Flashcards in Host Defense: Integration & Physiology Deck (29):
What are antimicrobial peptides?
Gene-encoded, small (10-45 AAs) cationic peptides
Antimicrobial peptides are active against?
3 antimicrobial peptides
How are defensins and IBD connected?
4 defensins in the intestine
Keeps WMD under tight control
1. Endogenous pyrogen
2. Lymphocyte activating factor
Loss of control of IL-1beta secreation leads to?
1. Familial cold auto-inflammatory syndrome (FCAs)
2. Muckle-Wells syndrom
→ reccurent episodes of rash, fever and joint pain
Cartilage catabolic factor
How is IL-1beta initially synthesized?
Inactive proIL-1beta after LPS stimulation
Posttranslational processing and release of IL-1beta
Second stimulas (ex: 1 mM ATP) required for efficient processing and release
Agents that promote IL-1beta maturation and release in vitro
1. ATP (1mM) via activation of P2X7 receptor (cation channel)
2. Clostridium difficile toxin-A
3. Staphylococcal alpha-toxin
Effect of human defensins on release of proIL-1beta from LPS-activated human PBMC
Effect of defensins on ATP-mediated IL-1beta release from LPS-activated human PBMC
Defensins are ______ regulators of IL-1beta
What is IBD?
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
IBD clinical signs
1. Persistent diarrhea
2. Abdominal pain
4. Rectal bleeding (sometimes)
Environmental factors leading to IBD
Genetic factors leading to IBD
Familial and multigenic → cytokine gene (IL-23) polymporphisms, NOD2 mutation
Immunological factors leading to IBD
1. Defective immune system (abnormal recognition of ubiquitous antigens)
2. Altered cytokine production (increased procution of other soluble mediators)
NOD stands for?
Nucleotide-biding and oligomerization domain
What is NOD2?
Intracellular receptor for MDP
Conserved bacterial cell wall component
Initiating immune responses against cytoinvasive pathogens
NOD@ mutations are associated with?
Reduced mucosal defensin expression in CD
Dextrane sulfate sodium → can induce colitis
Defensin deficiency can cause?
Over-production of IL-1beta → uncontrolled intestinal inflammation → IBD
How do defensins affect activity of IL-1beta-converting enzyme (ICE) capase-1
Do not inhibit