Innate Immunity 3

Question 1

what are the 3 locations of PRRs?

Answer 1

1. ON host cells
2. IN host cells (cytosolic)
3. host soluble proteins

Question 2

what is the purpose of having multiple PRR locations?

Answer 2

so cells can recognize PAMPs of any pathogen, even if intracellular

Question 3

what types of cells have PRRs?

Answer 3

all types of myeloid WBC

Question 4

what are 4 examples of myeloid WBC?

Answer 4

1. neutrophils
2. macrophages
3. basophils
4. mast cells

Question 5

what types of lymphoid cells are confirmed to have PRRs?

Answer 5

NK cells

Question 6

what types of lymphoid cells are not confirmed to have PRRs? why?

Answer 6

T cells, B cells

some ppl say PRRs help enhance T and B cell function but not confirmed

Question 7

what type of non myeloid/lymphoid cells have PRRs? and 3 examples

Answer 7

cells commonly exposed to infectious agents

1. epithelial cells on the skin
2. mucosal tissue
3. endothelial cells

Question 8

what do non myeloid/lymphoid cells produce upon activation of PRRs?

Answer 8

antimicrobial substances

Question 9

where are sensors of viral nucleic acids located?

Answer 9

in cytoplasm of MOST cells in body (not all are PRRs)

Question 10

what determines the location of PRRs?

Answer 10

the PAMP they recognize

Question 11

what are 5 types of PRRs?

Answer 11

1. Toll-like receptors
2. NOD-like receptors
3. RIGI-like receptors
4. C-type lectin receptors
5. Ficolins, MBL (lectin)

Question 12

what happens in general when PAMP binds PRR?

Answer 12

signaling pathways are activated and contribute to innate/inflammatory response

Question 13

where are TLRs located?

Answer 13

intracellularly and extracellularly

Question 14

what are 5 things can intracellular TLRs recognize?

Answer 14

1. bacteria
2. parasites
3. fungi
4. lipoproteins
5. flagellin

Question 15

what do TLRs recruit?

Answer 15

adaptor proteins

Question 16

what is the general role of adaptor proteins?

Answer 16

to link protein-binding partners and facilitate large signaling complexes

Question 17

what are 3 specific events caused by adaptor proteins?

Answer 17

1. NF-kB transcription factor activation
2. interferon regulating factor (IRF) pathways
3. MAP kinase downstream transcription factors (AP-1)

Question 18

what does TLR signaling lead to? (3 sequential steps)

Answer 18

1. activation of transcription factors
2. transcription of innate immune/pro-inflammatory genes
3. gene expression leads to specific impacts

Question 19

what often causes the activation of transcription factors?

Answer 19

phosphorylation

Question 20

what do transcription factors do once they become activated?

Answer 20

move from cytoplasm to nucleus to activate genes

Question 21

what are 2 key adaptor proteins

Answer 21

1. MyD88
2. TRIF

Question 22

what are 3 key transcription factors?

Answer 22

1. IRF3/7
2. NF-kB
3. AP-1

Question 23

what are the 8 general steps of signal transduction of TLRs?

Answer 23

1. PAMP binds PRR and causes receptor dimerization
2. recruitment + activations of kinases and adaptors
3. second messenger
4. activation and nuclear translocation of transcription factors
5. transcription factors bind specific gene to cause changes in gene expression
6. post transcriptional/translational modifications
7. functional response
8. effect outside of the cell

Question 24

where do transcription factors bind?

Answer 24

the promoter region

Question 25

where are C-type Lectin Receptors (CLRs) found?

Answer 25

membrane ONLY

Question 26

what 2 things do CLRs bind?

Answer 26

1. carbohydrates on pathogens 2. some allergens

Question 27

what are 2 examples of allergens that CLRs bind?

Answer 27

peanut and dust mite proteins

Question 28

why are allergens bound by CLRs?

Answer 28

allergens get mistaken for PAMPa

Question 29

what happens immediately after pathogen/allergen binds to CLR?

Answer 29

activation of tyrosine kinases

Question 30

what are the 5 steps of the cascade induced by activated tyrosine kinases? CLR

Answer 30

1. CARD adaptor protein recruited 2. IRF5 transcription factor activated 3. MAPK pathways activated 4. AP-1 and NF-kB transcription factors activated 5. induced expression of inflammatory cytokines

Question 31

where are RLRs location?

Answer 31

cytosol

Question 32

what do RLRs recognize?

Answer 32

viral dsRNA

Question 33

where are RLRs located inside the cell?

Answer 33

at mitochondria

Question 34

what protein anchors RLRs to mt membrane?

Answer 34

Mitochondrial AntiViral Signaling protein (MAVs)

Question 35

what do RLRs trigger?

Answer 35

trigger phosphorylation to activate transcription factors IRFs and NF-kB

Question 36

What does NOD stand for?

Answer 36

Nucleotide Oligomerization Domain (NOD)

Question 37

where are NOD-like receptors (NLRs) located?

Answer 37

cytosol

Question 38

what do NLRs recognize?

Answer 38

recognize peptidoglycan from bacterial cell wall

Question 39

when are NLRs activated?

Answer 39

when bacteria are engulfed in the phagolysosome

Question 40

what transcription factors do NLRs trigger?

Answer 40

NF-kB, AP-1, IRF signaling

Question 41

what enzyme do NLRs activate?

Answer 41

caspase-1 protease

Question 42

what does caspase-1 protease do?

Answer 42

cleaves IL-1beta/IL-18 into active forms for release for pro-inflammatory cytokines

Question 43

what type of modification does caspase-1 protease induce?

Answer 43

post translational modification

Question 44

what is another type of modification besides phosphorylation?

Answer 44

ubiquitination

Question 45

what is ubiquitination?

Answer 45

attachment of ubiquitin subunits to a target protein which can mediate formation for further signaling

Question 46

what does ubiquitination result in? (4)

Answer 46

1. activation of transcription factors for gene expression 2. post-translational modification 3. cytokines, signaling molecules 4. tag protein for degradation