Lecture 3 Flashcards

1
Q

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

A

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

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2
Q

What is the function of macrophages?

A

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

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3
Q

What is the function of dendritic cell?

A

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

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4
Q

What is dendritic cell differentiated by?

A

Factor Flt3L

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5
Q

What are monocytes differentiated by?

A

M-CSF

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6
Q

What do dendritic cells and monocytes have?

A

Different transcription factors

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7
Q

Where is location of dendritic cell?

A

Body surfaces
Organs
T cell areas of lymphoid organs

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8
Q

What are the sensors of dendritic cells?

A

Antigen uptake

Processing and presentation of peptide-MHC complexes

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9
Q

What is maturation of dendritic cells?

A

Response to microbial and other stimuli

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10
Q

What are the subsets of dendritic cells?

A

With distinct pattern recognition receptors and function

e.g. pDCs, CD8+ and DC

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11
Q

Where are majority of DC found?

A

Aortic Arch where the blood slows down

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12
Q

In the lymph node, where are macrophages found?

A

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

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13
Q

What does dendritic cell have an array of?

A

DAMP and PAMP to sense the environment

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14
Q

What are PAMP known to be?

A

Very stimulatory

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15
Q

What are different methods of uptake?

A

Specific

Non specific

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16
Q

Specific

A

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

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17
Q

Non specific

A

Engulf soluble antigens

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18
Q

What are endogenous pathogen?

A

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

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19
Q

What are exogenous pathogen?

A

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

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20
Q

Where is MHC I assembeld?

A

In ER with antigen coming from cytoplasm

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21
Q

What is an example of MHC I assembly?

A

Virus

Protein degraded in proteosome

22
Q

Where is MHC II assembled?

A

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

23
Q

Where is MHC I loaded?

A

ER

24
Q

Where is MHC II loaded?

A

Endocytic compartment

25
Q

What can dendritic cell initiate?

A

Adaptive immune response

26
Q

When does MHC class I only occur?

A

If the cell is infected

27
Q

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

A

Cross-presentation

28
Q

Cross-presentation of exogenous antigens on MHC I

A
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
29
Q

Semi-immature DC

A

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

30
Q

Mature DC

A

Induce immunity

Tell T cells what to do/activate them

31
Q

Super activated DC

A

When the stimulus is too strong

32
Q

What does surrounding environment of DC determine?

A

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

33
Q

What does DC maturation drive?

A

MHC-peptide complex formation

34
Q

What are MHC class II restricted to?

A

Macrophages
B cells
DC

35
Q

Why is macrophage/immature DC not a good APC?

A

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

36
Q

Mature DC

A

In a steady state

High basic PH in lysosome which block degradation of antigen

37
Q

What is the lysosomal PH of immature DC?

A

5.5

38
Q

What is the lysosomal PH of mature DC?

A

4.5

39
Q

What is the PH optimal for lysosomal proteases?

A

< pH 5

40
Q

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

A

Activation of catS and catL

This degrades Li chain

41
Q

What does HLR-DM remove?

A

CLIP
Allows peptide to bind to MHC II
Goes to membrane

42
Q

What can mature DC prevent?

A

Induction of autoimmunity

43
Q

Why does MHC II go to the membrane?

A

Degraded, recycled and synthesised continuously in a cycle

44
Q

What does MHC II have a signal for?

A

Proteosome degradation called MARCH 1

45
Q

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

A

facilitates interaction with T cells

46
Q

What does maturation cause?

A

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

47
Q

What are main features of DC maturation?

A

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

48
Q

What is the cell that induce cross-presentation?

A

cDC1

49
Q

What do CdC2 tend to be?

A

Better CD4 inducers

50
Q

What is CD103?

A

Very immunosuppressive in gut

Induce regulatory T cell recruitment

51
Q

What is Dendritic cells often a target for?

A

Vaccination

Only cells that produce adaptive immune r spines

52
Q

What are dendritic cell being manipulated for?

A

Immunotherapy