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Flashcards in 20. Mucosal barrier and microbiota Deck (57):
1

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

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

2

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

Mucus

3

What is mucin/mucus secreted by?

Goblet cells--10 liters a day

4

What is the composition of mucus?

Mucins
Water
Ions
Proteins
Lipids
Antibodies/antimicrobial peptides/bacteria

5

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

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

6

What are the mucus commensal interactions?

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

7

How is mucus involved with bacterial exclusion?

- Thickness/viscosity physically exclude bacteria
- Bacteria and LPS incude mucus gene expression

8

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

9

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

Lectins

10

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

Lysozyme
Peroxidases
SLPI
sPLA2

11

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

12

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

Lactoferrin
Lipocalin

13

What makes antimicrobial peptides?

WBCs
Epithelial cells lining mucosal surfaces

14

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

Defensins (alpha, beta, theta)

15

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

Beta

16

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

Alpha-defensins

17

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

18

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

sIgA

19

What shows a compensatory increase with IgA deficiency?

IgM

20

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

IgG

21

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

IgE

22

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

IgD

23

Serum IgA is mostly ___meric, while mucosal IgA is ___meric

Monomeric
Polymeric

24

What does the structure of IgA consist of?

Alpha chain
J chain (polymeric IgA)
Secretory component

25

How much IgA is secreted daily?

4 grams

26

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

1. DC can sent protrusions though the epithelial layer
2. Bacteria can pass through M cells of the peyers patches

27

What are the biological activities of IgA?

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

What are the main ways that microbes evade IgA?

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

What is the microbiome?

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

30

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

1. Symbionts
2. Commensals
3. Pathobionts

31

What are symbionts?

Mutual relationship with the host--health promoting

32

What are commensals?

No benefit or detriment to the host

33

What are pathobionts?

Live as commensals but have the potential to induce pathology

34

What is dysbiosis?

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

35

What are three organisms that are found in the duodenum?

Streptococcus
Staphlococcus
Lactococcus

36

What are four organisms found in the jejumum

Streptococcus *
Lactobacillus *
Enterococcus *
Yeast

37

What are four organisms that are found in the ileum?

Bacteroides *
Clostridium *
Enterobacteriaceae
Segemented filamenous bacteria

38

What are organisms that are found in the colon?

Bacterioides
Clostridium
Proteobacteria
Actinobacteria
Lachnospiraceae
Prevotellaceae
TM7
Fusobacteria
Verrucomicrobium

39

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

Oxygen
pH
Enzymes and bile salts
Mucus

40

What are the immune factors that sculpt the microbiota?

Defensins
IgA

41

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

Bifidobacterium longum infantis

42

What component of breast milk selects for bifidobacterium longum infantus?

HMO (human milk oligosaccharides)

43

What are the protective functions of the intestinal microbiota?

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

44

What are the structural functions of intestinal microbiota?

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

45

What are the metabolic functions of intestinal microbiota?

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

What was the result of mice lacking a bacterial colonization?

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

47

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

Fecal transplantation

48

What are several ways that commensal bacteria prevent pathogen colonization?

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

49

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

Butyrate
Acidic pH

50

How are bacteria involved in IBD?

Abnormal immune response to colonizing bacteria in a genetically susceptible host

51

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

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

52

How are bacteria involved with cancer?

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

53

How are bacteria involved with allergy?

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

What kind of transition of bacterial species occurs in IBD?

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

55

What is a probiotic?

Viable microbial food suppliment with benefits health of host

56

What are the criteria for probiotic selection?

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

57

What are the three ways that probiotics may treat immune disorders

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