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Immunology MDSC321 > Two Gene Theory > Flashcards

Two Gene Theory Flashcards

1
Q

What was proposed as a solution to the selective and instructional models?

A

Two gene theory

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2
Q

Who proposed the Two Gene Theory?

A

Dryer and Bennett

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3
Q

Two genes encode the Ig molecule. What are the genes for?

A

Variable Region

Constant Region

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4
Q

Why do we need many different copies of the variable gene?

A

Variable gene accounts for diversity

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5
Q

How many genes do we need for constant?

A

Only a few

One for each isotype

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6
Q

What does the Two Gene Theory say?

A

The few constant genes can be combined w any if the many variable genes to generate a Ig repertoire with huge diversity

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7
Q

Who confirmed the Two Gene Theory?

A

Tonegawa and Hozumi

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8
Q

How did Tonegawa and Hozumi prove the 2GT?

A

Analyzed Ig genes from Myeloma and embryonic cells and saw that the DNA was rearranged in the cancer cells and the DNA was germline in the embryonic cells

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9
Q

How many constant genes are there?

A

One for each isotype

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10
Q

What is the light chain variable region comprised of?

A

Variable (V) and a joining (J) gene segment

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11
Q

What is the heavy chain comprised of?

A

Variable, joining, and diversity gene segments

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12
Q

What are the two types if light chains?

A

Lambda and kappa

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13
Q

What type of bond is the backbone of a Ig?

A

Disulfide bonds

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14
Q

What does an Ig start as?

A

IgM > G,E,A

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15
Q

What is the order of genes in the light chain?

A

VJC

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16
Q

What is the order of genes in the heavy chain?

A

VDJC

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17
Q

How is additional genetic diversity generated?

A

Junctional diversity

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18
Q

Why does variation in the V(D)J joint greatly increase Ig diversity?

A

This seq corresponds to the third hypervariable loop which is where we contact the antibody

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19
Q

What are the 3 principles of Junctional diversity?

A
  1. Junctional flexibility
  2. P-nucleotide addition
  3. N-nucleotide addition
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20
Q

Junctional flexibility

A

Imprecise joining of the V(D)J gene segments

When we join two segments back together they are diff

21
Q

What does endonuclease do in junctional flexibility?

A

Deletes nucleotides from cut ends of the gene seg being joined which creates a frameshift

22
Q

Nonproductive

A

Frameshift

23
Q

P-nuc addition

A

Cutting of the hairpin loop not in the middle

24
Q

What does the p in pnuc addition stand for

A

palindromic

25
Q

What does pnuc result in

A

relocation of nucleotides from one strand to the other in the reverse sequence

26
Q

What happens to the nucleotides defiecient from the donor strand?

A

They are filled in complementary to the extneded strand

27
Q

Terminal deoxynucleotidyl transferase (TdT)

A

Enzyme that dds up to 15 random nuc to the end of a strand

28
Q

N-nucleotide addition

A

Uses TdT to add 15 nuc to end of the gene segment

29
Q

What does N stand for?

A

Non templated

30
Q

When is TdT expressed?

A

In H chain rearrangement

31
Q

N-nuc occur when?

A

Feature of the VDJ joint of H chains

32
Q

When does Ig rearrangement begin?

A

Early in B-cell development

33
Q

What kind of process is Ig rearrangement?

A

Tightly regulated
Sequential
Distinct steps

34
Q

What is rearrangement initatiated by?

A

RAG complex

35
Q

What does RAG recognize and do?

A

Recognizes the boarders of the gene segments and facilitates cleavage of the DNA

36
Q

What does a deficiency of RAG mean?

A

Bubble boy
Severe Combined Immune Deficiency (SCID)
You cannot make an adaptive immune system

37
Q

Choosing at the DNA level is

38
Q

Choosing at the RNA level

A

not permanent

39
Q

Which chain rearranges first?

40
Q

What are the inital H chain products paired with and where is the displayed?

A

Surrogate ligth chain

Pre-B-cell Receptor

41
Q

What is the surrogate ligth chain?

A

A placeholder with no diviersity

Vpre-B and lambda5

42
Q

How does the surrogate light chain start rearrangement?

A

Signalling thru the Pre-BCR induces the cell to begin L chain recomb.

43
Q

What must occur before the L chain rearranges?

A

A successful H chain recombination

44
Q

What is the hallmark of a surface Ig that it is ready for antigen?

45
Q

How does the cell (RAG) know where to cut the germline DNA?

A

The gene segments are flanked by short conserved sequences > (RSS) Recombination Signal Sequences

46
Q

What type of pattern do RSS have?

47
Q

What is RSS comprised of? (3)

A
  1. A conserved heptamer (7bp)
  2. A 12 or 23 bp non-conserved spacer sequence
  3. A conserved nonamer (9bp)
48
Q

12/23 rule

A

rearrangement always occur bw a RSS with a 12 or 23bp spacer

49
Q

What does the 12/23 rule make impossible

A

J-J or V-V
Has to be V-J (light)
No V-J in H
Just VDJ

Immunology MDSC321 (27 decks)

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