Autoinflammatory disease Flashcards
what is autoinflammation?
mutations in cells or molecules involved in
innate immunity at disease-prone sites
what is autoimmunity?
mutations associated with cells and molecules involved in adaptive immune responses
why are polygenic mutations harder to treat?
as they have multiple mutations to many different geners
what are some examples of polygenic mutations?
crohns disease
rheumatoid arthritis
multiple sclerosis
what is monogenic autoinflammatory diseases?
seemingly unprovoked attacks of inflammation
what occurs when you have monogenic autoinflammatory diseases?
absence of high-tier autoantibodies or antigen-specific T cells
in born errors of the innate immune system
what is CAPS?
cryopyrin associated periodic syndrome
what is the spectrum of CAPS?
Familial cold autoinflammatory syndrome(FCAS) - Rash, conjuctivitus
Muckle wall syndrome (MWS) - Urticarial rash
NOMID/CINCA - Sporadic, deafness, destructive artheritis
why are autoinflammatory diseases also named periodic fever syndrome?
as the individual will experience fluctuations as the diseased state flares up
what are NLR?
intracellular receptors
N-terminal effector domain - CARD n Prying domain
what is ASC?
CARD and pyrin domains
what happens when procaspase-1 is in contact with NLR?
cleaved into caspase-1, which cleaves pro-IL-1B and pro-IL-18 into IL-1B and IL-18
what happens when caspase-1 is formed ?
cleaves pro-IL-1b and pro-IL-18 into IL-1b and IL-18
what are inflammasomes?
innate immune system receptors/sensors that regulate activation of caspase-1 and induce inflammation
what are some examples of inflammasomes?
Four key inflammasomes, namely NLRP1, NLRP3, NLRC4, and AIM2
what happens when inflammasomes have been activated?
processing and secretion of inflammatory cytokines, including IL-1β and IL-18
what happens to people with CAPS responding to lipopolysaccharide (LPS)?
react more by producing more IL-1B to low concentrations of LPS (increasing sensitivity to LPS) and induces an immune response as the IL-1b levels are elevated
what does IL-1B act on?
what are the examples of anti-IL-1b therapies?
what are NOD sensors/receptors?
stimulate antimicrobial peptide (AMP) and Type 1 interferon production (IFNb)
what is blau syndrome?
Blau syndrome is a rare, autosomal dominant disease characterized by granulomatous skin/rash, eye and joint inflammation-arthritis.
mutated NOD2 sensor
how are misfolded proteins normally treated?
eliminated by degradation in the endoplasmic reticulum
how does unfolded protein response (UPR) react?
a homeostatic response balancing the cells folding capacity
what happens if there is an imbalance in the UPR?
leads to endoplasmic reticulum stress and causes an increase in the unfolded proteins
why is an increase in UPR a problem?
as this means there can be inhibition of translation causing cell death
and misfolded proteins accumulate extracellularly which induces an IL-1B production
how can physiological conditions alter the ERAD and protein folding?
what does ER stress induce?
what are the differences between autoinflammation and autoimmunity?
what is CAPS associated with?
elevated c-reactive protein
serum amyloid-a
what do A20 and OTULIN regulate? and how?
NF-kB and Cell death signalling
negatively
what does a decrease expression in A20 and OTULIN do?
activate NF-kB = release pro-inflame cytokines
what does an activated NF-kb do?
release pro-inflam cytokines
