cytokine mediated toxicity/inflammasome Flashcards
What do interferons do?
Modulate immune responses
What do interluekins do
Produced by leukocytes that are important in immunology and inflammation
Why is TGN1412 famous?
cytokine storm
What else can cause cytokine storm as main A/Es other than TGN1412?
CAR-T cell therapy
Where is TNF-alpha produced?
mainly by macrophages (kupffer cells in liver)
What is TNF-alpha’s functions?
Binds to TNF-alpha receptors and activation of receptors promotes apoptosis and inflammation
TNFR1 activation results in?
activation of caspase 8 and JNK1/2 which leads to apoptosis
can also activate NF-kB –> antioxidative factors
when NF-kB is impaired, apoptosis dominates
What does sab do?
mediate mitochondrial toxicity rhough JNK1/2
WHy/how is trovafloxacin hepatotoxic?
Only toxic when second stimuli (LPS) and results in TNF-alpha increase and apoptosis
What is NLPR?
A PRR, nucleoside-bining domain luecine rich repeat receptor
intracellular localisation
What are the 4 major compenents of the inflammasome
NLRP1, NLRC4, AIM2 and NLRP3
How is NLRP3 activated? (3)
P2X7-dependent pore formation
crystalline or particulate from lysosomal rupture
DAMPS and PAMPS and ROS
WHy is NLRP3 a useful target?
Associated with auto0-inflammatory diseases
What is the main activator (organelle) of NLRP3 (or inflammasome)
Mitochondria due to ROS production
How can paracetamol cause mitochondrial damage?
NAPQI formation and then interaction with proteins containing a thiol
