Dendritic Cells

Question 1

Characteristics of DCs?

Answer 1

Dendrites - long processes
Immature migrate from bone marrow to blood
Sense the environment for damage/infection and migrate towards the site
Several pathways of antigen uptake (better than macrophages)

Question 2

Types of DC?

Answer 2

Classical - cDC, in tissues, subsets 1 and 2
Plasmacytoid DCs
Sentinels for viral infections, secrete class 1 interferons
Also includes intracellular PRRs TLR7 and 9 for viral recognition
Monocyte-derived/inflammatory DCs
Respond to infection with monocyte factor and CCR2
Support effector T cells
Langerhans cells
In skin, can self renew

Question 3

cDCs?

Answer 3

cDC1 - needs BATF3 or IRF8
Cross-present to CD8+ T cells
Express CD8aa, DEC-205 or CD103
Produce more IL-12
Express TLR3 for biral recognition

cDC2 - IRF4 dependent
Good at priming naive t cells
TD4 responses
Express CD11b, DCIR2, CD301b, CD4 or SIRPa

Question 4

Intestinal DCs?

Answer 4

Needed for gut homeostasis, for protective immunity and tolerance of commensal bacteria
Tolerance via CD103+ DCs, using TGFbeta and retinoic acid, to generate Tregs

Question 5

cDCs in normal tissues?

Answer 5

Immature
Dendrites
Low expression of costimulatory molecules
Chemokine receptors for migration
Endocytosis of soluble antigens, containing many vesicles with MHCII and lysosomal proteins

Question 6

Antigen uptake in DCs?

Answer 6

Uses phagocytic receptors like complement Rs, FcRs, C-type lectins

Question 7

Types of antigen processing in DCs?

Answer 7

Receptor mediated phagocytosis
Macro-pinocytosis
Viral infection
Cross-presentation (after first 2)
Transfer from incoming to resident DC

Question 8

Cross presentation in DCs

Answer 8

Uses MHCI molecules (which act endogenously) for exogenous antigens
Uptake into phagolysosome, digested, antigens processed and presented on MHC1

Question 9

DC maturation

Answer 9

1. Pathogen recognition
   Uses PRRs = pathogen induced ‘licencing’

TLR signalling changes DC chemokine receptors, inducing CCR7 for CCL21 and down-regulating those needed for migration

2. DCs move in lymph to lymph nodes

Question 10

Morphology of mature DCs?

Answer 10

In circulation, membrane folds to increase surface area
In lymph nodes, MHC-peptide complexes expressed

High levels of costimulatory molecules
Reduced antigen uptake
Stable MHC molecules
Attract naive T cells with adhesion molecules and CCL18 chemokine secretion

Question 11

How do DCs activate T cells?

Answer 11

Priming - Ag presented to naive T cells, called polarising the immune response
Depend son accessory cells, DC subtype, TLR ligands (licensing DCs)
Cytokines
Cell type

Question 12

Main APCs?

Answer 12

Macrophages and DCs, activated by PRRs
B cells, activated by BCRs

BCs and macrophages interact with already primed effector CD4 t cells, so do not initiate the immune response like DCs do

Question 13

Application of DCs?

Answer 13

Can be used to boost immunity
In cancer, specific licencing of DCs with tumour cells may help recognise tumour self cells as dangerous (not very successful)

DC Vaccines
1st gen - safe, not effective
Second gen - better antigen prep and better clinical use

Next-gen - seems both safe and effective