Innate Immunity 2

Question 1

Adaptive immunity vs. innate immunity immune sensors

Answer 1

AI: immunite senses epitopes via the generation of a vast array of receptors via somatic rearrangements (T and B cell R)
II: senses danger through a set of fixed receptors called pattern recognition receptors (PRR)

Question 2

Receptors of innate cells

Answer 2

• encoded in germline

- nonclonal: identical receptors on all cells of same lineage

Question 3

Pattern Recognition Receptors (PRRs) categories and subcategories

Answer 3

1. Membrane bound: Toll like receptors (TLRs) and C-type lectin receptors (CLRs)
2. Cytosolic: Nod-like receptors (NLRs) and RIG-I like receptors (RLRs)

Question 4

3 places PRRs can be found and why may this be important?

Answer 4

• plasma membrane bound, bound to membranes of internal vesicles, or cytosolic
• some of this localization determines what ligands they see (internal R won’t see bacteria, but will see viruses)

Question 5

What are the PRR ligands called and give some examples.

Answer 5

1. Pathogen Associated Molecular Patterns (PAMPs): chemical motifs associated with non-mammalian pathogens that are highly conserved
   - LPS, flagellin, ssRNA, Hypomethylated CpG DNA
2. Danger Associated Molecular Patterns (DAMPs): endogenous mammalian ligands of PRRs
   - uric acid, HMGB1 (product of necrosis)

Question 6

PAMPs vs. DAMPs

Answer 6

• P: danger associated with pathogen/exogenous organism

- D: self-dangerous items

Question 7

Why have DAMPs if it doesn’t lead to pathogens?

Answer 7

• it actually might; innate immunity can use them to detect potential tissue damage that a pathogen creates, even if it doesn’t leave a trail of PAMP itself
• also useful for detecting mechanical injury

Question 8

Where are TLRs found?

Answer 8

• PM and internal endosome membrane

- limits what they will see: for example, can see foreign, bad DNA in endosome and not host in cytosol

Question 9

Final effect of TLRs

Answer 9

-leads to production of a number of cytokines that further influence the immune response

Question 10

What is an inflammasome?

Answer 10

-multi-molecular complex of NLRs and downstream effector proteases that upon activation lead to production of the inflammatory cytokine IL-1B

Question 11

Ligands of NLRs

Answer 11

-unclear, but likely PAMPs and DAMPs

Question 12

What is the effector cytokine made by inflammasome activation and leads to fever and other inflammatory responses?

Answer 12

-IL-1b

Question 13

Net goal of inflammasome

Answer 13

-produce active caspase-1 which mediates IL-1b release

Question 14

What does activated caspase-1 do in the context of innate immunity?

Answer 14

-cleaves pro-IL1b into active IL1b which is then secreted

Question 15

Yeast and crosstalk

Answer 15

• yeast contains PAMPs for both TLR2 and Dectin-1 (a CLR)

- activation of both of these receptors together produces a synergistic, optimal anti yeast response

Question 16

Crosstalk and specificity

Answer 16

• way to get specificity out of receptors that are not that specific (unlike B and T cells)
• innate immune system gets specificity by combining input from different receptors