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Molecule to Malady > Lecture 1 - B Cell Pathology > Flashcards

Lecture 1 - B Cell Pathology Flashcards

1
Q

Stem cell giving rise to all blood cellls

A

Long-term haematopoietic stem cell

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2
Q

Cell arising from long-term haematopoietic stem cell

A

Short-term haematopoietic stem cell

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3
Q

From which cell does a short-term haematopoietic stem cell arise?

A

Long-term haematopoietic stem cell

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4
Q

Cells arising from short-term haematopoietic stem cells
1)
2)

A

1) Common myeloid progenitor

2) Lymphoid-primed multipotent progenitor

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5
Q

From what cell type do lymphoid-primed multipotent progenitor cells arise?

A

Short-term haematopoietic stem cells

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6
Q

From what cell type do common myeloid progenitor cells arise?

A

Short-term haematopoietic stem cells

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7
Q

Which cell type arises from lymphoid-primed multipotent progenitors?

A

Early lymphoid progenitor

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8
Q

From which cell type do early lymphoid progenitors arise?

A

Lymphoid-primed multipotent progenitors

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9
Q

Cell types arising from early lymphoid progenitor cells
1)
2)
3)

A

1) B cell
2) T cell
3) NK cell

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10
Q 
Cell types giving rise to B cells
1)
2)
3)
4)
5)
A

1) Long-term haematopoietic stem cell
2) Short-term haematopoietic stem cell
3) Lymphoid-primed multipotent progenitor
4) Early lymphoid progenitor
5) B cell

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11
Q

Cell types arising from common myeloid progenitor cells

A

1) Granulocyte myeloid progenitor

2) Myeloid erythroid progenitor

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12
Q

Cell type from which myeloid erythroid progenitor arises

A

Common myeloid progenitor

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13
Q

Cell type from which granulocyte myeloid progenitor arises

A

Common myeloid progenitor

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14
Q

Cell types arising from granulocyte myeloid progenitor
1)
2)
3)

A

1) Granulocyte
2) Eosinophil
3) Macrophage

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15
Q

Cell types arising from myeloid erythroid progenitor
1)
2)

A

1) Erythrocytes

2) Megakaryocytes

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16
Q 
Cell types which give rise to erythrocytes
1)
2)
3)
4)
5)
A

1) Long-term haematopoietic stem cell
2) Short-term haematopoietic stem cell
3) Common myeloid progenitor
4) Myeloid erythroid progenitor
5) Erythrocyte

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17
Q 
Cell types which give rise to macrophages
1)
2)
3)
4)
5)
A

1) Long-term haematopoietic stem cell
2) Short-term haematopoietic stem cell
3) Common myeloid progenitor OR lymphoid-primed multipotent progenitor
4) Granulocyte myeloid progenitor
5) Macrophage

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18
Q

What is a primary immune disorder?

A

A disorder of the immune system which is genetic, NOT acquired.

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19
Q

When are most primary immune disorders diagnosed?

A

Under the age of 1

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20
Q

Examples of combined B and T cell deficiencies
1)
2)
3)

A

1) Severe combined immunodeficiency disorder
2) Complete DiGeorge syndrome
3) CD40 and CD40L deficiency

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21
Q

Examples of antibody deficiencies
1)
2)
3)

A

1) CD40 and CD40L deficiencies
2) X-linked agammaglobulinaemia
3) Common variable immunodeficiency

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22
Q

Hyper IgM syndrome

A

Antibodies cannot undergo isotype switching

Therefore, the only types of circulating antibodies are IgM

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23
Q

What is a severe combined immune deficiency?

A

Loss of both humoral and cellular immunity

Loss of CD4 T cells

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24
Q

Structure of an antibody

A

Disulphide-linked dimer of heavy and light chain heterodimers

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25
Q

Number of heavy chain classes

A

Nine

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26
Q

Types of heavy chain classes

A 
Mu
Delta
Gamma1, gamma2, gamma3, gamma4
Alpha1, alpha2
Epsillon
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27
Q

Number of heavy-chain constant regions

A

3 per arm of antibody

28
Q

Number of heavy chain variable regions

A

1 per arm of antibody

29
Q

Number of light chain constant regions

A

1 per arm of antibody

30
Q

Number of light chain variable regions

A

1 per arm of antibody

31
Q

Order of recombinations in heavy chain

A

1) DJ

2) VDJ

32
Q

Order of recombinations in light chain

A

1) VJ

33
Q

Which chain type has a diversity region?

A

Heavy chain

34
Q

How is diveristy generated in antibodies?
1)
2)
3)

A

1) Random selection of minigene joining at each locus
2) Independent rearangement at H and L chain loci
3) Imprecision of junctions

35
Q

Steps in V(D)J recombination
1)
2)
3)

A

1) Site recognition and cleavage
2) Non-homologous end joining
3) Ligation

36
Q

Enzymes involved in site recognition and cleavage
1)
2)
3)

A

1) RAG1
2) RAG2
3) HMG1

37
Q

Enzymes involved in non-homologous end joining
1)
2)
3)

A

1) DNA protein kinase catalytic subunit (DNAPKcs)
2) Artemis
3) Ku70 and Ku80

38
Q

Enzymes involved in ligation
1)
2)

A

1) Terminal deoxynucleotidyl transferase

2) XRCC4 DNA ligase IV

39
Q

What does TdT stand for?

A

Terminal deoxynucleotidyl transferase

40
Q

What happens during site recognition and DNA cleavage?
1)
2)

A

1) RAG1/RAG2 complex recognises, binds heptamer-spacer-nonamer sequence, cleaves between RSS and coding sequence
2) Coding ends and signal ends result

41
Q

What happens to signal ends?

A

Form a loop of DNA which is excised form the chromosome

42
Q

Function of Artemis

A

Makes a nick in DNA hairpins of coding ends

43
Q

Function of terminal deoxynucleotidyl transferase

A

Adds random nucleotides to V, D and J exons during recombination

44
Q

Which cells express RAG1 and RAG2?

A

T cells and B cells

45
Q

Which cells express Artemis, DNAPKcs, Ku70, Ku80?

A

All cells

These enzymes are involved in repair of DNA damage

46
Q

What is RSS?

A

Recombination signal sequence

Adjacent to eachminigene segment

47
Q

Function of recombination signal sequence

A

Recognised by RAG1/2

48
Q

Structure of RSS

A

Heptamer-spacer-nonamer

Spacer can be wither 12 or 23 base pairs long

49
Q

Function of spacer

A

length corresponds with either one or two turns of DNA helix

Segment with spacer of 12bp can only join with one of 23bp

50
Q

Function of RAG

A

Recombination activating gene

Recognition and cleavage functions

51
Q

Which cells express terminal deoxynucleotidyl transferase?

A

Only early B cells and T cells

52
Q

HMG1

A

High mobility group 1
Chromatin binding, structural protein required for rearrangement
Not only used in B cell recombination

53
Q

What does XRCC4 stand for?

A

X-ray repair complementing defective repair in Chinese hamster cells 4

54
Q

Function of DNA ligase IV/XRCC4

A

Joins DNA ends

55
Q

How are successful Ig gene rearrangements propagated?

A

B cell development is tied to successful Ig gene rearrangements

56
Q

Stages of B cell development

A

1) Pre-pro B
2) Pro B
3) Pre B
4) Pre-BII small
5) Immature IgM+ B cell

57
Q

What is happening in a pre-pro B?

A

D-J joining at heavy chain locus

58
Q

What is happening in a pro-b?

A

V-DJ joining at heavy chain locus

If successful, progresses to pre B

59
Q

What is happening in a pre b?

A

V-J joining at light chain locus

First at kappa, if unsuccessful, at lambda

60
Q

How many pro b make it to becoming pre b?

A

1/3
V segment contains AUG start sequence. Must be in frame for correct transcription to occur. 1/3 chance of reading frame being correct

61
Q

Enzyme necessary for pre-pro b arising from early lymphoid progenitor

A

E2B

62
Q 
Enzymes necessary for pre-B large to arise from pro b
1)
2)
3)
4)
A

1) RAG
2) PAX5
3) Syk
4) Igalpha, Igbeta

63
Q

Enzymes nexessary for pre-B large to give rise to pre-B small
1)
2)
3)

A

1) BTK
2) BLNK
3) SLC

64
Q

Function of Iga/b

A

Scaffolding proteins

65
Q

Function of Syk and BTK

A

Kinases

66
Q

Function of PAX5

A

Transcription factor that specifies B cell expression program

67
Q

When is terminal deoxynucleotidyl transferase used?

A

Heavy chain recombination.

Molecule to Malady (35 decks)

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