Innate immunity receptors

Question 1

what is a PRR? What does it detect? What expresses it?

Answer 1

pattern recognition receptor expressed on both innate and adaptive immune cells. It recognizes PAMPS and DAMPS

Question 2

What is a DAMP? Example?

Answer 2

danger associated molecular pattern –> these are self (host) molecules that are found in places they are not supposed to be (through apoptosis)

in contrast PAMPS are from foreign agents

Question 3

t or f, a foreign macro molecule is a PAMP

Answer 3

false, the macro molecule may contain PAMPS but is not a PAMP itself.

Question 4

what occurs when a PAMP / DAMP binds with a PRR?

Answer 4

when a pattern recognition receptor binds a PAMP / DAMP the immune system activates. Often cytokines are the first things to be released which act as instant messengers.

Question 5

what are the main pro-inflammatory cytokines?

Answer 5

IL-6
TNF-alpha
IL-1

alpha dominates therefore pro - inflammatory
+ other small numbers

Question 6

what are the main anti-inflammatory cytokines?

Answer 6

IL-10
TGF-beta

beta is weak, therefore anti-inflammatory + big number

Question 7

t or f, toll like receptors are examples of pattern recognition receptors (PRR’s)

Answer 7

true

Question 8

where are TLR’s located and what do they bind?

Answer 8

TLR’s can be found on the surface of cells or inside cells.

they bind both PAMPS and DAMPS

Question 9

Explain the structure of TLR receptors.

Answer 9

they look like a hook. They have tail imbedded into a membrane and poking out on the other side.

the hook structure sticks out and is made of leucine - rich repeats which is important for ligand interaction

Question 10

explain endosomal TLR’s verses PM TLR’s.

Answer 10

an endosomal TLR will be embedded into a endosome within the cell. The hook structure then sticks into the endosome.

a PM TLR will have its hook leucine structure stick away from the cell into the ECF

Question 11

What does TLR 4 recognize?

Answer 11

TLR 4 recognizes LPS of gram negative bacteria

Question 12

What is the signal pathway of TLR 4?

Answer 12

LPS binds with a co-factor called CD-14. This complex interacts with TLR 4 which induces a conformational change. this causes

MyD88 —> NF-kB –> alters transcription of cytokine production. typically pro-inflammatory

Question 13

after TLR 4 binds LPS, what changes occur within the cell? (2/3)

Answer 13

• NF-kB is produced which causes increased production of cytokines.
• cytokines recruit other cells and modulate inflammation
• proteins expressed on the cell surface also alter –> e.g. more MHC may be expressed for Ag presentation to T cells.

Question 14

true or false, dendritic cells have TLR’s.

Answer 14

true. e.g. a dendritic cell will use TLR 4 to recognize LPS of a gram negative bacteria. Phagocytosis will occur and the dendritic cell will express the antigen on MHC receptors (which TLR 4 induced). The dendritic cell will take this to lymph nodes and present it to T cells.

Question 15

what does TLR 7 recognize?

Answer 15

single stranded RNA

Question 16

where does TLR 7 detect ssRNA? explain how this occurs if ssRNA comes from a virus?

Answer 16

most viruses that enter a cell are engulfed into endosome’s. Now in an endosome, the ssRNA can be presented to endosomal TLR’s (in this case TLR 7).

TLR 7 wont detect nuclear or cystolic RNA.

Question 17

What is the signal pathway for TLR 7 once it has bound endosomal ssRNA?

Answer 17

The tail of TLR 7 will be in the cystol. After binding occurs

MyD88 –> series of conversions –> activation of type one interferon genes (IFN)

Question 18

true or false, TLR’s are always monomeric.

Answer 18

false, they can form hetero and homo dimers.

Question 19

what are the two common type one IFN’s? what can they do?

Answer 19

alpha and beta IFN

they can block virus replication and also act as messengers to other cells to prepare for an infection.

Question 20

what are NOD -like receptors (NLR’s) ? what do they bind and where are they found?

Answer 20

NOD = nucleotide-binding oligomerization domain

NLR’s are found freely in the cytoplasm. They bind bacterial ligands, often break down products of peptidoglycan.

Question 21

what is a NLR’s signal pathway?

Answer 21

bacterial ligand binds NLR which causes NF-kB production. This goes and induces cytokine gene activation.

Question 22

What are RIG-I-like helicase receptors (RLH)?

Answer 22

RIG-I = retinoic acid inducible gene one

they are free floating cytoplasm receptors that recognize viral RNA

Question 23

RLH, TLR, and NLR receptors are all PRR’s correct?

Answer 23

yes, all pattern recognition receptors

Question 24

why don’t RLH receptors bind our own RNA in the cytoplasm?

Answer 24

because our RNA is Capped with the 5’ cap and poly A tail. Viral RNA is not and this is detected by RLH.

Question 25

what does the binding of viral RNA to RLH cause in the cell?

Answer 25

the activation of type one IFN genes.

Question 26

true or false, TLR 7 is found in the plasma membrane and TLR 4 is found in the endosome.

Answer 26

false, TLR 4 is found in the PM where it detects LPS

TLR 7 is found in endosome’s where it detects ssRNA

Question 27

true or false, TRL 4 requires additional proteins to bind LPS.

Answer 27

true, it needs LPS binding protein and CD-14

note: TLR 7 doesn’t use additional proteins, it interacts with ssRNA directly