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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?

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
What is receptor editing?
- 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
What is receptor editing?
- 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
Can receptor editing happen on heavy chain?
- 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
Which chain rearranged first?
Heavy
29
Which chain rearranged first?
Heavy
30
How many epitopes does T cell recognize?
Only one
31
How many epitopes does T cell recognize?
Only one
32
Chains on T cell?
- Alpha and Beta - Each chain has variable and constant region - Their variable regions come together to make binding site
33
Is T & B cell concurrent in bone marrow?
No, T cells made in thymus
34
T and B cell on same chromosomes?
Yes
35
What are alpha and beta chains product of?
Alpha chain - product of V J rearrangement | Beta chain - product of VDJ rearrangement
36
Do T cells demonstrate allelic exclusion?
Yes
37
What mediates Rearragement in t cell?
Rag
38
What ar TRECs?
- T cell rearrangement excision circles | - Intervening DNA that is removed and deleted in rearrangement
39
How do you tell if patient is making Trecs?
See if they have TRECs
40
Different in T & B cell formation?
- 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
T/F: IG are encoded by gene segements on same chromosome?
False - Each family is on different chromosome
42
T/F: one Ig can have two types of light chain
False
43
T/F: myeloma proteins are result of polyclonal B cell activation
False
44
T/F: In pre B cells both heavy and light chain genes are rearranged?
False
45
When is hypermutation highly active?
Generation of memory B cells
46
What has rearranged in Plasma Cell?
VDJ on one allele | VJ on other allele
47
What has rearranged in Pre B lymphcyte?
No VJ DJ on one allele VDJ on other allele
48
Main anitbody of primary response?
IGM
49
Main antibody in secondary response?
- IGG | - IGG levels stay high longer here than IGM does in primary
50
Explain secondary reagent?
- 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

Host Defense (12 decks)

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