| Term | Definition |
|---|
| constant | for a given Ab isotype, the ______ regions are identical |
| same | the thousnds of BCR's of surface of single B cell will have _____ (same/different) Ag-binding site = (____ Vh and Vl for membrane Ig) |
| same | secreted Abs have _____ (same/different) Vh and Vl as membrane bound Abs on B cell that was activated |
| different | secreted mu chain protein has _______ (same/different) amino acids at C-terminus as/than membrane mu chain protein |
| hydrophilic | secreted IgM has ______ amino acids at C termini of its u chains that allow it to be secreted |
| hydrophobic | secreted IgM has _______ amino acids at C-terminus that make it a membrane protein |
| mIg | in primary immune response, B cells secrete IgM Abs with same Ag specificity as ___ on surface of mature B cell that give rise to those plasma cells |
| IgM | when memory cells get activated in secondary response, they secrete IgG or IgA or IgE Abs that have the same specifity as the ___ Abs secreted in primary response |
| exons | each C region gene consists of several ____ |
| C | there is 1 copy of the gene segment for each _ region isotype |
| leader | ______ sequence - encodes signal peptide that allows H chain to be translocated into ER so it can become membrane or secreted protein |
| H | there are multiple V, D, and J regions in the _ chain locus |
| Vh | each __ region is made of sequences from 1 V segment, 1 D segment, and 1 J segment |
| combinatorial | ______ theory = V x D x J = # of combinations |
| different | genes encoding the kappa and lamba chains are on _____ (same/different) chromosome(s) |
| 1 | there is _ kappa constant region(s) for light chain |
| 3 | there is _ lambda constant region(s) for light chain |
| H | only _ chain of C region determines Ab function |
| C | 3 lambda regions and k C region are functionally equivalent, and it doesn't matter which one an Ab has since H chain _ region determines Ab function. |
| D | light chains (both kappa and lambda) are made up only of V and J segments (no _ segments) |
| combinatorial | more _________ power: different Vh and Vl combinations yields differently shaped Ag-binding sites, different Ag specificies |
| 1 | single B cell uses _ Vh segment _ Dh segment _ Jh segment to make all its Abs |
| DNA | _____ rearrangement - allows B cell to 'pick' which V, D, and J segments to use |
| Vh | Vh, Dh and Jh segments that are joined together end up encoding the __ region of the H chain polypeptide |
| 2 | since you are diploid, you have _ chromosomes with IgH loci on them, (maternal paternal) |
| alleic | ______ exclusion - process of using copy of gene on one chromosome but not other |
| Vl | complete __ region is assembled by moving Vl segment next to Jl segment, cutting out the intervening DNA |
| J | only the V and _ segments end up encoding an L chain protein |
| 4 | you have _ chromosomes encoding light chain genes (maternal and paternal of kappa and lambda) |
| cannot | a single B cell ____ (can / cannot) make successful VDJ recombinations on both chromosomes containing IgH and all 4 chromosomes that contain IgL chain loci and make 8 different Abs for 8 different Ags |
| 1 | a single B cell is specific for _ Ag |
| 1 | on heavy chain locus, successful VDJ rearrangement happens on _ of 2 chromsomes. |
| 1 | on light chain locus, successful VJ rearrangement occurs at _ of 4 chromosomes that encode light chains |
| 1 | alleic exclusion ensures one cell one specificity by restricting single B cell to making only _ Vh region and _ Vl region, which combine to form _ unique Ag-binding site |
| lambda | B cell commits to making only kappa or _____ light chains |
| signals | ______ from complete BCR on cell surface is required for survival of pre-Bcells in bone marrow. you cannot get a complete BCR unless all 4 poly peptides (H chain, L chain + Ig-alpha/beta) are present) |
| RSS | ___ consists of 1) Conserved block of 7 nucleotides (heptamer) 2) Non-conserved spacer regions 12-23 nucleotides 3) Second conserved block of 9 nucleotides (nonamer) |
| RSS | spacer consists of 12-23 NT's, which corresponds to 1 or 2 turns on DNA helix, thus heptamer and nomaer of ___ will be on same side of double helix, and can be bound by same protein complex that mediates VDJ rearrangement |
| same | recombination occurs between gene segments located on the ____ chromosome |
| joined | 12/23 rule - gene segment with 12bp spacer can only be _____ to gene segment with 23bp spacer |
| D | in H chain, V can only be joined to _ |
| D | in H chain, J can only be joined to _ |
| J | in H chain, you cannot get V and _ to join together or multiple V's joined together |
| RSS | proteins bring together two gene segments, one flanked by ___ with 12 bp spacer and one flanked by ___ with 23 bp spacer |
| coding | cleavage of DNA occurs between boundary between RSS and the ____ region |
| breaks | the _____ in the DNA needs to be repaired so gene segments are joined together |
| looped | intervening DNA is ______ out |
| Abs | VDJ joining is essential for production of ___ and TCR's. SCID mice/boy in bubble have mutations in VDJ joining, and cannot make ___ or TCRs. No functional T or B cells. Can only live in germ-free environment |
| breaks | dsDNA ____ are very dangerous. Broken ends can invade other chromosomes and cause chromosomal recombinations -> changes in gene expression that cause cancer |
| VDJ | RAG1 and RAG 2 proteins are the only two lymphocyte-specific proteins required for ___ recombination |
| repair | other proteins involved in VDJ recombination are found in all cells, and they help in DNA _____ |
| RSS | RAG1 and RAG2 binds to the different ___'s to be joined, along with several other proteins. |
| nuclease | RAG protein complexes contain a _______ that cleaves DNA on both strands, at border between RSS and Ig gene segment. the ends of 2 DNA strands are joined to form a hairpin loop |
| TdT | 1) Complex of proteins binds to dsBreaks 2) Ku70/80 proteins binds to dsBreaks 3) DNA-PK binds to Ku proteins, recruits Artemis 4) Artemis cleaves DNA to break hairpin loop at random sites 5) ___ adds nt's, exonuclease substracts nt's at the ends 6) XRCC4 and DNA ligase joins ends of gene segments |
| shape | NT additions/subtractions at junctions between VJ (in light), VD, DJ (in heavy) will affect the ____ of the Ag binding site, since they code for CDR3 |
| junctional | ______ diversity - addition and substraction of variable numbers of nucleotides at sites of V D and J, introducing large amounts of diversity |
| TdT | ___ adds random non-templated nt's to H chain joints |
| junctional | _____ diversification adds a factor of 30 million different Ig-binding sites |
| stop | by randomly adding and subtracting varying numbers of nt's at sites of VDJ joining, ___ codons can be introduced. |
| stop | joined segments can be out of frame such that when you read DNA as 3 nucleotide codons, you are out of register and there are ___ codons instead of codons for aa |
| chromosome | if the rearrangement attempt on first chromosome is unsuccessful, then rearrangement can occur on the other _______ |
| Ab | if attempts on both chromosomes are unsuccessful, the cell cannot make an __ |
| survival | circulating B cells must pass through lymphoid follicles - specialized regions of lymphoid organs to receive _______ signals |
| limited | amount of space in lymphoid follices is _____, so B cells compete to get into lymphoid follicles. |
| more | memory B cells enter lymphoid follicles ____ (less/more) readily than naiive B cells |
| transposing | shark RAGS have homology to bacterial integrases and integration host factors, primitive systems for ______ pieces of DNA |
| gene conversion | in species that have very few functional VDJ segments, they use ____ _______ to generate diversity of Abs |
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