Lecture A4 + A5 - Mucosal Surfaces of the Gut

Question 1

What are the 3 layers of the oesophageal mucosa?

Answer 1

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.

Question 2

What secretion is important in the neutralisation of gastric reflux?

Answer 2

Bicarbonate secretion.

Question 3

What salivary secretions are in oesophageal mucus?

Answer 3

HCO3-, mucus MUC7 and MUC5B (anti-microbial activity).

Question 4

What is the main pepsin in man?

Answer 4

Pepsin 3

Question 5

What does gastric juice in PUD have the ability to do?

Answer 5

Enhanced ability to degrade mucosal barrier.

Question 6

What are the 2 main mucin polymeric structures?

Answer 6

1. Mucin polymer - gel forming, insoluble.
2. Mucin glycoprotein - proteinase resistant, soluble.

Question 7

Describe HP infection.

Answer 7

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.

Question 7

How does the shape of HP help it get under the mucus layer?

Answer 7

Corkscrew shape with multiple flagella.

Question 8

How is the HP protected and survive when it gets under the mucus layer?

Answer 8

Once it is under the mucus blanket it is protected by it.
Gets there by entering with food which acts as a buffer.

Question 9

What mucin interacts with Bab-A in HP?

Answer 9

MUC5AC (main carrier of Lewis B)

Question 10

What is breaking down the mucin within the mucus gel in a HP infection?

Answer 10

Ammonia produced by the HP.

Question 11

How does HP trick the immune system into thinking it is not an invader?

Answer 11

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.

Question 12

How does HP avoid being killed by immune cells?

Answer 12

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.

Question 13

What is the mucin expressed in the heart, kidney and lungs?

Answer 13

MUC14 - chromosome 4q24.
18-120KDa, 261 amino acids.
Transmembrane, cell surface localised on endothelial cells.
Has a serine/threonine rich extracellular domain.

Question 14

What are the gel forming mucins?

Answer 14

MUC5AC, MUC5B, MUC6 and MUC19.
Chromosomal location - 11P15.5 apart from MUC19 so there is a cluster of gel forming genes.

Question 15

What do turbinates do?

Answer 15

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.

Question 16

Describe mucus composition.

Answer 16

H2O - 95%
1-10% glycoprotein (mucin) which is salts, proteins, lipids, carbs, nucleic acid and secretory IgA.

Question 17

Why are mucus gels in the digestive tract important?

Answer 17

Digestive tract is moving all the time so it prevents the mucus from becoming permanently ruptured as it will reanneal.

Question 18

What mucin forms the gel in the small and large intestines?

Answer 18

MUC2
Highly kylocyslated in the middle and globular regions on the ends.

Question 19

What are the features of secreted mucin genes?

Answer 19

Clustered on chromosomal location 11p15.5.
Gel forming.
VNTR - Ser, Thr O-glycosylation
Upstream cysteine rich domains - D1, D2, D’-D3
Downstream cysteine rich domains - D4.
Downstream B, C, CK (cysteine knot).
Highly glycosylated in the middle to hold lots of water.

Question 20

What is N-glycosylation linked too?

Answer 20

Asparganine.
Close to the termini of the molecule.
Mannose, GlcNac, Gal, Fuc and sialic acid.

Question 20

What is O-glycosylation linked too?

Answer 20

Serine, threonine.
GalNac, GlcNac, Fun, Gal and sialic acid.

Question 21

Describe colonic mucus?

Answer 21

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.

Question 22

What is a way of measuring colonic mucus?

Answer 22

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.

Question 23

How can we measure colonic mucus thickness?

Answer 23

Probe with coloured solution goes in a touches the mucosa. Mucus thickness can be measured if the angle of the probe and sign on the probe is known by creating a right angled triangle.
600microns thick, maintained over the first 60 mins.
Sloppy mucus removed and will begin to replace itself, after 300 minutes the sloppy mucus has been completely reproduced.

Question 23

How do packed mucins form a gel mucus?

Answer 23

They expand 1000-3000 fold to take up water, forming a gel. The Ca is exchanged for sodium and the pH rises.
The reduction of Ca and the pH rise disrupts the N-terminal formed rings and increases the extension of the carb chains, pushing the mucins apart.
Cysteine knot domains act as a hinge resulting in an extended net based on hexagonal rings with the corners, N-terminal, D3 trimers and the sides of the PTS domains linked in the middle by C-terminal cysteine knots.

Question 24

Describe the colonic microflora.

Answer 24

Around 500 bacterial species.
Live in the sloppy mucus layer.
Use mucus and dietary fibre as energy source.
Binds to mucus sugars via fimbriae.

Question 25

How does mucus enhance gut homeostasis and oral tolerance?

Answer 25

Delivers immunorgulatory signals.
MUC2 imprints denrtici cells with anti-inflammatory properties.
So, pro-inflammatory cytokines IL-6, 8 and TNF alpha induced by LPS are reduced by MUC2.
IL-10 (anti-inflammatory) increased by MUC2.

Question 26

What does virulent shigella do?

Answer 26

Accumulates mucins at the cell apical surface, leading to the appearance of a gel like structure that favours bacterial access to the cell surface.