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