AM L4.2 Genetic links Flashcards
TLR - toll like receptors
TLR are a family of ….. receptors.
pattern recognition receptors
What happens when ligand binds to TLR?
recruit adaptor molecules and signal expression of immune response
How is TB linked to ATS?
TB infects the arterial cell wall leading to degenerative changes
Clinical studies link ATS with ….. infections
bacterial
What happens to TLR in macrophages on exposure to LDL
nothing
Where are TLR found?
on zee macrophages
What happens to TLR on exposure to oxoLDL?
TLR1,2 and 4 are upregulated
What activates TLR on bacteria?
LPS
Why is it hard to study activation of TLR?
Everything always seems to be contaminated with LDL
What endogeounous stuff is TLR activated by? (3)
MM-LDL
Heat-shock proteins
Fibrin extra domain
Necrosis of cells releases …….
heat shock proteins
What does MM-LDL stand for
minimally modified LDL ligand
When is MMLDL produced
activation of inflammatory genes in macrophages
MMLDL results in
endothelial secretion of IL8
heat shock proteins occur in what tissues?
Nearly all tissues
Depletion of fibronectin extracellular domain results in….
decreased progression of ATS
Which heat shock protein is show to interact with TLR4
Hsp60 from bacteria or humans
TLR form a complex at the membrane and signal….
NFKB
NFkB activation results in turning of genes for….
IL6 IL1beta IL12 VCAM MMP COX1 MCP1 & IL8
VCAM is important for
increasing WBCs
MCP1 & IL8 are involved in
recruitment of immune cells
Its thought that TLR activation results in (3)
Chemokine and cytokine
Activation of adaptive immunity
affects phenotype of smooth muscle cells/endothelial cells
Polymorphism of which (3) TLR has been linked to ATS?
2,4,9
Asp299Gly and THr299Lle are…
polymorphisms of TLR4 that result in hypersensitivity to LPS. People are LESS susceptible to ATS.
Chemokine polymorphisms associated with ATS
MCP-1
Fractalkine receptor
Cytokine polymorphism associated with ATS
IL-6 promotor regio
TNF-α receptor
IL-1 receptor and IL-1 receptor antagonist
P selectin is a …… protein, expression associated with….
Adhesion protein
ATS
E selectin is associated with….
ATS in younger patients
Adhesion proteins are found on …. cells
endothelial
Lipoprotein lipase does what….
digests chinomicrons and VLDLS into fatty acids
Lipoprotein lipase polymorhpism associated with
early onset diabetes and ATS
mutations in what enzyme result in high homocysteine
Cystathionine β-synthase
high homocysteine can be a result in environmental factors such as
lack of folate or vit B 12
