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50 Cards in this Set
- Front
- Back
what is an antibody repertoire?
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the collection of DIFFERENT antibody molecules in an individual, and each different antibody has a different variable amino acid sequence
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the collection of different antibody molecules in an individual (with each different antibody having a different variable amino acid sequence) is called what?
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antibody repertoire
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what does it mean to have 'different' antibodies?
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each different antibody has a different variable region amino acid sequence which is NOT dependent on an antigen
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what is the genetic mechanism of antibody variability?
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gene rearrangement
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what is another term for gene rearrangement?
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somatic recombination
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what is another term for somatic recombination?
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gene rearrangement
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what are the general features of gene arrangement?
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variable regions, joining regions, and constant regions
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what is the process of gene rearrangement?
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a loop forms bring a variable region in contact with a joining region, a circle of DNA is excised and cut edges of gene are spliced (with nucleotide insertions), to form a functional gene
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what does gene rearrangement produce?
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lymphocytes that each have different rearrangements and insertions
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can germline configurations of genes encoding B cell and T cell receptors be transcribed?
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no, gene rearrangement must occur first
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how many variable regions are there at λ light chain locus?
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29-33
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how many variable regions are there at κ light chain locus?
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31-36
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how many variable regions are there at heavy chain locus?
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38-46
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how many constant regions are there at heavy chain locus?
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9
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how many constant regions are there at λ light chain locus?
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4-5
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how many constant regions are there at κ light chain locus?
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1
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when are Ig gene segments rearranged?
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during B cell development
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what is rearranged during B cell development?
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Ig gene segments
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Ig gene rearrangements BLANK antigen-dependent?
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is not
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light chain germline DNA undergoes gene rearrangement into what?
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VJ-joined rearranged DNA
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heavy chain germline DNA undergoes gene rearrangement into what?
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VDJ-joined rearranged DNA
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what flanks V, J, and D genes?
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recombination signal sequences
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where are recombination signal sequences found?
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flanking V, J, and D genes
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what are recombination signal sequences?
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areas of the genome recognized by enzymes that induce recombination
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where are gene segments joined?
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at recombination signal sequences
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what happens at recombination signal sequences?
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gene segments are joined
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what is a RAG?
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recombination activating genes
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what is a term for recombination activating genes?
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RAG
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what does RAG do?
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recognizes recombination signal sequences (marks, doesn't ligate)
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what can be added at the site of V-J or V-d-J joinings?
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single nucleotides
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what does the addition of single nucleotides at the site of V-J or V-D-J joining cause?
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junctional diversity
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what is junctional diversity?
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variations in the nucleotied at which V-J or V-D or D-J genes are joined
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how does junctional diversity occur?
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the RAG complex cleaves the recombination signal sequences yielding DNA hairpins, opens the hairpins by nicking one strand of the DNA, generation palindromic P-nucleotides, N-nucleotides added , strands paired, unpaired nucleotides are removed by exonuclease, and gaps are filled by DNA synthesis and ligation to form coding joint
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what does N nucleotide stand for?
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non-template nucleotides
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what does adding N-nucleotides cause?
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random variability due to slight differences (junctional diversity)
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what is another mechanism of antibody variability?
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any heavy chain can associate with any light chain to form the Fab portion of antibody that binds antigen
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once Ig gene rearrangement is complete, variable gene usage BLANK change
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does not
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Can a B cell genes change once Ig gene rearrangement is complete?
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No
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Each B cell can synthesize what?
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many copies of only one heavy chain and only one light chain
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what is the result of gene rearrangement?
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a pool of B cells that each has a different receptor for antigen and after division and differentiation into plasma cells, each secretes different antibodies
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in serum protein electrophoresis, why is γ-globuling fraction heterogeneous?
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each different antibody has a different ammino acid sequence and thus a different overall charge
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how is Ig gene rearrangement in B cell leukemia detected?
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The probe for C region and V region will be at the same level, rather than separate because gene rearrangment brings them together, while germlines will keep them separate, if a single dominant band occurs after Ig gene PCR indicates B cell leukemia and a single dominant band after TCR gene PCR indicated T cell leukemia
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what does TCR stand for?
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T cell receptor
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what does PARR stand for?
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PCR for Antigen Receptor Rearrangement
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what is myeloma?
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a tumor of an antibody producing plasma cell
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a tumor of an antibody producing plasma cell is called what?
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myeloma
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what do myeloma cells produce?
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myeloma proteins
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what are myeloma proteins?
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antibody molecules produced by myeloma cells
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what produces myeloma proteins?
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myeloma cells
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why is myeloma a monoclonal gammopathy?
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plasma cells developing after division and differentiation of a single B cell produce the same antibody
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