L7 Immunogenetics - Hudig Flashcards

1
Q

When stimulated with IL2, which B cells divide?

A

only the ones specific for the stimulating ag

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2
Q

Do TCRs and Ig chains follow the one gene one protein rule>?

A

no

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3
Q

How are TCR and Ab receptors encoded?

A

variable cassette regions

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4
Q

Where does the Ag bind on the TCR?

A

variable region, made of variable light (VL) and variable heavy (VH)

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5
Q

What holds the chains together?

A

disulfide bonds

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6
Q

What loci contain the D minigene? (3)

A

Ig H, TCR beta/delta

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7
Q

What are the only two regions of the minigenes that undergo somatic mutation?

A

IgL and H variable regions

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8
Q

How many cassettes of minigenes does each locus have?

A

2-3

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9
Q

What are the 7 variable region genes?

A
V (insert below letter)
alpha
beta
delta
gamma
lambda
kappa
Heavy
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10
Q

which V genes encode B cells?

A

Vheavy
V lambda Ig L
V kappa Ig L

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11
Q

Which V genese encode T cells

A

Valpha
Vbeta
Vdelta
Vgamma

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12
Q

What two enzymes are essential for T and B cell receptor formation?

A

RAG1 and RAG2

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13
Q

Complete loss of RAG1/2 results in complete loss of T and B cells resulting in (blank)

A

SCID

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14
Q

Tumors that express RAG1/2 are derived from early developmental stages of (blank)

A

lymphocytes

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15
Q

Tumors that express TdT are derived from early developmental stages of (blank)

A

lymphocytes

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16
Q

In T and B cells, is the somatic DNA for Ag receptors the same as the germline DNA?

A

no

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17
Q

Does germline rearrangement involve somatic mutation?

A

No, the DNA is rearranged/spliced WITHOUT mutation

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18
Q

What is the result of germline rearrangement?

A

The various mature B cells have different DNAs for Ig, different receptors and will make different antibodies.

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19
Q

What enzymes are necessary for DNA breaking and rejoining within the minicassettes?

A

RAG1/2

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20
Q

(blank) fills in a “wild card” nucleotide at the rejoining sections between minicassette selections

A

TdT (terminal deoxynucleotide tranferase)

21
Q

What are the 4 subunits that make up a heavy Ig chain and what enzyme fills in the gaps?

A
Vh
Dh
Jh
Ch
filled in by TdT
22
Q

Describe the process of germline rearrangement?

A
  1. Splice D and J together
  2. Splice V and DJ together
  3. VDJ used as primary RNA transcript
  4. RNA processing removes extra intron AND EXON sequences to form mRNA
23
Q

What are the extra exon sequences removed in germline rearrangement?

A

alternate forms of V/D/J

24
Q

How many cassettes does the light chain use?

A

2; VJ

25
Q

How many cassettes does the heavy chain use?

A

3; VDJ

26
Q

Does TdT cause mutations of the original DNA sequence?

A

No technically, it is creating NEW sequences by filling in the gaps around the original sequence

27
Q

Are the RAGs and TdT needed at each splicing step?

A

yes

28
Q

How many splicing steps are there in the rearrangement>?

A

2

29
Q

Do TCRs have hypermutation regions?

A

no, only Ig

30
Q

When does hypermutation occurr?

A

After minigene rearrangement

31
Q

In what gene region does hypermutation occur?

A

CDR region

32
Q

Somatic mutation occurs (the first/each) time an antigen is encountered.

A

Each time

33
Q

Explain how Ag reexposure causes B cell evolution?

A

Ag selects for B cells with highest affinity; so Ag boosters increase Ag affinity

34
Q

“Cold spots” for DNA mutation likely encode what gene?

A

constant regions

35
Q

Is Ab specificity retained after isotype switching of B cells?

A

yes

36
Q

What cell type is needed to aid in the switching of B celsl?

A

T helper

37
Q

Is the VDJ region changed during an isotype switch?

A

nope

38
Q

Th2 releases what cytokine and induces what Ig isotype?

A

IL4, IgE, inhibits IgG3

39
Q

TH1 releases what cytokine and induces what Ig isotype?

A

IgG3, inhibits IgE

40
Q

TGF-beta induces what Isotype?

A

IgG2 and IgA

41
Q

IL5 induces what isotype?

A

IgA

42
Q

What DNA region is deleted to result in class switching?

A

Heavy chain constant regions

43
Q

A preparation of identical antibodies, all with the same L and same H chains, derived from one (blank).

A

initial immune B cell

44
Q

Can monoclonal abs be cross-reactive>?

A

yes, when epitopes are similar, such as in the case in conserved regions of viruses

45
Q

hybridomas contain the chromosomes of what two cells?

A

tumor cell and immune B cell

46
Q

Explain the process of creating a humanized Ab?

A
  1. Make mouse anti-human antibody
  2. Splice out the CDR region from the mouse Ig and plug it onto the end of a human Ig
  3. Replace the intervening sequences between the CDR regions on the mouse bit you stuck onto the human Ig with human intervening sequences, so EVERYTHING except the specific CDR regions is totally human—no more reactivity and totally safe!
47
Q

what is the name for a chimeric mouse anti-human Ab?

A

ximab

48
Q

what is the name for a fully humanized Mab?

A

zumab

49
Q

Are human Mabs the same as humanIZED Mabs?

A

no!