chemical barriers
paneth cells
alpha-defensins Reg-3
skin
psoriasin lysosyme
TLR'S signal
MyD88 or TRIF
to NF-KB
to IL-1, IL-6, TNF, IFN
outside TLRs
2/6
2/1
5
4 + MD2
inside TLRs
3
7
9
TLR 2/6
DIACYL LIPOPEPTIDES
TLR-2/1
TRIACYL LIPOPEPTIDES
TLR-5
FLAGELLIN
TLR-4/MD-2
LPS
TLR-3
dsRNA
TLR-7
ssRNA
TLR-9
CpGRNA
interaction of TLRs with LPS
LPS binding protein (LBP)
binds CD14 on phagocyte
interaction with MD-2/TLR4
NF-KB
Extravasion
rolling activation arrest/adhesion
diapedesis
rollling
selectins and mucins
activation
chemokines
arrest/adhesion
integrins/ICAM
How does inflammation wall off infection
vasodilation adhesion extravasion
clotting
Induced innate immunity (inflammation) pathway
tissue damage cytokine release
diapedesis phagocytosis chemotaxis
protein responsible for assembly of NADPH oxidase in phagocytes
Rac2
Rac2 activated by
fMet-Leu-Phe
complex that associates with internalized bacteria
phox, fusion with granules in neutrophil
TIR
Toll-IL-1 Receptor
PAMP
Pathogen Associated Molecular Patterns
TLR (3, 7, 9)
detect PAMP as dsRNA
TRIF
IRF3, IRF7
IFN
cytokines
RIG-1, MDA-5
detect PAMP as dsRNA
IRF3, IRF7
IFN
cytokines
TLR (2/6, 2/1, 5, 4)
MyD88
NF-KB
cytokines
NOD2
RICK
NF-KB
cytokines
NLRP3
cytosolic inflammasome
detects cell damage by K+
caspase cleavage and IL-1, IL-18
Rac2
protein responsible for assembly of NADPH oxidase in phagocytes
Reg3
Antimicrobial enzyme in crypt from Paneth cells
Rag
clips gene sequence, responsible for recombination of V(D)J
Ku70:Ku80
binds hairpins
Artemis
opens hairpins
TdT
adds nucleotides, responsible for diversity of coding joints
IL-1, IL-18
associated with NLRP3, inflammasomes, and caspase cleavage
PYCARD
associates with NLRP3, cleaves caspase 1
caspase 1
releases IL-1, IL-18 when cell damage occurs
DAMP
Damage-Associated Molecular Pattern