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BIOL2022- Immunology, Infection & Inflammation > Innate Immunity: Toll Like Receptors > Flashcards

Innate Immunity: Toll Like Receptors Flashcards

1
Q

What is PRR?

A

Pathogen recognition receptors

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2
Q

What are PAMPs?

A

Pathogen-associated molecular patterns

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3
Q

Give an example of PRR?

A

Toll Like Receptor 4
TLR4

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4
Q

Give an example of PAMP?

A

LPS from gram-negative bacteria

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5
Q

What is DAMPs?

A

Danger-associated molecular patterns
From host cells

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6
Q

Example of DAMPs?

A

Amyloid Beta
Amyloid plaques formed in Alzheimer’s disease affect the brain.

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7
Q

Pathogen recognition receptors recognize…

A

PAMPS
Induce immune response

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8
Q

What does the recognition of PAMPS initiate?

A

Chemokines/ cytokines to recruit cells
Phagocytosis of pathogens
Lysis of pathogens by antimicrobial peptides

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9
Q

What are 3 individual immune responses of interferons and cytokines?

A
  1. Signal neighboring cells to put up barriers
  2. Signal infected cells to die
  3. Recruitment of white blood cells (neutrophil +monocytes) to stimulate long-lasting immunity
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10
Q

Describe TLR4?

A

Expressed surface of phagocyte
Inactive- not bound to ligand
Bind to ligand- brings 2 changes together which allows activation of downstream signaling cascade
Results- transcription of inflammatory mediators/TRIF pathway

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11
Q

How many pathways does the binding of TLR4 and LPS induce?

A

2
1. MyD88 dependent pathway -> Nf-kB
2. TRIF dependent pathway -> IRFs

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12
Q

Explain TLR4 intracellular signaling cascade leading to NF-Kb?

A

LPS binds to TLR4
Adaptor molecule -MyD88
NF-Kb

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13
Q

What is NK-Kb?

A

Transcription factor
Gene expression of wide range of inflammatory genes

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14
Q

What inflammatory genes are expressed by the transcription factor NF-Kb?

A

Cytokines - TNF, IL-1, IL-6
Chemokines (CCL2, CXCL8)
Endothelial adhesion molecules (E-selectin)
Costimulatory molecules (CD80, CD86) - adaptive immune response

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15
Q

What is the significance of endothelial adhesion molecules (E-selectin)?

A

Cells that line the blood vessel walls
Allow recruitment of neutrophil and monocyte to site of infection.

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16
Q

Explain TLR4 intracellular signaling cascade leading to IRFs.

A

TLR4 + LPS
TRIF
IRFs
-> expression of type I interferon (IFN a/b) genes -> secretion of type I interferon

17
Q

What are chemokines?

A

Chemical signals
Attract immune cells toward the site of infection
Change adhesion cells (line blood vessel wall)

18
Q

What are interferons important for?

A

Driving an antiviral response.

19
Q

What is the structure of TLR?

A

Extracellular circle of repeated leucine (amino acid)
Without ligand- not active
Interacts with ligand - active
Conformational change intracellular TIR domain

20
Q

What is TIR domain?

A

Intracellular domain
Transmembrane Interleukin Receptor (TIR)

21
Q

Explain the TLR4 downstream cascade in detail.

A

Binding of LPS induces conformation change in TIR
Allows binding of universal adaptor molecule MyD88
Promotes association of IRAK 1&4 Kinases
Creating docking site for TRAF6
TRAF-6-IRAK1 dimer complex dissociates
Complexes with TAK1 (+ other proteins) causing kinase activation
-> Activates NFkappaB + Map kinase pathways -> increased transcription of inflammatory genes

22
Q

How to activate NFkappa B?

A

Inactive- NFKappa B with IKappB (bound to it) (IKB)
TRAF6 - Results in activation, phosphorylation of IKB
Degraded in proteosome
Degradation of IKB -> NFKappaB free to move inside the nucleus
Binds to promoter and activates gene transcription of all inflammatory genes

22
Q

How to activate NFkappa B?

A

Inactive- NFKappa B with IKappB (bound to it) (IKB)
TRAF6 - Results in activation, phosphorylation of IKB
Degraded in proteosome
Degradation of IKB -> NFKappaB free to move inside the nucleus
Binds to promoter and activates gene transcription of all inflamatory

23
Q

TLR activation in macrophages results in…

A
  1. Oxidative burst
    -> production of oxygen radicals
    ->produced in lysosomes (phagolysosome)
    -> directly kill bacteria (phagocytosis)
  2. Inflammatory cytokine/ chemokine release
24
Q

TLR activation in dendritic cells results in…

A
  1. Inflammatory cytokines
  2. Antigen presentation on surface -> related to adaptive immune system (T cells -> memory response)
25
Q

How many types of TLR exist?

A

Up to 10

BIOL2022- Immunology, Infection & Inflammation (14 decks)

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