Lecture 5- Dendritic cells

Question 1

Who discovered the dendritic cell?

Answer 1

Ralph M. Steinman.
Thought they may activate T cells.
They are the best antigen presenting cell at activating and programming naive t cells.

Question 2

What are the 3 main types of dendritic cells?

Answer 2

1. Conventional DCs:
   Tissue resident, immature

2. Plasmacytoid DCs:
Deal with viral infections. Secrete lots of class I interferon.

3. Inflammatory DCs:
   Recruited to tissues in response to infection. Monocyte derived. Can also migrate to lymph node and activate T cells.

Question 3

What are the classes of conventional DCS? (classified by cell-markers they express)

Answer 3

1. CD11Chi CD8alpha or lymphoid
2. CD11Chi CD11b+ or myeloid
3. CD11Chi CD103+ (enriched in e.g. Gut)
4. Langerin+ DCs (skin)

Question 4

What markers do dendritic cells express?

Answer 4

1. Lost of cells express cd11c,not just DCs
2. Zbtb46 seems to be unique to DCs
3. DCs don’t tend to express CXCR1, which is on macrophages

Question 5

Which are better at phagocytosis? DCs or macrophages?

Answer 5

Macrophages are much better than DCs at phagocytosis

Question 6

What is unique about gut dendritic cells?

Answer 6

Food and commensal bacteria are not rejected in gut. But need to decide when pathogens are bad in gut.

Question 7

Unique intestinal DCs

Answer 7

CD103+ DCs in the gut are able to drive “tolerance” to oral antigens from food and commensal bacteria.

Induce the generation of reg. T cells.

Dependent on TGF-beta and retinoic acid (a metabolite of vitamin A)

Question 8

Structure of DCs?

Answer 8

Have long finger-like processes- dendrites.
high expression of costimulatory molecules e.g. CD80.
Chemokine receptors e.g. CCR5, CCR6.
Take up particulate/soluble antigens by endocytosis.
Many endocytic vesicles (contain MHC II and lysosomal proteins)

Question 9

Where are DCs?

Answer 9

Immature DC migrate from bone marrow via blood to enter tissues.
In tissues they sample the environment and act as sensors for damage or infection.
Often found under surface epithelia.

Question 10

What gives DCs the “licence” to mature?

Answer 10

Pattern Recognition Receptors

Question 11

How do DCs take up antigen?

Answer 11

Many ways.
1. Take up liquid non-specifically -> macropinocytosis

2. Also phagocytose via their:
   complement R, FcR (bind antibody antigen complexes), C-type lectins e.g. mannose R, langerin
3. Some DCs express TLR7 and TLR9 and respond to viral infection.

Question 12

Briefly, give some routes of Ag processing by DCs?

Answer 12

1. Receptor-mediated phagocytosis
2. Macro-pinocytosis
3. Viral infection
4. cross-presentation after phagocytic or macropinocytic uptake
5. transfer from incoming dendritic cell to resident dendritic cell

Question 13

What does the cross presentation pathway enable you to do?

Answer 13

Allows exogenous proteins to be presented by MHC I. (which is needed to switch on cd8 t cells)
This means that the APC does not need to be infected to present antigen.
Peptides from pathogens, infected dying cells, tumour cells.
So you’ve never had to actually become infected, you’ve recognised the viral cell

Question 14

What is the licencing stage?

Answer 14

When we activate a response to pathogens via pattern recognition receptors (PRRs) like TLRs.
DAMPs e.g. uric acid or cytokins can also promote licencing.

Question 15

What are DAMPs?

Answer 15

Danger Associated Molecular Patterns

Question 16

What happens after licencing by the PRRs?

Answer 16

The TLR signalling induces changes in the dendritic cell. The most striking of which is changes in chemokine receptor expression.

CCR5 and CCR6 are downregulated and CCR7 is switched on.
CCR7 recognises a chemokine called CCL21 which allows DCs to go to the lymph nodes. Important!

Question 17

What does CCR7 do?

(Why is it important that it’s switched on after pathogen induced licencing when TLR signalling alters DC chemokine receptor expression?)

Answer 17

CCR7 recognises a chemokine called CCL21 which allows DCs to go to the lymph nodes via lymph. Important!

Question 18

What are the features of mature DCs migrating via lymph to lymphoid tissue?

Answer 18

1. Express CCR7 (which recognises ccl21)
2. Morphology changes- have very veiled strucutre.. membrane folds-> veils.
3. Express very stable MHC/peptide complexes on their surface
4. High levels of costimulatory molecules which allows them to have stable interaction with a T cell.
5. They’re shit at taking up antigens now.
6. High levels of long lived MHC molecules
7. Attract Naive T cells

Question 19

What is the process of switching a t cell on called?

Answer 19

Priming.
Present Ag to naive T lymphocytes.
Activate any antigen specific T cells to divide into effector cells that enter circulation

Question 20

What does DC polarisation of T cells mean?

Answer 20

DCs tell T cells what to become.
E.g. Treg cell, th2 cell or whatever.
depends on environment (e.g. cytokines and parasites) what the DC tells the T cell to become.

Question 21

What does IL12 promote?

Answer 21

Th1 cells

Question 22

What does suppressed IL12 signal promote?

Answer 22

Th2 cells

Question 23

What do secretary products from hookworm promote?

Answer 23

Treg cells- to dampen down immune response

Question 24

What are the 3 main types of APC?

Answer 24

1. Macrophages (via PRR)
2. B cells (via BcR)
3. Dendritic cells (via PRR)

Question 25

Why are DCs such a special type of APC?

Answer 25

B cell and macrophages specialise in processing and presenting Ag from intracellular pathogens and soluble antigens.

DCs can process a wide range of antigens
Found in T cell areas of Lymph nodes.
Drive the initial clonal expansion and differentiation of naive T cell into effector cells.

Question 26

Why are DCs the champion APC?

Answer 26

They are the only APCs adapted to PRIME NAIVE T cells!!!