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37 Cards in this Set
- Front
- Back
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How many multigene families are there for Heavy Chains and Light Chains?
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One for each type of chain.
-one heavy chain multigene family -one light chain multigene family Each family contains many gene segments. |
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There are many gene segments on the Kappa-chain (light) multigene family;
-How many V segments? -How many J segments? -How many C segments? |
85
5 1 Only one of each segment type contributes to the light chain protein. |
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What are the three types of multigene families?
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-Lambda
-Kappa -Heavy chain |
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What gene segment types contribute to variable regions on antibodies?
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VJ and VDJ
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What gene segments contribute to non-variable (Fc) regions of antibodies?
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C
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describe the gene segment rearrangement process in general, and where does it occur?
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random gene rearrangement that occurs in the primary lymphoid organs = thymus and bone marrow.
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What are the 2 main components of the mechanism that allows/directs gene rearrangement?
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1. RSS - Recombinational Signal Sequences
2. Enzymatic gene segment joining |
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What are RSSs?
How many types are there? |
Recombinational Signal Sequences.
They show where recombination (making joints) should occur. 2 types: One-turn RSS and two-turn RSS; |
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What is the significance of the two different types of RSSs?
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One-turns recognize 2-turns. They recognize each other;
The D segments only have 1-turn on either side of the segment, The V and J segments only have 2-turn. Therefore, V can only join D, and VD can only join J. (no VJD) |
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What enzymes participate in enzymatic joining of gene segments?
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Rag-1 and Rag-2
Endonuclease Terminl deoxynucleotidyl transferase (TDT) DSBR |
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What are RAG 1/2?
What do they do? |
Recombination activating genes.
-Bring together RSS's -Cut DNA to form HAIRPIN |
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What does Endonuclease do?
Why? |
Cuts the hairpin formed by RAG1/2.
To form a place to do P- and N-additions. |
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What is P-addition?
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Addition of nucleotides to the cleaved hairpin (by endonuclease). Forms a
PALINDROME. |
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What is N-addition?
What does it? |
Addition of Nucleotides to cut hairpin.
Terminal deoxynucleotidyl transferase TDT |
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What repairs the dna after Gene segment joining and hairpin/addition?
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DSBR - doubl. strand break repair enzymes; repair/join coding sequences.
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2 results of random gene rearrangement/joining:
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-formation of coding joint
-formation of signal joint. |
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What is the "coding joint" a code for?
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the variable regions (VJ and VDJ) of the immunoglobulin DNA.
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If you don't have Rag enzymes or DSBR, what is the result?
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SCID - severe combinatorial immune deficiency
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What is Evidence for gene rearrangement?
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presence of circular dna in the thymus
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what is "junctional flexibility"?
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imprecise joining of the coding sequence.
Meaning, codons are 3-aa sequences; if a V and J segment join and make a STOP codon, it is NONPRODUCTIVE. |
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2 products of junctional flexibility:
what is the consequence? |
In-phase or Out-of-phase joining.
In-phase can be translated. Out of phase contains a premature stop codon and will not be translated into protein. |
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What is unique about Rag 1/2 and TdT expression?
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only occurs in lymphoid cell lines; that's the only place where this REARRANGEMENT occurs; not in other chromatic DNA.
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Why do T and B cell genes rearrange?
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to create a diverse reportoire of cells that can recognize all different Ags.
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What do animals with defective gene rearrangement lack?
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MATURE B/T cells; leads to SCID, the lack of ANY specific immune response;
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What mechanism produces either Membranous or Secretory Ig?
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Differential RNA processing.
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Which cells have Membranous Ab?
Which cells have Secretory Ab? |
Membranous: Native/memory B cells
Secretory: Plasma cells - the effectors |
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What is Allelic exclusion?
When does it happen? What is the significance? |
the inhibition of one copy of the Ig genes (from one parent) so that only one set is expressed. Occurs once one set is properly rearranged.
Significance: if you had two sets expressed, you would have two antibody clones for the same antigen. |
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What is Somatic Hypermutation?
WHERE does it happen? When does it happen? Why? |
-Random gene mutations on the VJ or VDJ gene segments.
-In activated B cells, in the germinal center. -After activation by Antigen. -to generate different affinities in the antibodies, to select the best population. |
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7 things that generate ANTIBODY diversity:
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1. Fact that there are multiple gene segments in each multigene family.
2. Random combinations of those segments. 3. Junctional flexibility 4. P-addition 5. N-addition 6. Somatic Hypermutation 7. Combinatorial association of LC and HC |
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What follows somatic hypermutation?
why? |
Affinity maturation
to select the B cells with better affinity that was generated by the random mutations of somatic hypermutation. |
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What maturational level are the B cells that undergo
-Variable region rearrangement -Constant region rearrangement |
Variable: immature, in the primary lymphoid organs.
Constant: Mature, in the peripheral lymphoid tissues, after Ag activation. Then they differentiate into effector/memory cells. |
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What is the mechanism of class switching? When/where?
What happens? |
DNA looping; after Ag stimulation, in the peripheral lymphoid tissues.
DNA loops and VDJ joins with one of the Constant heavy segments. |
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What does class switching explain?
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How one specific mother antibody clone can have different effects (different Fc regions).
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What Switch Factor tells the Bcell which class to switch to?
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Cytokines.
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What does Differential RNA processing allow?
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Expression of both IgM and IgD on one naive B cell - the two differ in which membrane is bound, but b
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What is Differential RNA processing?
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Cleavage of the RNA transcript (ripe and ready for expression) before or after segments that encode secretory or membrane-bound genes for the C region.
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Why can IgM and IgD be expressed in one naive B-cell simultaneously?
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There's no switch site between their C gene segments; the RNA transcipt is not cleaved during RNA processing, so they both get transcribed and translated.
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