recognition of pathogens

examples of PAMPs?

dsRNA, lipopolysaccharide, lipoteichoic acid, peptidoglycan, mannose glycans etc

examples of damage-associated molecular patterns (DAMPs)

nuclear-cystolic proteins released from cells, such as DNA, heparin sulfate and S100

damaged cells are recognised by ____ components via _______, includes molecules produced by cells under stress such as ____, ____ _____

innate

damage associated molecular patterns

heat-shock proteins

fragments of hylauronic acid

where are PAMP and DAMP receptors located?

ER, cell surface, vesicles and cytossol!

the two main families of pattern recognition receptors?

toll-like receptors

nod-like receptors

where are TLRs found?

cell surface/internal membranes of phagocytes and mast cells

are TLRs structurally conserved?

yes

TLRS contain multiple regions of ____ ____ in the extracellular region does

leucin richness

what do toll like receptors do?

identify infectious agents

what do TLRS bind to?

diverse range of ligands

• nucleic acids

• proteins

• lipids

• polysaccharides

how many mammalian TLRS are there?

13

TLRs 3,7,8 recognise?

bacterial nucleic acids

TLR-4 recognise?

lipopolysaccharide

TLR-5 recognises?

flagellin

TLR-9 recognises?

unmethylated CpG islands

what transcription factors are activated when TLRs are bound?

activation of gene encoding inflammatory mediators

• cytokines

• adhesion molecules

• enzymes

what does stimulation of dendritic cells and TLRs result in?

initiation of adaptive immunity

type I IFN production and proinflammatory cytokines are the result of the ____ pathway?

TLR

what do nod-like receptors do?

recognises DAMPs and PAMPs in the cytosol - the stress signal

what does NOD1, NOD2 and cryoprin recognise? specifically?

bacterial cell wall peptidoglycan

disaccharide components^

what does NOD-like receptors recognising activate?

prod. of inflammatory mediators

what do NLR proteins do?

oligomerise and activate downstream signalling molecules

where are NLRs found?

phagocytes and epithelial cells

why are NLRS similar to TLRs?

linked to signal transuction

NLR have how many family?

23

What are the three NLR/TLR domains?

C-terminal leucine-rich repeat domain (LRR)

central nucleotide binding + oligomerization

• NACHT NOD NBD

N-terminal effector binding domain (EBM)

• CARD, PYD, BIR

what are other cellular receptors?

RIG-like receptors - binds to viral RNA

scavenger receptors

complement receptors

dectin-1—b glucan

DEC 205 - CpG oligonucleotides

CD 14 - leucine rich repeats

how are normal cells protected from recognition?

express regulatory molecules

NOD response to bacterial cell wall peptidoglycan includes what 2 molecules?

NOD-1: iE-DAP

NOD-2: MDP

NOD 1

recognises DAP (diaminopimelic acid) derived mainly from gram -ve peptidoglycans

NOD 2

recognises MDP (muramyl dipeptide derived from BOTH gram -ve and gram +ve peptidoglycans

where is NOD 2 highly expressed in?

paneth cells

mutations to NOD 2 occur in what disease?

chrons disease, bacteria overgrowth leading to chronic inflammation

NLR signalling pathway that includes inflammasome

large protein complex that activates caspase-1 to generate IL-1

what does inflammasome contain?

NLR subfamily, non-NLR and caspase-1 (inactive)

2 signals are required for NLRP3 inflammasome activation

1st - microbial ligand also need endogenous cytokines

2nd - bacteria, viruses and pore-forming toxins AND particulates