Lecture 4: Innate Immunity

Question 1

PAMPs

Answer 1

Pathogen associated molecular patterns

No structural similarity with self Ags

Question 2

PRRs

Answer 2

Patter recognition receptors

Cell receptors that recognize PAMPs

Question 3

Phagocytes, PRRs and fMet

Answer 3

Phagocytes have PRRs to distinguish self from non-self
These can help phagocytes bind proteins starting with fMet, and use them to control motility and initiate phagocytosis.
fMet is present in prokaryotes but not eukaryotes

Question 4

Endosomal TLRs respond to

Answer 4

Only to nucleic acids

Question 5

Which TLR recognizes lipoproteins

Answer 5

2

Question 6

Which TLR recognizes LPS

Answer 6

4

Question 7

T or F: One pathogen is recognized by one TLR

Answer 7

False. One pathogen can be recognized by multiple TLRs

Question 8

ssRNA viruses recognized by which TLRs

dsRNA recognized by which TLRs

Answer 8

7, 8

3

Question 9

Unmethylated CpG-rich DNA recognized by TLR

Answer 9

9

Question 10

Gram-positive bacteria recognized by which TLRs

Answer 10

1, 2, 6, 9

Question 11

Gram-negative bacteria recognized by which TLRs

Answer 11

4, 5, 9

Question 12

Fungi recognized by which TLRs

Answer 12

2, 9

Question 13

Protists recognized by which TLRs

Answer 13

2, 4

Question 14

TRIF dependent signaling

Answer 14

TLR3 uses only the adaptor protein TRIF to activate NF-kB and IRF transcription proteins

Question 15

MyD88/TRIF dependent signaling

Answer 15

TLR4 uses both MyD88 and TRIF to activate NF-kB and IRF transcription proteins

Question 16

MyD88 dependent signaling

Answer 16

TLRs 1, 2, 5, 6, 7, 8 and 9 use only the adaptor protein MyD88 to activate transcription factors NF-kB and IRF

Question 17

TLRs are expressed where

Answer 17

Immune cells including monocytes, neutrophils, macrophages and DCs

Question 18

TLR dependent signaling pathways activate __ which results in

Answer 18

NF-kB and IRF which results in transcription of pro-inflammatory genes

Question 19

What controls the adaptive T-cell immune response

Answer 19

Cytokine IL-12

Question 20

How can activation of TLRs be detrimental to host

Answer 20

Can contribute to tissue injury by inducing apoptosis

Can lead to septic shock

Question 21

TLR4 complete complex on macrophage surface

Answer 21

TLR4, MD2, CD14 and LPS on macrophage surface

Question 22

TLR4 first steps in function

Answer 22

MyD88 binds TLR4 and activates IRAK4 to phosphorylate TRAF6, which leads to phosphorylation and activation of IKK

Question 23

TLR4 second set of steps

Answer 23

IKK phosphorylates IkB, leading to its degradation and the release of NF-kB, which enters the nucleus

Question 24

TLR4 third set of steps

Answer 24

NF-kB activates transcription of genes for inflammatory cytokines, synthesized in cytoplasm and secreted via ER

Question 25

NLRs

Answer 25

NOD-like receptors- intracellular proteins | Play critical role in regulation of the host innate immune response

Question 26

NLRs act as ___ | They control __

Answer 26

Scaffolding proteins that trigger NF-kB and MAPK signaling pathways They control the activation of inflammatory caspases

Question 27

NLRs respond to _____&_____ by

Answer 27

PAMPs and DAMPs, by binding other proteins and forming an inflammasome

Question 28

Inflammasome activates

Answer 28

Caspase-1

Question 29

Caspase-1 function

Answer 29

Cleave inactive precursor forms of cytokines IL-1B and IL-18 | Secreted forms of these cytokines drive inflammation

Question 30

Inflammasome activation induced by

Answer 30

Variety of cytoplasmic stimuli associated with infections and cell stress -Microbrial products, crystals, reduction in cytosolic K+ concentrations

Question 31

NLRP3 senses

Answer 31

Many DAMPs and PAMPs including uric acid crystals, aluminum hydroxide and ATP

Question 32

Pyroptosis

Answer 32

Form of programmed cell death induced by inflammasome. Macrophages and DCs (but not neutrophils and other cell types) are affected.

Question 33

Scavenger receptors are important for

Answer 33

Tissue remodeling after collateral damage due to inflammation and infections

Question 34

Cellular domains of SRs

Answer 34

SRCR (Absent in SR-AII) Collagen-like domain alpha-helical coiled-coil domain (absent in MARCO)

Question 35

Collagen-like domain function

Answer 35

Implicated in the binding of polyanionic ligands

Question 36

What type of receptors are SRs

Answer 36

PRRs- Pattern recognition receptors

Question 37

SR-AI, SR-AII and MARCO are all expressed on ___ and mediate

Answer 37

Macrophages | Mediate recognition/phagocytosis of microorganisms via recognition of PAMPs

Question 38

What would happen to an SR knock-out mouse

Answer 38

It would have increased susceptibility to infection

Question 39

Carbohydrate (mannose) receptors

Answer 39

Member of Lectin family Recognize microbial mannose Trigger secretion of cytokines

Question 40

Mannose receptor on phagocytes is involved in

Answer 40

Phagocytosis of microbes

Question 41

Causes of inflammation

Answer 41

Increased blood supply to area Increased capillary permeability Influx of neutrophils, monocytes, macrophages Distortion of homeostasis and loss of function

Question 42

DAMPs will activate

Answer 42

NF-kB

Question 43

Examples of DAMPs that activate NF-kB

Answer 43

HMGB1 Uric acid HSPs

Question 44

Defensins are

Answer 44

Small cationic peptides with cationic and hydrophobic sequences

Question 45

Defensins produced by, synthesis is stimulated by

Answer 45

Neutrophils, NK cells and cytotoxic t cells | Stimulated by cytokines/microbes

Question 46

Defensins have direct or indirect toxicity to microbes | Method of action?

Answer 46

Direct toxicity | Insert into and disrupt function of microbial membrane

Question 47

Defensins can regulate

Answer 47

Activation of immune cells involved in inflammatory responses

Question 48

Cathelicidins- what produces it, what stimulates production

Answer 48

Produced by neutrophils | Production stimulated by microbes/cytokines

Question 49

Cathelicidens bind

Answer 49

LPS to neutralize it

Question 50

NK cells respond to ___ secreted by ___

Answer 50

IL-12 secreted by macrophages

Question 51

NK cells release ___ which

Answer 51

IFN-y which activates macrophages to kill phagocytized microbes

Question 52

NK cell activating receptors

Answer 52

KIRs- activate PTKs (protein tyrosine kinases), trigger killing of cell

Question 53

NK inhibitory receptors

Answer 53

Recognize class I MHC molecules on normal cells, therefore inhibiting the killing of that cell

Question 54

NK cell killing method

Answer 54

Releases perforins, which perforate enemy cell membrane Granzymes enter cell and degrade enzymes, triggering apoptosis Macrophage engulfs and digests cell