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MIIM30002 - Principles of Immunology > Lecture 14 - APCs I > Flashcards

Lecture 14 - APCs I Flashcards

1
Q

Where are DCs normally found?

A

Residents of the tissues:
• Gut
• Lung
• Skin

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2
Q

Describe the function of DCs

A
  • Constantly phagocytosing; sampling the environment
  • Migrate to the lymph nodes when they take up foreign antigen
  • Present the antigen to naïve T cells
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3
Q

What are Langerhans cells?

A

DCs of the skin and mucosa

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4
Q

What are the different types of DC?

A

cDC: conventional DC
iDC: inflammatory DC
pDC: plasmacytoid DC

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5
Q

Outline the features of cDCs

A 
(Conventional DCs)
Two types:
1. Peripheral tissue resident cDCs
 • Found in all peripheral organs
 • Not all peripheral organs have the same DCs
  1. Lymphoid tissue resident cDCs
    • Located in LNs and the spleen
    • Able to prime T cells
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6
Q

Outline the features of iDCs

  • Function
  • Location
  • Derivation
A

(Inflammatory DCs)

Function:
• Present antigen to effector T cells (not naïve)

Location:
• Non-existent in steady state

Derivation:
• Differentiate from monocytes under inflammatory conditions

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7
Q

Outline the features of pDCs

  • Function
  • Location
A

(Plasmacytoid DCs)

Considered part of innate immunity
“Sentinels for viral immunity”

Function
• Detection of viruses through PRRs
• Very potent producers of type I IFN, thus inducing the anti-viral state
• Controversial role in T cell stimulation

Location:
• Blood and tissue

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8
Q

What are type I and type II IFN?

A

Type I:
• IFN-α
• IFN-β
(all except IFN-γ)

Type II:
• IFN-γ

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9
Q

Which DCs are seen in the blood?

A

pDCs

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10
Q

Which DCs are seen in peripheral organs?

A

Peripheral tissue-resident cDCs

pDCs

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11
Q

Which DCs are seen in the skin?

A

Langerhans cells

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12
Q

Which DCs are seen in lymphoid organs?

A

Lymphoid tissue-resident cDCs

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13
Q

Describe the features of the immature DC state

A 
(Not yet activated)
 • High phagocytic activity
 • Weaved into keratinocyte network with E-cadherin
 • Poor antigen presentation
 • No CCR7 expression
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14
Q

Describe maturation of DCs

A

– Immature state –
• Much sampling of environment
• Interwoven in keratinocyte matrix

– Activation –
• PAMP-PRR signalling

-- Maturation --
 • Increased CCR7 expression
 • Increased co-stimulatory molecule expression (CD80, CD86, CD40)
 • Decreased E-cadherin expression
 • Decreased phagocytosis
 • Increased antigen presentation on MHC
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15
Q

What are the PRRs on DCs?

Describe the location of each

A

Toll like receptors (TLRs)
• Always membrane bound
• Cell surface or endosome

RIG-I-like receptors (RLRs)
• Cytosol

NOD-like receptors (NLRs)
• Associated with inflammasomes in the cytosol

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16
Q

What is triggered in DCs by facultative intracellular bacteria?

A

Extracellular: surface: TLR5 (flagellin)

Intracellular: TLR3 (dsRNA) and TLR11 (profillin & flagellin) in the endosome

17
Q

What is the ligand for TLR9?

A

DNA (bacterial and viral)

18
Q

What is the ligand for RIG-1?

A

dsRNA

19
Q

What is the ligand for NLRC4?

A

Flagellin

20
Q

What are CD103+ cells?

A

IELs

21
Q

Compare function of cDCs and pDCs

A

cDCs:
• Sample environment, take up protein, process it, migrate to LNs and present it to T cells

pDCs:
 • Part of innate immunity
 • Sentinels for viral infection 
 • Type I interferon production
 • Not thought to process and present antigen for T cell activation
22
Q

What type of APC are Langerhans cells?

A

Peripheral tissue resident cDCs

23
Q

Which type of DCs is primarily involved in the action of naïve T cells?

A

cDCs

24
Q

Which type of DCs are ‘sentinels for viral infection’?

A

pDCs

25
Q

How do DCs enter lymphoid organs once activated?

A

Through afferent lymphatics

as opposed to naïve T cells, which enter through HEVs

26
Q

What is the result of DC PRR engagement?

A
  1. Production of pro-inflammatory cytokines

Through activation of intracellular signal transduction cascade

  1. Maturation of the DC to phenotype that is better able to present antigen to naïve T cells
27
Q

How do DCs sense extracellular bacteria?

A

TLR4 - LPS

TLR5 - Flagellin

28
Q

How do DCs sense cytosolic bacteria?

A

Inflammasome associated NLRC4 - Flagellin

29
Q

How do DCs sense extracellular and engulfed viruses?

A

TLR3 and TLR9 recognise DNA / RNA

30
Q

How do DCs sense cytosolic virus?

A

RIG-I and MDA5 recognise dsRNA / DNA

31
Q

Which PRR is associated with inflammasomes?

What does it sense?

A

NLRC4

Flagellin

Leads to the production of IL-1β, IL-18 and IL-33

32
Q

From which tissue are DCs derived?

A

Bone marrow

33
Q

Describe the various outcomes of PRR signalling

A 
IL-6 transcription
 • TLR4
 • TLR5
 • TLR11
 • RIG-1
 • MDA5
Type I IFN transcription
 • TLR3
 • RIG-I
 • MDA-5
 • TLR9

IL-12
• TLR9

IL-1β, IL-18, IL-33
• NLRC4

MIIM30002 - Principles of Immunology (30 decks)

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