Lecture 1 - B Cell Pathology Flashcards Preview

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Flashcards in Lecture 1 - B Cell Pathology Deck (67):
1

Stem cell giving rise to all blood cellls

Long-term haematopoietic stem cell

2

Cell arising from long-term haematopoietic stem cell

Short-term haematopoietic stem cell

3

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

Long-term haematopoietic stem cell

4

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

1) Common myeloid progenitor
2) Lymphoid-primed multipotent progenitor

5

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

Short-term haematopoietic stem cells

6

From what cell type do common myeloid progenitor cells arise?

Short-term haematopoietic stem cells

7

Which cell type arises from lymphoid-primed multipotent progenitors?

Early lymphoid progenitor

8

From which cell type do early lymphoid progenitors arise?

Lymphoid-primed multipotent progenitors

9

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

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

10

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

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

11

Cell types arising from common myeloid progenitor cells

1) Granulocyte myeloid progenitor
2) Myeloid erythroid progenitor

12

Cell type from which myeloid erythroid progenitor arises

Common myeloid progenitor

13

Cell type from which granulocyte myeloid progenitor arises

Common myeloid progenitor

14

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

1) Granulocyte
2) Eosinophil
3) Macrophage

15

Cell types arising from myeloid erythroid progenitor
1)
2)

1) Erythrocytes
2) Megakaryocytes

16

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

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

17

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

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

18

What is a primary immune disorder?

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

19

When are most primary immune disorders diagnosed?

Under the age of 1

20

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

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

21

Examples of antibody deficiencies
1)
2)
3)

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

22

Hyper IgM syndrome

Antibodies cannot undergo isotype switching
Therefore, the only types of circulating antibodies are IgM

23

What is a severe combined immune deficiency?

Loss of both humoral and cellular immunity
Loss of CD4 T cells

24

Structure of an antibody

Disulphide-linked dimer of heavy and light chain heterodimers

25

Number of heavy chain classes

Nine

26

Types of heavy chain classes

Mu
Delta
Gamma1, gamma2, gamma3, gamma4
Alpha1, alpha2
Epsillon

27

Number of heavy-chain constant regions

3 per arm of antibody

28

Number of heavy chain variable regions

1 per arm of antibody

29

Number of light chain constant regions

1 per arm of antibody

30

Number of light chain variable regions

1 per arm of antibody

31

Order of recombinations in heavy chain

1) DJ
2) VDJ

32

Order of recombinations in light chain

1) VJ

33

Which chain type has a diversity region?

Heavy chain

34

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

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

35

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

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

36

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

1) RAG1
2) RAG2
3) HMG1

37

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

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

38

Enzymes involved in ligation
1)
2)

1) Terminal deoxynucleotidyl transferase
2) XRCC4 DNA ligase IV

39

What does TdT stand for?

Terminal deoxynucleotidyl transferase

40

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

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

41

What happens to signal ends?

Form a loop of DNA which is excised form the chromosome

42

Function of Artemis

Makes a nick in DNA hairpins of coding ends

43

Function of terminal deoxynucleotidyl transferase

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

44

Which cells express RAG1 and RAG2?

T cells and B cells

45

Which cells express Artemis, DNAPKcs, Ku70, Ku80?

All cells
These enzymes are involved in repair of DNA damage

46

What is RSS?

Recombination signal sequence
Adjacent to eachminigene segment

47

Function of recombination signal sequence

Recognised by RAG1/2

48

Structure of RSS

Heptamer-spacer-nonamer
Spacer can be wither 12 or 23 base pairs long

49

Function of spacer

length corresponds with either one or two turns of DNA helix

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

50

Function of RAG

Recombination activating gene
Recognition and cleavage functions

51

Which cells express terminal deoxynucleotidyl transferase?

Only early B cells and T cells

52

HMG1

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

53

What does XRCC4 stand for?

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

54

Function of DNA ligase IV/XRCC4

Joins DNA ends

55

How are successful Ig gene rearrangements propagated?

B cell development is tied to successful Ig gene rearrangements

56

Stages of B cell development

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

57

What is happening in a pre-pro B?

D-J joining at heavy chain locus

58

What is happening in a pro-b?

V-DJ joining at heavy chain locus
If successful, progresses to pre B

59

What is happening in a pre b?

V-J joining at light chain locus
First at kappa, if unsuccessful, at lambda

60

How many pro b make it to becoming pre b?

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

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

E2B

62

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

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

63

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

1) BTK
2) BLNK
3) SLC

64

Function of Iga/b

Scaffolding proteins

65

Function of Syk and BTK

Kinases

66

Function of PAX5

Transcription factor that specifies B cell expression program

67

When is terminal deoxynucleotidyl transferase used?

Heavy chain recombination.