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The different classes of immunoglobulins differ in the sequences of their heavy chain constant regions. As a result, each class of antibody has distinct effector functions. Nonetheless, they are all found at about equal concentrations in the serum of healthy individuals.

A) True
B) False

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Most of the enzymes involved in immunoglobulin gene rearrangement are ubiquitously expressed in all cells of the body. However, the specific recombination events between V, J, and D gene segments that generate antibody diversity occur only in developing B cells. How do RAG-1 and RAG-2 ensure that recombination takes place at antibody gene segments?

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RAG-1 and RAG-2 form a heterotetrameric ...

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When first discovered, investigators found it surprising that some single-gene defects causing immunodeficiency syndromes were associated with hypersensitivities to ionizing radiation, thereby leading to increased rates of cancer. The genes accounting for this dual impairment encode ubiquitously expressed DNA repair proteins.

A) True
B) False

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A mutagenesis screen performed on mice identified a gene with an important function in B cells. Analysis of B cells from the spleens of these mutant mice showed the results shown in Figure. However, when the C δ\delta coding sequences were determined, no mutations in these DNA sequences were found. To study this further, genetic crosses were set-up with another mouse strain carrying an allelic variant of the immunoglobulin heavy chain locus. The original mutant mouse strain (strain A) carries IgMa and IgDa alleles of these heavy chain genes. The second mouse strain (strain B) carries the IgMb and IgDb alleles of the heavy chain genes. These two parental strains were crossed together, generating progeny that were all heterozygous for IgM and IgD alleles B were obtained.  A mutagenesis screen performed on mice identified a gene with an important function in B cells. Analysis of B cells from the spleens of these mutant mice showed the results shown in Figure. However, when the C \delta  coding sequences were determined, no mutations in these DNA sequences were found. To study this further, genetic crosses were set-up with another mouse strain carrying an allelic variant of the immunoglobulin heavy chain locus. The original mutant mouse strain (strain A)  carries IgM<sup>a</sup> and IgD<sup>a</sup> alleles of these heavy chain genes. The second mouse strain (strain B)  carries the IgM<sup>b</sup> and IgD<sup>b</sup> alleles of the heavy chain genes. These two parental strains were crossed together, generating progeny that were all heterozygous for IgM and IgD alleles B were obtained.        Based on these data, the mutation in the original mutant mouse strain most likely inactivates: A)  The gene for a transcription factor required for IgD gene transcription B)  A regulatory region in the immunoglobulin heavy chain gene locus required for IgD gene transcription C)  The gene for a factor required for alternative mRNA splicing of the immunoglobulin heavy chain primary mRNA transcript D)  The gene encoding the RAG-1 or RAG-2 recombinase E)  The gene for a factor that is required for IgD surface expression  A mutagenesis screen performed on mice identified a gene with an important function in B cells. Analysis of B cells from the spleens of these mutant mice showed the results shown in Figure. However, when the C \delta  coding sequences were determined, no mutations in these DNA sequences were found. To study this further, genetic crosses were set-up with another mouse strain carrying an allelic variant of the immunoglobulin heavy chain locus. The original mutant mouse strain (strain A)  carries IgM<sup>a</sup> and IgD<sup>a</sup> alleles of these heavy chain genes. The second mouse strain (strain B)  carries the IgM<sup>b</sup> and IgD<sup>b</sup> alleles of the heavy chain genes. These two parental strains were crossed together, generating progeny that were all heterozygous for IgM and IgD alleles B were obtained.        Based on these data, the mutation in the original mutant mouse strain most likely inactivates: A)  The gene for a transcription factor required for IgD gene transcription B)  A regulatory region in the immunoglobulin heavy chain gene locus required for IgD gene transcription C)  The gene for a factor required for alternative mRNA splicing of the immunoglobulin heavy chain primary mRNA transcript D)  The gene encoding the RAG-1 or RAG-2 recombinase E)  The gene for a factor that is required for IgD surface expression Based on these data, the mutation in the original mutant mouse strain most likely inactivates:


A) The gene for a transcription factor required for IgD gene transcription
B) A regulatory region in the immunoglobulin heavy chain gene locus required for IgD gene transcription
C) The gene for a factor required for alternative mRNA splicing of the immunoglobulin heavy chain primary mRNA transcript
D) The gene encoding the RAG-1 or RAG-2 recombinase
E) The gene for a factor that is required for IgD surface expression

F) None of the above
G) B) and D)

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In spite of their low affinity for binding to their antigen, IgM antibodies can be quite effective at promoting the elimination of extracellular bacterial infections. This is due to:


A) The ability of IgM antibodies to traffic across epithelial surfaces
B) Multivalent binding of IgM pentamers to repetitive epitopes on bacterial surfaces
C) The high concentration of IgM antibodies in the serum and in all tissues
D) The early production of IgM antibodies during an immune response
E) The high rate of somatic hypermutation in the genes encoding IgM antibodies

F) C) and E)
G) A) and E)

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Some T cells express γ\gamma : δ\delta T-cell receptors rather than α\alpha : β\beta T-cell receptors. The organization of the α\alpha locus and the δ\delta locus helps to ensure that each T cell cannot express both types of T-cell receptors. The mechanism involved is that:


A) The rearrangement of a T-cell receptor α\alpha gene deletes the δ\delta locus on that allele.
B) The rearrangement of a T-cell receptor δ\delta gene deletes the α\alpha locus on that allele.
C) The RAG recombinase enzymes are down-regulated immediately after the first T-cell receptor genes rearrange.
D) The α\alpha : β\beta T-cell receptor signals the T cell to delete the δ\delta locus.
E) The γ\gamma : δ\delta T-cell receptor signals the T cell to delete the α\alpha locus.

F) C) and D)
G) A) and B)

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Recombination signal sequences are conserved heptamer and nonamer sequences that flank the V, J, and D gene segments which undergo recombination to generate the final V region coding exon. Some of these have 12-nucleotide spacers between the heptamer and nonamer, and others have 23-nucleotide spacers. The reason recombination signal sequences come in these two forms is:


A) To ensure the correct assembly of gene segments so that a VH recombines to a DH and not to another VH, for instance
B) To ensure that the heptamer and nonamer are found on the same face of the DNA double helix
C) To ensure that κ\kappa , λ\lambda , and heavy chains recombine within a locus and not between loci
D) To ensure that κ\kappa , λ\lambda , and heavy chain gene segments do not undergo recombination with non-immunoglobulin genes
E) To ensure that the RAG recombinase cuts the DNA between the last nucleotide of the heptamer and the coding sequence

F) A) and D)
G) C) and D)

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Figure shows the germ-line configuration of three V gene segments (#1, 2, 3) , and two J gene segments (#4, 5) . Which of the choices below represents a DNA configuration that would result from V-to-J recombination? Figure shows the germ-line configuration of three V gene segments (#1, 2, 3) , and two J gene segments (#4, 5) . Which of the choices below represents a DNA configuration that would result from V-to-J recombination?    A)   B)   C)   D)   E)


A) Figure shows the germ-line configuration of three V gene segments (#1, 2, 3) , and two J gene segments (#4, 5) . Which of the choices below represents a DNA configuration that would result from V-to-J recombination?    A)   B)   C)   D)   E)
B) Figure shows the germ-line configuration of three V gene segments (#1, 2, 3) , and two J gene segments (#4, 5) . Which of the choices below represents a DNA configuration that would result from V-to-J recombination?    A)   B)   C)   D)   E)
C) Figure shows the germ-line configuration of three V gene segments (#1, 2, 3) , and two J gene segments (#4, 5) . Which of the choices below represents a DNA configuration that would result from V-to-J recombination?    A)   B)   C)   D)   E)
D) Figure shows the germ-line configuration of three V gene segments (#1, 2, 3) , and two J gene segments (#4, 5) . Which of the choices below represents a DNA configuration that would result from V-to-J recombination?    A)   B)   C)   D)   E)
E) Figure shows the germ-line configuration of three V gene segments (#1, 2, 3) , and two J gene segments (#4, 5) . Which of the choices below represents a DNA configuration that would result from V-to-J recombination?    A)   B)   C)   D)   E)

F) A) and D)
G) C) and D)

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The variable lymphocyte receptors (VLRs) of lampreys represent a highly diverse set of proteins with structural similarity to the mammalian Toll-like receptors. Yet the VLRs and the lymphocytes that produce them are thought to be components of the lamprey's adaptive immune system. This is because:


A) The VLRs are highly diverse and have been shown to bind to pathogens.
B) Both membrane-bound and secreted forms of VLRs are found in the lampreys.
C) VLR coding genes are formed by DNA rearrangement events.
D) VLRs are clonally distributed such that each lymphocyte expresses only one form of VLR.
E) VLR gene rearrangements occur by a process similar to gene conversion.

F) All of the above
G) None of the above

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The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as:


A) Overall variability in CDR3 sequence is needed to create a sufficiently diverse antibody repertoire.
B) The CDR3 region is more important in binding antigen than the CDR1 and CDR2 regions are.
C) Some light chains bind better to heavy chains with longer CDR3 region sequences.
D) Longer CDR3 sequences generally create antibodies with higher affinity for the antigen.
E) Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen.

F) B) and E)
G) A) and D)

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In rare instances, B cells can be found that have two immunoglobulin light chain alleles, both of which are rearranged in frame, and can encode functional light chain proteins. Yet, on the surface of the B cell, only one of the two light chain proteins is detected in the membrane-bound immunoglobulin receptor. The reason these rare cells have two functional light chain rearrangements but only express one of the two light chains as part of the B-cell receptor is:


A) One of the two light chains is formed from rearrangement of a V gene segment that is a pseudogene.
B) One of the two light chain proteins doesn't form a stable complex with the heavy chain expressed in this cell.
C) One of the two light chain alleles is not transcribed efficiently, and produces only low levels of protein.
D) One of the two light chain alleles uses a V gene segment that is not targeted very often by the RAG recombinase.
E) One of the two light chains is rapidly degraded after synthesis due to improper folding.

F) B) and C)
G) All of the above

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For α\alpha : β\beta T-cell receptors, sequence diversity is heavily concentrated at the junctions formed by the rearrangement of gene segments during the generation of the expressed V α\alpha and V β\beta regions. The result of this organization is to position the most variable part of the T-cell receptor over a certain region of the ligand recognized by this receptor. Which region (outlined in red in Figure ) indicates this part of the ligand recognized by the T-cell receptor?


A)  For  \alpha : \beta  T-cell receptors, sequence diversity is heavily concentrated at the junctions formed by the rearrangement of gene segments during the generation of the expressed V \alpha  and V \beta  regions. The result of this organization is to position the most variable part of the T-cell receptor over a certain region of the ligand recognized by this receptor. Which region (outlined in red in Figure )  indicates this part of the ligand recognized by the T-cell receptor?  A)    B)    C)    D)    E)
B)  For  \alpha : \beta  T-cell receptors, sequence diversity is heavily concentrated at the junctions formed by the rearrangement of gene segments during the generation of the expressed V \alpha  and V \beta  regions. The result of this organization is to position the most variable part of the T-cell receptor over a certain region of the ligand recognized by this receptor. Which region (outlined in red in Figure )  indicates this part of the ligand recognized by the T-cell receptor?  A)    B)    C)    D)    E)
C)  For  \alpha : \beta  T-cell receptors, sequence diversity is heavily concentrated at the junctions formed by the rearrangement of gene segments during the generation of the expressed V \alpha  and V \beta  regions. The result of this organization is to position the most variable part of the T-cell receptor over a certain region of the ligand recognized by this receptor. Which region (outlined in red in Figure )  indicates this part of the ligand recognized by the T-cell receptor?  A)    B)    C)    D)    E)
D)  For  \alpha : \beta  T-cell receptors, sequence diversity is heavily concentrated at the junctions formed by the rearrangement of gene segments during the generation of the expressed V \alpha  and V \beta  regions. The result of this organization is to position the most variable part of the T-cell receptor over a certain region of the ligand recognized by this receptor. Which region (outlined in red in Figure )  indicates this part of the ligand recognized by the T-cell receptor?  A)    B)    C)    D)    E)
E)  For  \alpha : \beta  T-cell receptors, sequence diversity is heavily concentrated at the junctions formed by the rearrangement of gene segments during the generation of the expressed V \alpha  and V \beta  regions. The result of this organization is to position the most variable part of the T-cell receptor over a certain region of the ligand recognized by this receptor. Which region (outlined in red in Figure )  indicates this part of the ligand recognized by the T-cell receptor?  A)    B)    C)    D)    E)

F) All of the above
G) A) and B)

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In some cases, antibody binding to a pathogen will prevent the pathogen from adhering to and/or from infecting host cells. This antibody function does not require the Fc region of the antibody. Nonetheless, the Fc region is still required to facilitate the removal of the antibody:pathogen complex from the body. Explain why.

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Antibodies can protect the body in a var...

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