Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
27 Cards in this Set
- Front
- Back
|
germ line theory
|
genome contributed by egg and sperm contains the entire repertorie of immunoglobulin genes
|
|
|
somatic-variation theory
|
the genome has a small number of genes and recombination/mutation explains diveristy
|
|
|
Dreyer and Bennett
|
proposed the 2 gene one polypeptide model
|
|
|
Tonegawa
|
found the immunoglobulin genes rearrange into one strand
|
|
|
signal (leader) peptide
|
each V segment is preceded by an exon that encodes this peptide. It helps guide the heavy/light chain through the ER and then is cleaved
|
|
|
Which genes rearrange first?
|
the heavy chain variable region gene segments (VDJ)
specifically D and J which then combines with V |
|
|
What does the final rearranged heavy chain gene include?
|
a short L exon, an intron, a joined VDJ segment, another intron, and a series of C segments
|
|
|
recombination signal sequences
|
RSSs
flank the V gene segments and function as signals for recombination contain a heptamer (7), an interveneing 12 or 23 bp sequence, and a nonamer (12) there are one-turn and two-turn recombinases |
|
|
VDJ recombinase
|
enzymes that catalyze VDJ recombination
|
|
|
RAG-1 and RAG-2
|
recombination-activating genes that encode proteins that mediate VDJ joining
|
|
|
TdT
|
an enzyme that adds N region nucleotides in a random fashion
|
|
|
non-productive rearrangements
|
occurs when the reading frame gets thrown off and creates stop codons
this is caused by imprecise joining of the codon regions |
|
|
Allelic exclusion
|
the B cell expresses rearranged antibody gene sequences from only one chromosome
|
|
|
7 means of antibody diversity
|
numerous germ-line V,D,J segments
Recombinatorial diversity junctional flexibility P addition (part of junctional flex) N addition Somatic hypermutation comabinations of heavy and light chains |
|
|
Class Switching
|
the VDJ heavy chain unit can combine with any of the C region genes causing it to change isotype
at the DNA level involves switch regions determined by cytokines (IL-4) |
|
|
switch regions
|
upstream from C(h)
|
|
|
What enzyme is used?
|
activation-induce cytidine deaminase (AID)
the key mediator of somatic hypermutation and class switching deaminates cytosine turning them into uracil |
|
|
Looping out
|
the downstream C regions from the C region with the activated switch region get spliced and and can never be expressed again.
|
|
|
secreted form of Ig
|
has a hydrophilic sequence in carboxyl-terminal domain
polyadenalated at the FIRST SITE |
|
|
membrane form of Ig
|
has a hydrophilic segment outside cell, hydrophobic transmembrane segment, and a short hydrophilic cytoplasmic segment
polyadenalated at the SECOND SITE |
|
|
IgM and IgD
|
close together
both can by expressed by alternative splicing polyadenalate at different spots |
|
|
Where are the light chain and heavy chains assembled?
|
in the RER
|
|
|
promoters
|
upstream from initiation
have TATA box |
|
|
enhancers
|
bind transcription factors
activate promoter sequence |
|
|
chimeras
|
engineered antibodies
variable region from mouse constant from human |
|
|
HAMA response
|
human antimouse antibody
|
|
|
humanized antibody
|
all antibody is from human except CDR
|
