Deck 7: The Development of T Lymphocytes

Question 1

Which of the following statements regarding positive selection is correct?

A)All subsets of developing T cells undergo positive selection before export to the peripheral circulation.
B)T-cell receptor editing is linked to the process of positive selection.
C)Positive selection results in the production of T cells bearing T-cell receptors that have the capacity to interact with all allotypes of MHC class I and class II molecules,and not just those of the individual.
D)Positive selection ensures that autoreactive T cells are rendered non-responsive.
E)If there is a genetic defect in AIRE,then T-cell development is arrested as positive selection commences.

Answer 1

B

Question 2

Genetic deficiencies in all of the following would impair the development of a fully functional T-cell repertoire except

A)RAG-1 or RAG-2
B)Notch1
C)Pax-5
D)IL-7 receptor (CD127)
E)TAP-1 or TAP-2.

Answer 2

C

Question 3

Which of the following statements about Notch 1 is correct? (Select all that apply.)

A)Notch 1 is expressed on thymic epithelial cells.
B)In the absence of Notch 1 expression,T cells can complete their differentiation.
C)Notch 1 is to T-cell development as Pax-5 is to B-cell development.
D)Notch 1 contains two distinct domains,one of which is proteolytically cleaved and becomes a transcription factor in the nucleus.
E)The extracellular domain of Notch 1 must interact with a ligand on thymic epithelium to initiate cleavage and separation of the Notch 1 extracellular and intracellular domains.

Answer 3

C,D,E

Question 4

Which of the following processes is not dependent on an interaction involving MHC class I or class II molecules? (Select all that apply.)

A)positive selection of α:β T cells
B)intracellular signaling by pre-T-cell receptors
C)negative selection of αβ T cells
D)peripheral activation of mature naive T cells
E)positive selection of γ:δ T cells.

Question 5

a double-negative thymocyte has just completed a productive β-chain gene rearrangement,which of the following describes the immediate next step in the development of this thymocyte?

A)A pre-T-cell receptor is assembled as a superdimer.
B)Rearrangement of γ- and δ-chain genes commences.
C)Expression levels of RAG-1 and RAG-2 are elevated.
D)The linked δ-chain genes are eliminated.
E)This cell will inevitably differentiate into a committed γ:δ T cell.

Question 6

Thymocytes that are not positively selected

A)undergo genetic reprogramming and differentiate into a different cell type
B)are exported to the periphery,where they are phagocytosed by macrophages
C)make up about 98% of developing thymocytes and die by apoptosis in the thymic cortex
D)are eliminated because of their reactivity with self antigens
E)try out different β chains to acquire reactivity with self-MHC molecules.

Question 7

Which of the following is mismatched:

A)double-negative CD3- thymocytes: cortico-medullary junction
B)double-negative CD3- thymocytes: subcapsular zone
C)double-positive CD3+ thymocytes: cortico-medullary junction
D)cortical epithelial cells: subcapsular regions
E)dendritic cells: cortico-medullary junction.

Question 8

Which of the following statements are true of a T cell that expresses two α chains (and thus two different T-cell receptors)as a result of ineffective allelic exclusion of the α chain during rearrangement? (Select all that apply.)

A)Engaging either of the T-cell receptors on MHC molecules of the thymic epithelium will result in positive selection.
B)One of the T-cell receptors will be functional while the other will most probably be non-functional.
C)If either T-cell receptor binds strongly to self-peptides presented by self-MHC molecules,the thymocyte will be negatively selected.
D)One of the T-cell receptors may be autoreactive but escape negative selection because its peptide antigen is present in tissues other than the thymus.
E)Subsequent gene rearrangements may give rise to a γ:δ T-cell receptor.

Question 9

Which of the following is the first stage of T-cell receptor gene rearrangement in α:β T cells?

A)V_α→D_α
B)D_α →J_α
C)V_β→ D_β
D)D_β→J_β
E)V_α→J_α.

Question 10

which of the following ways does the developmental pathway of α:β T cells differ from that of B cells? (Select all that apply.)

A)Their antigen receptors are derived from gene rearrangement processes.
B)When the first chain of the antigen receptor is produced it combines with a surrogate chain.
C)Cells bearing self-reactive antigen receptors undergo apoptosis.
D)MHC molecules are required to facilitate progression through the developmental pathway.
E)T cells do not rearrange their antigen-receptor genes in the bone marrow.

Question 11

_______ of thymocytes is necessary to produce a T-cell repertoire capable of interacting with self-MHC molecules.

A)positive selection
B)negative selection
C)apoptosis
D)receptor editing
E)isotype switching.

Question 12

Which of the following is the first T-cell receptor complex containing the β chain to reach the cell surface during the development of T lymphocytes?

A)γ:β:CD3
B)β:CD3
C)α:β:CD3
D)β:CD44
E)pTα:β:CD3.

Question 13

There are many parallels between the development of B cells and T cells.Identify the incorrectly matched counterpart in B cells (left)versus T cells (right).

A)VpreBλ5: pTα
B)Igα/Igβ:CD3
C)Pax-5: FoxP3
D)multiple κ and λ light-chain gene rearrangements: multiple α-chain gene rearrangements.

Question 14

Which of the following cell-surface glycoproteins is characteristic of stem cells,but stops being expressed when a cell has committed to the T-cell developmental pathway?

A)CD2
B)CD3
C)CD25
D)CD34
E)MHC class II.

Question 15

_____ is a T-cell-specific adhesion molecule expressed before the expression of a functional T-cell receptor while the thymocytes are still in their double-negative stage of development.

A)CD4
B)CD8
C)CD25
D)CD2
E)CD3.

Question 16

What is Notch1?
B.Which cells express the ligand of Notch1?
C.How does the interaction between Notch1 and its ligand mediate T-cell development?

Question 17

After interaction with thymic stromal cells,_____,a glycoprotein not expressed by the uncommitted progenitor cell is activated in developing thymocytes.(Select all that apply.)

A)CD2
B)CD34
C)CD5
D)CD127 (IL-7 receptor)
E)CD44.

Question 19

T-cell receptor β-chain locus can undergo successive gene rearrangements to rescue unproductive V(D)J rearrangements.
A.What aspects of gene segment rearrangement at the TCRβ locus make this possible?
B.Can the immunoglobulin heavy-chain locus,which is also composed of V,D,and J segments,undergo successive rearrangements? If not,give the reasons for the difference.

Question 20

a thymocyte has productively rearranged a β-chain gene,which of these event(s)can occur subsequently? (Select all that apply.)
a.β binds to pTα and is expressed on the cell surface with the CD3 complex and ζ chain.
b.Rearrangement of β-,γ-,and δ-chain genes ceases as a result of the suppression of expression of RAG-1 and RAG-2.
c.The pre-T cell proliferates and produces a clone of cells all expressing an identical β chain.
d.Expression of CD34 and CD2 gives rise to double-positive thymocytes.
e.α-,γ-,and δ-chain loci rearrange simultaneously.

Question 21

we age,our thymus shrinks,or atrophies,by a process called involution,yet T-cell immunity is still functional in old age.
A.Explain how T-cell numbers in the periphery remain constant in the absence of continual replenishment from the thymus.
B.How does this differ from the maintenance of the B-cell repertoire?

Question 22

the process of positive selection did not occur,then

A)a condition resembling immune dysregulation,polyendocrinopathy,enteropathy,X-linked syndrome (IPEX)would develop
B)a condition resembling autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)would develop
C)naive T cells would be unable to undergo differentiation in secondary lymphoid tissues
D)malignant transformation would be more likely because of the accumulation of multiple mutations
E)only a very small percentage of circulating T lymphocytes would be able to become activated.

Question 23

Allelic exclusion occurs for all of the following except

A)T-cell receptor α genes
B)T-cell receptor β genes
C)B-cell receptor heavy-chain genes
D)B-cell receptor κ-chain genes
E)B-cell receptor λ-chain genes.

Question 24

Immediately after positive selection

A)the thymocyte reaches maturity and is exported to the periphery
B)RAG proteins are degraded and are no longer synthesized
C)receptor editing commences to eliminate reactivity against self antigens
D)the developing thymocyte acquires a double-negative phenotype
E)expression of pTα is repressed.

Question 25

function of negative selection of thymocytes in the thymus is to eliminate

A)single-positive thymocytes
B)double-positive thymocytes
C)alloreactive thymocytes
D)autoreactive thymocytes
E)apoptotic thymocytes.

Question 26

Healthy individuals have approximately ____ of CD4 T cells compared with CD8 T cells.

A)one quarter the number
B)half the number
C)equal numbers
D)twice the number
E)four times the number

Question 27

T cells,allelic exclusion of the α-chain locus is relatively ineffective,resulting in the production of some T cells with two T-cell receptors of differing antigen specificity on their cell surface.
A.Will both these receptors have to pass positive selection for the cell to survive? Explain your answer.
B.Will both receptors have to pass negative selection for the cell to survive? Explain your answer.
C.Is there a potential problem in having T cells with dual specificity surviving these selection processes and being exported to the periphery?

Question 28

Giulia McGettigan was born full term with a malformed jaw,cleft palate,a ventricular septal defect,and hypocalcemia.Within 48 hours of birth she developed muscle tetany,convulsions,tachypnea,and a systolic murmur.A chest X-ray showed an enlarged heart and the absence of a thymic shadow.Blood tests showed severely depleted levels of CD4 and CD8 T cells; B-cell numbers were low but within normal range.Parathyroid hormone was undetectable.Fluorescence in situ hybridization of the buccal mucosa revealed a small deletion in the long arm of chromosome 22.Giulia failed to thrive and battled chronic diarrhea and opportunistic infections,including oral candidiasis and Pneumocystis jirovecii,the latter infection causing her death.Giulia most probably had which of the following immunodeficiency diseases?
a.AIDS
b.DiGeorge syndrome
c.bare lymphocyte syndrome
d.chronic granulomatous disease
e.hyper IgM syndrome.

Question 29

class II deficiency is inherited as an autosomal recessive trait and involves a defect in the coordination of transcription factors involved in regulating the expression of all MHC class II genes (HLA-DP,HLA-DQ,and HLA-DR).
A.What is the effect of MHC class II deficiency?
B.Explain why hypogammaglobulinemia is associated with this deficiency.

Question 30

What is the role of regulatory CD4 T cells (T_reg)?
B.How can T_reg be distinguished from other non-regulatory CD4 T cells?

Question 31

Mature B cells undergo somatic hypermutation after activation,which,after affinity maturation,results in the production of antibody with a higher affinity for antigen than in the primary antibody response.Suggest some reasons why T cells have not evolved the same capacity.

Question 32

Double-negative thymocytes initiate rearrangement at the _____ locus (loci)before all other T-cell receptor genes.

A)γ and δ
B)β
C)α and β
D)α,γ,and δ
E)β,γ,and δ.

Question 33

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)is caused by a defect in

A)cathepsin L
B)a transcription factor that regulates tissue-specific gene expression in the thymus
C)the production of regulatory CD4 T cells
D)FoxP3
E)T-cell receptor gene rearrangement.

Question 34

Individuals with a defective autoimmune regulator gene (AIRE)exhibit

A)DiGeorge syndrome
B)autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
C)severe combined immunodeficiency (SCID)
D)MHC class I deficiency
E)MHC class II deficiency.

Question 35

Identify which of the following describes how antigen processing and presentation of self antigens by thymic epithelial cells differs from that of antigen-presenting cells in peripheral tissues.(Select all that apply.)

A)Thymic epithelium expresses MHC class I molecules but not MHC class II molecules.
B)Thymic epithelium uses cathepsin L for proteolytic degradation of self proteins.
C)Thymic epithelium expresses MHC class II molecules but not MHC class I molecules.
D)Thymic epithelium uses the transcription factor AIRE to activate thymic expression of tissue-specific genes.
E)Thymic epithelium expresses transcription repressor protein FoxP3.

Question 36

surrogate light chain operating during pre-B-cell development is made up of VpreB:λ.Its expression with μ on the pre-B-cell surface is an important checkpoint in B-cell maturation.Name the T-cell analog of VpreB:λ5 and discuss how it is functionally similar.

Question 37

Explain two ways in which the expression and processing of self antigens in thymic epithelium differs from the expression and processing of self antigens outside the thymus.
B.In what way is the thymic situation advantageous for the purposes of negative selection?

Question 38

of the following types of protein are processed and presented by macrophages in the thymus except _____ proteins.

A)tissue-specific
B)soluble proteins from extracellular fluids
C)ubiquitous proteins
D)proteins made by macrophages
E)proteins derived from other cells that macrophages phagocytose.

Question 39

Which of the following statements is correct?

A)In adults the mature T-cell repertoire is self-renewing and long-lived and does not require a thymus for the provision of new T cells.
B)T cells and B cells are both short-lived cells and require continual replenishment from primary lymphoid organs.
C)The human thymus is not fully functional until age 30,at which time it begins to shrink and atrophy.
D)In DiGeorge syndrome the bone marrow takes over the function of the thymus and produces mature peripheral T cells.
E)None of the above statements is correct.

Question 40

human thymus begins to degenerate as early as one year after birth.This process is called ______ and is marked by the accumulation of ___ once occupied by thymocytes.

A)thymectomy; dendritic cells
B)involution; fat
C)differentiation; γ:δ T cells
D)negative selection; γ:δ T cells
E)involution; thymic stroma.

Question 41

What is immunological tolerance?
B.What is the general name for the antigens against which the immune system is normally tolerant?
ANSWERS