Flashcards in Inflammasomes and antimicrobial immunity Deck (55):
Give examples of extracellular bacteria?
staph; strep; klebsiella
Give an example of cell surface bacteria
Give eamples of intra-vacuolar bacteria?
salmonella; legionella; mycobacterium
Give examples of cytosolic bacteria?
What type of protein are injectisomes related to?
What is the gram stain of salmonella?
Why is the injectisome useful for the innate immune system to recognise?
What type of pathogen is listeria?
gram pos cytosolic pathogen
How does listeria move wtihin the cell and spread to adjacent cells?
host actin machinery and produce listeriolyin O
What is the function of listeriolyin O?
pore forming toxin
What cells does TB live and replicate inside?
What is essential for the virulence of TB?
ESX secretion system
What cytokines protect against M.tb?
IL-12; IFNy and IL-1b
What do AIM2 receptors recognise?
Describe the PYHIN family proteins?
can activate inflammasomes; sontain can N-terminal pyrin domain but lack the LRR domain of NLRs instead have HIN domain
Name a member of the PYHIN family?
What cells does IL-18 act upon?
NK cells and T cells
What cytokine does IL-18 induce NK cells and T cells to make?
What is the result of IFN-induced cell autonomous defensce?
iNOS; NADPH oxidase; autophagy; GBP
What is an inflammasome?
a large multiprotein complex that activates caspase-1 via the adaptor protein Asc
How is pro-caspase 1 activated?
self-proteolytic cleavage into p20 and p10 active subunits
What are the inflammatory outcomes of inflammasome activation?
IL-1b and IL18 release; alarmin release; pyroptosis
What alarmins does inflammasome activation result in the release of?
IL-1a and HMGB1
What domain is responsible for recruiting Asc to the receptor?
What domain links Asc to caspase -1?
What happens when there is a gain of function in caspase-1?
autonimmune/inflammatory diseases; fever syndromes
Why does gain of function in caspase-1 result in fever syndromes?
IL-1b acts on hypothalamus to cause fever
What does inflammasome pathways require?
priming of cells- expression of receptors and substrates
How does AIM2 cause inflammasome assembly?
HIN domains oligomerise around DNA leaving PYD open for binding to Asc which then polymerises and binds caspase1
What do NAIPs recognise?
T3SS rod or needle or bacterial flagellin
What do ligand bound NAIPs bind?
happens when NLRC4 is activated by NAIP?
able to activate caspase-1 by ASc or sometimes directly by its N-terminal CARD domain
What is the inflammasome assembly described as being like?
What type of bacteria do not have T3SS?
How does listeria activate NLRP3?
produces toxin which produces pore resulting in K efflux and dissociation of NLrp3 chaperone proteins allowing its LRR domsns to join and bind Asc
What inflammasomes are activated by M.tb?
NLRP3 and AIM2
What are the features of pyroptosis?
osmotic swelling and bursting of cells; spillage of cellular contents and enhanced infalmmation
What protien is essential in pyroptosis?
What is the function of gasdermin-D?
forms pores in membranes
What cleaves gasdermin-D?
What is the functions of caspases 4 and 5?
cytosolic receptors for LPS
What is the mechanism of inflammasome activation by caspases 4 and 5?
How do caspase 4 and 5 result in inflammasome activation?
cleave gasdermin D which makes pores in membrane or by processing pannexin1 resulting K effluc and NLRP3 activation
What is the equivalent of caspases 4 and 5 in mice?
Why do cytosolic gram negative bacteria trigger pyroptosis?
result of direct activation of capse 4 by LPS
What 2 death domains does ASC consist of?
pyrin domain and CARD domain
What viral infections is AIM2 important in?
What domain on caspases 4 and 5 binds to LPS?
What domain in NLRs mediates self-oligomerisation?
By what mechanism are IL-1b and IL18 released from the cell?
unconventional secretion- independent of the ER and golgi
What are the regultors of inflammasome assembly that modulate the interactions of death fold domains?
CARD-only proteins- COPs and PYD-only proteins (POPs)
How are COPs thought to work?
sequester caspase 1 thereby negative regulating inflammasomes
What is thought to be the function of caspase-12?
interacts with caspase 1 resulting in reduced caspase 1
What is the function of POPs?
binds ASC with its pyrin domain preventing its binding to other pyrin domains