Dendritic Cells Flashcards
Who discovered DCs and when?
Ralph Steinman in 1973
What are immature DCs main function?
What are mature DCs main function?
What do each do (in general)?
Immatures are good for Ag uptake and processing. They contribute to tolerance.
Mature DCs present Ag, are co-stimulatory, and activate T cells. They are good for immunity.
What are the stages of DC maturation?
Differentiation
Ag uptake/innate immune sensing
Ag processing/presentation
Phenotype maturation (cell surface markers)
Functional maturation (cytokines/co-stimulation)
Briefly describe DC phenotypic maturation.
Change in morphology.
Upregulation of co-stimulatory molecules CD80, ICOSL, and CD83.
CD86 is always expressed.
What is DC functional maturation?
The ability of DC to activate T cells in the presence and type of Ag/co-stimulatory molecules, and secretion/type of cytokines.
Describe some DC-T cell co-stimulatory signals between molecules and define if they are activation or inhibition sensors.
CD80/86 -- CTLA4 = inhibition CD80/86 -- CD28 = activation ICOSL -- ICOS = activation OR inhibition depending on CD28 signalling CD40 -- CD40L = Activation OX40L -- OX40 = inhibition
Why does DC maturation state matter?
levels of receptors and signals changes and they can’t react as well to certain situations in other forms.
Which signal dominates in immature DCs? What does it do?
Which signal dominates in mature DCs? What does it do?
ICOSL signal stabilizes IL-10R expression and induces T cell anergy/iTreg = tolerance
CD80/86 signal down regulates IL-10R to effect T cells leading to immunity
Where do DCs reside? What are their functions there?
Blood (mDCs and pDCs) and skin (LCs, dermal DCs x2).
mDCs activate CD4/CD8 cells and inflammatory responses - mDCs cross present!
pDCs are for antiviral immunity and link immune systems
LCs activate CTL and differentiate CD4 to Th2
Dermal diff CD4 into Tfh
Other dermal for CD8 activation
How does the DC migrate to the lymph node?
DCs reside in barrier sites like skin and mucosa. Maturation enhances migratory capacity via upreg of CCR7 and help bring T cells to SLOs. Activated DCs cease further Ag uptake.
Why do activated DCs stop further Ag uptake?
To reflect current state in site of infection
Do not assimilate with other Ag on the way.
Give the function of the following: Conventional DC Langerhans cells Plasmacytoid DC Monocyte derived DC
Ag processing/presentation
Resident DC in skin
Major IFN producers in viral infection
Drives inflammation
What do the following produce? What do their products secrete? TLR signalling on DC w NK cell CLR signalling on DC w basophil CLR signalling on DC (solo) CD11/18 recognition on DC (solo)
Th1 cell = IFN gamma and TNF alpha
Th2 cell = ILs-4, 5, and 13
Th17 cell = TNF alpha, and many ILs
Treg cell = IL-10 and TGFbeta
