Parham Fragen Kapitel 7 Flashcards
Which of the following describes the developmental pathway for T cells?
a. thymus → bone marrow → spleen
b. thymus → bone marrow → thymus
c. bone marrow → thymus → lymph nodes
d. lymph nodes → thymus → spleen
e. bone marrow → lymph nodes → thymus.
c. bone marrow → thymus → lymph nodes
Which of the following statements is false concerning T-cell development?
a. γ and δ rearrangements may occur at two different stages, once at the committed double-negative stage and again at the uncommitted double-positive stage.
b. If α-chain rearrangement is successful, it is still possible to produce a committed γ:δ T cell.
c. Neither γ nor δ chains associate with pTα.
d. T-cell development is biased in favor of α:β lineage commitment.
e. A maximum of four attempts can be made to produce a functional β chain because there are two Cβ genes and associated Dβ and Jβ segments per β-chain locus.
f. γ:δ T cells are not subject to positive or negative selection processes in the thymus.
b. If α-chain rearrangement is successful, it is still possible
to produce a committed γ:δ T cell.
Which of the following statements regarding γ:δ T cells is
incorrect? (Select all that apply.)
a. They do not require CD3 proteins for cell-surface
expression of their antigen receptors.
b. They comprise the minority subpopulation of T
lymphocytes.
c. They rearrange their antigen receptor genes in the
periphery.
d. The do not pair the γ- or δ-chains with pTα at any stage
in their developmental pathway.
e. They originate from the same bone marrow-derived
precursor that gives rise to α:β T cells.
a. They do not require CD3 proteins for cell-surface
expression of their antigen receptors.
c. They rearrange their antigen receptor genes in the
periphery.
An adult who has been thymectomized will have a T-cell
repertoire that _____.
a. resembles a patient with DiGeorge syndrome
b. is MHC-independent
c. is dominated by γ:δ T cells
d. fails to provide protective T-cell immunity
e. is self-renewing and long lived and does not require
replenishment from the thymus.
e. is self-renewing and long lived and does not require
replenishment from the thymus.
During the early developmental stages of α:β T cells in the thymus, there are two key checkpoints that must be satisfied to permit the progression of T-cell development. Explain what occurs at each checkpoint.
The first checkpoint occurs after the rearrangement of the β-chain locus, which tests for the ability of the β-chain to associate with pTα, the surrogate light chain, and form the pre-T-cell receptor on the cell surface. The second check-point occurs after the rearrangement of the α-chain locus, which tests for the ability of the α-chain to associate with the β-chain and form the T-cell receptor on the cell surface.
Match the term in Column A with its correct description
in Column B.
a. Th-POK
b. Notch1
c. superdimer
d. FoxP3
e. AIRE
- β chain/pTα:β chain/pTα
- facilitates expression of tissue-specific genes in thymic epithelium
- transcription factor required for CD4 T-cell development from double-positive thymocytes
- facilitates the expression of genes required for T-cell development
- transcriptional repressor protein of regulatory T cells
a—3
b—4
c—1
d—5
e—3
Positive selection occurs in the _____ and involves _____
thymocytes
a. cortex; double-positive
b. cortex; double-negative
c. medulla; double-positive
d. medulla; double-negative
e. medulla; uncommitted progenitors of.
a. cortex; double-positive
Which of the following statements about the successive
rearrangement of α:β T-cell receptors is correct? (Select all that apply.)
a. Unproductive rearrangement to the Cβ1 locus can be
rescued by a second rearrangement to the Cβ2 locus.
b. Unproductive rearrangement to the Cβ2 locus can be
rescued by a second rearrangement to the Cβ1 locus.
c. Unproductive rearrangements between Vα and Jα can
be rescued by a second rearrangement between
upstream Vα and downstream Jα segments.
d. When the α chain undergoes a successive gene
rearrangement, the unproductive intervening
rearranged gene segments are deleted.
e. The δ-chain locus is permanently deleted as an
extrachromosomal circle when the α-chain gene
rearranges.
a, c, d, e
During positive selection, if the selecting MHC molecule
is class I, then
a. gene expression of CD8 is halted
b. the thymocyte is committed to the CD8 lineage
c. continued α-chain rearrangement occurs on the other locus to produce a mature T cell with two receptors
d. the thymocyte differentiates into a CD4 T cell
e. gene expression of CD4 is enhanced.
b. the thymocyte is committed to the CD8 lineage
MHC restriction is best described as
a. elimination of thymocytes bearing T-cell receptors that
are unable to interact with self-MHC molecules
b. preferential survival and proliferation of thymocyes that
survive negative selection
c. T-cell recognition of a peptide antigen only when it is
bound to a particular form of MHC molecule
d. a state of non-responsiveness to a peptide antigen
e. a condition in which either MHC class I or class II
molecules are not expressed on cells.
c. T-cell recognition of a peptide antigen only when it is
bound to a particular form of MHC molecule
Match the term in Column A with its correct description
in Column B.
a. T-cell receptor editing
b. positive selection
c. bare lymphocyte syndrome
d. negative selection
e. MHC restriction
- absence of either CD4 T cells or CD8 T cells in the circulation
- elimination of autoreactive thymocytes
- continued α-chain gene rearrangement until a functional T-cell receptor is generated
- T-cell repertoire selection based on interaction with the individual’s MHC allotypes
- activation of a T cell only if an appropriate MHC molecule presents antigenic peptide
a—3
b—4
c—1
d—2
e—5
If a T-cell receptor on a double-positive thymocyte binds
to a self-peptide:self-MHC class I complex with low affinity the result is
a. negative selection and apoptosis
b. cell proliferation
c. rearrangement of the second β-chain locus
d. positive selection of a CD4 T cell
e. positive selection of a CD8 T cell
e. positive selection of a CD8 T cell
The expression of MHC class II molecules is restricted to
a small number of cell types.
A. What are these cell types?
B. Which of these cell types populate the thymus or circulate through it, and what role do they play in mediating positive and/or negative selection?
C. Can you explain why it would be detrimental for non-circulating cells that populate tissues and glands to express MHC class II molecules?
A. Cells that express MHC class II are the professional antigen-presenting cells (B cells, macrophages, and dendritic cells), thymic epithelial cells, neural microglia, and activated T-cells (in humans).
B. Macrophages, dendritic cells, and thymic epithelial cells either populate the thymus or circulate through it. Cortical thymic epithelial cells participate in positive selection by presenting MHC class I and class II molecules with self peptides to double-positive (CD4 CD8) thymocytes. These are developing T cells that have successfully rearranged the TCRα and TCRβ genes. Only T cells that have T-cell receptors that can interact with self MHC are positively selected, thus shaping a T-cell repertoire that is specific for self-MHC molecules.
If the affinity for self-peptide:
self-MHC is too weak, the T cells die by neglect, through apoptosis. Cortical and medullary thymic epithelium may also participate in negative selection by inducing the apoptosis of thymocytes that bear a T-cell receptor with high affinity for self MHC, self peptide or a combination of the two. Thymic epithelium, circulating macrophages, and dendritic cells found primarily at the cortico-medullary junction participate in negative selection and aid in the elimination of potentially self-reactive T cells bearing high-affinity T-cell receptors for complexes of self peptides:self MHC. Because these cells are circulating between tissues, organs, and the thymus, a heterogeneous array of self peptides will be transported to the thymus and displayed. This is important because some self peptides are expressed in locations other than the thymus and may be encountered in secondary lymphoid organs.
C. Although circulating dendritic cells and macrophages are effective at endocytosing cellular debris in extra thymic locations and then presenting self peptides derived from this debris to thymocytes, some self proteins are excluded from this housekeeping function. Some of these self proteins are located in immunologically privileged sites where leukocytes do not usually circulate. These sites are normally MHC class II negative, which is important because it avoids the presentation by MHC class II of any self peptides that were not presented in the thymus during negative selection. It should be pointed out, however, that some of these tissues can be induced to express MHC class II molecules under the influence of certain cytokines, for example interferon-γ, during an inflammatory response. This is believed to be one mechanism by which tolerance can be broken, resulting in autoimmunity.
Generally, in healthy individuals and in the absence of infection, a mature naive T cell that encounters a self antigen outside the thymus may _____. (Select all that apply.)
a. induce an autoimmune attack on the cell presenting
that antigen
b. be suppressed by a regulatory T cell
c. undergo activation-induced cell death
d. be rendered anergic
e. continue to rearrange its α-chain genes.
b. be suppressed by a regulatory T cell
c. undergo activation-induced cell death
d. be rendered anergic
All of the following are characteristic of regulatory T cells
except
a. they express CD25
b. they facilitate the proliferation of naive T cells interacting with the same antigen-presenting cell
c. they express CD4
d. they express the transcriptional repressor FoxP3
e. they express MHC class II-restricted T-cell receptors specific for self antigen.
b. they facilitate the proliferation of naive T cells interacting with the same antigen-presenting cell
