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PBL SEM 4 > mucins and mucus > Flashcards

mucins and mucus Flashcards

1
Q

what are the 2 layers of the mucus barrier?

A
  • mucus barrier on top = gel-like, highly organised, responsive to environment, mesh like (made of mucin glycoproteins)
  • epithelial glycoprotein layer = sugar-rich, on apical cell surface
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2
Q

the mucus layer is home to what kind of microbes?

A

commensal

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3
Q

what do goblet cells make?

A

mucins

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4
Q

what pathologies can happen if there is too little mucus?

A
  • gastric/duodenal ulcers
  • ulcerative colitis
  • crohn’s disease
  • dry eye
  • xerostomia (dry mouth)
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5
Q

what pathologies can happen if there is too much mucus?

A
  • asthma
  • cystic fibrosis
  • chronic obstructive pulmonary disease (COPD)
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6
Q

what does mucus line?

A

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

eg. mouth, resp tract, GI tract, urine genital tract, eyes and ears

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7
Q

what are some challenges of the GI mucosal interface?

A
  • complex range of functions including secretion and absorption
  • a very large SA exposed to adverse biological, chemical and physical challenges
  • non-sterile and potentially exposed to microbial pathogens and eukaryotic parasites
  • provides a niche for commensal bacteria (1012 organisms/gram in the colon)
  • microbial content and diversity is determined by the environment and thus alters with changes in the mucus
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8
Q

both layers in the mucus have the same molecules but the open layer molecules have been what?

A

degraded by proteolytic enzymes to make it more open

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9
Q

where can bugs live freely?

A

the loosely adherent mucus layer

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10
Q

what is the dual function of the intestinal mucus barrier?

A

home for the mcirobiota and protection against infection

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11
Q

what happens when the inner adherent layer breaks down?

A

the commensal bacteria can become pathogenic

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12
Q

what are the properties of the GI tract mucus?

A
  • resistant barrier (physical and chemical)
  • viscous highly hydrated layer
  • prevents dehydration of mucosal surfaces, provides lumbricals on for movement of liminal 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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13
Q

what is mucus made up of and what kind of material is it?

A

viscoelastic material — has the viscous behaviour of a liquid and the elastic properties of a solid

  1. 90% : water and ions
  2. 5-10% : proteins (glycoproteins)
  3. 1-5% : mucus glycoproteins (mucins)
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14
Q

what are the key structural components of the mucus barrier?

A

mucins

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15
Q

where are mucins stored?

A

in goblet cells in storage granules — mucins can be released to produce a layer when there is a challenge

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16
Q

what is the family of gel-forming mucins?

A
  • 5 identified members - MUC
  • MUC 2, 5AC, 5B, 6 + 19
  • share same generic structure - all very similar
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17
Q

what MUC mucins are found mainly in the stomach vs rest of intestine?

A

stomach = MUC5AC + MUC6

rest of intestine = MUC2

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18
Q

what happened in rats with no Muc2?

A
  • no intestinal mucus barrier
  • infection (bacterial and parasite)
  • increased susceptibility to colitis and tumours
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19
Q

mucin size?

A

ENORMOUS

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20
Q

how does increasing the number of mucins affect the mucus?

A

more mucins = thicker mucus

21
Q

mucins are repeating units, linked end to end via what?

A

disulphide bonds

22
Q

what are the central regions of mucins covered in?

A

sugars

23
Q

mucins are repeated what?

A

serine/threonine

24
Q

what sugars are attached to the middle of mucins?

A

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

25
Q

the sugars in mucins have receptors for what?

A

pathogens

26
Q

how do mucins underpin protection?

A
  • space filling — entanglement of large polymers hydrogel formation
  • pathogen binding/evasion
27
Q

cross links vs entanglement in mucins

A
  • cross links are more permanent — thicker mucus
  • entanglement makes a thinner, dynamic, transient mucus

the gut has more cross links on top of entanglement — therefore more protective (than eg. in lungs)

28
Q

what is the glycocalyx?

A

a dense, gel-like meshwork that surrounds the cell, constituting a physical barrier for any object to enter the cell

  • on apical cell surface
  • sugar rick
  • defence
29
Q

what are proteins called when they are bound to a sugar?

A

lectins

30
Q

how can mucins act as decoys?

A
  • pathogen breaks throguh the mucus layer adn can bind to the same sugars but on the apical surface of the cell
  • it is then shed and acts as a decoy to remove potential for infection
31
Q

most mucosal bacterial pathogens are ______ - allows them to swim in mucus

A

flagellated

32
Q

many mucosal pathogens produce enzymes to degrade the ____ and thereby disassemble the mucus barrier

A

mucins

33
Q

bacteria produce soluble toxins that can do what?

A

kill epithelial cells and/or arrest intestinal cell division

34
Q

many pathogens attach to the apical surface of the epithelial cells and do what?

A

inject bacterial toxins

35
Q

many mucosal toxins do what between adjacent epithelial cells?

A

disable tight junctions

36
Q

pH, bacteria growth and antibiotics?

A

increasing the pH raises growth of bacteria, but antibitoics become more effective when bacteria is in growth phase

37
Q

what is the bacterium causing peptic ulcer disease?

A

Helicobacter pylori

38
Q

what part of the stomach does H.pylori affect?

A

infects the lower part of the stomach, antrum

39
Q

what % of the world’s population are chronically infected with H.pylori?

A

roughly 50% — majority are asymptomatic or have very mild symptoms

  • decreased to 20-30% in the western world and up to 90% in the developing world
40
Q

infected individuals with H. pylori can develop what?

A

chronic inflammation with persistent infection (gastritis)

41
Q

what are serious pathologies resulting from chronic gastritis?

A
  • gastric and duodenal ulcers
  • gastric carcinoma (5% of the world cancer burden)
42
Q

adhesin genes (colonisation) — glycan binding proteins

what are there?

A

SabA gene — sialic acid binding adhesin

BabA gene — Lewis b binding adhesin

—> adhesins specific for binding sugars — colonise

43
Q

what is the CagA gene?

A
  • CagA pathogenicity island (epithelial pathology)
  • type IV secretion system, disabling of epithelial tight junctions
44
Q

what is VacA gene?

A
  • CagA pathogenicity island (epithelial pathology)
  • cytotoxin
45
Q

MUC5AC vs MUCA6 location in the stomach

A

MUCA6 closer to cell surface

46
Q

H. pylori has adhesins for ____ on cell surface glycoproteins adn glycoplipds found on the ____ epithelial surface = ___ and ____

A
  • glycan structures
  • gastric
  • BabA and SabA
47
Q

MUC5AC vs MUC6 function

A

MUC5AC = binding
MUC6 = growth inhibition

both in mucus layer

bug binds to MUC5AC and is kept at a distance so can’t bind at epithelial surface

provide 2 layers of defence

48
Q

what is a transmembrane mucin similar to MUC5AC?

A

MUC1

49
Q

MUC1 function

A

is shed from the cell surface (acts as a decoy) when H. pylori binds

PBL SEM 4 (50 decks)

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