Lecture 14 - APCs I Flashcards
Where are DCs normally found?
Residents of the tissues:
• Gut
• Lung
• Skin
Describe the function of DCs
- Constantly phagocytosing; sampling the environment
- Migrate to the lymph nodes when they take up foreign antigen
- Present the antigen to naïve T cells
What are Langerhans cells?
DCs of the skin and mucosa
What are the different types of DC?
cDC: conventional DC
iDC: inflammatory DC
pDC: plasmacytoid DC
Outline the features of cDCs
(Conventional DCs) Two types: 1. Peripheral tissue resident cDCs • Found in all peripheral organs • Not all peripheral organs have the same DCs
- Lymphoid tissue resident cDCs
• Located in LNs and the spleen
• Able to prime T cells
Outline the features of iDCs
- Function
- Location
- Derivation
(Inflammatory DCs)
Function:
• Present antigen to effector T cells (not naïve)
Location:
• Non-existent in steady state
Derivation:
• Differentiate from monocytes under inflammatory conditions
Outline the features of pDCs
- Function
- Location
(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
What are type I and type II IFN?
Type I:
• IFN-α
• IFN-β
(all except IFN-γ)
Type II:
• IFN-γ
Which DCs are seen in the blood?
pDCs
Which DCs are seen in peripheral organs?
Peripheral tissue-resident cDCs
pDCs
Which DCs are seen in the skin?
Langerhans cells
Which DCs are seen in lymphoid organs?
Lymphoid tissue-resident cDCs
Describe the features of the immature DC state
(Not yet activated) • High phagocytic activity • Weaved into keratinocyte network with E-cadherin • Poor antigen presentation • No CCR7 expression
Describe maturation of DCs
– 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
What are the PRRs on DCs?
Describe the location of each
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
What is triggered in DCs by facultative intracellular bacteria?
Extracellular: surface: TLR5 (flagellin)
Intracellular: TLR3 (dsRNA) and TLR11 (profillin & flagellin) in the endosome
What is the ligand for TLR9?
DNA (bacterial and viral)
What is the ligand for RIG-1?
dsRNA
What is the ligand for NLRC4?
Flagellin
What are CD103+ cells?
IELs
Compare function of cDCs and pDCs
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
What type of APC are Langerhans cells?
Peripheral tissue resident cDCs
Which type of DCs is primarily involved in the action of naïve T cells?
cDCs
Which type of DCs are ‘sentinels for viral infection’?
pDCs
How do DCs enter lymphoid organs once activated?
Through afferent lymphatics
as opposed to naïve T cells, which enter through HEVs
What is the result of DC PRR engagement?
- Production of pro-inflammatory cytokines
Through activation of intracellular signal transduction cascade
- Maturation of the DC to phenotype that is better able to present antigen to naïve T cells
How do DCs sense extracellular bacteria?
TLR4 - LPS
TLR5 - Flagellin
How do DCs sense cytosolic bacteria?
Inflammasome associated NLRC4 - Flagellin
How do DCs sense extracellular and engulfed viruses?
TLR3 and TLR9 recognise DNA / RNA
How do DCs sense cytosolic virus?
RIG-I and MDA5 recognise dsRNA / DNA
Which PRR is associated with inflammasomes?
What does it sense?
NLRC4
Flagellin
Leads to the production of IL-1β, IL-18 and IL-33
From which tissue are DCs derived?
Bone marrow
Describe the various outcomes of PRR signalling
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