6 – Innate Immunity III

Question 1

what are PAMPs

Answer 1

pathogen-associated molecular pattern
-Specific molecular pattern that supports their lifestyle

Question 2

PAMPs recognized by

Answer 2

PRRs – pattern recognition receptors

Question 3

what are PRRs

Answer 3

-PRR are on/in host cells & soluble (in circulation) proteins
-Range of location ensure cells can recognize PAMPs of virtually any pathogen

Question 4

PRRs also bind to…

Answer 4

DAMPs – damage-associated molecular patterns

Question 5

what cells have PRRs?

Answer 5

-All types of myeloid white blood cells have PRRs
-also some lymphoid cells: T, B, NK cells
-some other cell types

Question 6

waht other cells also express PRR?

Answer 6

-Those commonly exposed to infectious agent
-Epithelial cells of ski & mucosal tissues
-Endothelial cell lining the blood vessels
-Lead to antimicrobial substance production

Question 7

most, if not all, cells express

Answer 7

Cytosolic sensors of viral nucleic acids

Question 8

PRRs located at different sites depending on PAMP they recognize, what are some of those sites

Answer 8

Cell surface
Intracellular
Secreted soluble proteins

Question 9

Once PAMP bind to PRR, it leads to

Answer 9

Signaling pathways are activated inside the cell – contribute to innate/inflammatory responses

Question 10

groups of PRRs

Answer 10

TLRs – Toll-like receptors
NLRs – NOD-like receptors
RLRs – RIG-I-like-receptors
CLRs – C-type lectin receptors
Ficolins, MBL, C1q

Question 11

TLRs stands for:
2 types of TLRs:

Answer 11

Toll-like receptors
intracellular & extracellular

Question 12

Extracellular TLRs bind to

Answer 12

-liposacharrides/carbohydrates things on the surface of extracellular pathogens
-actual extracellular pathogens: parasites, bacteria, fungi, parts of cell wall of bacteria

Question 13

Intracellular TLRs bind to

Answer 13

mainly nucleic acids

Question 14

are TLRs membrane bound or soluble?

Answer 14

it is membrane bound for both intracellular & extracellular

Question 15

what happens when TLR binds to PAMP?

Answer 15

-activates signaling pathways
-Different TLR recruit different adaptor proteins

Question 16

what are adpator proteins and what do they do

Answer 16

-*Link protein-binding partners tgt
-Facilitate large signaling complexes
-lead to doesntream signalling

Question 17

Different adaptor proteins lead to…, including

Answer 17

different events,
include activation of different TF

Question 18

transcription factor activation (3)

Answer 18

-NF-KB transcription factor activation
-IRF – interferon regulating factor pathways
-MAP kinase pathway downstream transcription factor
(AP-1)

Question 19

Signaling leads to…

Answer 19

activation of TF – transcription of innate immune/pro-inflammatory genes

Question 20

Once genes are expressed, …

Answer 20

they have specific impacts

Question 21

signaling & gene expression cascade:

Answer 21

1. PAMP bind to PRR
2. signaling cascade - involve many proteins (like adaptor proteins: MyD88, TRIF)
3. lead to other proteins activated downstream
4. Phosphorylation activates proteins
   activation of TF - IRF, Ap-1, NF-kB in cytoplasm
5. once activated, TF go to nucleus to turn on expression of genes
6. gene expressed codes for cytokines/chemokines/other antimicrobial peptides

Question 22

General features of Signaling transduction

Answer 22

-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

Question 24

CLRs stand for:

Answer 24

C-type Lectin receptors

Question 25

C-type Lectin receptors are ... PRRs, they bind to ..., and activates...

Answer 25

-Membrane-bound PRRs -Bind carbohydrates on pathogens & some allergens (peanut & dust mite proteins) -Activates tyrosine kinases which trigger signaling cascades

Question 26

CLR's signaling cascade:

Answer 26

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

Question 27

what are the 2 intracellular PRRs

Answer 27

RLR (RIG-I-like receptors ) & NLR (NOD-like receptors )

Question 28

RLRs are

Answer 28

Functional cytosolic PRRs

Question 29

RLRs recognize

Answer 29

viral double-stranded RNAs & certain structures single-stranded RNA

Question 30

RLR associated proteins:

Answer 30

MAVS - mitochondrial antiviral signaling protein

Question 31

Trigger signaling pathway for RLR:

Answer 31

1. 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 5. lead to expression of certain genes 6-translation 7-secreted proteins

Question 32

NLRs – NOD-like receptors can be...

Answer 32

floating or membrane bound

Question 33

NLRs are..., recognize...

Answer 33

-cytosolic PRR -recognize peptidoglycan from bacterial cell wall (Must be in the cytosol )

Question 34

what does NOD stand for

Answer 34

Nucleotide oligomerization domain

Question 35

what does NLRs trigger

Answer 35

-Trigger NF-kB, AP-1 & IRF signaling -go in nucleus, lead to gene expression

Question 36

NLS activates and what does it do. AN example of post translational modification

Answer 36

-Activate caspase-1 protease -Cleaves IL-1β/IL-18 into active forms for release (pro-inflammatory cytokines)

Question 37

PRR Signaling pathways

Answer 37

-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