20. Mucosal barrier and microbiota Flashcards

1
Q

What are the 4 types of extrinsic defenses of the GI?

A
  1. Mechanical/involuntary: cough, gag, peristalsis
  2. Structural: mucus
  3. Chemical: acid, enzymes, antimicrobial peptides/polypeptides
  4. Microbiological: commensal bacteria
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2
Q

What is the viscoelastic gel that defines the structure of the extrinsic barrier?

A

Mucus

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3
Q

What is mucin/mucus secreted by?

A

Goblet cells–10 liters a day

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4
Q

What is the composition of mucus?

A
Mucins
Water
Ions 
Proteins 
Lipids
Antibodies/antimicrobial peptides/bacteria
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5
Q

What are the three main roles of mucins in host defense?

A
  1. Mucus-commensal interactions
  2. Bacterial exclusion
  3. Containment of secreted antibodies and antimicrobials
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6
Q

What are the mucus commensal interactions?

A

Mucus binds commensals with adhesins
Graze on mucus
Some digest mucus to prevent clogging

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7
Q

How is mucus involved with bacterial exclusion?

A
  • Thickness/viscosity physically exclude bacteria

- Bacteria and LPS incude mucus gene expression

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8
Q

How does mucus act to contain secreted antibodies/antimicrobials?

A
  • IgA and other antibodies bind mucus with low affinity

- Cationic AMP (antimicrobial peptides) contrained via electrostatic interactions with the mucus

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9
Q

What are lung surfactant proteins that act as reg proteins in the GI?

A

Lectins

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10
Q

What are some enzymes and inhibitors that are involving in GI chemical defences?

A

Lysozyme
Peroxidases
SLPI
sPLA2

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11
Q

What are the two cationic anti-microbial peptides that directly kill bacteria by forming pores in the microbial cell walls

A

Defensins (alpha, beta, theta)

Cathelicidins

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12
Q

What are two antimicrobial peptides that are involved in iron sequestration to prevent bacteria from using the iron?

A

Lactoferrin

Lipocalin

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13
Q

What makes antimicrobial peptides?

A

WBCs

Epithelial cells lining mucosal surfaces

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14
Q

What is a group of cationic antimicrobial peptides char by invariant 6-cysteine array involved in intramolecular disulfide bonding?

A

Defensins (alpha, beta, theta)

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15
Q

What type of defensins are produced by the mucosal epithelium and can be constitutive or inducible?

A

Beta

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16
Q

What type of defensins are synthesized by PMNs and paneth cells constitutively?

A

Alpha-defensins

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17
Q

Paneth cell granule contents

A
alpha defensins (HD5 and HD6)
CRS peptides 
Lysozyme
sPLA2
RegIII gamma
Angiogenin-4
alpha-1-antitrypsin
TNF-alpha
IL17a
MMP7
IgA
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18
Q

What is the predominant immunoglobulin in mucosal secretions, can be monomeric and polymeric?

A

sIgA

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19
Q

What shows a compensatory increase with IgA deficiency?

A

IgM

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20
Q

What ig is found at the same levels as IgA, with the proportion varying by site and time of collection?

A

IgG

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21
Q

What Ig is found at low concentrations in the GI and is associated with mucosal allergic rxns

A

IgE

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22
Q

What Ig is found at a low conc in the milk and saliva?

A

IgD

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23
Q

Serum IgA is mostly ___meric, while mucosal IgA is ___meric

A

Monomeric

Polymeric

24
Q

What does the structure of IgA consist of?

A

Alpha chain
J chain (polymeric IgA)
Secretory component

25
Q

How much IgA is secreted daily?

A

4 grams

26
Q

What are the two ways that DCs can be exposed to bacteria in the gut lumen?

A
  1. DC can sent protrusions though the epithelial layer

2. Bacteria can pass through M cells of the peyers patches

27
Q

What are the biological activities of IgA?

A
  1. Inhibition of adherence to epith: surrounds microbe, agglutinate microbe by Fc-Fc interactions
  2. Mucus trapping: associate with mucins, trap microbes in mucus blanket
  3. Virus neutralization: inhib. attachement
  4. Enzyme and toxin neutralization
  5. Inhibition of antigen penetration
28
Q

What are the main ways that microbes evade IgA?

A
  1. IgA proteases: cleave prolyl-seryl or prolyl-threonyl bonds
  2. Wide-spectrum proteases
  3. Glycosidases: damages glycosylation on IgA, disrupting conformation, charge, etc
  4. IgA binding proteins that bind IgA non-specifically (Fc) or lectin binding of O-linked carbohydrate in IgA hinge region
29
Q

What is the microbiome?

A

Totality of native microbes, their genetic info, and the mileu in which they interact

30
Q

Healthy microbiota contains a balances of the three major classes of bacteria:

A
  1. Symbionts
  2. Commensals
  3. Pathobionts
31
Q

What are symbionts?

A

Mutual relationship with the host–health promoting

32
Q

What are commensals?

A

No benefit or detriment to the host

33
Q

What are pathobionts?

A

Live as commensals but have the potential to induce pathology

34
Q

What is dysbiosis?

A

Altered microbial composition, associated with diseases like IBD, AI diseases, obesity, asthma, allergy, colorectal carcinoma

35
Q

What are three organisms that are found in the duodenum?

A

Streptococcus
Staphlococcus
Lactococcus

36
Q

What are four organisms found in the jejumum

A

Streptococcus *
Lactobacillus *
Enterococcus *
Yeast

37
Q

What are four organisms that are found in the ileum?

A

Bacteroides *
Clostridium *
Enterobacteriaceae
Segemented filamenous bacteria

38
Q

What are organisms that are found in the colon?

A
Bacterioides 
Clostridium
Proteobacteria
Actinobacteria 
Lachnospiraceae
Prevotellaceae
TM7
Fusobacteria
Verrucomicrobium
39
Q

What are the non-immune factors that sculpt the microbiota?

A

Oxygen
pH
Enzymes and bile salts
Mucus

40
Q

What are the immune factors that sculpt the microbiota?

A

Defensins

IgA

41
Q

What is the bacteria that is one of the first colonizers of a baby’s GI?

A

Bifidobacterium longum infantis

42
Q

What component of breast milk selects for bifidobacterium longum infantus?

A

HMO (human milk oligosaccharides)

43
Q

What are the protective functions of the intestinal microbiota?

A
  1. Pathogen displacement
  2. Nutrient competition
  3. Receptor competition
  4. Antimicrobial factors like bacteriocins and lactic acids
44
Q

What are the structural functions of intestinal microbiota?

A
  1. Barrier fortification
  2. Induction of IgA
  3. APical tightening of junctions
  4. Immune system development
45
Q

What are the metabolic functions of intestinal microbiota?

A
  1. Control intestinal epi cell differentation
  2. Met dietary carcinogens
  3. Synthesized vitamin K, biotin, folate
  4. Ferment non-digestible residue
  5. Ion absorption
46
Q

What was the result of mice lacking a bacterial colonization?

A

Underdevo of lymphatic tissues
Delayed B cell migration in response to bacterial antigen
Reduced antibody diversity
Reduced lymphocyte responsiveness

47
Q

What is a new tx for C diff colitis due to antibiotic clearance of normal flora?

A

Fecal transplantation

48
Q

What are several ways that commensal bacteria prevent pathogen colonization?

A
Bacteriocin production
SCFA production
Oxygen consumption
Competition for nutrients and attachement sites 
Induction of epithelial antimicrobials
Induction of mucus production/secretion
49
Q

What is an important energy product of SCFA metabolism by gut bacteria?
What is the effect of SCFA metabolism on the gut pH?

A

Butyrate

Acidic pH

50
Q

How are bacteria involved in IBD?

A

Abnormal immune response to colonizing bacteria in a genetically susceptible host

51
Q

How are bacteria involved in obesity and obesity-related disease , like diabetes and fatty liver disease?

A

Efficiency of bacterial fermentation and production of metabolic byproducts can contribute to obesity and complications

52
Q

How are bacteria involved with cancer?

A

Byproducts of bacterial metabolism can promote cell growth and act as carcinogens

53
Q

How are bacteria involved with allergy?

A
  1. Hygene hypothesis–decreased early inf leads to immune dysreg
  2. Microflora hypothesis–dysbiosis leads to immune dysreg
  3. Vanishing microbiota hypothesis–loss of co-evolved microbes can result in allergic hyper-responsiveness
54
Q

What kind of transition of bacterial species occurs in IBD?

A

From obligate anaerobic bacteria to facultative anaerobic species, predominantly proteobacteria
Associated with increased oxygen tension from inflammation

55
Q

What is a probiotic?

A

Viable microbial food suppliment with benefits health of host

56
Q

What are the criteria for probiotic selection?

A
  1. Origin
  2. Stability in GI
  3. Viability
  4. Adherence to human intestinal mucus
  5. Antimicrobial activity against pathogens
57
Q

What are the three ways that probiotics may treat immune disorders

A

Restore healthy biota
Restore barrier function
Skey T cell immune response to Th1 type