Integration

Question 1

How are defensins and inflammatory bowel disease connected?

Answer 1

Loss of control of IL-1B leads to systemic inflammation

Question 2

What is Catabolin?

Answer 2

Cartilage catabolic factor

Question 3

What is another disease associated with lymphocyte activating factor (IL-1B)?

Answer 3

Familial Cold Autoinflammatory Syndrome

Question 4

What is the IL-1B precursor molecule?

Answer 4

ProIL-B1 synthesized after LPS stimulation

ATP cleaves to IL-1B

Question 5

Name examples that stimulate IL-1B release

Answer 5

ATP
Clostridium difficile toxin
Staphylococcal a-toxin

Question 6

Will defensins trigger the release of IL-B1?

Answer 6

No, defensins inhibit the release of proIL-B1 and the cleavage to IL-B1

Question 7

Name 2 human defensins

Answer 7

HNP-1

HD-5

Question 8

Name 2 Paneth cell types

Answer 8

Crp-3

Crp-4

Question 9

Do defensin knockout mice (MMP7 -/-) produce more or less colonic IL-1B?

Answer 9

More

Question 10

How is NOD2 and Chron’s disease associated?

Answer 10

NOD2 mutations are associated with reduced mucosal defensin expression and increased processing of IL-1B

Question 11

Does NOD2 mutation increase or decrease bowel inflammation?

Answer 11

Increase because no defensins to inhibit IL-1B

Question 12

Are defensin-deficient mice more or less susceptible to changes due to DSS-induced colitis?

Answer 12

More, because there are no defensins to inhibit IL-1B

Question 13

Do MMP mice produce more or less IL-1B than WT after exposure to 2% DSS?

Answer 13

more

Question 14

Describe the flow chart between defensin-deficiency and IBD

Answer 14

Defensin-deficiency -> lower antimicrobial capacity & increased IL-1B production -> Loss of intestinal immune homeostasis -+DSS-> Over-production of IL-1B -> uncontrolled intestinal inflammation

Question 15

How do defensins block IL-1B?

Answer 15

Defensins block the release of proIL-1B and mature IL-1B but not the activity of capase-1 activating enzyme

Precursors and mature can’t escape cell

Question 16

Do defensins inhibit the release of TNF-alpha from LPS-activated human monocytes?

Answer 16

No

Question 17

What are the 4 possible pathways from IL-1B to get out of the cell?

Answer 17

Microvesicle shedding pathway (Capase & precursor)

Direct transport (IL-1B or precursor)

Secretory lysosome (Capase, IL-1B, precursor)

Multivesicular exocytosis
(Capase, IL-1B, precursor)

Question 18

Where do defensins bind to in human monocytes?

Answer 18

Plasma membrane