Antigen Recognition by Lymphocytes III

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34 Terms

1
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Even though we need diversity, what consistency do we need to maintain?

Consistency to recognize self HLA or use the constant regions of heavy chains

2
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What are the two possible models for diversity?

  1. Germ-line theory

  2. Somatic variation

3
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What is germ-line theory?

There is a different gene for each immunoglobulin/BCR (it is somehow encoded in our genome)

4
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What is somatic variation?

The genome only has a few genes but they recombine to generate diversity (have all the parts but it is how you assemble them that makes the diversity) (encodes it in the genome but varies at the cellular level)

5
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What is the concept behind VDJ recombination?

Assemble all the components in all the different combinations and release them to see if it can see that antigen. If it can’t then it will die

6
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How does the immune system generate diversity?

With volume and by recombining gene fragments in many combinations

7
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How is TCR and BCR diversity generated?

By permanent editing of genetic loci in individual cells

8
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How do B cells generate diversity?

  1. VDJ recombination/rearrangement

  2. Romantic hypermutation/affinity maturation

  3. Isotype switching

9
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How do T cells generate diversity?

VDJ recombination/rearrangement

10
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How are different isotypes generated?

Regions of the BCR locus can be put together in different combinations to have antibodies with different heavy chains (isotypes)

11
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What is the variable region generated by?

VDJ recombination

12
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Why might the B cell want to change its constant region?

This is because of what it might see in the environment

13
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What can the same CH or CL region be connected to?

Millions of different VH or VL regions

14
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What can the same VH region be connected to?

Different CH regions

15
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Can B cells crop out pieces of their DNA?

Yes

16
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What is the order for antibody production on the locus?

MADGE

17
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If the B cell cuts out M from the locus will you ever get M again? Can you go from A to M?

No to both

18
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Are there separate loci for each of the heavy chains in the genome?

Yes and they are selectively cut in B cells

19
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Do separate genes encode the V and C regions in immunoglobulins?

Yes

20
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What is the difference between individual and mature B cells?

Individual B cells had different sequences at the BCR locus and mature B cells were often missing parts of the constant locus

21
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Why are B cells cutting pieces of DNA out of the locus?

To sequence the same locus over and over again

22
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What os BCR diversity generated by?

Shuffling the constant and variable regions

23
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What does the immune system encode for TCR and BCR?

Alternates for the gene loci

24
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What does the random combination of the loci generate?

Extensive diversity while only taking up a bit of space in the genome (don’t have to keep replicating DNA because you keep certain segments)

25
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What does a mature B cell encode? What is this process called?

A BCR locus where one of each of VDJ or VJ is retained then joined to a constant region (Heavy and light chain rearrangement)

26
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Is the locus further edited and activated after VDJ or VJ is joined to the constant region?

Yes

27
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Is VDJ the light or heavy chain?

Heavy chain

28
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Is VJ the light or heavy chain?

Light chain

29
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Will the B cell die if it can’t undergo heavy and light chain rearrangement?

Yes

30
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Do B cells have two chromosomes (two loci)?

Yes

31
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What is allelic exclusion? Does this occur in B cells?

It is when one locus is silenced in each B cell and one locus is kept one. This is to ensure the B cell only has specificity for one antigen. It is now able to make a BCR for that specific antigen

32
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What is the end product of BCR gene recombination?

A B cell capable of making only one type of BCR

33
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Is TCR recombination the same as BCR recombination? Does it include allelic exclusion

Yes for both

34
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What is something different between TCR and BCR gene recombination?

TCR can not further mature beyond this stage so all the diversity is generated during VDJ rearrangement