49-Barriers and Pathogen Recognition Flashcards
physical barrier of skin
multiple layers with tight junctions
mechanical barrier of skin
shedding every 28 days and perspiration
chemical barrier of skin
dry, cool, salty, acidic pH 5, lysozyme to degrade peptidoglycan, sebum
physical barrier of mucous membrane
goblet cells creating slime layer, epiglottis blocking respiratory tract
mechanical barrier of mucous membrane
cilia in lower respiratory
tears, blinking, urination, defecation, sneezing, coughing, vomiting
chemical barrier of mucous membrane
low pH in stomach and vagina, release of antibodies, lysozyme in tears and saliva
what is normal microbial flora
commensal bacteria found all over body, different species at each site of colonization
how does normal flora inhibit pathogens
compete for nutrients, compete for space, produce toxins, alter growing conditions
how do barriers fail
wounds, defective barrier, chronic disease, malnutrition, insect bite, pathogenicity
what happens when barriers fail
innate immune response starts quickly
what does it mean that the innate is constitutive
does not change over your life
what does it mean that the innate is conserved
responds to conserved features of pathogens like cell wall, peptidoglycan
what are the goals of the innate response?
detect and kill pathogen, sound alarm to bring in more cells, activate the adaptive response
what are pattern recognition receptors
recognize infection in coming by recognizing pathogens
what are the types of pattern recognition receptors
Toll like (TLR) Nod like (NLR) RIG-I
what do TLR recognize
PAMPs-conserved features of pathogens essential for viability
DAMPs- human derived signals which start inflammation
what are Pathogen Associated Molecular Patterns
PAMPs, conserved features of pathogens essential for viability
What are Danger Associated Molecular Patterns
DAMPs, human derived signals, drive non infectious inflammation and start inflammation caused by infection
Where are TLRs found
cell surface and intracellularly (phagolysosome or endosome)
what do cell surface TLRs recognize
bacterial and fungal cell wall
what do intracellular TLRs recognize
nucleic acid
what happens with inappropriate TLR activation
chronic inflammation and human disease
what activates TLR
dimerization with leucine ligands
intracellular region has Toll/IL-1 (TIR) domain
what drives intracellular signaling of TLR
dimerization if TIR domain
all TLR except TLR3 interact with MyD88 drive activation of NF-kB for inflammation
what do TLR4 and TLR3 bind to
TRIF to activate NF-kB and IRF3 to produce type 1 interferons for antiviral
where are NLR found
cytoplasm of multicellular eukaryotes
what facilitates oligomerization of NLR
NACHT domain
what facilitates ligand sensing and regulate NLR
leucine rich repeats
what drives intracellular signaling of NLR
N terminal domain
what activates NLR
many things: bacterial, viral, fungal, ion efflux, ATP, human protiens
Explain how NLRs drive expression of inflammatory cytokine
1-oligomerization of NLR using NLR ligand
2- recruitment of intracellular signaling molecules to activate NF-kB and MAP
3-NF-kB and MAP induce inflammation and chemokines
altered activation of NLR leads to what
autoimmune disease
1- Loss of function-prevent NF-kB activation, Crohn’s disease
2-gain of function- constitutive NF-kB activation, autoinflammatory
what induces inflammasome
NLRP1, 3, 4, 6
how do NLRs induce inflammasome
1-priming induces production of pro IL-1B and pro IL-18
2-presence of ROS, PAMP, DAMP, ion efflux result in the formation of inflammasome
3-inflammasome (caspase 1) cleaves to IL-1B and IL-18
what activates NLRP3
potassium efflux, ROS, phagolysosomal release
polymorphisms in inflammasome lead to what
autoimmunity, gain of function and chronic inflammation
what has anakinra been approved for
RA as a IL-1 receptor antagonist
how do pathogens influence inflammasome
inhibit it to enhance pathogenesis
what are the RIG-I family members
RIG-I, MDA5, and LGP2
what does the helicase domain/DExD/H do in RIG-I family
bind viral RNA ligand
what does the regulatory domain in RIG-I family do
control receptor funciton
what does the CARD domain do in the RIG-I family
intracellular signaling in RIG-I and MDA5
regulates RIG-I and MDA5 in LGP2
RIG-I binds to what
short viral RNA on terminal 5’ triphosphate
MDA5 binds to what
large RNA molecules internally and results in oligomerization
what activates the CARD domains
binding of viral RNA to RIG-I or MDA5
activated RIG-I and MDA do what
bind to adaptor protein IPS-1 (found on mitochondria)
activation of IPS-1 does what
NF-kB and IRF3 activation to produce interferons and antiviral
how do viruses suppress function of RIG-I and what does it lead to
inhibit RIG-I signaling
chronic viral infections
