Lecture 6 Flashcards

1
Q

What is major rule of antibody synthesis?

A
  • Single B cell only makes one type of antibody
  • Occurs by allelic exclusion
  • Same is true for plasma cell
  • Only one type of H chain and one type of L chain
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2
Q

What has occured in ProB cell?

A
  • Heavy DJ rearrangement

- No light chain rearrangement

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3
Q

When does DJ rearrangement occur?

A

ProB stage

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4
Q

What do mature B cells have on surface

A

IgM & IgD with same variable region

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5
Q

What mediates VDJ rearrangement?

A

RSS

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6
Q

What do RAG1/2 do?

A

Enzymes that recognize and align RSS and cleave sequence between

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7
Q

Are all RAG rearrangements functional?

A

No

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8
Q

How do IgM and IgD end up on same cell?

A

Alternative splicing of nuclear RNA

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9
Q

What is junctional diversity?

A
  • N region addition
  • Nucleotides (B sequences) not present in germ line that are added to junctions of rearranged VDJ during rearrangement
  • Adds to diverstiy
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10
Q

What facilitates junctional diversity?

A

TdT

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11
Q

3 contributions to Ig Diversity?

A
  1. VDJ rearrangement
  2. Junctional diversity
  3. Combination of H & L chain
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12
Q

What happens to non functional VDJ rearrangements?

A

They are deleted

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13
Q

What happens to self reactive B cells?

A
  1. Become anergic
  2. Deletion
  3. Rescued by receptor editing
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14
Q

What happens to self reactive B cells?

A
  1. Become anergic
  2. Deletion
  3. Rescued by receptor editing
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15
Q

Where does isotype switching occur?

A

In periphery, not in marrow

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16
Q

What causes isotype switching?

A

B cell interaction with antigen

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17
Q

What can isotype switch result in?

A

IgG
IgE
IgA

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18
Q

What is necessary for isotype switch?

A
  • AID - Enzyme that will cleave loop
  • Cleaved region is ligated associating VDJ region with new gene
  • Cleaved region is deleted from genome
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19
Q

Can B cell undergo multiple isotype switches?

A

Yes

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20
Q

Where does generation of antibody diversity occur?

A

Generation of antibody diversity occurs in bone marrow in antigen independent manner

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21
Q

What is hypermutation?

A
  • Variable regions of Ig genes undergo BP mutation of 1/1000 when leave marrow
  • Known as hypermutation as rates exponentially greater than what’s seen in normal cells
  • Results in AA change in binding site changing its specificity
  • This does not occur in the bone marrow and this IS in response to antigen
22
Q

Is hyermutation in response to antigen?

A

Yes

23
Q

What is an anegic cell?

A
  • Non responsive, will not be activated when react with self
  • This can happen to self reactive cells
24
Q

What is danger of anergic cells?

A
  • Dangerous if become mutated and become activated

- Cause autoimmune disorders

25
Q

What is receptor editing?

A
  • Rescues self reactive B cells by changing receptor
  • Instead of getting signal to die, RAG is upregulated allowing for another VJ rearrangement resulting in new B cell that is hopefully not self reactive
26
Q

What is receptor editing?

A
  • Rescues self reactive B cells by changing receptor
  • Instead of getting signal to die, RAG is upregulated allowing for another VJ rearrangement resulting in new B cell that is hopefully not self reactive
  • Only happen on light chain
27
Q

Can receptor editing happen on heavy chain?

A
  • Cannot happen on heavy chain as all the “D’s” were deleted in initial rearrangement
  • However, simply changing light chain changes specificity of receptor
28
Q

Which chain rearranged first?

A

Heavy

29
Q

Which chain rearranged first?

A

Heavy

30
Q

How many epitopes does T cell recognize?

A

Only one

31
Q

How many epitopes does T cell recognize?

A

Only one

32
Q

Chains on T cell?

A
  • Alpha and Beta
  • Each chain has variable and constant region
  • Their variable regions come together to make binding site
33
Q

Is T & B cell concurrent in bone marrow?

A

No, T cells made in thymus

34
Q

T and B cell on same chromosomes?

A

Yes

35
Q

What are alpha and beta chains product of?

A

Alpha chain - product of V J rearrangement

Beta chain - product of VDJ rearrangement

36
Q

Do T cells demonstrate allelic exclusion?

A

Yes

37
Q

What mediates Rearragement in t cell?

A

Rag

38
Q

What ar TRECs?

A
  • T cell rearrangement excision circles

- Intervening DNA that is removed and deleted in rearrangement

39
Q

How do you tell if patient is making Trecs?

A

See if they have TRECs

40
Q

Different in T & B cell formation?

A
  • T cells do not display somatic hypermutation
  • T cells do not display isotype switch
  • T cells do not display differential splicing to get membrane & secreted form
41
Q

T/F: IG are encoded by gene segements on same chromosome?

A

False - Each family is on different chromosome

42
Q

T/F: one Ig can have two types of light chain

A

False

43
Q

T/F: myeloma proteins are result of polyclonal B cell activation

A

False

44
Q

T/F: In pre B cells both heavy and light chain genes are rearranged?

A

False

45
Q

When is hypermutation highly active?

A

Generation of memory B cells

46
Q

What has rearranged in Plasma Cell?

A

VDJ on one allele

VJ on other allele

47
Q

What has rearranged in Pre B lymphcyte?

A

No VJ
DJ on one allele
VDJ on other allele

48
Q

Main anitbody of primary response?

A

IGM

49
Q

Main antibody in secondary response?

A
  • IGG

- IGG levels stay high longer here than IGM does in primary

50
Q

Explain secondary reagent?

A
  • Inject Human IGG in animal and they make antibody it
  • Take human blood and mix with tetanus or something you were vaccinated for hoping that it will bind the antigen in tray
  • Take the animal generated antibodies to IGG and add them to tray and they should bind the human IGG
  • You label animal antibody with something you can detect
  • Secondary antibodies are directed against FC region of antibody