and used for presenting to lymphocytes sampling antigens in this way typically results in so-called tolerate any activation where the immune system initiates an anti-inflammatory response with their cargo of antigen these dendritic cells then traffic to the T cell zones of the payers patch upon encounter with specific T cells the dendritic cells convert them into an immunomodulatory cell called a regulatory t-cell or T reg defects in the function of these cells are associated with inflammatory bowel disease in both animals and humans these T regs then migrate to the lamina propria of the villi via the lymphatics here the T regs secrete a molecule called il-10 which exerts a suppressive action on immune cells within the lamina propria and upon the epithelial layer itself il turn is therefore critical in maintaining immune quiescence and preventing unnecessary inflammation however a breakdown in this process of immune homeostasis results in gut pathology and when this occurs over a prolonged period and in an uncontrolled manner it can lead to inflammatory bowel disease chemical mechanical or pathogen triggered barrier disruption coupled with particular genetic susceptibilities may all combine to set off inflammation epithelium coming into contact with bacteria is activated leading to bacterial influx alarm molecules released by the epithelium activate immune cells and tear eggs in the vicinity scale down their il-10 secretion to enable an immune response to proceed dendritic cells are also activated by this environment and start to release key inflammatory molecules such as il-6 il-12 and il-23 effective t-cells also appear on the scene and these coordinate an escalation of the immune response by secreting their own inflammatory molecules tumor necrosis factor alpha interferon gamma and il-17 soon after the affected t-cells have arrived a voracious Vega site called a neutrophil is recruited neutrophils are critical for the clearance of bacteria one weapon in the neutrophil armory is the ability to undergo dramatic form of self destruction called neurosis this leaves behind a jumble of DNA saturated with enzymes called a neutrophil extracellular trap although this can effectively destroy bacterial invaders and plug in E breaches in the apathy lleol wall it also causes collateral damage to tissues slowly the tide begins to turn and the bacterial invasion is repulsed any remaining neutrophils die off via apoptosis a non inflammatory form of cell death and are cleared by macrophages epithelial integrity is restored by replacement of any damaged cells with new ones from the intestinal crypts finally tear eggs are recruited once again to calm the immune response targeting the molecules involved in gut pathology is leading to effective therapies for inflammatory bowel disease you

Channel: nature video

Views: 676,839

Rating: 4.9445572 out of 5

Keywords: Nature, Nature Immunology, NPG, gut, gut mucosa, Nature (journal), bacteria, microflora, IBS, inflamatory bowel disease, immunology, immune system, immune cell, immune cells, animation, Arkitek, Disease (Organization Sector), science, research, Health

Id: gnZEge78_78

Length: 6min 52sec (412 seconds)

Published: Tue Feb 05 2013

Reddit Comments

[u/Positronix]

Nice explanation.

To add on to this, dietary Advanced Glycation Endproducts cause inflammation in the intestinal tract and are correlated with aging. dAGE's are formed from food processed at high temperatures with low water content, like fries. Sugar/lipids/proteins form covalently bound adducts which the gut recognizes through RAGE (Receptors of Advanced Glycation Endproducts). RAGE induces an inflammatory response. This is one of the reasons a diet of fast food is bad for you.

[u/iamaxc]

very cool, never knew about those neutrophil NETs before!