Innate Immunity 3 Flashcards
what are the 3 locations of PRRs?
- ON host cells
- IN host cells (cytosolic)
- host soluble proteins
what is the purpose of having multiple PRR locations?
so cells can recognize PAMPs of any pathogen, even if intracellular
what types of cells have PRRs?
all types of myeloid WBC
what are 4 examples of myeloid WBC?
- neutrophils
- macrophages
- basophils
- mast cells
what types of lymphoid cells are confirmed to have PRRs?
NK cells
what types of lymphoid cells are not confirmed to have PRRs? why?
T cells, B cells
some ppl say PRRs help enhance T and B cell function but not confirmed
what type of non myeloid/lymphoid cells have PRRs? and 3 examples
cells commonly exposed to infectious agents
- epithelial cells on the skin
- mucosal tissue
- endothelial cells
what do non myeloid/lymphoid cells produce upon activation of PRRs?
antimicrobial substances
where are sensors of viral nucleic acids located?
in cytoplasm of MOST cells in body (not all are PRRs)
what determines the location of PRRs?
the PAMP they recognize
what are 5 types of PRRs?
- Toll-like receptors
- NOD-like receptors
- RIGI-like receptors
- C-type lectin receptors
- Ficolins, MBL (lectin)
what happens in general when PAMP binds PRR?
signaling pathways are activated and contribute to innate/inflammatory response
where are TLRs located?
intracellularly and extracellularly
what are 5 things can intracellular TLRs recognize?
- bacteria
- parasites
- fungi
- lipoproteins
- flagellin
what do TLRs recruit?
adaptor proteins
what is the general role of adaptor proteins?
to link protein-binding partners and facilitate large signaling complexes
what are 3 specific events caused by adaptor proteins?
- NF-kB transcription factor activation
- interferon regulating factor (IRF) pathways
- MAP kinase downstream transcription factors (AP-1)
what does TLR signaling lead to? (3 sequential steps)
- activation of transcription factors
- transcription of innate immune/pro-inflammatory genes
- gene expression leads to specific impacts
what often causes the activation of transcription factors?
phosphorylation
what do transcription factors do once they become activated?
move from cytoplasm to nucleus to activate genes
what are 2 key adaptor proteins
- MyD88
- TRIF
what are 3 key transcription factors?
- IRF3/7
- NF-kB
- AP-1
what are the 8 general steps of signal transduction of TLRs?
- PAMP binds PRR and causes receptor dimerization
- recruitment + activations of kinases and adaptors
- second messenger
- activation and nuclear translocation of transcription factors
- transcription factors bind specific gene to cause changes in gene expression
- post transcriptional/translational modifications
- functional response
- effect outside of the cell
where do transcription factors bind?
the promoter region
where are C-type Lectin Receptors (CLRs) found?
membrane ONLY
what 2 things do CLRs bind?
- carbohydrates on pathogens
- some allergens
what are 2 examples of allergens that CLRs bind?
peanut and dust mite proteins
why are allergens bound by CLRs?
allergens get mistaken for PAMPa
what happens immediately after pathogen/allergen binds to CLR?
activation of tyrosine kinases
what are the 5 steps of the cascade induced by activated tyrosine kinases? CLR
- CARD adaptor protein recruited
- IRF5 transcription factor activated
- MAPK pathways activated
- AP-1 and NF-kB transcription factors activated
- induced expression of inflammatory cytokines
where are RLRs location?
cytosol
what do RLRs recognize?
viral dsRNA
where are RLRs located inside the cell?
at mitochondria
what protein anchors RLRs to mt membrane?
Mitochondrial AntiViral Signaling protein (MAVs)
what do RLRs trigger?
trigger phosphorylation to activate transcription factors IRFs and NF-kB
What does NOD stand for?
Nucleotide Oligomerization Domain (NOD)
where are NOD-like receptors (NLRs) located?
cytosol
what do NLRs recognize?
recognize peptidoglycan from bacterial cell wall
when are NLRs activated?
when bacteria are engulfed in the phagolysosome
what transcription factors do NLRs trigger?
NF-kB, AP-1, IRF signaling
what enzyme do NLRs activate?
caspase-1 protease
what does caspase-1 protease do?
cleaves IL-1beta/IL-18 into active forms for release for pro-inflammatory cytokines
what type of modification does caspase-1 protease induce?
post translational modification
what is another type of modification besides phosphorylation?
ubiquitination
what is ubiquitination?
attachment of ubiquitin subunits to a target protein which can mediate formation for further signaling
what does ubiquitination result in? (4)
- activation of transcription factors for gene expression
- post-translational modification
- cytokines, signaling molecules
- tag protein for degradation