Lecture 3 - Early Recognition of Foreign Invaders Flashcards
What cells recognize alarm signals?
sentinel cells
What do sentinel cells have that recognize alarm signals?
pattern recognition receptors
Alarm signals are generated by what 2 things
- invading microorganisms (PAMPs)
- dead or dying host cells (DAMPs or Alarmin)
What are exogenous signals
PAMPs
What are endogenous signals
DAMPs or Alarmins
Recognition of pathogens by sentinel cells leads to activation of …
innate immune system
What are PAMPS
conserved molecular structures or patterns that occur in a diverse range of potential microbial invaders
Examples of PAMPs
- bacterial lipopolysaccharides
- bacterial peptidoglycans
- bacterial DNA
- viral nucleic acids
What is another name for LPS
endotoxin
What bacteria have LPS
gram-negative
What bacteria have peptidoglycan
gram-positive
Why is bacterial DNA a PAMP
its unmethylated
What is the PAMP in gram-negative bacteria
LPS
What is the PAMP in gram-positive bacteria
peptidoglycan
What is the PAMP in acid fast bacteria
mycolic acid
When are intracellular DAMPS generated
released when cells die
When are extracellular DAMPs generated
connective tissue is damaged
Why might damaged mitochondria from dead host cells be recognized as bacteria?
DNA resembles bacterial DNA, which is rich in unmethylated CpG
Examples of extracellular DAMPs
-hyaluronic acid
-heparan sulfate
-fibrinogen
-collagen-derived peptides
-fibronectin
-laminin
-elastin
Examples of intracellular DAMPs
-HMGB1
-uric acid
-chromatin
-andenosine
-galectin
-S100 proteins
-cathelicinds
-defensins
-N-formyl peptides
-lactoferrin
-heat-shock proteins
What is an important intracellular DAMP
HMGB1
What is the main affect of HMGB1?
inflammation; tissue damage
What is the adverse effect of too much HMGB1
shock
What types of PRRs soluble
-collectins
-ficolins
-complement
-pentraxins
What PRRs are within vesicles
-TLR 3, 7, 8, 9
Whaat PRRs are cytoplasmic
-Rig-1
-NOD-like
-peptidoglycan receptors
-DNA receptors
What PRRs are membrane-bound
-TLRs
-Lectins
-Mannose receptor
-Langerin
-Dectins
-Scavenger receptors
-intergrins
What are the most important PPRs
TLRs
What type of receptors are TLRs
transmembrane proteins
List the 3 PRR receptors
- toll-like receptors
- retinoic acid inducible gene (RIG)-1like receptors
- nucelotide-binding oligomerization domain (NOD)-like receptors (NLRs)
What do TLRs play a critical role in sensing?
bacteria, fungi, viruses
What do TLRs located on the cell surface recognize?
extracellular invaders such as bacteria and fungi
What do TLRs located within cells recognize
intracellular invaders such as viruses
How many TLRs do mammals possess
10-12
What TLR do humans and cattle have
TLR1-TLR10
What TLR do mice have
TLR 1-13 EXCEPT TLR10
What are the cell surface TLRs
1, 2, 4, 5, 6, 11, 12
What do cell surface TLRs recognize
bacterial and fungal proteins, lipoproteins, and LPS
What do intracellular TLRs recognize
viral and bacterial nucleic acids
What are the intracellular TLRs
3, 7, 8, 9, 10, 13
TLR1 ligand
triacylated lipoprotein
TLR2 ligand
lipoproteins
TLR3 ligand
dsRNA
TLR4 ligand
LPS
TLR5 ligand
flagellin
TLR6 ligand
diacylated lipoprotein
TLR7 ligand
ssRNA, guanosine
TLR8 ligand
ssRNA
TLR9 ligand
CpG DNA, dsDNA
TLR10 ligand
regulates TLR2 responses
TLR11 ligand
profilin and flagellin
TLR12 ligand
profilin
TLR13 ligand
unmethylated RNA
TLR1 pathogens recognized
bacteria
TLR2 pathogens recognized
bacteria, viruses, parasites
TLR3 pathogens recognized
viruses
TLR4 pathogens recognized
bacteria, viruses
TLR5 pathogens recognized
bacteria
TLR6 pathogens recognized
bacteria, viruses
TLR7 pathogens recognized
viruses, bacteria
TLR8 pathogens recognized
viruses, bacteria
TLR9 pathogens recognized
viruses, bacteria, protozoa
TLR10 pathogens recognized
suppresses inflammation
TLR11 pathogens recognized
protozoa, bacteria
TLR12 pathogens recognized
protozoa
TLR13 pathogens recognized
bacteria
What receptors bind to HMGB1
RAGE
What is the signal cascade when LPS binds to a TLR
upregulate caspase 1 to act on ProTNF, ProIL-1, Pro-IL6 to turn into active form
Why is IBD common in GSDs?
single-nucleotide polymorphisms (SNPs) in TLR4/5 genes are common in GSDs, which reduces ability to defend against bacterial invasion resulting in predisposition to enteric infections
What do RIG-1-like receptors recognize
viral dsRNA
What happens after RLRs are activated
activate caspase and trigger signaling pathways, leading to production of type 1 interferons (IFN)
What do NOD1 receptors recognize
bacterial peptidoglycans
What do NOD2 receptors recognize
muramyl dipeptide and serves as a general sensor of intracellular bacteria
What does binding to NLR activates?
NF-B pathway and triggers production of proinflammatory cytokines
What does NOD2 also trigger production of
defensins
What are defensins
antimicrobial proteins