6 – Innate Immunity III Flashcards
what are PAMPs
pathogen-associated molecular pattern
-Specific molecular pattern that supports their lifestyle
PAMPs recognized by
PRRs – pattern recognition receptors
what are PRRs
-PRR are on/in host cells & soluble (in circulation) proteins
-Range of location ensure cells can recognize PAMPs of virtually any pathogen
PRRs also bind to…
DAMPs – damage-associated molecular patterns
what cells have PRRs?
-All types of myeloid white blood cells have PRRs
-also some lymphoid cells: T, B, NK cells
-some other cell types
waht other cells also express PRR?
-Those commonly exposed to infectious agent
-Epithelial cells of ski & mucosal tissues
-Endothelial cell lining the blood vessels
-Lead to antimicrobial substance production
most, if not all, cells express
Cytosolic sensors of viral nucleic acids
PRRs located at different sites depending on PAMP they recognize, what are some of those sites
Cell surface
Intracellular
Secreted soluble proteins
Once PAMP bind to PRR, it leads to
Signaling pathways are activated inside the cell – contribute to innate/inflammatory responses
groups of PRRs
TLRs – Toll-like receptors
NLRs – NOD-like receptors
RLRs – RIG-I-like-receptors
CLRs – C-type lectin receptors
Ficolins, MBL, C1q
TLRs stands for:
2 types of TLRs:
Toll-like receptors
intracellular & extracellular
Extracellular TLRs bind to
-liposacharrides/carbohydrates things on the surface of extracellular pathogens
-actual extracellular pathogens: parasites, bacteria, fungi, parts of cell wall of bacteria
Intracellular TLRs bind to
mainly nucleic acids
are TLRs membrane bound or soluble?
it is membrane bound for both intracellular & extracellular
what happens when TLR binds to PAMP?
-activates signaling pathways
-Different TLR recruit different adaptor proteins
what are adpator proteins and what do they do
-*Link protein-binding partners tgt
-Facilitate large signaling complexes
-lead to doesntream signalling
Different adaptor proteins lead to…, including
different events,
include activation of different TF
transcription factor activation (3)
-NF-KB transcription factor activation
-IRF – interferon regulating factor pathways
-MAP kinase pathway downstream transcription factor
(AP-1)
Signaling leads to…
activation of TF – transcription of innate immune/pro-inflammatory genes
Once genes are expressed, …
they have specific impacts
signaling & gene expression cascade:
- PAMP bind to PRR
- signaling cascade - involve many proteins (like adaptor proteins: MyD88, TRIF)
- lead to other proteins activated downstream
- Phosphorylation activates proteins
activation of TF - IRF, Ap-1, NF-kB in cytoplasm - once activated, TF go to nucleus to turn on expression of genes
- gene expressed codes for cytokines/chemokines/other antimicrobial peptides
General features of Signaling transduction
-Ligand binding to its receptor
-Recruit/activate kinases & adaptors
-Second messenger
To tell to get activated (by phosphorylation)
-Activate/translocation in nucleus of TF
-Change in gene expression
-Post-transcriptional/post translational modifications
-Functional responses
-secreted out of cell
CLRs stand for:
C-type Lectin receptors
C-type Lectin receptors are … PRRs, they bind to …, and activates…
-Membrane-bound PRRs
-Bind carbohydrates on pathogens & some allergens (peanut & dust mite proteins)
-Activates tyrosine kinases which trigger signaling cascades
CLR’s signaling cascade:
CLR binds to carbs on pathogen, activates tyrosine kinase that:
-activates CARD adaptor protein
-IRF5 activation (TF)
-MAPK pathways activation – activation of AP-1 & NFkB
-Induce expression of inflammatory cytokines
what are the 2 intracellular PRRs
RLR (RIG-I-like receptors ) & NLR (NOD-like receptors )
RLRs are
Functional cytosolic PRRs
RLRs recognize
viral double-stranded RNAs & certain structures single-stranded RNA
RLR associated proteins:
MAVS - mitochondrial antiviral signaling protein
Trigger signaling pathway for RLR:
- RIG-I-Like receptor binds to viral double-stranded RNA
2- tell MAVS that PAMP is here
3- PAMP activates other proteins
4- IRK, NF-kB activated
-translocation to nucleus - lead to expression of certain genes
6-translation
7-secreted proteins
NLRs – NOD-like receptors can be…
floating or membrane bound
NLRs are…, recognize…
-cytosolic PRR
-recognize peptidoglycan from bacterial cell wall (Must be in the cytosol )
what does NOD stand for
Nucleotide oligomerization domain
what does NLRs trigger
-Trigger NF-kB, AP-1 & IRF signaling
-go in nucleus, lead to gene expression
NLS activates and what does it do.
AN example of post translational modification
-Activate caspase-1 protease
-Cleaves IL-1β/IL-18 into active forms for release (pro-inflammatory cytokines)
PRR Signaling pathways
-PRR recognize PAMPs – consider type of pathogen & its location
-Signaling cascade – series of proteins activated by:
-Modifications: phosphorylation/ubiquitination
-Activation of TF
-Gene expression (DNA->mRNA->protein)
-Result in post-translation/post-transcriptional modifications
-These carry out a function
