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26 Cards in this Set
- Front
- Back
What did Tonegawa conclude about 'Jumping Genes'?
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As the B cell matures, rearrangements in DNA of heavy and light chains occur --> different gene segments brought together to code for entire V region, intervening sequences removed
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How does the immune system make a wide range of proteins from single segments of DNA?
What about this process is completely unique to the immune system? |
By making different arrangements of V-, J-, and D-regions
Rearrangement leads to PERMANENT loss of intervening chromosomal material |
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What do RAG-1 and RAG-2 do?
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Recombinases that help rearrange DNA to bring V, D, and J segments together
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What encodes the V regions of the heavy chain?
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3 gene segments:
V (variable) D (diversity) J (joining) |
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What is the order of recombination in encoding for the V region of the heavy chain?
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D first recombines with J, then V combines with DJ
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On what chromosome is the Human H chain locus?
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Chromosome 14
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What regions are responsible for encoding the light chain?
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V and J
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What are two types of L chains?
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V kappa, V lambda
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On which chromosome is the kappa chain locus?
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Chromosome 2
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On which chromosome is the lambda chain locus?
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Chromosome 22
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In what order are the H chains and L chains made via gene rearrangement?
On what type of cells does this process only occur? |
H chain first
L chains next: kappa, then lambda Only occurs on B cells, angtigen-independent |
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What are the steps for production of a heavy chain?
Where do these events occur? |
Nucleus:
Germline DNA --> somatic recombination --> DJ together --> somatic recombination --> VDJ --> transcription --> RNA Cytoplasm: RNA splicing --> mRNA --> translation --> polypeptide chain |
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What are the steps for production of a light chain?
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Nucleus
Germline DNA --> somatic recombination --> VJ joined --> transcription --> RNA Cytoplasm: RNA --> splicing --> mRNA --> translation --> polypeptide chain |
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What are heptamer/nonamer recognition sequences?
How are they removed? |
23 or 12 base pair separations between V, D, and J regions
Removed when RAG recombination proteins bind, create double stranded DNA breaks--> gaps filled in by DNA polymerase |
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What is allelic exclusion?
What does this create? |
Each cell selects only ONE parental Vheavy and one parental Vlight (kappa or lambda)
Each B cell clone has one BCR |
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What is the process of allelic exclusion of heavy chains?
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Rearrangement starts on both alleles
When one rearrangement is successful, other allele is silenced --> stimulates kappa gene rearrangement If neither allele successful, cell death |
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What is the process of allelic exclusion in light chains?
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Kappa chain rearrangement first; if successful, silences other allele, starts lambda allele
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What is combinational diversity?
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Different V, D, and Js
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What is junctional diversity?
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Random removal/insertion of nucleotides between V, D, and J
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What is somatic hypermutation?
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When IgM and IgD are expressed on B cells, Tcell-Bcell interaction activates neurotransmitter sequence changes in the VDJ area
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What is clonality?
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Net outcome of allelic exclusion = single B cell Ig has 2 identical H chains, 2 identical L chains, and one specificity determined by the shape/size of the VH/VL binding groove
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What are 6 factors that contribute to the generation of diversity?
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1. Multiple V, D, and J segments to choose from
2. Combinatorial diversity - V, D, and J order 3. Junctional diversity - imprecise joining of V, D, and J 4. N-region diversity - insertion/deletion of extra nucleotides (exonucleotides remove nucleotides, TdT adds) 5. Random assortment of heavy chain with 2 light chains 6. Receptor editing |
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What are the two types of TCR?
What kinds of gene segments make them up? |
alpha-beta
delta-gamma alpha and gamma determined by VJ beta and delta determined by VDJ |
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What are the chromosomal locations of the following human TCR genes?
a. TCR beta b. TCR alpha and delta c. TCR gamma |
a. chrom. 7
b. chrom 14 c. chrom 7 |
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What are 5 factors that promote TCR diversity?
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a. Multiple V, D, and J segments
b. Junctional diversity c. combinatorial diversity d. N-region diversity e. alpha chain is not allelicaly excluded (some T cells have 2 receptors) |
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What are 2 differences between ab and dg TCRs?
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1. gd-TCRs have fewer V, D, J segments --> less diversity; also less junctional diversity
2. ab-TCRs can be biclonal (2 alphas) or monoclonal gd-TCRs are allelically excluded, always monoclonal |