20. Mucosal barrier and microbiota

Question 1

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

Answer 1

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

Question 2

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

Answer 2

Mucus

Question 3

What is mucin/mucus secreted by?

Answer 3

Goblet cells–10 liters a day

Question 4

What is the composition of mucus?

Answer 4

Mucins
Water
Ions 
Proteins 
Lipids
Antibodies/antimicrobial peptides/bacteria

Question 5

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

Answer 5

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

Question 6

What are the mucus commensal interactions?

Answer 6

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

Question 7

How is mucus involved with bacterial exclusion?

Answer 7

• Thickness/viscosity physically exclude bacteria

- Bacteria and LPS incude mucus gene expression

Question 8

How does mucus act to contain secreted antibodies/antimicrobials?

Answer 8

• IgA and other antibodies bind mucus with low affinity

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

Question 9

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

Answer 9

Lectins

Question 10

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

Answer 10

Lysozyme
Peroxidases
SLPI
sPLA2

Question 11

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

Answer 11

Defensins (alpha, beta, theta)

Cathelicidins

Question 12

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

Answer 12

Lactoferrin

Lipocalin

Question 13

What makes antimicrobial peptides?

Answer 13

WBCs

Epithelial cells lining mucosal surfaces

Question 14

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

Answer 14

Defensins (alpha, beta, theta)

Question 15

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

Answer 15

Beta

Question 16

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

Answer 16

Alpha-defensins

Question 17

Paneth cell granule contents

Answer 17

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

Question 18

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

Answer 18

sIgA

Question 19

What shows a compensatory increase with IgA deficiency?

Answer 19

IgM

Question 20

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

Answer 20

IgG

Question 21

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

Answer 21

IgE

Question 22

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

Answer 22

IgD

Question 23

Serum IgA is mostly ___meric, while mucosal IgA is ___meric

Answer 23

Monomeric

Polymeric

Question 24

What does the structure of IgA consist of?

Answer 24

Alpha chain
J chain (polymeric IgA)
Secretory component

Question 25

How much IgA is secreted daily?

Answer 25

4 grams

Question 26

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

Answer 26

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

Question 27

What are the biological activities of IgA?

Answer 27

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

Question 28

What are the main ways that microbes evade IgA?

Answer 28

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

Question 29

What is the microbiome?

Answer 29

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

Question 30

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

Answer 30

1. Symbionts 2. Commensals 3. Pathobionts

Question 31

What are symbionts?

Answer 31

Mutual relationship with the host--health promoting

Question 32

What are commensals?

Answer 32

No benefit or detriment to the host

Question 33

What are pathobionts?

Answer 33

Live as commensals but have the potential to induce pathology

Question 34

What is dysbiosis?

Answer 34

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

Question 35

What are three organisms that are found in the duodenum?

Answer 35

Streptococcus Staphlococcus Lactococcus

Question 36

What are four organisms found in the jejumum

Answer 36

Streptococcus * Lactobacillus * Enterococcus * Yeast

Question 37

What are four organisms that are found in the ileum?

Answer 37

Bacteroides * Clostridium * Enterobacteriaceae Segemented filamenous bacteria

Question 38

What are organisms that are found in the colon?

Answer 38

``` Bacterioides Clostridium Proteobacteria Actinobacteria Lachnospiraceae Prevotellaceae TM7 Fusobacteria Verrucomicrobium ```

Question 39

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

Answer 39

Oxygen pH Enzymes and bile salts Mucus

Question 40

What are the immune factors that sculpt the microbiota?

Answer 40

Defensins | IgA

Question 41

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

Answer 41

Bifidobacterium longum infantis

Question 42

What component of breast milk selects for bifidobacterium longum infantus?

Answer 42

HMO (human milk oligosaccharides)

Question 43

What are the protective functions of the intestinal microbiota?

Answer 43

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

Question 44

What are the structural functions of intestinal microbiota?

Answer 44

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

Question 45

What are the metabolic functions of intestinal microbiota?

Answer 45

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

Question 46

What was the result of mice lacking a bacterial colonization?

Answer 46

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

Question 47

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

Answer 47

Fecal transplantation

Question 48

What are several ways that commensal bacteria prevent pathogen colonization?

Answer 48

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

Question 49

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

Answer 49

Butyrate | Acidic pH

Question 50

How are bacteria involved in IBD?

Answer 50

Abnormal immune response to colonizing bacteria in a genetically susceptible host

Question 51

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

Answer 51

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

Question 52

How are bacteria involved with cancer?

Answer 52

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

Question 53

How are bacteria involved with allergy?

Answer 53

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

Question 54

What kind of transition of bacterial species occurs in IBD?

Answer 54

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

Question 55

What is a probiotic?

Answer 55

Viable microbial food suppliment with benefits health of host

Question 56

What are the criteria for probiotic selection?

Answer 56

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

Question 57

What are the three ways that probiotics may treat immune disorders

Answer 57

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