Host Defense: Integration & Physiology

Question 1

What are antimicrobial peptides?

Answer 1

Gene-encoded, small (10-45 AAs) cationic peptides

Question 2

Antimicrobial peptides are active against?

Answer 2

1. Bacteria
2. Fungi
3. Viruses

Question 3

3 antimicrobial peptides

Answer 3

1. Defensins
2. Cathelicidins
3. Hepcidins

Question 4

How are defensins and IBD connected?

Answer 4

IL-1beta

Question 5

4 defensins in the intestine

Answer 5

1. HNP-1
2. HD-5
3. Crp-3
4. Crp-4

Question 6

IL-1 system

Answer 6

Keeps WMD under tight control

Question 7

IL-1

Answer 7

1. Endogenous pyrogen
2. Lymphocyte activating factor
3. Catabolin

Question 8

Loss of control of IL-1beta secreation leads to?

Answer 8

Systemic inflammation:

1. Familial cold auto-inflammatory syndrome (FCAs)
2. Muckle-Wells syndrom

→ reccurent episodes of rash, fever and joint pain

Question 9

Catabolin

Answer 9

Cartilage catabolic factor

Question 10

How is IL-1beta initially synthesized?

Answer 10

Inactive proIL-1beta after LPS stimulation

Question 11

Posttranslational processing and release of IL-1beta

Answer 11

Second stimulas (ex: 1 mM ATP) required for efficient processing and release

Question 12

Agents that promote IL-1beta maturation and release in vitro

Answer 12

1. ATP (1mM) via activation of P2X7 receptor (cation channel)
2. Clostridium difficile toxin-A
3. Staphylococcal alpha-toxin

Question 13

Effect of human defensins on release of proIL-1beta from LPS-activated human PBMC

Answer 13

Inhibit

Question 14

Effect of defensins on ATP-mediated IL-1beta release from LPS-activated human PBMC

Answer 14

Block

Question 15

Defensins are ______ regulators of IL-1beta

Answer 15

Negative regulators

Question 16

What is IBD?

Answer 16

1. Chronic disorder causing inflammation of digestive tract
2. Includes Crohn’s disease and ulcerative colitis
3. Can occur at any age → 1 mil Americans have IBD

Question 17

IBD clinical signs

Answer 17

1. Persistent diarrhea
2. Abdominal pain
3. Fever
4. Rectal bleeding (sometimes)

Question 18

Environmental factors leading to IBD

Answer 18

1. Diet
2. Stress
3. Pathogens
4. Smoking

Question 19

Genetic factors leading to IBD

Answer 19

Familial and multigenic → cytokine gene (IL-23) polymporphisms, NOD2 mutation

Question 20

Immunological factors leading to IBD

Answer 20

1. Defective immune system (abnormal recognition of ubiquitous antigens)
2. Altered cytokine production (increased procution of other soluble mediators)

Question 21

NOD stands for?

Answer 21

Nucleotide-biding and oligomerization domain

Question 22

What is NOD2?

Answer 22

Intracellular receptor for MDP

Question 23

DMP

Answer 23

Muramyl dipeptide

Conserved bacterial cell wall component

Question 24

NOD2 role

Answer 24

Initiating immune responses against cytoinvasive pathogens

Question 25

NOD@ mutations are associated with?

Answer 25

Reduced mucosal defensin expression in CD

Question 26

DSS

Answer 26

Dextrane sulfate sodium → can induce colitis

Question 27

Defensin deficiency can cause?

Answer 27

Over-production of IL-1beta → uncontrolled intestinal inflammation → IBD

Question 28

How do defensins affect activity of IL-1beta-converting enzyme (ICE) capase-1

Answer 28

Do not inhibit

Question 29

How do defensins affect release of TNF-alpha from LPS-activated monocytes?

Answer 29

Do not inhibit