Chapter 4 Flashcards
What is the major signal transduction pathway that TLR engage to activate cells?
NF-kB
Receptors of innate immune system are encoded by () genes whereas receptors of adaptive immunity are generated by () genes.
Germline gene
Somatic gene
Name the structures recognised by innate immune system.
1) molecules produced by microbial pathogens
2) endogenous molecules produced by damaged cells
1) PAMP (pathogen-associated molecular patterns)
2) DAMP (damage-associated molecular patterns)
List the entities under PAMP & DAMP.
PAMP (nucleic acids, proteins, cell wall lipids, carbohydrates)
DAMP (stress-induced proteins, crystals, proteolytically cleaved ECM, mitochondria, nuclear proteins)
List the entities under cell-associated & soluble pattern recognition receptors.
Cell-associated PRP
- membrane (TLR, CLR, scavenger receptors, N-Formyl met-leu-phe receptors)
- cytosolic (NLR, RLR, CDS)
Soluble PRP
- pentraxins, collectins, ficolins, complement
What is the signalling structure for TLR?
This structure is also found in () & ().
Toll/IL-1 receptor (TIR) domain in cytoplasmic tails
*TIR is also found in IL-1 & IL-8.
TLR also recognises endogenous molecules whose expression or location indicate cell damage. What are these molecules?
HSP (heat shock proteins)
HMGB1 (for transcription & DNA repair)
() & () bind to lipid A of LPS, forming a complex that interacts with TLR4 & initiates signalling.
MD2 (myeloid differentiation protein 2)
CD14 (for efficient LPS-induced signalling)
Which protein in ER is required for endosomal localisation & proper function of TLR3, 7, 8 & 9?
Genetic deficiency of this protein leads to susceptibility of which infection?
UNC-93B
Herpes simplex encephalitis
All TLRs signal through MyD88 except ().
The above TLR signals through ().
TLR3
TRIF
Which TLR signals through MyD88 & TRIF?
TLR4
These TLR are most highly expressed in plasmacytoid DC, signal through MyD88-dependent, TRIF-independent pathway that activates NF-kB & IRF.
Endosomal TLR7 & TLR8
Name 3 major transcription factors activated by TLR.
Nuclear factor kB (NF-kB)
Activation protein (AP-1)
Interferon response factor (IRF3 & IRF7)
Name the surface TLR(s) that recognise
1) bacterial polypeptide
2) bacterial peptidoglycan
3) lipopolysaccharide
4) bacterial flagellin
1) TLR1:TLR2 & TLR2:TLR6
2) TLR2
3) TLR4
4) TLR5
Name the endosomal TLR(s) that recognise
1) dsRNA
2) ssRNA
3) CpG DNA
1) TLR3
2) TLR7 & TLR8
3) TLR9
Name 4 cytosolic receptors for PAMP & DAMP.
NOD-like receptors (NLR)
Cytosolic DNA sensors (CDS) & STING pathway
RIG-like receptors (RLR)
Inflammasomes
Name 3 NLR subfamilies & their respective effector domain that serve innate immunity.
NLRB uses BIR
NLRC uses CARD (NOD1 & NOD2)
NLRP uses Pyrin
Defect in Pyrin domain of NLRP causes which disease?
And what’s the gene involved?
Familial Mediterranean fever in MEFV gene mutation
NOD2 is produced by () which recognises () to stimulate expression of (). Gain-of-function mutation of NOD2 causes increased NOD signalling & NF-kB activation leading to ().
Paneth cells
MDP (muramyl dipeptide)
Defensins
Blau syndrome
NOD1 recognises () derived mainly from gram-negative bacterial peptidoglycan.
DAP (diaminopimelic acid)
Function of NLRB.
Detect flagellin to control Legionella pneumophila infection.
Function of NLRP.
Caspase 1 activation
CDS detects () in cytosol & induces () pathway which is ()-induced activation of () responses.
microbial dsDNA
STING (stimulator of IFN genes)
dsDNA
Type 1 IFN
Name 2 CDS that work through STING independent pathway.
RNA polymerase 3 activates RIG-1 pathway.
AIM2 forms inflammasome, generates IL-1b.
() is the cytosolic sensor of viral RNA (dsRNA & RNA-DNA) that respond by inducing production of antiviral type 1 interferons.
RIG-like receptors (RLR)
Give 2 examples of RLR.
RIG-1 (retinoid-inducible gene 1)
MDA5 (melanoma differentiation-associated gene 5)
RLR are recruited to outer mitochondrial membranes by () which activates (), () & () to induce type 1 interferon production.
MAVS (mitochondrial antiviral-signalling) protein
IRF3, IRF7 & NF-kB
Functions of inflammasomes.
To generate active form of IL-1b & IL-18 (caspase-1)
Inflammasome activation causes () characterised by apoptosis of macrophage & DC but not neutrophils & others.
Pyroptosis
() recognise microbial surface carbohydrates to facilitate microbe phagocytosis & chemokine secretion.
C-type lectin receptors