Lecture 4 Flashcards

1
Q

What does pax5 do?

A

Tells the stem cell is going to be a B cell and stays in the bone marrow

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2
Q

What does pax5 have in order for the B cell to stay in the bone marrow?

A

A transcription factor

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3
Q

How many B cells are produced per day?

A

3 x 10^10

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4
Q

What does the formation of a b cell contain?

A

Re arrangement and expression of IG genes

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5
Q

What does CD19 do?

A

An early molecule on the cell surface identifies it has a B cell

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6
Q

What do lots of B cels express?

A

CD19

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7
Q

What is the process that allows the removal of self-reactive cells?

A

Negative selection - is an attempt to avoid immunity

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8
Q

What is the first constant region?

A

Im

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9
Q

What does it mean if a b cell recognises an antigen outside the bone marrow?

A

It means it is a good B cell

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10
Q

What do B cell precursors in the bone marrow respond to?

A

Cytokines delivered to the B cell precursors by bone marrow stromal cells

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11
Q

What happens if a B cell does not recognise the antigen?

A

The antigen will die

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12
Q

Where does negative selection occur?

A

In the bone marrow

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13
Q

What happens once the b cell is activated by an antigen?

A

B cell further differentiates

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14
Q

How does a B cell encounter an antigen?

A

It circulates through the circulatory system to lymphoid organs

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15
Q

What rearranges first in the B cell?

A

H chain genes

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16
Q

Where do the H chain genes move to?

A

Move to the cell surface with Igalpga and Igbeta

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17
Q

What are H chain expressed with?

A

Surrogate light chains

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18
Q

What is the structure of a pre-B cell?

A

A heavy chain with a light chain surrogate attached to it

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19
Q

What do the light chains do?

A

Rearrange and displace the surrogate chain

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20
Q

What is the surrogate of the surrogate chain?

A

V preB and lambda5 chains

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21
Q

When does the light chain get turned on?

A

If the light chain binding is good a signal is sent back to the B cell and it gets turned on

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22
Q

Why doesn’t a B cell have a BCR on its surface?

A

Because it’s rearranging the heavy chain

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23
Q

What tells us the heavy chain looks okay?

A

Prebiotic and lambda 5 bind to all heavy chains if they can then the heavy chain is okay

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24
Q

What does RAG allow?

A

Allows B cell to replicate on the H chain

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25
Q

What does the pre-BCR do?

A

Delivers signal to pre-B cell that H chain looks functional

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26
Q

What does the first signal from the pre-BCR do?

A

Tuens the RAG off which allows B cells to replicate

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27
Q

What happens when the Rag genes are off?

A

Surrogate light chain expression stops

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28
Q

What happens when the RAG genes are turned on?

A

L chain rearrangements starts

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29
Q

What does each light chain express?

A

Either kappa or lambda

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30
Q

What is put in-between the V,D,J segments when they come together?

A

Additional base Pairs put in By enzymes

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31
Q

What happens if the heavy chain is non-functional?

A

The surrogate light chain can check

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32
Q

What happens if the b cell fails twice to rearrange?

A

The b cell will die

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33
Q

How many goes does the b cell have to make a functional kappa and lambda

A

2 on each

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34
Q

How many goes can a B cell have on each chromosome?

A

5

35
Q

What happens if a cell fail to re arrange H and L gene?

A

It dies

36
Q

What happens if a pre-B cell fails to generate re-arrangements of a light chain?

A

It can be rescued by put to 10 further arrangements on the same locus as there are 5 Jkappa genes on each chromosome

37
Q

What happens if a V chain binds to the 3rd v3?

A

It will have two to choose from as there are 5Vs

38
Q

What happens if all V5 fail?

A

It can start binding on the lambda protein

39
Q

What happens if an immature b cell bind to multivalent self antigen?

A

Clonal deletion or receptor editing

40
Q

What is clonal deletion?

A

Cell dies by apoptosis

41
Q

What is receptor editing?

A

Further light chain gene rearrangements of variable regions

42
Q

What happens if an immature B cell binds soluble self antigens?

A

Cell becomes unresponsive (anergic)

43
Q

How can a B cell avoid dying?

A

If it turns on RAG genes

44
Q

What does it mean if a B cell is anergic?

A

They turn down their BCR and sneak out the bone marrow as they don’t ahve enough autoreactive BCRs

45
Q

Where do T cells originate from?

A

Bone marrow stem cells

46
Q

What happens if T cell does express pax5?

A

They leave the bone marrow quickly and go to the thymus

47
Q

What do T cells express?

A

CD4+ and CD8+

48
Q

Why are T cells positively selective?

A

As they can bind MHC

49
Q

What happens if they recognise self MHC?

A

Could be autoreactive

50
Q

What is a notch molecule?

A

Tells the cell it’s going to be a T cell

51
Q

When does the notch molecule become active?

A

Once the thymocyte gets a signal from the notch molecule

52
Q

What do thymocytes develop into?

A

Immature T cells

53
Q

What is an immature T cell capable of?

A

Leaving the thymus and recognising self MHC and antigen s

54
Q

What does an immature T cell not do?

A

Doesn’t recognise any peptides that were presented to it in the thymus

55
Q

What are express makers called?

A

CD3, CD4 and CD8

56
Q

What do the express markers do to the T cell development?

A

Undergo positive and negative selection while still in the thymus

57
Q

What is the structure of the thymus?

A

Bi-lobed organ in anterior mediastinum

58
Q

What are the two zones called?

A

Outer cortex and inner medulla

59
Q

What are the cells involved in the thymus?

A

Lymphoid cells, epithelial cells and macrophages and dendritic cells

60
Q

How do pro-thymocytes enter the thymus?

A

Enter the cortex via blood vessels from bone marrow

61
Q

What happens once the T cell are inside the thymus?

A

They are rearranged to TCR genes

62
Q

What are TCR genes expressed with?

A

Pre-T cell receptor

63
Q

What TCR occurs first?

A

TCRbeta then cells proliferate and rearrange TCRalpha

64
Q

What is found outside the thymus?

A

Either CD8 or on another CD4 never both like the inside

65
Q

What can T cell express

A

Either one of CD3,CD4 or CD8

66
Q

What does TCR expression require?

A

CD3 complex

67
Q

What is different about the CD3 complex?

A

It has epsilon, lambda, delta chains and a zeta dimmer

68
Q

What does the cd3 complex do?

A

Delivers a signal to turn on genes allowing them to recognise antigen s

69
Q

What can some TCR also express as well as alpha beta

A

Lambda delta

70
Q

How many T cells come out of the thymus?

A

1-5%

71
Q

What happens to alpha and beta receptors that rearrange?

A

They become double positive

72
Q

What do double negative thymocytes not contain?

A

They don’t contain CD4 or CD8

73
Q

What are the groups that thymocytes end up with?

A

CD4+ and CD8- or CD8+ and CD4-

74
Q

What are the 3 things T cells express in a randomly arranged alpha/beta TCR may do?

A
  1. Recognise self MHC plus peptide from a foreign antigen
  2. Recognise self MHC plus peptide from self antigen
  3. Not be able to recognise self mHC
75
Q

What do T cells need to keep?

A

TCR 1

76
Q

When does positive selection occur?

A

When there is double positive T cells on the MHC

77
Q

Where does positive selection occur?

A

In the cortex and epithelial cells that express mHC

78
Q

What are the cells given that express MHC

A

A survival signal

79
Q

What happens if the T cells pass positive selection?

A

They move into the medulla

80
Q

What happens to the cells that don’t bind MHC?

A

They die via apoptosis

81
Q

Where does negative selection take place?

A

On dendritic cells and macrophages with high affinity

82
Q

What happens if cell bind too well in negative selection?

A

They die by apoptosis

83
Q

What is the ultimate goal for a T cell?

A

Low affinity for self peptide and self MHC

84
Q

Wat is the best affinity for t CELLS?

A

LOW AFFINITY