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Block 6 Week 1 > Genetics of Ig and TCR Diversity-Hudig > Flashcards

Genetics of Ig and TCR Diversity-Hudig Flashcards

1
Q

What is infliximab?

A

it is a humanized monoclonal antibody to TNF alpha that reduces immune responses and inflammation (used for rheumatoid arthritis and chrons)

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2
Q

Do we have enough DNA to encode all the different antiodies and TCR receptors? THen how do we have them?

A 
no, 
genetics with cassettes for variable regions for both immunoglobulin and T cell receptors.
Genetics of the immunoglobulin class switch. somatic mutation of ig antigen binding sites
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3
Q

What is a class switch?

A

it is when a B cell switches from making IgM to a different kind of Ig but still has the same antigen binding specificity

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4
Q

The receptors of T and B cells have variable regions and the remainder of the receptors are constant regions.
T or F

A

T

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5
Q

Genes for Ig and TCR contain (blank) for variable regions.

A

cassettes

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6
Q

Each gene locus for Ig has how many cassettes of minigenes?

A

2 or 3

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7
Q

What is a cassette?

A

minigenes for making the light and heavy chains with alternative splicing to get different introns

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8
Q

T or F
both light and heavy chains have constant domains. The constant regions are the same for ALL antibodies of the same isotype

A

T

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9
Q

How do you make a heavy chain out of the cassettes?

A

you need a V, a D, and a J

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10
Q

How do you make a light chain?

A

One V and one J, NO D’s

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11
Q

How many chromosomes have V,D,J cassettes and what are they?

A 
7
For B cells
o	B cell heavy chain – Vh
o	B cell lambda light chain – Vlambda 
o	B cell kappa light chain – Vkappa
For T cells
o	TCR alpha chain - Valpha
o	TCR beta chain – Vbeta
((((((superantigens bind to V beta)))))))))
o	TCR gamma chain - Vgama
o	TCR delta chain – Vdelta
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12
Q

Where do you find the D minigene cassette?

A

ony Ig H, TCR beta and TCR delta loci

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13
Q

Where can you get somatic mutation in Ig?

A

in Ig L and H variable regions

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14
Q

Do you get somatic changes in TCR?

A

NOOOOOO!!!!

only in Ig

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15
Q

What do you need to make the T and B cell receptors and what will you get if you dont have them?

A

RAG1 and RAG2

(they splice minigene cassettes to make diffferent B and T receptors) without either of these you will get SCID

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16
Q

What do the 7 loci to make the B and C receptors have in common?

A

They all have variable regions

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17
Q

RAG1 and RAG2 are expressed only in (blank)

A

developing lymphocytes (thymus and bone marrow)

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18
Q

Tumors that express RAG1 and RAG2 are derived from eary developmental stages of (blank)

A

lymphocytes

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19
Q

(blank) adds N-nucleotides to the V,D, and J exons during antibody gene recombination, enabling the phenomenon of junctional diversity.

A

TdT

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20
Q

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

A

lymphocytes

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21
Q

(blank) is DNA inherited in the embryo and kept unchanged in the gonadal germline cells.

A

Germline DNA

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22
Q

(blank) is DNA found in differentiated cells. It’s the same as germline DNA for most cells.

A

Somatic DNA

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23
Q

T and F
For both of the chains of TCRs and immunoglobulin, DNA segments are selected from the germline DNA and the DNA is rearranged (with DNA removed) to form somatic genes that will encode the light and heavy chain proteins.

A

T

24
Q

T and B cell receptors are considered somatic DNA why?

A

because the DNA is messed with, rearranged, spliced, deleted therefore making it different from the germline DNA

25
Q

How do you get germline rearrangments for B cells?

A

Casettes of minigenes
some are used and some are deleted. The DNA then becomes rearranged without mutation. This makes for production of different antibodies, different, and different receptors

26
Q

(blank) and (blank) are necessary fro DNA breaking and rejoinging insides the mini cassettes

A

Rag 1 and Rag 2 (recombinase-activating gene)

27
Q

What does TdT do?

A

allows for the rejoining of mnicassettes after there has been alterations

28
Q

How do you make a heavy Ig chain?

A

1 VH minigene, 1 DH minigene, I JH minigene plus CH filled in by TdT to create a heavy Ig chain.

29
Q

(blank) fills in gaps where DNA was cut and joined. The original DNA retains its original sequence, so TdT fills in new sites so TdT does not cause mutations of the original DNA.

A

Terminal deoxynucleotide transferase (TdT)

30
Q

How do you make an antibody?

A

with one light chain and one heavy chain

31
Q

Hypermutation at hot spots occurs (before/after) the V region minigenes are rearranged, in the CDR (complementary determining regions)

A

after

32
Q

(blank) occurs each time an antigen is re-encountered

A

somatic mutation

33
Q

One Ig Heavy chain is made of 1 Vh V minigene, 1 D minigene, 1 J minigene, and a Ch. The (blank) region determines the isotype

A

The Ch (constant region)

34
Q

o T and B cells don’t have somatic DNA to germline DNA
 The chosen V,D and J genes are spliced together, with a loss of the intravening region
—-Selection is random
WHich minigene is the one transcribed to make the Ig??

A

The nearest minigene to the constant region is the one transcribed to make Ig

35
Q

T or F

• Sometimes rearrangements don’t work. If the spliced DNA can’t be transcribed into RNA, then it hasn’t worked.

A

T

36
Q

(blank) is also how the naïve B cell can express two different antibodies, IgM and IgD

A

Differential splicing

37
Q

Describe the sequential events of B cell responses?

A

Stem cells in bone marrow make b cells-> naive or virgin make IgD or IgM-> Antigen response-> isotype switch> plasma cells form -> More B cells are made in peyers patches, spleen, lymph nodes-> antibodies in blood-> production of IgG, IgA, IgE

38
Q

Rearrangments to make different antibodies sometimes doesnt work. If the spliced DNA cant be transcribed into RNA then it hasnt worked. What are the reasons that it wont work?

A

if both chromosomes are unable to survive rearrangment. Each B cell has 2 changes to rearrange the heavy chain and four chances to rearrange the light chain (kappa or lambda)

39
Q

How can somatic mutation increase affinity?

A

one B cell has an antibody that binds to antigen. The affinity is low but still enough to activate the B cell. So the B cell starts to divide. TO improve the affinity, there is somatic mutation-> this process is called affinity maturation.

40
Q

Within the V (D) J regions, there are hot spots of mutation. Each time the B cell divides, the hot spots of mutation (blank) the VDJ regions. What does this mean?

A

mutate
THis means each B cell clone is different, and so each one will have a different affinity. (some will have higher affinity, some will have worse affinity, then one with the best affinity will be selected and replicated)

41
Q

Everytime the body encounters (blank), you drive more division and thus more selection for higher and higher affinity.

A

antigen

42
Q

What is cytidine deaminase?

A

an inducible enzyme that can deaminate and then cause the insertion of a random nucelotide

43
Q

Do T cells mutate to increase affinity?

A

no, they keep their original specificity

44
Q

What is Ig switch controlled by?

A

T cell cytokine concentrations

45
Q

Memory B cells have (blank), (blank), or (blank) receptors

A

IgA, IgG, IgE

46
Q

Different types of TH pull the switches and tells the original proiferating B cell which way to go? When you have a lot of IL-4 secreted by TH2 what do your B cells make?
What if you have a lot of IFN-gamma secreted by TH1?

A

IgG1 and IGE

IgG3

47
Q

What are polyclona antibodies?

A

Antibodies made in vivo

48
Q

What is a monoclonal antibody (Mab)?

A

antibody derived in a lab

49
Q

How do you make a monoclonal antibody?

A

prep of identical antibodies, all w/ the same L and H chains, derived from one initial immune B cell.
It is secreted by a hybrid tumor cell to form hybridoma so the cellular source of the antibody is immortal.

50
Q

Can monoclonal antibodies still be cross-reactive when epitopes are similar?

A

Yes :(

51
Q

What is Ximab?

A

chimeric

52
Q

What zumab?

A

fully humanized

53
Q

What is a monoclonal antibody?

A

a humanized monoclonal antibody is a mouse Mab to a human epitope, with the mouse constants replaced

54
Q

A (blank) monoclonal antibody is a mouse Mab to a human epitope, with the mouse constants replaced. However this form still contains mouse DNA that is intervening between the genes regions that form the variable region (VDJ regions). In order to be a (blank) Mab the intervening mouse regions are replaced with human DNA. This process is repeated for the light Ig chain to complete a complete Mab

A

“humanized”

“fully humanized”

55
Q

Monoclonal antibodies can now be made from immune human B cells
T or F

A

T

56
Q

A human monoclonal antibody is different from a humanized mAB T or F

A

T

57
Q

(blank) – antibody is human except for the tiny complimentarity determining region – almost no chance of rejection

A

humanized monoclonal antibody

Block 6 Week 1 (13 decks)

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