Diversity vs Specificity (Bowden) Flashcards
What stages are lymphocytes when found in generative organ(BM or thymus)
Stem Cell, Pro-lymph Pre-lymph and immature lymphocytes
What stage of lymphocyte development is it self-antigen dependent
when transitioning from immature to mature
What is the Immune Repertoire concept
that a person makes more different forms of Ab than all other proteins combined
Describe clonal selection
Gene rearrangement events occur in absence of Ag
When are clones activated
by specific antigens
What are the 2 mechanisms of Primary Ig Rearrangement
Multiple germ line genes: Combinatorial diversification
Junctional diversity
What is the mechanism for secondary Ig rearrangement
Somatic hypermutation
What cytokines play a role in converting stem cell to pro -B
IL3 and IL7
What enzymes are expressed to convert pro-B into Pre- Bcell
Rag and TdT
What phase in B cell maturation does recombination occur
Between pro-B and pre-B
What are the CD markers for Pro-B cells
CD43+ CD19+ CD10+
Where is the H chain locus and what are its components
chromosome 14 Variable regions n~100 with leader exon in front. Diversity regions n~23 Joining regions Constant regions
Where is the kappa light chain locus and describe gene
chromosome 2
Variable regions n~35 with leader exon in front
Joining regions n~5
1 constant region C kappa
Where is the lambda light chain locus and describe gene
chromosome 22
Variable regions n~30 with leader exon in front
Joining regions n~4 in front of constant regions
Constant regions n~4
What is encoded for in the Constant regions of the heavy chain
each class and subclass of immunoglobulin, one for hinge other for domain
Explain allelic Exclusion
maternal or paternal chromosome. not both
heavy chain can be from either chromosome, and the light chains can be from either chromosome.
Why do we need allelic exclusion
expression of both alleles would render B cell multispecific
DNA Rearrangements of making heavy chain
one of the D regions at random is joined with one of the J regions. Then one of the V genes is rearranged to the D/J region
How does the DNA H chain become transcriptionally active
Promoted associated with V gene is borught close the enhancer which is between J and Cmu region.
Two ways pre-mRNA of H chain is processed
VDJ next to C mu gene(IgM) or VDJ next to Cdelta (IgD) coding then for either mu chain or delta
Where do the heavy and light chains assemble together
in the ER
What are the recombination signal sequences
they flank the V J and D exons
What is the struture of each RSS
conserved nonamer and heptamer that are separated by either 12 or 13 base pairs. so either one or two turns of the DNA helix
Where does recombination of the RSS usually occur
between a 1 turn and 2 turn signal
What enzymes assist in recombination
Rag-1 and Rag-2 catalyze the recombination in both H chains and light chains
Junctional Diversity
At the junction between D and J there is insertion of nucleotides. Leads to diversity in third hyper variable region (Idiotype)
What catalyzes the additoin of nucleotides in Junctional diversity
TdT WITHOUT template
What are the nucleotides added by TdT referred to as
N nucleotides
how are P nucleotides added
asymmetrically hairpins, templated manner
What does the pre-B lymphocyte Receptor look like
complete IgM H chain with surrogate light chains
Undergoes 3D conformation check
What light chain is made first
Kappa
Describe making the kappa chain
one V gene joins J gene when intron removed and then actively spliced so have continuous VJC eons and transported to ER to join H chain
What if the light chain produced is non-productive
5’ Vk gene will recombine with an unused 3’ Jk gene. up to 5 tries and fails goes to lambda chain
Once the light chains are recombined what phase is the B cell
Immature B cell
components of immature B Cell receptor
mIgM or D and Igalpha and Igbeta
NEgative vs positive selection
negative: binds self too much- apoptosed
positive: if binds- okay, can communicate with self. If doesn’t bind- apoptosed.
Are all gene segments functional
no. some are psuedogenes
T/F: VDJ segments alone are essential
no, not one is essential, reduces evolutionary pressure
What percentage of lymphocytes make it to maturation
12.5
Largest contribution to the diversity
from junctional diversity
What can cause triple diversity
frameshifts, or recombination erros that bring V to D/J or D next to J
What area does junctional diversity take place in
hypervariable region
Combination of genes is dependent on Ag or independent
Independent
children of Consanguinous parents are more likely to have what effected enzyme in recombination
Rag, severe immunodeficiency
SCID
X linked, mutations in IL-7. Lethal need bone marrow transplant
“Bubble kids”
What is Bruton’s Agammaglobulinemia
X-linked Agammaglobulinemia
Bruton Tyrosine Kinase delivers signal from Pre-BCR to survival.
Get recurrent infections
