Immune Response Genetics (22,23)

Question 1

What makes up the structure of an antibody?

a. Two non-identical heavy chains
b. A single antigen binding site
c. Two identical light chains
d. Two antigen binding sites formed by the C terminals of the light and heavy chain

Answer 1

c. Two identical light chains

Question 2

What is not a property of antibodies?

a. There is a vast diversity of specificities
b. Each chain has a variable region and constant region
c. Multiple isotypes with the same antigen specificity can exist
d. The constant region is the same in all antibodies produced by one person

Answer 2

d. The constant region is the same in all antibodies produced by one person

Question 3

What can explain the properties of antibodies?

a. The somatic variation hypothesis suggests that variation is generated by mutation and recombination in somatic cells
b. The germ line hypothesis suggests that there are one or more genes for the variable region and another gene for the constant region
c. The two gene model suggests that the variable region is inherited through the germ line
d. The single polypeptide hypothesis suggests that specificity is due to alternative splicing of antibody mRNA

Answer 3

a. The somatic variation hypothesis suggests that variation is generated by mutation and recombination in somatic cells

Question 4

How do B cells develop and become active?

a. B cells develop in peripheral lymphoid organs
b. B cells are activated by specific antigens in the bone marrow
c. B cells of different specificity are present in circulation and only active when they encounter their specific antigen
d. Effector B cells secrete a variety of antibodies with varying specificity to fight infection

Answer 4

c. B cells of different specificity are present in circulation and only active when they encounter their specific antigen

Question 5

What is clonal ignorance?

a. When the concentration of antigen is too high and B antibodies become saturated and unable to interact with lymphocytes
b. When a lymphocyte is unaffected by the presence of an antigen due to low affinity or low concentration
c. When an antigen interacts with a lymphocyte and directly causses apoptosis
d. When clonal selection fails to occur due to a non-homologous end joining event in the antibody heavy chain

Answer 5

b. When a lymphocyte is unaffected by the presence of an antigen due to low affinity or low concentration

Question 6

What makes up the immunoglobulin genes?

a. The λ light chain has the following gene segments: 85V, 5J, 1C
b. The κ light chain has the following gene segment: 3V, 4J, 4C
c. The heavy chain has the following gene segments: 51V, 27D, 6J, >5C
d. The λ and κ light chains have the following gene segments: 85V, 4J, 5C

Answer 6

c. The heavy chain has the following gene segments: 51V, 27D, 6J, >5C

Question 7

What ensures that a B cell has single antigenic specificity?

a. Allelic exclusion ensures that heavy and light chain genes of only one parental chromosome is expressed
b. Genomic imprinting means that all B cells express either maternal or paternal heavy and light chain genes
c. Allelic inclusion up-regulates the expression of heavy and light chain genes from one parental chromosome
d. Alternative splicing and random recombination within heavy chain DNA

Answer 7

a. Allelic exclusion ensures that heavy and light chain genes of only one parental chromosome is expressed

Question 8

What recognition sequence is involved in the NHEJ of V and J gene segments and reflects the “12-23” rule?

a. V λ -7 mer – 23 – 9 mer —– 9 mer – 23 – 7 mer - J λ
b. V κ -7 mer – 12 – 9 mer —– 9 mer – 23 – 7 mer - J κ
c. V H -7 mer – 23 – 9 mer —– 9 mer – 12 – 7 mer - J H
d. V κ -7 mer – 12 – 9 mer —– 9 mer – 12 – 7 mer - J λ

Answer 8

b. V κ -7 mer – 12 – 9 mer —– 9 mer – 23 – 7 mer - J κ

Question 9

• In an antibody, the variable regions mark specificity and the constant regions mark the class of antibody.

Answer 9

T

Question 10

• B cell and antibody variation is induced by the presence of a specific antigen.

Answer 10

F

Question 11

• The λ, κ and heavy chains are all on chromosome 22 in humans and chromosome 16 in mice.

Answer 11

F

Question 12

• D gene segments are only found in light chains.

Answer 12

F

Question 13

• The first step in generating the κ light chain is splicing.

Answer 13

F (recombination, random V-J joining)

Question 14

How can a P nucleotide insertion form?

a. Nicking of hairpin structures leads to double stranded extensions
b. They arise in signal joints
c. Blunt ends are nicked off centre
d. Single strand extensions are filled in and incorporated in junctions

Answer 14

d. Single strand extensions are filled in and incorporated in junctions

Question 15

What is untrue about VJD recombination?

a. RAG proteins make a double stranded break in DNA and are assisted by HMG proteins
b. NHEJ requires KU70, Ku80, DNA-dependent protein kinase catalytic subunit, Artemis, and the XRCC4/DNA ligase IV/Cernunnos complex
c. HMG-box family proteins cleave DNA to form hairpins
d. RAG1 binds to the nonamer of RSS

Answer 15

c. HMG-box family proteins cleave DNA to form hairpins

Question 16

What does DNA-dependent protein kinase do?

a. It binds and phosphorylates the hairpin endonuclease Artemis
b. It acts in conjunction with Ku70 and Ku80
c. It seals the coding and signal joins
d. Activation leads to NHEJ which often leads to cancer

Answer 16

a. It binds and phosphorylates the hairpin endonuclease Artemis

Question 17

Which protein is correctly matched to its role in generating immunoglobulin diversity?

a. Ku70 and Ku80 seal coding and signal joints to prevent transposition
b. Cryptic RSSs are located around open chromatin structure and prevent NHEJ occurring
c. The XRCC4/DNA ligase IV/Cernunnos complex seals signal and coding joins
d. Artemis is a DNA helicase that functions independently to unwind tight chromatin sturture

Answer 17

c. The XRCC4/DNA ligase IV/Cernunnos complex seals signal and coding joins

Question 18

What is involved in generating antibody diversity?

a. Recombination occurs in a homologous fashion
b. VDJ joining is “transposition” like and Ig genes have a high mutation rate
c. It follows the “one gene one polypeptide” principal
d. Double strand breaks occur at random

Answer 18

b. VDJ joining is “transposition” like and Ig genes have a high mutation rate

Question 19

What is a feature of somatic hypermutation?

a. The process results in point mutations in the antibody constant region
b. DNA repair mechanisms are efficient in clearing point mutations that arise due to Activation-induced cytidine deaminase
c. Mutations lead to antibody variants with enhanced affinity for a specific antigen
d. Mutations arise at a rate of 10^30 per basepair/generation

Answer 19

c. Mutations lead to antibody variants with enhanced affinity for a specific antigen

Question 20

What is Activation-induced cytidine deaminase (AID) ?

a. It converts uridine to cytidine
b. It blocks hyper-mutation in T cells
c. It activates the hairpin endonuclease Artemis
d. It initiates hyper-mutation

Answer 20

d. It initiates hyper-mutation

Question 21

What is a feature of SCID?

a. Nucleotide metabolites build up and this is toxic to developing T cells
b. It can be caused by too much Adenosine deaminase (ADA) and Purine nucleotide phosphrylase (PNP)
c. It affects the translation of purines
d. Recessive X-linked SCID can be due to DNA repair defects and has been used to study VJD recombination

Answer 21

a. Nucleotide metabolites build up and this is toxic to developing T cells

Question 22

Which is not one of the four main mechanisms of antibody diversification?

a. Separation and diversification of gene segments
b. Junctional diversification during gene segment joining
c. Combinatorial L and H chains
d. Somatic hyper mutation

Answer 22

a. Separation and diversification of gene segments

Question 23

Which would not result in a SCID phenotype?

a. NHEJ repair mutants
b. DNA-dependent protein kinase mutants
c. Constitutive Artemis/XRCC4 mutants
d. Deficient in Adenosine deaminase (ADA) and Purine nucleotide phosphrylase (PNP)

Answer 23

c. Constitutive Artemis/XRCC4 mutants

Question 24

• Unlike in non-B cells, a double stranded DNA break is considered normal and happens during VDJ recombination.

Answer 24

T

Question 25

• A lot of information on the process of immunoglobulin diversity has been found through studying SCID individuals.

Answer 25

T

Question 26

• Coding ends are usually discarded following DNA cleavage by Rag proteins.

Answer 26

F (signal ends)