Lecture 3

Question 1

Why was it difficult for Steinman to convince people dendritic cells were a different type of cell rather than a subset of macrophages?

Answer 1

Both express markers such as CD11c and F4/80
Both express MCH II
Both phagocytic
Both sensors - have receptors on their membrane to recognise foreign material

Question 2

What is the function of macrophages?

Answer 2

Clear up necrosis, infected cells, bacterial infection.
They destroy pathogen
Induce inflammatory response
Remain in tissue where pathogens are

Question 3

What is the function of dendritic cell?

Answer 3

Messengers
Eat a small amount of pathogen to see if it’s healthy or infected
Migrate to lymph nodes - instruct T cells

Question 4

What is dendritic cell differentiated by?

Answer 4

Factor Flt3L

Question 5

What are monocytes differentiated by?

Answer 5

M-CSF

Question 6

What do dendritic cells and monocytes have?

Answer 6

Different transcription factors

Question 7

Where is location of dendritic cell?

Answer 7

Body surfaces
Organs
T cell areas of lymphoid organs

Question 8

What are the sensors of dendritic cells?

Answer 8

Antigen uptake

Processing and presentation of peptide-MHC complexes

Question 9

What is maturation of dendritic cells?

Answer 9

Response to microbial and other stimuli

Question 10

What are the subsets of dendritic cells?

Answer 10

With distinct pattern recognition receptors and function

e.g. pDCs, CD8+ and DC

Question 11

Where are majority of DC found?

Answer 11

Aortic Arch where the blood slows down

Question 12

In the lymph node, where are macrophages found?

Answer 12

Marginal zone around the outside
Clumps of B cells
T cells are on the inside with dendritic cell

Question 13

What does dendritic cell have an array of?

Answer 13

DAMP and PAMP to sense the environment

Question 14

What are PAMP known to be?

Answer 14

Very stimulatory

Question 15

What are different methods of uptake?

Answer 15

Specific

Non specific

Question 16

Specific

Answer 16

Receptor in the membrane e.g. Clathrin(receptors for sugars)
Uptake is common for uptake of bacteria
Phagocytosis

Question 17

Non specific

Answer 17

Engulf soluble antigens

Question 18

What are endogenous pathogen?

Answer 18

Virus
Pathogen will be presented with a MHC I molecule
Activate CD8 T response

Question 19

What are exogenous pathogen?

Answer 19

Bacteria
Phagocytosed and processed and presented with a MHC class II molecule
Activate CD4 T response

Question 20

Where is MHC I assembeld?

Answer 20

In ER with antigen coming from cytoplasm

Question 21

What is an example of MHC I assembly?

Answer 21

Virus

Protein degraded in proteosome

Question 22

Where is MHC II assembled?

Answer 22

ER
2 alpha and 2 Beta chains stabilised by invariant chain
Travels through Golgi to late endosomes
Lysosome in presence of low PH = degraded
Frees space for the peptide to bind MHC II
Antigen binds and then go to membrane

Question 23

Where is MHC I loaded?

Answer 23

ER

Question 24

Where is MHC II loaded?

Answer 24

Endocytic compartment

Question 25

What can dendritic cell initiate?

Answer 25

Adaptive immune response

Question 26

When does MHC class I only occur?

Answer 26

If the cell is infected

Question 27

How do you present an MHC class II response when not infected?

Answer 27

Cross-presentation

Question 28

Cross-presentation of exogenous antigens on MHC I

Answer 28

``` Antigen phagocytosed Enters endosomes which become leaky Antigen leaks to cytoplasm Goes to proteosome where it is degraded Loaded in the ER onto MHC I complex and presented in membrane ```

Question 29

Semi-immature DC

Answer 29

Have some activation but not enough to produce a cell response Doesn’t respond to dangerous pathogens

Question 30

Mature DC

Answer 30

Induce immunity | Tell T cells what to do/activate them

Question 31

Super activated DC

Answer 31

When the stimulus is too strong

Question 32

What does surrounding environment of DC determine?

Answer 32

Which type of T cell response will be induced via cytokines production

Question 33

What does DC maturation drive?

Answer 33

MHC-peptide complex formation

Question 34

What are MHC class II restricted to?

Answer 34

Macrophages B cells DC

Question 35

Why is macrophage/immature DC not a good APC?

Answer 35

Once the antigen is taken up, it binds to lysosome which has a very low PH Degrades the protein = destroyed

Question 36

Mature DC

Answer 36

In a steady state | High basic PH in lysosome which block degradation of antigen

Question 37

What is the lysosomal PH of immature DC?

Answer 37

5.5

Question 38

What is the lysosomal PH of mature DC?

Answer 38

4.5

Question 39

What is the PH optimal for lysosomal proteases?

Answer 39

< pH 5

Question 40

When MHC II reaches the lysosome and there’s a drop in PH, what does it induce?

Answer 40

Activation of catS and catL | This degrades Li chain

Question 41

What does HLR-DM remove?

Answer 41

CLIP Allows peptide to bind to MHC II Goes to membrane

Question 42

What can mature DC prevent?

Answer 42

Induction of autoimmunity

Question 43

Why does MHC II go to the membrane?

Answer 43

Degraded, recycled and synthesised continuously in a cycle

Question 44

What does MHC II have a signal for?

Answer 44

Proteosome degradation called MARCH 1

Question 45

Why does MHC II remain in the membrane for much longer?

Answer 45

facilitates interaction with T cells

Question 46

What does maturation cause?

Answer 46

Rapid migration of splenic and LN DC to T cell area Promotes upregulation of costinulation and cytokine production Increase antigen presentation Reduce phagocytosis

Question 47

What are main features of DC maturation?

Answer 47

Enhance antigen processing Migration to lymph node Production of cytokines/ chemokines Up-regulation of co-stimulatory molecules

Question 48

What is the cell that induce cross-presentation?

Answer 48

cDC1

Question 49

What do CdC2 tend to be?

Answer 49

Better CD4 inducers

Question 50

What is CD103?

Answer 50

Very immunosuppressive in gut | Induce regulatory T cell recruitment

Question 51

What is Dendritic cells often a target for?

Answer 51

Vaccination | Only cells that produce adaptive immune r spines

Question 52

What are dendritic cell being manipulated for?

Answer 52

Immunotherapy