Lecture A4 + A5 - Mucosal Surfaces of the Gut Flashcards
What are the 3 layers of the oesophageal mucosa?
Deepest - basal, 1-3 cells think actively involved in mitosis.
Prickle cell layer - space between cells filled with glycoconjugate material.
Outermost layer - functional layer, 1-2 cells thick, cells leaky and die that shed into the lumen.
What secretion is important in the neutralisation of gastric reflux?
Bicarbonate secretion.
What salivary secretions are in oesophageal mucus?
HCO3-, mucus MUC7 and MUC5B (anti-microbial activity).
What is the main pepsin in man?
Pepsin 3
What does gastric juice in PUD have the ability to do?
Enhanced ability to degrade mucosal barrier.
What are the 2 main mucin polymeric structures?
- Mucin polymer - gel forming, insoluble.
- Mucin glycoprotein - proteinase resistant, soluble.
Describe HP infection.
Gastritis, aetiological factor in the pathogenesis of peptic ulceration.
Located under the mucus layer.
90% of gastric cancer cases are associated with a pre-existing HP infection.
How does the shape of HP help it get under the mucus layer?
Corkscrew shape with multiple flagella.
How is the HP protected and survive when it gets under the mucus layer?
Once it is under the mucus blanket it is protected by it.
Gets there by entering with food which acts as a buffer.
What mucin interacts with Bab-A in HP?
MUC5AC (main carrier of Lewis B)
What is breaking down the mucin within the mucus gel in a HP infection?
Ammonia produced by the HP.
How does HP trick the immune system into thinking it is not an invader?
Hides under the mucus which prevents immunoglobulins and polymorphs from reaching it.
Expressed the blood group LewisX to convince the host it is part of it, not an invading organism.
How does HP avoid being killed by immune cells?
Produces catalyse and SOD which destroys the ROS from the immune cells to kill the bacteria.
Opens up the tight junctions to allow for leakage of albumin which is a good food source for HP.
IgA blocking antibodies on the surface.
What is the mucin expressed in the heart, kidney and lungs?
MUC14 - chromosome 4q24.
18-120KDa, 261 amino acids.
Transmembrane, cell surface localised on endothelial cells.
Has a serine/threonine rich extracellular domain.
What are the gel forming mucins?
MUC5AC, MUC5B, MUC6 and MUC19.
Chromosomal location - 11P15.5 apart from MUC19 so there is a cluster of gel forming genes.
What do turbinates do?
Create turbulence up the nose and the mucus produced on them traps little particles in the air being breather in to stop them from entering the body.
Describe mucus composition.
H2O - 95%
1-10% glycoprotein (mucin) which is salts, proteins, lipids, carbs, nucleic acid and secretory IgA.
Why are mucus gels in the digestive tract important?
Digestive tract is moving all the time so it prevents the mucus from becoming permanently ruptured as it will reanneal.
What mucin forms the gel in the small and large intestines?
MUC2
Highly kylocyslated in the middle and globular regions on the ends.
What are the features of secreted mucin genes?
Clustered on chromosomal location 11p15.5.
Gel forming.
VNTR - Ser, Thr O-glycosylation
Upstream cysteine rich domains - D1, D2, Dā-D3
Downstream cysteine rich domains - D4.
Downstream B, C, CK (cysteine knot).
Highly glycosylated in the middle to hold lots of water.
What is N-glycosylation linked too?
Asparganine.
Close to the termini of the molecule.
Mannose, GlcNac, Gal, Fuc and sialic acid.
What is O-glycosylation linked too?
Serine, threonine.
GalNac, GlcNac, Fun, Gal and sialic acid.
Describe colonic mucus?
Mucus gel on the surface that is the thickest in the body.
Mucus coming from the GI tract as well as mucus that is being produced in the colon.
Dynamic balance between secretion and erosion.
What is a way of measuring colonic mucus?
Rat model used.
Colon taken outside of the body but still connected to the blood supply.
Exposed to a light source and then mucus secretion and thickness can be measured for up to 6 hours for evert 10 mins.
