20. Mucosal barrier and microbiota Flashcards
What are the 4 types of extrinsic defenses of the GI?
- Mechanical/involuntary: cough, gag, peristalsis
- Structural: mucus
- Chemical: acid, enzymes, antimicrobial peptides/polypeptides
- Microbiological: commensal bacteria
What is the viscoelastic gel that defines the structure of the extrinsic barrier?
Mucus
What is mucin/mucus secreted by?
Goblet cells–10 liters a day
What is the composition of mucus?
Mucins Water Ions Proteins Lipids Antibodies/antimicrobial peptides/bacteria
What are the three main roles of mucins in host defense?
- Mucus-commensal interactions
- Bacterial exclusion
- Containment of secreted antibodies and antimicrobials
What are the mucus commensal interactions?
Mucus binds commensals with adhesins
Graze on mucus
Some digest mucus to prevent clogging
How is mucus involved with bacterial exclusion?
- Thickness/viscosity physically exclude bacteria
- Bacteria and LPS incude mucus gene expression
How does mucus act to contain secreted antibodies/antimicrobials?
- IgA and other antibodies bind mucus with low affinity
- Cationic AMP (antimicrobial peptides) contrained via electrostatic interactions with the mucus
What are lung surfactant proteins that act as reg proteins in the GI?
Lectins
What are some enzymes and inhibitors that are involving in GI chemical defences?
Lysozyme
Peroxidases
SLPI
sPLA2
What are the two cationic anti-microbial peptides that directly kill bacteria by forming pores in the microbial cell walls
Defensins (alpha, beta, theta)
Cathelicidins
What are two antimicrobial peptides that are involved in iron sequestration to prevent bacteria from using the iron?
Lactoferrin
Lipocalin
What makes antimicrobial peptides?
WBCs
Epithelial cells lining mucosal surfaces
What is a group of cationic antimicrobial peptides char by invariant 6-cysteine array involved in intramolecular disulfide bonding?
Defensins (alpha, beta, theta)
What type of defensins are produced by the mucosal epithelium and can be constitutive or inducible?
Beta
What type of defensins are synthesized by PMNs and paneth cells constitutively?
Alpha-defensins
Paneth cell granule contents
alpha defensins (HD5 and HD6) CRS peptides Lysozyme sPLA2 RegIII gamma Angiogenin-4 alpha-1-antitrypsin TNF-alpha IL17a MMP7 IgA
What is the predominant immunoglobulin in mucosal secretions, can be monomeric and polymeric?
sIgA
What shows a compensatory increase with IgA deficiency?
IgM
What ig is found at the same levels as IgA, with the proportion varying by site and time of collection?
IgG
What Ig is found at low concentrations in the GI and is associated with mucosal allergic rxns
IgE
What Ig is found at a low conc in the milk and saliva?
IgD