Lecture 6 Flashcards

1
Q

What are the 4 mechanisms that generate antibody diversity?

A
  1. Somatic recombination
  2. Imprecise recombination junctions
  3. Combinational pairing
  4. Somatic hypermutation
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2
Q

Which antibody diversity mechanisms occur BEFORE antigen stimulation?

A

-Somatic recombination
-Imprecise junctions
-Combinatorial pairing

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3
Q

Which antibody diversity mechanisms occur AFTER antigen stimulation?

A

Somatic hypermutation

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4
Q

True or false: the 4 mechanisms of antibody diversity occurs in both the variable and constant regions

A

False
-happens in VARIABLE regions of light and heavy chains

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5
Q

What happens in somatic recombination?

A

Alternative versions of the variable region (variable, joining, and diversity) are brought together by DNA rearrangement

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6
Q

How many segments are encoded by the variable light chain?

A

2
-Variable
-Joining

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7
Q

How many segments are encoded by the heavy chain?

A

3
-Variable
-Joining
-Diversity

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8
Q

True or false: The variable light chain has a diversity segment

A

False
-Only variable and joining segment

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9
Q

Where does rearrangements of the V and J occur?

A

Germline
-At DNA level

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10
Q

How does somatic recombination lead to B cell diversity?

A

By randomly picking pieces there are many different versions of B cell for variable region sin the light and heavy chains that will make different specificity

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11
Q

True or false: Only developing B cells rearrange their Ig loci

A

True

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12
Q

How does gene recombination work?

A

RAG proteins bind to RSS (signal sequence) flanks segments that need to be recombined and breaks DNA at the joint

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13
Q

How is a coding joint formed?

A

RAG gets rid of a portion of immunoglobulin loci which brings V and J making a coding joint

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14
Q

How does imprecise recombination further increase diversity?

A

Uses TDT enzyme that adds nucleotides to junctions after RAG cleaves
-Adds/subtracts nucleotides RANDOMLY to each developing cell which makes diff junctions

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15
Q

Why does CDR3 have the highest variability?

A

Has 2 imprecise junctions

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16
Q

What is combinatorial pairing?

A

Pairs different combinations of heavy and light chains which adds diversity

17
Q

What is somatic hypermutation?

A

Uses AID to introduce random mutations by using nontemplated nucleotides in variable region of light and heavy chain
-occurs after antigen stimulation

18
Q

What is AID?

A

Used in somatic hypermutation
-introduces non-templated nucleotides that cause mutations to Variable region of light and heavy chain

19
Q

Does AID affect the constant region?

A

No, only affects variable regions

20
Q

Why can somatic hypermutation lead to antibodies withy higher, similar, or lower affinities?

A

Because it is a random process

21
Q

Before antigen encounter, the only heavy chains expressed by mature B cells are?

A

u and delta

22
Q

What does the Cu and Cdelta encode for?

A

IgM and IgD respectively

23
Q

What regions determine isotype swtiching?

A

switch regions

24
Q

Naive immature B cells express?

A

ONLY IgM
-only Cu region

25
Q

Naive mature B cells express?

A

Can make both IgM and IgD
-make both Cu and Cdelta
-IgD CANNOT be secreted

26
Q

What determines if Cu and/or Cdelta is made?

A

Alternative mRNA splicing

27
Q

True or false: Alternative mRNA splicing is a type of isotype switching

A

False
It is not a type of isotype switching b/c does not use switch sites and isotype switching occurs AFTER antigen encounter
-Alternative mRNA splicing happens before antigen encounter

28
Q

After antigen encounter occurs what is needed to do isotype switching?

A

T cell help (CD4 T cells)

29
Q

Which isotypes occur before antigen encounter and isotype swtiching?

A

IgM and IgD

30
Q

What happens when there is antigen stimulation accompanied by T cell help?

A

T cell help allows for isotype switching through induction of AID–>allows for switching
-Variable region does NOT change

31
Q

Does variable region change during isotype switching?

A

No, it is the same from somatic recombination
- constant region changes

32
Q

What happens when there is antigen stimulation without T cell help?

A

Only IgM is produced
-NO isotype switching

33
Q

How do B cells secrete their receptor/antibody after activation?

A

Eliminate trans-membrane region via RNA processing

34
Q

How does isotype switching work?

A
  1. BEFORE antigen encounter: Naive B cells only make Cu (immature) or Cu/Cdelta (mature)–>RNA splicing determines
  2. AFTER antigen encounter: isotype switching occurs via DNA recombination of switch sequences when AID is induced and T cell help