Ch 8 Book Questions Flashcards
A one year old boy with a history of severe infections is found to have very few circulating mature T cells or NK cells, but normal numbers of B cells. Genetic studies reveal he has X-linked severe combined immunodeficiency syndrome. Defective signaling by the receptor for which cytokine is the underlying cause of this disease?
a. IL-1
b. IL-2
c. IL-4
d. IL-7
e. GM-CSF
d. IL-7
X-linked severe combined immunodeficiency syndrome (X-linked SCID) caused by mutations in the common γ chain which is a signaling polypeptide in the multimeric cytokine receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Although signaling from all of these receptors would be defective in X-linked SCID, only IL-7 is required for early development of T cells and NK cells in the thymus of humans.
In both B and T cell development, there is stage when a pre-antigen receptor (pre B cell receptor or pre T cell receptor) is expressed. Which of the following accurately describes an important function of these pre-antigen receptors?
a. Positively select for lymphocytes that have successfully undergone a first round of V-D-J recombination required to express functional antigen receptors
b. Negatively select for self-reactive lymphocytes
c. Instruct the differentiation of the lymphocytes into different subsets of effector cells
d. Positively select lymphocytes that recognize microbial antigens
e. Bind to chemokines that keep the lymphocytes from migrating out of the generative lymphoid organs
a. Positively select for lymphocytes that have successfully undergone a first round of V-D-J recombination required to express functional antigen receptors
Signals generated by the pre-antigen receptors are required for survival of developing lymphocytes. Since the pre B cell receptor contains an Ig μ heavy chain, and the pre T cell receptor contains a TCR β chain, only developing lymphocytes that have successfully rearranged Ig μ or TCR β genes will survive, and have a chance of rearranging and expressing Ig light chain or TCR α chain genes. Therefore, the pre-antigen receptors provide a checkpoint mechanism by which useless cells that will never be able to express an antigen receptor are purged. The pre-antigen receptors do not stimulate lymphocyte differentiation into effector cells, but they do stimulate proliferation and further molecular events in development of mature naïve lymphocytes. Since pre-antigen receptors are not fully formed antigen receptors, they cannot mediate selection for or against self or foreign antigens, and they have no chemokine binding capacity.
Which of the following mechanisms contributes most to both Ig and TCR diversity?
a. Multiple possible combinations of the different V, D, and J segments
b. Changes in the nucleotide sequences at the junctions between recombined V, D, and J segments
c. Somatic mutation of variable genes
d. Isotype switching
e. Polymorphism
b. Changes in the nucleotide sequences at the junctions between recombined V, D, and J segments
Junctional diversity is caused by deletions and additions of base pairs between V, D, and J segments during somatic recombination, resulting in new junctional sequences not present in the germline. This accounts for the majority of Ig and TCR diversity. Combinatorial diversity is the second major mechanism for diversity, based on the large number of different V, D, and J segments inserted in the germline that can be used during somatic recombination, but it contributes much less to diversity than does junctional variability. Somatic mutation of variable genes occurs during the germinal center reaction in B cells only, and its impact on diversity is far less than the mechanism of junctional diversity. Isotype switching (of Ig molecules only) changes the non–antigen-binding region and does not contribute to diversity of antigen receptor specificity. Polymorphism refers to the presence of different alleles of a gene in the population, not in an individual, and is not a mechanism of diversity of the antigen receptor repertoires.
Which enzyme contributes to antigen receptor junctional diversity by adding random nucleotides at the junctions between V, D, and J segments and is also useful as a marker of neoplasia of pro-B and pro-T cells?
a. Terminal deoxyribonucleotidyl transferase (TdT)
b. Activation-induced deaminase (AID)
c. Recombinase activating gene-1 (RAG-1)
d. DNA-dependent protein kinase
e. DNA polymerase
a. Terminal deoxyribonucleotidyl transferase (TdT)
Terminal deoxyribonucleotidyl transferase (TdT) is the enzyme that adds random nontemplate nucleotides (called N nucleotides) at the junctions between V, D and J segments, mainly in the recombined Ig heavy chain and TCRβ chain genes. The enzyme is expressed mainly during the time in B cell and T cell development when the IgH and TCRβ chain genes are undergoing recombination. Activation-induced deaminase is an enzyme involved in somatic mutation and isotype switching of Ig genes. Recombinase activating gene-1 (RAG-1) is a component of the V(D)J recombinase that mediates the joining of the discrete gene segments, and DNA-dependent protein kinase participates in the recombination and joining process, but these enzymes do not contribute on their own to junctional diversity.
Why do Ig and TCR genes only undergo rearrangements in B and T cells and not other cell types?
a. The hepatmer/nonamer recombination signal sequences (RSSs) adjacent to V, D, and J gene segment are present only in B and T cells
b. The Ig and TCR α genes are deleted in other cell types
c. Recombinase activating genes (RAG-1 and RAG 2) are expressed only in developing lymphocytes
d. Activation induced deaminase (AID) is expressed only in developing lymphocytes
e. DNA-dependent protein kinase is only expressed in developing lymphocytes
c. Recombinase activating genes (RAG-1 and RAG 2) are expressed only in developing lymphocytes
A complex of RAG-1 and RAG-2 is the V-(D)-J recombinase that recognizes RSSs adjacent to V, D, and J gene segment, and cuts the DNA at these locations. This is an essential step for V-(D)-J rearrangements. The RAG proteins are only expressed in developing B and T cells, and only at certain times during development. The actual inherited Ig and TCR gene sequences in developing lymphocytes before recombination occurs, including coding gene segments and RSSs, are identical to the sequences in all other cells. AID is required for Ig gene switch recombination and somatic mutation of Ig V genes, but does not play a role in antigen receptor V-(D)-J rearrangements. DNA-dependent protein kinase is a DNA repair enzyme necessary but not sufficient for the antigen receptor rearrangements, and it is not unique to B and T cells.
Which of the following mechanisms accounts for the fact that all of the TCRs produced by a single T cell have identical β chains?
a. X inactivation
b. Light chain isotype exclusion
c. Antigen receptor gene homozygosity
d. Linkage disequilibrium
e. Allelic exclusion
e. Allelic exclusion
In TCR allelic exclusion, expression of the β chain gene encoded by a successfully recombined gene on one chromosome inhibits recombination of the β chain gene on the other chromosome. The inhibitory signals are generated by the pre-TCR. This ensures that the T cell will not produce receptors with two different β chains. However, allelic exclusion does not occur for TCR α chain genes, and many T cells may express TCRs with two different α chains. Heavy chain allelic exclusion occurs by a similar mechanism in B cell development.
Receptor editing is a mechanism to achieve self tolerance if a self reactive lymphocyte develops. How, where, and when does self editing work?
a. High avidity self antigen recognition by an immature B cell in the bone marrow leads to reactivation of RAG genes, production of a new Ig light chain, and a change in the B cell specificity.
b. High avidity self antigen recognition by an immature T cell in the thymus leads to production of a new TCR and a change in the T cell specificity.
c. High avidity self antigen recognition by an immature B cell in the bone marrow leads to enzymatic alteration of Ig light chain proteins, and a change in the B cell specificity.
d. High avidity self antigen recognition by an immature T cell in the thymus leads to enzymatic alteration of the TCR α chain, and a change in the T cell specificity.
e. High avidity self antigen recognition by an immature B cell in the bone marrow leads to reactivation of RAG genes, additional heavy chain V-D-J recombination events, production of a new Ig heavy chain, and a change in the B cell specificity.
a. High avidity self antigen recognition by an immature B cell in the bone marrow leads to reactivation of RAG genes, production of a new Ig light chain, and a change in the B cell specificity.
Receptor editing occurs only in immature B cells in the marrow after high avidity recognition of self antigens, is due to re-expression of the RAG-1 and -2 genes and rearrangement of a previously rearranged Ig light chain gene locus.
