Case 2 - mucus and mucins

Question 1

what is the mucus barrier

Answer 1

a multifunctional interface with a critical role in innate immunity

Question 2

what does the mucus layer sit on top of

Answer 2

the epithelial cell glycoprotein layer

Question 3

where is the glycoprotein layer

Answer 3

on the apical layer

Question 4

what are the consequences of too little mucus

Answer 4

gastric or duodenal ulcers
ulcerative colitis
Crohn’s disease
dry eye
xerostomia

Question 5

what is xerostomia

Answer 5

dry mouth

Question 6

what are the consequences of too much mucus

Answer 6

asthma
cystic fibrosis
chronic obstructive pulmonary disease

Question 7

what does decreased epithelial cell protection lead to

Answer 7

increased mucus permeability

Question 8

what does impaired mucocilliary clearance lead to

Answer 8

decreased mucus permeability

Question 9

where is mucus found

Answer 9

on the outside of our insides

Question 10

where does it line and what does it do

Answer 10

it lines the epithelal surfaces that are in contact with the environment for entry, release or exchange of materials

Question 11

where in the body is mucus found

Answer 11

mouth
respiratory tract
gastrointestinal tract
urogenital tract
eyes and ears

Question 12

what are two of the main functions of GI mucus

Answer 12

secretion and absorption

Question 13

is the GI mucus barrier heterogenous

Answer 13

yes

Question 14

what are the two layers of mucus

Answer 14

the firmly adherent mucus layer
the loosely adherent mucus layer at the bottom

Question 15

what is the mucus a home for

Answer 15

microbiota and protection against infection

Question 16

where are commensal and pathogenic microbes found

Answer 16

the outer loose layer

Question 17

some properties of the GI tract mucus

Answer 17

resistant barrier (physical and chemical)
Viscous highly hydrated layer
Prevents dehydration of mucosal surfaces, provides lubrication for movement of luminal contents in the gut
Porous to large macromolecules up to very small particulate matter (not cellular microbes)
Allows absorption and secretion to continue
Self organises around particulate matter and promotes removal (mechanism is unclear)

Question 18

what is mucus

Answer 18

viscoelastic material

it has the viscous behaviour of a liquid and the elastic properties of a solid

Question 19

what is the composition of mucus

Answer 19

mostly water and ions - 90%
Proteins (glycoproteins) - 5-10%
Mucus glycoproteins (mucins) - 1-5%

Question 20

what are the key structural components of the mucus barrier

Answer 20

mucins

Question 21

what are mucin producing cells

Answer 21

goblet cells

Question 22

what are the two histological stains used for mucins

Answer 22

periodate Schiff’s (PAS)
Alcian blue (AB)

Question 23

what are the 5 identified members of the family of gel-forming mucins

Answer 23

MUC 2, 5AC, 5B, 6 and 19
Share same genetic structure

Question 24

what mucins do we normally see in the stomach

Answer 24

MUC5AC and MUC6

Question 25

what mucins do we normally see in the rest of the intestine

Answer 25

MUC2

Question 26

what are mucins

Answer 26

enormous glycoprotein polymers

Question 27

what are these polymers linked by

Answer 27

specific bonds called disulphide bonds

Question 28

what are mucins dominated by

Answer 28

glycans - sugars

Question 29

what is the consequence of having all these sugars

Answer 29

very resistant to being attacked by pathologic proteases

Question 30

what region is between two polymers in mucins

Answer 30

the repeated serine/threonine region

Question 31

in these region, there is a scaffold for sugars - what are these sugars?

Answer 31

N-acetylgalactosamine, N-acetylglucosamine, galactose, fucose and sialic acid

Question 32

what is this scaffold resistant to

Answer 32

breakdown by proteolytic enzymes

Question 33

what are glycans important for

Answer 33

function

Question 34

how do mucins underpin protection

Answer 34

space filling - hydrogel formation Entanglement of large polymers Cross links between them - make them very permanent Pathogen binding/evasion

Question 35

what is another mechanism of host cell defence

Answer 35

sugar coated cells - glycocalyx is the outside sugar of the cell

Question 36

what are these sugars

Answer 36

binding sites for bacteria

Question 37

what do the extracellular parts of the mucus act as

Answer 37

decoy receptors

Question 38

what do the mucins do

Answer 38

bind to pathogens and act as decoys - bind to sugars

Question 39

what is another protective factor

Answer 39

shedding

Question 40

feature of most mucosal bacterial pathogens

Answer 40

they are flagellated

Question 41

where do many pathogens attach

Answer 41

to the apical surface of the epithelial cells and inject bacteria toxins

Question 42

what are the adhesion genes (colonisation) - glycan binding proteins

Answer 42

sabA gene - sialic acid binding adhesin babA gene - lewis b binding adhesin

Question 43

CagA pathogenicity - epithelial pathology

Answer 43

cagA gene - type IV secretion system, disabling of epithelial tight junctions vacA gene - cytotoxin

Question 44

what is the MUC5AC layer for

Answer 44

binding - found on the very outside

Question 45

what is the MUC6 mucus layer for

Answer 45

growth inhibition - inside the MUC5AC layer

Question 46

H.pylori has adhesions for what structures on cell surface and gastrin epithelial surface

Answer 46

for glycan structures on cell surface glycoproteins and glycolipids found on the gastric epithelial surface - BabA and SabA

Question 47

what are glycans on MUC5AC shared with

Answer 47

cell surface MUC1

Question 48

what do glycans on MUC6 do

Answer 48

inhibit cell wall synthesis of H pylori and prevent infection

Question 49

what happened so MUC1 when H pylori binds

Answer 49

it is shed from the cell surface