Diversity vs Specificity (Bowden) Flashcards

1
Q

What stages are lymphocytes when found in generative organ(BM or thymus)

A

Stem Cell, Pro-lymph Pre-lymph and immature lymphocytes

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2
Q

What stage of lymphocyte development is it self-antigen dependent

A

when transitioning from immature to mature

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3
Q

What is the Immune Repertoire concept

A

that a person makes more different forms of Ab than all other proteins combined

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4
Q

Describe clonal selection

A

Gene rearrangement events occur in absence of Ag

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5
Q

When are clones activated

A

by specific antigens

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6
Q

What are the 2 mechanisms of Primary Ig Rearrangement

A

Multiple germ line genes: Combinatorial diversification

Junctional diversity

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7
Q

What is the mechanism for secondary Ig rearrangement

A

Somatic hypermutation

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8
Q

What cytokines play a role in converting stem cell to pro -B

A

IL3 and IL7

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9
Q

What enzymes are expressed to convert pro-B into Pre- Bcell

A

Rag and TdT

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10
Q

What phase in B cell maturation does recombination occur

A

Between pro-B and pre-B

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11
Q

What are the CD markers for Pro-B cells

A

CD43+ CD19+ CD10+

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12
Q

Where is the H chain locus and what are its components

A
chromosome 14
Variable regions n~100 with leader exon in front.
Diversity regions n~23
Joining regions
Constant regions
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13
Q

Where is the kappa light chain locus and describe gene

A

chromosome 2
Variable regions n~35 with leader exon in front
Joining regions n~5
1 constant region C kappa

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14
Q

Where is the lambda light chain locus and describe gene

A

chromosome 22
Variable regions n~30 with leader exon in front
Joining regions n~4 in front of constant regions
Constant regions n~4

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15
Q

What is encoded for in the Constant regions of the heavy chain

A

each class and subclass of immunoglobulin, one for hinge other for domain

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16
Q

Explain allelic Exclusion

A

maternal or paternal chromosome. not both

heavy chain can be from either chromosome, and the light chains can be from either chromosome.

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17
Q

Why do we need allelic exclusion

A

expression of both alleles would render B cell multispecific

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18
Q

DNA Rearrangements of making heavy chain

A

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

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19
Q

How does the DNA H chain become transcriptionally active

A

Promoted associated with V gene is borught close the enhancer which is between J and Cmu region.

20
Q

Two ways pre-mRNA of H chain is processed

A

VDJ next to C mu gene(IgM) or VDJ next to Cdelta (IgD) coding then for either mu chain or delta

21
Q

Where do the heavy and light chains assemble together

22
Q

What are the recombination signal sequences

A

they flank the V J and D exons

23
Q

What is the struture of each RSS

A

conserved nonamer and heptamer that are separated by either 12 or 13 base pairs. so either one or two turns of the DNA helix

24
Q

Where does recombination of the RSS usually occur

A

between a 1 turn and 2 turn signal

25
What enzymes assist in recombination
Rag-1 and Rag-2 catalyze the recombination in both H chains and light chains
26
Junctional Diversity
At the junction between D and J there is insertion of nucleotides. Leads to diversity in third hyper variable region (Idiotype)
27
What catalyzes the additoin of nucleotides in Junctional diversity
TdT WITHOUT template
28
What are the nucleotides added by TdT referred to as
N nucleotides
29
how are P nucleotides added
asymmetrically hairpins, templated manner
30
What does the pre-B lymphocyte Receptor look like
complete IgM H chain with surrogate light chains | Undergoes 3D conformation check
31
What light chain is made first
Kappa
32
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
33
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
34
Once the light chains are recombined what phase is the B cell
Immature B cell
35
components of immature B Cell receptor
mIgM or D and Igalpha and Igbeta
36
NEgative vs positive selection
negative: binds self too much- apoptosed positive: if binds- okay, can communicate with self. If doesn't bind- apoptosed.
37
Are all gene segments functional
no. some are psuedogenes
38
T/F: VDJ segments alone are essential
no, not one is essential, reduces evolutionary pressure
39
What percentage of lymphocytes make it to maturation
12.5
40
Largest contribution to the diversity
from junctional diversity
41
What can cause triple diversity
frameshifts, or recombination erros that bring V to D/J or D next to J
42
What area does junctional diversity take place in
hypervariable region
43
Combination of genes is dependent on Ag or independent
Independent
44
children of Consanguinous parents are more likely to have what effected enzyme in recombination
Rag, severe immunodeficiency
45
SCID
X linked, mutations in IL-7. Lethal need bone marrow transplant "Bubble kids"
46
What is Bruton's Agammaglobulinemia
X-linked Agammaglobulinemia Bruton Tyrosine Kinase delivers signal from Pre-BCR to survival. Get recurrent infections