Lecture 15 - Antigen-Presenting Cells II Flashcards
Prototypical mediators of DC activation and maturation
TLRs
Do activated DCs move actively or passively to lymph nodes?
Actively
DCs in the epithelium of the skin
Langerhans cells
How do Langerhans cells sit in the skin?
Intimately associated with keratinocytes, to keep skin integrity (associate with E-cadherin).
How do activated Langerhans cells reach lymph nodes?
Express CCR7
CCR7 detects chemokines CCL19, CCL21.
Which part of lymph nodes do activated DCs move to?
Paracortex
How do naive T cells enter lymph nodes?
Via blood, through the walls of high endothelial venules
How do DCs enter lymph nodes?
Via lymphatics
Where are tumour antigens presented?
MHCI
NFkB dimer stimulated by TLR binding
p50, p65
How do DCs detect intracellular bacteria?
Inflammosomes
How do DCs detect facultative intracellular bacteria?
Surface via TLR5
Endosome via TLR3, TLR11
How do DCs detect viruses?
Extracellular or engulfed - TLR3, TLR9 in phagosome
Intracellular - Inflammasome, MDA5, RIG1
Basic overview of DCs
1)
2)
3)
1) Mostly exist in immature state of high phagocytic activity, low presentation
2) Possess a wide array of PRRs to integrate environmental cues
3) Stimulation initiates maturation, lowers phagocytosis, increases presentation, migration to lymph node
Surface chemokine receptor expressed by mature DCs
CCR7
How is MHCI/peptide complex transported to cell surface?
Via Golgi
What is DC cross-presentation?
Extracellular, phagocytosed antigens being presented on MHCI, to stimulate CD8+ T cells
Why is cross-presentation used?
1)
2)
1) If a virus kills DCs, so DCs need to present to CD8+ T cells without being infected (need infection to present on class I by direct pathway)
2) If a virus is present in the periphery where there are no naive CD8+ T cells (EG: herpes simplex). DCs can take up antigen, present on MHCI and travel to lymph nodes.
DC surface proteins expressed upon activation for T cell activation
CD80, CD86
How are DCs stopped from eliciting a T cell response against self antigens?
1)
2)
1) CD80 and CD86 are only upregulated if a foreign antigen stimulates PRRs.
2) CD80, CD86 needed to stimulate a T cell. Even if a T cell is cognate with DC presenting a self antigen, without CD80/CD86, nothing will happen
Types of antigens presented through cross-presentaiton
Viral antigens
Pathogen presented from receptor-mediated endocytosis
Extracellular bacteria
Pathogen presented from macro-pinocytosis
Extracellular bacteria, soluble antigen, viral antigen
Signal 1, 2 and 3
1) TCR - MHC interaction
2) CD80/CD86 - CD28 interaction
3) Cytokines to bias T cell type
Signal 1 role
Activation of T cell
Signal 2 role
Survival of T cell
Signal 3 role
T cell differentiation
Do activated CD8+ T cells need a signal 2?
No.
They will be in the periphery, killing non-professional APCs, which can’t costimulate
Type of T cell that doesn’t require signal 2
Activated CD8+ T cell
