Lecture 4: Innate Immunity Flashcards

1
Q

PAMPs

A

Pathogen associated molecular patterns

No structural similarity with self Ags

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2
Q

PRRs

A

Patter recognition receptors

Cell receptors that recognize PAMPs

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3
Q

Phagocytes, PRRs and fMet

A

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

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4
Q

Endosomal TLRs respond to

A

Only to nucleic acids

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5
Q

Which TLR recognizes lipoproteins

A

2

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6
Q

Which TLR recognizes LPS

A

4

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7
Q

T or F: One pathogen is recognized by one TLR

A

False. One pathogen can be recognized by multiple TLRs

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8
Q

ssRNA viruses recognized by which TLRs

dsRNA recognized by which TLRs

A

7, 8

3

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9
Q

Unmethylated CpG-rich DNA recognized by TLR

A

9

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10
Q

Gram-positive bacteria recognized by which TLRs

A

1, 2, 6, 9

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11
Q

Gram-negative bacteria recognized by which TLRs

A

4, 5, 9

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12
Q

Fungi recognized by which TLRs

A

2, 9

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13
Q

Protists recognized by which TLRs

A

2, 4

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14
Q

TRIF dependent signaling

A

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

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15
Q

MyD88/TRIF dependent signaling

A

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

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16
Q

MyD88 dependent signaling

A

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

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17
Q

TLRs are expressed where

A

Immune cells including monocytes, neutrophils, macrophages and DCs

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18
Q

TLR dependent signaling pathways activate __ which results in

A

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

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19
Q

What controls the adaptive T-cell immune response

A

Cytokine IL-12

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20
Q

How can activation of TLRs be detrimental to host

A

Can contribute to tissue injury by inducing apoptosis

Can lead to septic shock

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21
Q

TLR4 complete complex on macrophage surface

A

TLR4, MD2, CD14 and LPS on macrophage surface

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22
Q

TLR4 first steps in function

A

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

23
Q

TLR4 second set of steps

A

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

24
Q

TLR4 third set of steps

A

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

25
Q

NLRs

A

NOD-like receptors- intracellular proteins

Play critical role in regulation of the host innate immune response

26
Q

NLRs act as ___

They control __

A

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

27
Q

NLRs respond to _____&_____ by

A

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

28
Q

Inflammasome activates

A

Caspase-1

29
Q

Caspase-1 function

A

Cleave inactive precursor forms of cytokines IL-1B and IL-18

Secreted forms of these cytokines drive inflammation

30
Q

Inflammasome activation induced by

A

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

31
Q

NLRP3 senses

A

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

32
Q

Pyroptosis

A

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

33
Q

Scavenger receptors are important for

A

Tissue remodeling after collateral damage due to inflammation and infections

34
Q

Cellular domains of SRs

A

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

35
Q

Collagen-like domain function

A

Implicated in the binding of polyanionic ligands

36
Q

What type of receptors are SRs

A

PRRs- Pattern recognition receptors

37
Q

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

A

Macrophages

Mediate recognition/phagocytosis of microorganisms via recognition of PAMPs

38
Q

What would happen to an SR knock-out mouse

A

It would have increased susceptibility to infection

39
Q

Carbohydrate (mannose) receptors

A

Member of Lectin family
Recognize microbial mannose
Trigger secretion of cytokines

40
Q

Mannose receptor on phagocytes is involved in

A

Phagocytosis of microbes

41
Q

Causes of inflammation

A

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

42
Q

DAMPs will activate

A

NF-kB

43
Q

Examples of DAMPs that activate NF-kB

A

HMGB1
Uric acid
HSPs

44
Q

Defensins are

A

Small cationic peptides with cationic and hydrophobic sequences

45
Q

Defensins produced by, synthesis is stimulated by

A

Neutrophils, NK cells and cytotoxic t cells

Stimulated by cytokines/microbes

46
Q

Defensins have direct or indirect toxicity to microbes

Method of action?

A

Direct toxicity

Insert into and disrupt function of microbial membrane

47
Q

Defensins can regulate

A

Activation of immune cells involved in inflammatory responses

48
Q

Cathelicidins- what produces it, what stimulates production

A

Produced by neutrophils

Production stimulated by microbes/cytokines

49
Q

Cathelicidens bind

A

LPS to neutralize it

50
Q

NK cells respond to ___ secreted by ___

A

IL-12 secreted by macrophages

51
Q

NK cells release ___ which

A

IFN-y which activates macrophages to kill phagocytized microbes

52
Q

NK cell activating receptors

A

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

53
Q

NK inhibitory receptors

A

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

54
Q

NK cell killing method

A

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