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40 Cards in this Set

  • Front
  • Back
For immunoglobulin genes, the joining of a number of the exons occurs via a rearrangement of the gene segments at what level?
DNA rather than at the level of mRNA
What does Ig expression start with?
IgM and IgD to the final Ig AGE
What do the C gene segments (constant regions) give rise to?
GAMED isotypes
What are the gene segments that heavy chain genes are assembled from?
VDJ and C
What are the two types of light chains?
kappa and lambda
Each of the Ig light chain genes is assembled by the rearrangement of what?
VJ and C gene segments
How does rearrangement occur?
Between specific sites on the DNA called Recombination signal sequences or RSS
What is rearrangement catalyzed by?
RAG-1 and RAG-2
inverted repeats that allow the DNA to form a stem-loop with them aligning on the stem.
RSS
RSS 7 and 9 signal sequences are separated by what?
1 turn of DNA (12 bp spacer) or 2 turns of DNA (23 bp spacer)
Ensures that gene segments are joined in the correct order
12/23 rule of RSS
Joint made in forming the small circle of DNA that has no function in the rearrangement process
Signal joint
occurs if the number of nucleotides added across the joining region allows the genetic code to be read in phase.
Productive rearrangement
occurs if the number of nucleotides added across the joining region causes the genetic code to be read out of phase (the majority of times).
Nonproductive rearrangement
What does a nonproductive rearrangement result in?
an incomplete antibody (run into stop codons) B cell may be able to productively rearrange the Ig gene on the other chromosome, otherwise death of the B cell.
occurs when only one of two alleles is expressed.
Alleleic Exclusion
ensures that a given B cell will make antibody molecules with only a single specificity.
Alleleic Exclusion
Mature (but not activated) B cells initially express what on their external cell membranes?
IgD and IgM
As mature B cells are activated to divide and differentiate by their cognate antigen, they switch from membrane-bound IgD and IgM to what?
secretory IgM
Where does the choice of expressing IgD or IgM on a B cell occur and why does this matter?
Occurs at the level of processing mRNA so a given B cell can both express IgD and IgM
Where does the switch from membrane bound IgD and IgM to secretory IgM occur?
the level of processing of mRNA transcripts
What levels of switching occur at the level of DNA?
IGM --> G->E-->A
If the second polyadenylation site is read, then the mRNA for membrane-bound what is generated by splicing?
IgM
If the fourth polyadenylation site is read, then the mRNA for membrane-bound what is generated by alternate splicing?
IgD
Of the secreted IgM what establishes the creation of S-S bonds between IgM antibodies?
Cysteine
When is the mRNA for secreted IgM produced?
When the M1, M2 exons are spliced out
What is required for class switching to cocur?
Activation of the B cell
What leads to the production of IgG mRNAs?
Looping event that cuts out the constant regions for IgM and IgD at the level of DNA
Proliferation cytokines
IL 2,4,5
What class switching does IFN-gamma stimulate?
IgG2a
What class switching does IL-4 stimulate?
IgG1, IgE
What class switching does IL-5 stimulate?
IgE
What happens if mutations lead to less Ab affinity?
The B cell dies
Mutations that accumulate in the Ig gene as the B cell proliferates
Somatic Hypermutation
Where are mutations of Ig concentrated?
in the variable region
When a mutation leads to an antibody that binds the antigen more firmly
Affinity maturation
What chromosome do you see in CML?
Philadelphia (novel chromo 22) Translocation of 9 to 22
Translocation of chromo 9 and 22
CML
Reciprocal translocation of choromo 8 and 14
Burkitt's lymphoma
Concept of making an antibody that mimics an antigen
Anti-Idiotopic antibody