TLR’s
-Part of innate and adaptive immune response recognize PAMP’s.
NF-KB
-Transcription factor downstream of TLR’s turns on pro-inlammatory genes
CD-14
-TLR on macrophages that responds to LPS on gram negative bacterial cell Surfaces
Arachadonic Acid
-Cleaved by PLA2, inhibited by steroids
COX Pathway
5-Lipo Oxygenase Pathway
LTB4
-Attracts Neutrophils
Attract Neutrophils
Mast Cells
Histamine
-Vasodilation and Increased vascular permiability, released from mast cells
Complement
Classical Pathway
-Activation upon Ag binding to IgM or IgG
Alternative Pathway
-Activated upon attachment to bacterial products
MBL Pathway
-Mannose Binding lectin binds mannose on the surface of bacteria and stabalizes comlement
C3
C5
Hageman Factor (XII)
DIC
Caused by Hegeman factor in Sepsis
-Activated by endotoxin and lipid A
Kinin Cascade
-Hageman factor cleaves High Molecular Weight Kinin to Badykinin
PGE2
- Causes fever by increasing hypothalamic set point
Bradykinin
-Causes pain and increases vascular permeability and vasodilation
Redness and Warmth
-Vasodilation from Histamine, PGE2,D2,I2 and Bradykinin
Swelling
-Histamine and damage to endothelium
Pain
-Bradykinin and PGE2