Case 2 - mucus and mucins Flashcards

1
Q

what is the mucus barrier

A

a multifunctional interface with a critical role in innate immunity

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2
Q

what does the mucus layer sit on top of

A

the epithelial cell glycoprotein layer

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3
Q

where is the glycoprotein layer

A

on the apical layer

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4
Q

what are the consequences of too little mucus

A

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

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5
Q

what is xerostomia

A

dry mouth

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6
Q

what are the consequences of too much mucus

A

asthma
cystic fibrosis
chronic obstructive pulmonary disease

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7
Q

what does decreased epithelial cell protection lead to

A

increased mucus permeability

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8
Q

what does impaired mucocilliary clearance lead to

A

decreased mucus permeability

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9
Q

where is mucus found

A

on the outside of our insides

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10
Q

where does it line and what does it do

A

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

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11
Q

where in the body is mucus found

A

mouth
respiratory tract
gastrointestinal tract
urogenital tract
eyes and ears

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12
Q

what are two of the main functions of GI mucus

A

secretion and absorption

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13
Q

is the GI mucus barrier heterogenous

A

yes

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14
Q

what are the two layers of mucus

A

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

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15
Q

what is the mucus a home for

A

microbiota and protection against infection

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16
Q

where are commensal and pathogenic microbes found

A

the outer loose layer

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17
Q

some properties of the GI tract mucus

A

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)

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18
Q

what is mucus

A

viscoelastic material

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

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19
Q

what is the composition of mucus

A

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

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20
Q

what are the key structural components of the mucus barrier

A

mucins

21
Q

what are mucin producing cells

A

goblet cells

22
Q

what are the two histological stains used for mucins

A

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

23
Q

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

A

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

24
Q

what mucins do we normally see in the stomach

A

MUC5AC and MUC6

25
Q

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

A

MUC2

26
Q

what are mucins

A

enormous glycoprotein polymers

27
Q

what are these polymers linked by

A

specific bonds called disulphide bonds

28
Q

what are mucins dominated by

A

glycans - sugars

29
Q

what is the consequence of having all these sugars

A

very resistant to being attacked by pathologic proteases

30
Q

what region is between two polymers in mucins

A

the repeated serine/threonine region

31
Q

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

A

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

32
Q

what is this scaffold resistant to

A

breakdown by proteolytic enzymes

33
Q

what are glycans important for

A

function

34
Q

how do mucins underpin protection

A

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

35
Q

what is another mechanism of host cell defence

A

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

36
Q

what are these sugars

A

binding sites for bacteria

37
Q

what do the extracellular parts of the mucus act as

A

decoy receptors

38
Q

what do the mucins do

A

bind to pathogens and act as decoys - bind to sugars

39
Q

what is another protective factor

A

shedding

40
Q

feature of most mucosal bacterial pathogens

A

they are flagellated

41
Q

where do many pathogens attach

A

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

42
Q

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

A

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

43
Q

CagA pathogenicity - epithelial pathology

A

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

44
Q

what is the MUC5AC layer for

A

binding - found on the very outside

45
Q

what is the MUC6 mucus layer for

A

growth inhibition - inside the MUC5AC layer

46
Q

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

A

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

47
Q

what are glycans on MUC5AC shared with

A

cell surface MUC1

48
Q

what do glycans on MUC6 do

A

inhibit cell wall synthesis of H pylori and prevent infection

49
Q

what happened so MUC1 when H pylori binds

A

it is shed from the cell surface