Case 2 - mucus and mucins Flashcards
what is the mucus barrier
a multifunctional interface with a critical role in innate immunity
what does the mucus layer sit on top of
the epithelial cell glycoprotein layer
where is the glycoprotein layer
on the apical layer
what are the consequences of too little mucus
gastric or duodenal ulcers
ulcerative colitis
Crohn’s disease
dry eye
xerostomia
what is xerostomia
dry mouth
what are the consequences of too much mucus
asthma
cystic fibrosis
chronic obstructive pulmonary disease
what does decreased epithelial cell protection lead to
increased mucus permeability
what does impaired mucocilliary clearance lead to
decreased mucus permeability
where is mucus found
on the outside of our insides
where does it line and what does it do
it lines the epithelal surfaces that are in contact with the environment for entry, release or exchange of materials
where in the body is mucus found
mouth
respiratory tract
gastrointestinal tract
urogenital tract
eyes and ears
what are two of the main functions of GI mucus
secretion and absorption
is the GI mucus barrier heterogenous
yes
what are the two layers of mucus
the firmly adherent mucus layer
the loosely adherent mucus layer at the bottom
what is the mucus a home for
microbiota and protection against infection
where are commensal and pathogenic microbes found
the outer loose layer
some properties of the GI tract mucus
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)
what is mucus
viscoelastic material
it has the viscous behaviour of a liquid and the elastic properties of a solid
what is the composition of mucus
mostly water and ions - 90%
Proteins (glycoproteins) - 5-10%
Mucus glycoproteins (mucins) - 1-5%
what are the key structural components of the mucus barrier
mucins
what are mucin producing cells
goblet cells
what are the two histological stains used for mucins
periodate Schiff’s (PAS)
Alcian blue (AB)
what are the 5 identified members of the family of gel-forming mucins
MUC 2, 5AC, 5B, 6 and 19
Share same genetic structure
what mucins do we normally see in the stomach
MUC5AC and MUC6
what mucins do we normally see in the rest of the intestine
MUC2
what are mucins
enormous glycoprotein polymers
what are these polymers linked by
specific bonds called disulphide bonds
what are mucins dominated by
glycans - sugars
what is the consequence of having all these sugars
very resistant to being attacked by pathologic proteases
what region is between two polymers in mucins
the repeated serine/threonine region
in these region, there is a scaffold for sugars - what are these sugars?
N-acetylgalactosamine, N-acetylglucosamine, galactose, fucose and sialic acid
what is this scaffold resistant to
breakdown by proteolytic enzymes
what are glycans important for
function
how do mucins underpin protection
space filling - hydrogel formation
Entanglement of large polymers
Cross links between them - make them very permanent
Pathogen binding/evasion
what is another mechanism of host cell defence
sugar coated cells - glycocalyx is the outside sugar of the cell
what are these sugars
binding sites for bacteria
what do the extracellular parts of the mucus act as
decoy receptors
what do the mucins do
bind to pathogens and act as decoys - bind to sugars
what is another protective factor
shedding
feature of most mucosal bacterial pathogens
they are flagellated
where do many pathogens attach
to the apical surface of the epithelial cells and inject bacteria toxins
what are the adhesion genes (colonisation) - glycan binding proteins
sabA gene - sialic acid binding adhesin
babA gene - lewis b binding adhesin
CagA pathogenicity - epithelial pathology
cagA gene - type IV secretion system, disabling of epithelial tight junctions
vacA gene - cytotoxin
what is the MUC5AC layer for
binding - found on the very outside
what is the MUC6 mucus layer for
growth inhibition - inside the MUC5AC layer
H.pylori has adhesions for what structures on cell surface and gastrin epithelial surface
for glycan structures on cell surface glycoproteins and glycolipids found on the gastric epithelial surface - BabA and SabA
what are glycans on MUC5AC shared with
cell surface MUC1
what do glycans on MUC6 do
inhibit cell wall synthesis of H pylori and prevent infection
what happened so MUC1 when H pylori binds
it is shed from the cell surface
