PRRs

Question 1

PRRs

Answer 1

Pattern recognition receptors

Question 2

5 families of PRRs

Answer 2

Toll like receptors (TLR: surface, endosomal)
CLRs 
NOD-like receptors (NLRs) family 
RIG-like receptors (RLRs) family)
Cytosolic DNA sensors (CDS) family

Question 3

PRRs on cell surface can

Answer 3

bind pathogen associated molecular patterns from ECM pathogens

Question 4

TLRs: location, PAMP/DAMP ligands

Answer 4

surface and endosomal membranes of DCs, phagocytes, B cells, endothelial cells

PAMP/DAMP: microbial Ags (LPS, peptidoglycans, viral nucleic acids)

Question 5

NLRs: location, PAMP/DAMP ligands

Answer 5

Cytosol of phagocytes, epithelial cells

intracellular crystals (urate and silica); changes in concentrations of ATP and ions lysosomal damage

Question 6

RLRs: location, PAMP/DAMP ligands

Answer 6

cytosol

viral RNA

Question 7

CDSs: location, PAMP/DAMP ligands

Answer 7

cytosol of many cell types

bacterial and viral DNA

Question 8

CLRs: location, PAMP/DAMP ligands

Answer 8

plasma membranes of phagoctyes

microbial carbohydrates with terminal mannose of fructose

Question 9

TLRs general

Answer 9

evolutionarily conserved PRR

form homodimers/heterodimers, recognize PAMPs and DAMPs

TLRs 1,2,4,5,6 expressed on cell surface
TLRs 3,7,8,9 expressed in endosomes

recognized CpG

receptor is TIR, Toll/IL-1 receptor homology domain

Question 10

Signaling pathways of TLRs 1,2,4,5,6

Answer 10

1,2,4,5,6 use adaptor protein MyD88

MyD88 activates transcription factor NF-kB and AP-1

Question 11

TLR 3

Answer 11

uses adaptor TRIP to activate IRF3 or IRF7 transcription factors

only TLR that doesn’t use MyD88

Question 12

TLR 4

Answer 12

can activated both pathways

Question 13

TLRs 7, 9

Answer 13

in endosome, use MyD88 and activated both NFkB and IRF7

Question 14

Function of TLRs 1,2,4,5,6

Answer 14

1, 2, 5, 6 + MyD88 —> activation of transcription factors NF-kB and AP1

Question 15

Function of TLRs 3

Answer 15

uses adaptor protein TRIF and activates the IRF3 and IRF7 transcription factors

Question 16

Function of TLRs 4

Answer 16

can activated both pathways

Question 17

Function of TLRs 7 and 9

Answer 17

in endosome, uses MyD88 to activate both NF-kB and IRF7

Question 18

Role of TLRs in Innate Immune Response

Answer 18

expressed especially on macrophages and dendritic cells

Question 19

IL-12

Answer 19

cytokine which controls the adaptive T-cell immune response

Question 20

Activation of TLRs trigger what kind of pathways

Answer 20

ones that directly kill the pathogen

Question 21

Health problems related to TLRs

Answer 21

can contribute to tissue injury by inducing apoptosis

can lead to life threatening symptoms of septic shock

Question 22

Major TLR Signaling Pathways (major themes)

Answer 22

all use MyD88 except TLR3

TLR4 and 2 also engage TIRAP

TLR3 signals through TRIF

Question 23

Match the signaling mediator with the TLR

TRIF
TIRAP
TRAM

Answer 23

TRIF = TLR3
TRAP = TLR4, TLR2
TRAM used with TRIF in TLR4-MyD88 pathway

Question 24

NF-kB and AP-1

Answer 24

nuclear factor kB and activation protein 1: stimulate expression of molecules like inflammatory cytokines (TNS and IL-1 importantly)

Question 25

IRF3 and 7

Answer 25

stimulate expression of type I interferons IFN-alpha and IFN beta

Question 26

Lipoproteins/Lipopolysaccharide/CpG DNA ---> TLR ---> _________ ----> _______ -----> _________ (4 outcomes)

Answer 26

NF-kB ---> DNA ---> a. if tissue damage, apotosis of cell or b. sepsis c. antimicrobial response d. influence adaptive immunity (cell mediated)

Question 27

LPS activates cells through

Answer 27

TLR4

Question 28

CpGs activate

Answer 28

TLR9

Question 29

Microbial lipoprotein activates

Answer 29

TLR2

Question 30

How do TLRs influence cell mediate immunity?

Answer 30

by signaling the transcription of IL-12