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I&I SC1 > Humoral Adaptive Immunology II > Flashcards

Humoral Adaptive Immunology II Flashcards

1
Q

What is the goal of B-cell development?

A

To create a unique B-cell receptor

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2
Q

Which steps are taken in commitment from a HSC to a B-cell lineage? (4)

A
  1. Hematopoietic stem cell -> multilineage progenitor (MLP)
  2. MLP -> common lymphoid progenitor (CLP)
  3. CLP -> pro-B-cell
  4. Pro-B-cell -> pre-B-cell
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3
Q

What is the restriction step in the process of B-cell development?

A

The step from multilineage progenitor to common lymphoid progenitor

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4
Q

Which factors are important for the restriction step in B-cell development? (2)

A
  1. Ikaros
  2. PU.1
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5
Q

What is the specification step of B-cell development?

A

The step from common lymphoid progenitor to pro-B-cell

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6
Q

Which factors are important for the specification step in B-cell development? (2)

A
  1. E2A
  2. EBF
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7
Q

Can a pro-B-cell differentiate into other cells than B-cells?

A

Yes, although it has already gone through a specification step, it is not yet committed

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8
Q

What is the commitment step of B-cell development?

A

The step from pro-B-cell to pre-B-cell

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9
Q

Which factor is important in the commitment in B-cell development?

A

Pax5

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10
Q

What is the marker for HSC’s and MLP’s? (=very immature cells)

A

CD117

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11
Q

What is the marker for immature B-cells?

A

CD34

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12
Q

What is the marker of all B-cells?

A

CD22

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13
Q

The BCR is presented on the cell membrane with a complex of proteins. Which complex is this, and what is its function?

A

CD79a/CD79b heterodimer
Provides intracellular signaling

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14
Q

What happens to the IGH-gene in pre-B-cells, and why?

A

This gene is contracted, to facilitate rearrangements (bringing segments closer together)

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15
Q

What are the steps in Ig-gene rearrangement? (6)

A
  1. Opening of locus of the segments that are due to be rearranged (first D+J, later V)
  2. RAG introduces dsDNA break
  3. dsDNA break closed by hairpins
  4. Hairpins opened by Artemis
  5. TdT introduces random nucleotides at the joint between two segments
  6. Ligation of segments by DNA ligase IV
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16
Q

Which gene segments arrange during the pro-B-cell stage?

A

D-J (heavy chain)

17
Q

Which gene segments rearrange during the pre-B-I-stage?

A

V-DJ (heavy chain)

18
Q

At which stage does the pre-BCR checkpoint take place?

19
Q

Most arrangements of the heavy chain are [succesful/unsuccesful]

A

Unsuccessful

20
Q

Which factors can lead to unsuccesful gene rearrangements? (3)

A
  1. Sequence no longer in frame (non triplet-coding)
  2. Introduction of stop codons by insertion/deletion of nucleotides
  3. Non-functional protein due to use of pseudogenes
21
Q

What happens at the pre-BCR checkpoint?

A

The rearranged heavy chain is presented together with a surrogate light chain

If succesful rearrangement of heavy chain: signalling will occur
If unsuccesful rearrangement: death by neglect

22
Q

Which processes are kicked off after succesful pre-BCR signaling? (4) Which signals are responsible for each of these?

A
  1. Cell proliferation and survival via IL-7
  2. Closing of the IGH-locus to prevent further rearrangement via Syk-signaling
  3. Opening of the light chain locus -> Btk-signaling
  4. Downregulation of the surrogate light chain (Btk-signaling)
23
Q

Which step in B-cell development is defect in the case of agammaglobulinaemia? Which protein is often mutated, and what does the lack of this protein cause??

A

Pre-BCR signaling
Btk -> necessary to trigger further processes in development, so defects cause no B-cell development to take place

24
Q

What does abnormal pre-BCR activation result in?

A

Lymphoblastic leukaemia

25
Q

What can trigger abnormal pre-BCR signaling? (2)

A
  1. Activating mutations
  2. Translocations
26
Q

Where is the κ-locus of the Ig light chain located?

A

Chromosome 2

27
Q

Where is the λ-locus of the Ig light chain located?

A

Chromosome 22

28
Q

During which stages does light chain rearrangement take place?

A

Pre-B-II small and onwards

29
Q

Which of the light chain loci rearranges first? What triggers rearrangement of the other locus?

A

κ-locus
Unsuccesfull rearrangement of both κ-loci triggers λ-rearrangement

30
Q

What happens to the κ-locus when they are unsuccesfully rearranged?

A

They are shut down by κ-deleting element -> deletes the constant domain of the κ-locus

31
Q

What characteristic of the CDR’s of Ig-receptors is associated with autoreactivity?

A

Long CD3 domains with positively charged amino acids

32
Q

How is autoreactivity of B-cells detected?

A

Activation of the BCR in the bone marrow

I&I SC1 (20 decks)

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