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Immunology-Nicole > Assignment #10: Adaptive Immunity > Flashcards

Assignment #10: Adaptive Immunity Flashcards

1
Q

B cells arise in the bone marrow from what?

A

Progenitor Lymphoid Cells

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2
Q

Explain central tolerance, in reference to developing B cells

A

Selection processes occur that ensure that developing B cells that express receptors for self antigen, are inactivated or deleted.

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3
Q

what is the main purpose of B cell maturation?

A

central tolerance

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4
Q

B cell receptor complex includes what?

A

B cell antigen recognizing receptor (BCR) and associated heterodimers CD79a/CD79b

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5
Q

what is the role of the B cell receptor (BCR)?

A

cell surface membrane immunoglobulin (mIg) that recognizes and interacts with intact antigens

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6
Q

Is the BCR linked to any signal transduction pathways?

A

NO (remember its a cell surface membrane immunoglobulin)

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7
Q

what does link the BCR to the signal transduction pathway then?

A

CD79a/CD79b (Igalpha-Igbeta)

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8
Q

All naive (mature) B cells express, what two mIg isotypes?

A

IgM and IgD

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9
Q

Immunoglobulin (mIg) molecules are composed of what?

A

two identical heavy chains and two identical light chains linked by a disulfide bond. With each chain made up of a variable and constant region.

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10
Q

In mature (naive) B cells, what are the heavy chain and light chain constant regions made up of?

A

Heavy Chain –> Mu and Delta

Light Chain –> Kappa and Lambda

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11
Q

what segments are the heavy and light chains made up of?

A

Heavy –> V,D,J

Light –> V and J

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12
Q

Exquisite specificity (and hence diversity) is made possible because of what?

A

the V,D, and J gene segments, which encode the variable regions, are present on multiple germline genes that are rearranged to make unique variable regions.

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13
Q

Somatic recombination (construction of unique variable regions) is a result of 4 things.

A
  1. Multiple copies of germline V,D,and J gene
  2. Junctional diversity (due to the addition or deletion of bases)
  3. Random selection and combination of V,D, and J gene segments
  4. Random Assortment of light and heavy chains
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14
Q

The process in which DNA in the loci that encode the variable regions is cut and recombined to make an intact gene for the variable regions of the light and heavy chains is….?

A

Somatic recombination

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15
Q

What then triggers this somatic recombination process?

A

Activation of recombinases, which are the nuceloprotein products of the RAG-1 and RAG-2 genes

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16
Q

Explain what combinational diversity is

A

Random selection of V, D and J gene segments

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17
Q

Explain what junctional diversity is?

A

Additional DNA nucleotides may be deleted, or inserted at V,D,J gene segment junctions in order to maintain (downstream) an open reading frame

18
Q

Incorporation of nucleotides at junctions is mediated by a template independent DNA polymerase, called?

A

terminal deoxynucleotidyl transferase (Tdt)

19
Q

Explain what random association/assortment is

A

light chain with any heavy chain allows for another level of diversity in creating unique antigen binding sites

20
Q

What is allelic exclusion?

A

Successful rearrangement of a heavy chain variable region from one chromosome inhibits the somatic recombination of the heavy chain variable region on the other member of the chromosome pair .

21
Q

what is the net effect of allelic exclusion?

A

all mIg present on the surface of any one B cell will have the same heavy chain variable region.

22
Q

In general when does B cell differentiation in the bone marrow occur?

A

Prior to any exposure to foreign antigens

23
Q

In general what is B cell differentiation?

A

expression and silencing of distinct sets of genes at discrete stages of development.

24
Q

What is the ultimate goal of B cell differentiation?

A

generation of B cell receptor that is non autoreactive.

25
Q

B cell differentiation occurs in multiple stages, the first stage is the Pro-B cell stage, what in general occurs during this stage?

A

transcription of multiple genes including RAG-1 and RAG-2, CD19, Tdt, and CD79a/CD79b.

26
Q

What kinase is expressed during the transition from Pro-B to Pre-B cells stages?

A

Btk

27
Q

The next stage in B cell differentiation is Pre-B cell stage, what in general occurs in this stage?

A

expression of a pre-B cell receptor (pre-BCR) in association with the CD79a/CD79b heterodimer.

28
Q

The pre-BCR complex is composed of what?

A

two (mu) heavy chains whose variable regions have been rearranged. paired with two invariant pseudo light chains

29
Q

Does somatic recombination occur during the pre-B cell stage?

A

yes

30
Q

what is expressed during the pre-B cell stage?

A

CD-20

31
Q

does CD-20 persist throughout all stages of B cell development?

A

yes

32
Q

The third stage in B cell differentiation is, immature B cell stage, in general what occurs?

A

Assembly of newly synthesized light chain with heavy chain ( aka pre-BCR to BCR shift)

33
Q

Tolerance induction occurs in the immature B cell stage, explain what happens during tolerance induction

A

specific inactivation of B cells expressing autoreactive mIg (immunoglobulin) is accomplished by apoptosis (destruction) or induction of anergy (non responsiveness)

34
Q

Immature B cells that survive tolerance induction in the bone marrow migrate to where?

A

to the spleen to complete their maturation

35
Q

The final stage of B cell differentiation is mature or naive B cell stage, in general what happens in this stage

A

immature B cells transiton to naive (mature) B cells that express both IgM and IgD on the cell surface.

36
Q

The ability of co-expression of IgM and IgD on the mature B cell is due to what?

A

consequence of alternative splicing and occurs at the hnRNA level.

37
Q

what cell surface protein is expressed in the transition from immature to mature B cell

A

CD40

38
Q

Btk (Bruton’s Tyrosine Kinase) is mutated or not expressed in patient with?

A

X-linked agammaglobulinemia

39
Q

what is the consequence of a mutated Btk?

A

pre-B cells that form are defective and so maturation is halted.

40
Q

What is a leaky B cell?

A

Small numbers of B cells are present in the peripheral blood of most XLA (x-linked agammaglobulinemia) patients.

Immunology-Nicole (20 decks)

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