genetic influences Flashcards
describe glial cells in central immune system
905 CNS = microglia + astrocytes
immunocompetent cells = exogenous signal = stress, subclinical infection, drugs. endogenous signal = heat shock protein
important modulating neuronal responses
- pain singal = chronic pain w/fibromyalgia, gulf war illness
describe glial-neuronal cross-talk
glial cells have TLR4 rec
activator binds directly to neuron for response
or to TLR4 => proinflamm cytokines eg IL-1
IL-4 can also bind to neurons to inc response of signal eg pain signal
immune neuron interaction
naive glia -> primed state when come across stress, infectionm drugs
primed = inc exp TLR4 => inc proinflam cytokines release -> act on neurons
primed state + exposure to stressors = activated state = extra inc TLR4 -> inc act on neurons
genetics = naive -> active transition after priming signal only once
describe immune components of chronic pain
gen + maintenance enhances pain states
act TLR4, release inflam factors
chronic pain contributing factors
more females than males (fibromyalgia, migraine, headace), inc pain sensitive bc sex hormones
env triggers = sleep
genetic variability = single nucleotide polymorphisms (SNPs) in inflam factors
fibromyalgia chronic pain aims
investigate ass b/immune + genetic variability + pain severity
investigate ass b/patient demo + env factors + pain sev
FMS results with immune genetics
worst day = no SNPs related to pain sev
best day = 28% could be related to immune genetics
best day = TGFb, encodes for TGF-b, MYD88 encodes for MYD88 protein (accessory protein in TLR signalling)
FMS results dem/env factors
worst = 49% related (depression, ethnicity, tobacco use, daily act)
best = 20% related (pain score on worst day and stiffness)
Glia + GWI
were exposed to toxic chems
animal models = inc pain when exposed to stressor, + associated w/inc glial cell act
GWI other genetics
HLA genetics = immune recog + response = protection for GWI
BChE = breaks fown chemicals = variants cause less active enzyme + related to GWI
PON1 = enzyme breaks down nerve agents, variant = less active enzyme + related to GWI
GWI results
TGF + IL6R = lower wild-type + higher variant genotypes for GWI = linked to inc inflam conditions
TLR4 = inc wild type, lower variant genotype for GWI = variant = less inflam
important role in immune genetics for predicting GWI risk
GWI results
TGF + IL6R = lower wild-type + higher variant genotypes for GWI = linked to inc inflam conditions
TLR4 = inc wild type, lower variant genotype for GWI = variant = less inflam
important role in immune genetics for predicting GWI risk
