Diversity vs Specificity (Bowden)

Question 1

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

Answer 1

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

Question 2

What stage of lymphocyte development is it self-antigen dependent

Answer 2

when transitioning from immature to mature

Question 3

What is the Immune Repertoire concept

Answer 3

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

Question 4

Describe clonal selection

Answer 4

Gene rearrangement events occur in absence of Ag

Question 5

When are clones activated

Answer 5

by specific antigens

Question 6

What are the 2 mechanisms of Primary Ig Rearrangement

Answer 6

Multiple germ line genes: Combinatorial diversification

Junctional diversity

Question 7

What is the mechanism for secondary Ig rearrangement

Answer 7

Somatic hypermutation

Question 8

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

Answer 8

IL3 and IL7

Question 9

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

Answer 9

Rag and TdT

Question 10

What phase in B cell maturation does recombination occur

Answer 10

Between pro-B and pre-B

Question 11

What are the CD markers for Pro-B cells

Answer 11

CD43+ CD19+ CD10+

Question 12

Where is the H chain locus and what are its components

Answer 12

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

Question 13

Where is the kappa light chain locus and describe gene

Answer 13

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

Question 14

Where is the lambda light chain locus and describe gene

Answer 14

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

Question 15

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

Answer 15

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

Question 16

Explain allelic Exclusion

Answer 16

maternal or paternal chromosome. not both

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

Question 17

Why do we need allelic exclusion

Answer 17

expression of both alleles would render B cell multispecific

Question 18

DNA Rearrangements of making heavy chain

Answer 18

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

Question 19

How does the DNA H chain become transcriptionally active

Answer 19

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

Question 20

Two ways pre-mRNA of H chain is processed

Answer 20

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

Question 21

Where do the heavy and light chains assemble together

Answer 21

in the ER

Question 22

What are the recombination signal sequences

Answer 22

they flank the V J and D exons

Question 23

What is the struture of each RSS

Answer 23

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

Question 24

Where does recombination of the RSS usually occur

Answer 24

between a 1 turn and 2 turn signal

Question 25

What enzymes assist in recombination

Answer 25

Rag-1 and Rag-2 catalyze the recombination in both H chains and light chains

Question 26

Junctional Diversity

Answer 26

At the junction between D and J there is insertion of nucleotides. Leads to diversity in third hyper variable region (Idiotype)

Question 27

What catalyzes the additoin of nucleotides in Junctional diversity

Answer 27

TdT WITHOUT template

Question 28

What are the nucleotides added by TdT referred to as

Answer 28

N nucleotides

Question 29

how are P nucleotides added

Answer 29

asymmetrically hairpins, templated manner

Question 30

What does the pre-B lymphocyte Receptor look like

Answer 30

complete IgM H chain with surrogate light chains

Undergoes 3D conformation check

Question 31

What light chain is made first

Answer 31

Kappa

Question 32

Describe making the kappa chain

Answer 32

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

Question 33

What if the light chain produced is non-productive

Answer 33

5’ Vk gene will recombine with an unused 3’ Jk gene. up to 5 tries and fails goes to lambda chain

Question 34

Once the light chains are recombined what phase is the B cell

Answer 34

Immature B cell

Question 35

components of immature B Cell receptor

Answer 35

mIgM or D and Igalpha and Igbeta

Question 36

NEgative vs positive selection

Answer 36

negative: binds self too much- apoptosed
positive: if binds- okay, can communicate with self. If doesn’t bind- apoptosed.

Question 37

Are all gene segments functional

Answer 37

no. some are psuedogenes

Question 38

T/F: VDJ segments alone are essential

Answer 38

no, not one is essential, reduces evolutionary pressure

Question 39

What percentage of lymphocytes make it to maturation

Answer 39

12.5

Question 40

Largest contribution to the diversity

Answer 40

from junctional diversity

Question 41

What can cause triple diversity

Answer 41

frameshifts, or recombination erros that bring V to D/J or D next to J

Question 42

What area does junctional diversity take place in

Answer 42

hypervariable region

Question 43

Combination of genes is dependent on Ag or independent

Answer 43

Independent

Question 44

children of Consanguinous parents are more likely to have what effected enzyme in recombination

Answer 44

Rag, severe immunodeficiency

Question 45

SCID

Answer 45

X linked, mutations in IL-7. Lethal need bone marrow transplant
“Bubble kids”

Question 46

What is Bruton’s Agammaglobulinemia

Answer 46

X-linked Agammaglobulinemia
Bruton Tyrosine Kinase delivers signal from Pre-BCR to survival.
Get recurrent infections