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Immunology > Lymphocyte receptor development and antigen receptor gene rearrangement > Flashcards

Lymphocyte receptor development and antigen receptor gene rearrangement Flashcards

1
Q

At what stage in development does a B cell begin DH to JH rearrangement?

A

Pro-B cell

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2
Q

At what stage in development does a B cell complete VJ rearrangement for kappa and/or lamba chains?

A

Immature B cell

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2
Q

At what stage in development does a B cell complete VH to DJH rearrangement?

A

Pre-B cell

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3
Q

At what stage in development does a B cell begin to express IgM?

A

Immature B cell

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4
Q

At what stage in development does a B cell begin to express IgD?

A

Mature B cell

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4
Q

Which surface marker(s) are present on B stem cells?

A

CD43+

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5
Q

Which surface marker(s) are present on pro-B cells?

A

CD43+, CD19+, CD10+

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6
Q

Which surface marker(s) are present on pre-B cells?

A

B220lo, CD43+

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7
Q

Which surface marker(s) are present on mature B cells?

A

IgM+ and IgDhi

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7
Q

Which surface marker(s) are present on immature B cells?

A

IgM+, CD43-

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8
Q

At what stage in development does a T cell begin DB to JB gene rearrangement?

A

Pro-T cell

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9
Q

At what stage in development does a T cell complete Va to Ja gene rearrangement?

A

Double positive T cell

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9
Q

At what stage in development does a T cell complete VB to DJB gene rearrangement?

A

Pre-T cell

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10
Q

At what stage in development does a T cell begin to express aB TCR?

A

Double positive T cell

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11
Q

Which surface marker(s) are present on T stem cells?

A

c-KIT+
CD44+
CD25-

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12
Q

Which surface marker(s) are present on pro-T cells?

A

c-KIT+
CD44+
CD25+

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13
Q

Which surface marker(s) are present on pre-T cells?

A

c-KIT+
CD44-
CD25+

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14
Q

Which surface marker(s) are present on double positive T cells?

A

CD4+/CD8+
TCR/CD3lo

15
Q

Which transcription factors are associated with B lineage hematopoiesis?

A

EBF, E2A, and PAX5

16
Q

Which transcription factors are associated with T lineage hematopoiesis?

A

Notch 1 and GATA3

17
Q

Which transcription factors are associated with innate lymphoid cell hematopoiesis?

A

Id2

18
Q

What are the components of the pre-BCR?

A

u heavy chain, invariant surrogate light chains (v pre-B protein and lamba5 protein), and signal-transducing Iga and IgB

19
Q

What are the components of the pre-TCR?

A

TCR B chain, invariant pre-T alpha (pTa) chain and signal-transducing CD3 and zeta proteins

20
Q

What are the signals propagated by the pre-BCR?

A
  1. Proliferation of pre-B cells
  2. Inhibition of H chain recombination (allelic exclusion)
  3. Stimulation of kappa light chain recombination
  4. Shut off surrogate light chain transcription
21
Q

What are the signals propagated by the pre-TCR?

A
  1. Proliferation of pre-T cells
  2. Inhibition of B chain gene recombination
  3. Stimulation of alpha chain rearangement
  4. Shut off pre-Ta chain transcription
  5. Expression of CD4 and CD8
22
Q

What is the pathophysiology of X-linked agammaglobulinemia?

A

Mutations in Bruton tyrosine kinase prevent delivery of signals from BCR that mediate survival, proliferation and maturation beyond the pre-B cell stage.

23
Q

What is somatic hypermutation?

A

High frequency point mutations in Ig heavy and light chains that occur in germinal center B cells in response to signals from Tfh cells. It is present in B cells only. Mutations are clustered in V regions, mostly in CDRs.

24
Q

Which enzyme mediates somatic hypermutation?

A

AID

25
Q

What is receptor editing?

A

Inducement of further Ig gene rearrangements in strongly self-reactive immature B cells

26
Q

Which enzyme in the thymus induces expression of self antigens usually only expressed in specific peripheral organs?

A

autoimmune regulator (AIRE)

27
Q

What is the end result of positive selection of T cells?

A

Cells with TCRs that recognize MHC
Expression of coreceptor (CD4 , CD8) complementary to MHC recognized

28
Q

What is the end result of negative selection of T cells?

A

Elimination of cells with high affinity for self antigens (clonal deletion)

29
Q

What is the end result of positive selection of B cells?

A

Cells with functional BCRs

30
Q

What is the end result of negative selection of B cells?

A

Induction of further Ig gene rearrangements in self-reactive cells
Elimination of cells whose rearrangements continue to contribute to formation of self-reactive cells (clonal deletion)

31
Q

Where do positive and negative selection of B cells occur?

A

Bone marrow

32
Q

Where does positive selection of T cells occur?

A

Thymic cortex

33
Q

Where does negative selection of T cells occur?

A

Thymic medulla

34
Q

In which order do positive and negative selection of B and T cells occur?

A

Positive selection occurs first, followed by negative selection

35
Q

What are the four steps of VDJ rearrangement?

A
  1. Synapsis
  2. Cleavage
  3. Hairpin opening and end-processing
  4. Joining
36
Q

Describe synapsis in V(D)J recombination.

A

Coding segments and adjacent recombination signal sequences (RSSs) brought together by chromosomal looping event

37
Q

Describe cleavage in V(D)J recombination.

A

V(D)J recombinase (RAG1 and RAG2) creates double stranded breaks at RSS-coding sequence junctions.

38
Q

Describe hairpin opening and end-processing in V(D)J recombination.

A

ARTEMIS opens hairpins. Terminyl deoxynucleotidyl transferase (Tdt) adds nucleotides to broken DNA ends.

39
Q

Describe joining in V(D)J recombination.

A

DNA-dependent protein kinase (DNA-PK) and DNA ligase join segments together.

40
Q

Describe the 12/23 rule.

A

Recombination only occurs between two segments if one segment is flanked by a 12-nucleotide spacer and the other by a 23-nucleotide spacer. 12- and 23- nucleotide spacers correspond to 1 or 2 turns of a DNA helix and ensure that two RSSs are brought close to each other for recombination.

Immunology (10 decks)

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