Question 1

Which of the following statements about induction or maintenance of T cell tolerance is NOT true?
A)Central tolerance is induced when immature developing T cells in bone marrow or thymus encounter self antigens.
B)Peripheral T cell tolerance results when mature naive T cells recognize antigens without adequate B7-1- or B7-2-mediated costimulation.
C)Peripheral T cell tolerance results when T cells recognize antigen in the setting of an innate immune response to the antigen.
D)Peripheral T cell tolerance to some antigens is induced when mature T cells recognize antigen and bind B7-1 or B7-2 via the inhibitory CTLA-4 receptor.
E)Peripheral T cell tolerance to an antigen may be induced by persistent and repeated stimulation of lymphocytes by that antigen in tissues.

Accepted Answer

Innate immune responses are usually required for induction of adaptive immune responses and may actually contribute to breaking tolerance to self antigens.Central tolerance occurs because of the susceptibility of immature lymphocytes to death in response to antigen receptor signals.Autoreactive lymphocytes that are not deleted during development must be regulated by a mechanism of peripheral tolerance,which is induced in T cells by antigen receptor stimulation without costimulation,with CTLA-4-mediated negative signaling,by repeated and persistent stimulation by antigen,and by suppression by regulatory T cells.

Question 2

For each feature of self-tolerance described in questions ,choose the term (letters A-K)that most closely matches it.
-Tolerance-sensitive stage of T cell maturation
A)Immature (IgM+IgD-)
B)Thymic cortex
C)Bone marrow
D)Antigen recognition without T cell help
E)Receptor editing
F)Activation-induced cell death
G)Regulatory T cell-mediated suppression
H)Antigen recognition with costimulation
I)Double positive (CD4+CD8+)
J)Anergy
K)Thymic medulla

Accepted Answer

Central T cell tolerance is induced largely by clonal deletion (negative selection)in the thymus at the CD4+CD8+ stage of T cell maturation.

Question 3

Failure of self-tolerance is the cause of which one of the following types of diseases?
A)Allograft rejection
B)Autoimmunity
C)Atopy
D)Anergy
E)Acne

Accepted Answer

Autoimmunity is an immune reaction against self (autologous)antigens.For this reaction to occur,normal mechanisms of tolerance must fail.Allograft rejection is an immune reaction against allogeneic,not autologous,antigens.Atopy is the name for allergic diseases,which are caused by IgE and mast cell-mediated immune responses to foreign antigens.Acne is an infection of hair follicles in the skin and was included as a choice because it begins with the letter A;it is not an autoimmune disease.

Question 4

For each feature of self-tolerance described in questions ,choose the term (letters A-K)that most closely matches it.
-Mechanism of peripheral tolerance induction of B cells but not T cells
A)Immature (IgM+IgD-)
B)Thymic cortex
C)Bone marrow
D)Antigen recognition without T cell help
E)Receptor editing
F)Activation-induced cell death
G)Regulatory T cell-mediated suppression
H)Antigen recognition with costimulation
I)Double positive (CD4+CD8+)
J)Anergy
K)Thymic medulla

Accepted Answer

B cell recognition of antigen in the periphery without concomitant helper T cell-derived signals may render the B cells anergic or unable to enter follicles for further differentiation.

Question 5

The AIRE protein is expressed by thymic medullary epithelial cells and is required for tolerance to many self-antigens.Which one of the following statements about how AIRE functions is correct?
A)AIRE is secreted by thymic medullary epithelial cells,and then binds and blocks the T cell receptors on developing T cells.
B)AIRE suppresses MHC expression by thymic medullary epithelial expression
C)AIRE is secreted by thymic medullary epithelial cells binds to soluble self antigens.
D)AIRE is required for thymic medullary epithelial expression of peripheral tissue antigens,which are then presented to immature T cells.
E)AIRE stimulates expression of immunosuppressive cytokines by thymic medullary epithelial cells.

Accepted Answer

AIRE induces thymic medullary epithelial cell expression of proteins otherwise only expressed in selected tissue,such as insulin in the pancreatic islets.These proteins are then processed and presented as peptide-MHC antigens to immature T cells,leading to the death of the T cells specific for the self antigens or their development into regulatory T cells.The result is T cell tolerance to these peripheral tissue antigens.

Question 6

Immunologic tolerance is defined as:
A)The removal of an antigen,or the microbes expressing the antigen,by the immune system,so that the host can tolerate the infection
B)Activation of only B cells,and not T cells,on exposure to an antigen
C)Unresponsiveness of the immune system to an antigen,which is induced by previous exposure to that antigen
D)The production of memory B cells and T cells on primary exposure to an antigen,which allows the host to tolerate a secondary exposure to the antigen
E)Vaccination of individuals against particular pathogens to prevent subsequent infections

Accepted Answer

Immunologic tolerance refers to the unresponsiveness of the immune system to particular antigens and develops on previous exposure to the antigen.Although the exact requirements for inducing tolerance have not been clearly defined,factors that do influence tolerance include the concentration of antigen,the mode of administration of the antigen,and the presence of costimulatory molecules on antigen-presenting cells for peptide antigens.

Question 7

For each feature of self-tolerance described in questions ,choose the term (letters A-K)that most closely matches it.
-Site of central T cell tolerance induction
A)Immature (IgM+IgD-)
B)Thymic cortex
C)Bone marrow
D)Antigen recognition without T cell help
E)Receptor editing
F)Activation-induced cell death
G)Regulatory T cell-mediated suppression
H)Antigen recognition with costimulation
I)Double positive (CD4+CD8+)
J)Anergy
K)Thymic medulla

Accepted Answer

Double-positive T cells,which are the cells susceptible to central T cell tolerance induction,are found in the thymic cortex.The developing T cells that are not deleted at the double-positive stage mature into single-positive (CD4+ or CD8+)thymocytes and migrate into the medulla before exiting the thymus.

Question 8

For each feature of self-tolerance described in questions ,choose the term (letters A-K)that most closely matches it.
-Mechanism of peripheral tolerance for T cells but not B cells
A)Immature (IgM+IgD-)
B)Thymic cortex
C)Bone marrow
D)Antigen recognition without T cell help
E)Receptor editing
F)Activation-induced cell death
G)Regulatory T cell-mediated suppression
H)Antigen recognition with costimulation
I)Double positive (CD4+CD8+)
J)Anergy
K)Thymic medulla

Accepted Answer

Regulatory T cells are known to suppress T cells but not B cells.Helper T cell-dependent B cell responses may be indirectly suppressed by this mechanism.

Question 9

CTLA-4,expressed by regulatory T cells and activated effector T cells,is crucial for self-tolerance as well as regulation of T cell responses of foreign antigens.Which of the following is a property of CTLA-4 that is important for its function?
A)CTLA-4 binds to CD28 and blocks its function.
B)CTLA-4 binds B7-1 and B7-2 with high affinity blocking their binding to CD28.
C)CTLA-4 binds class I MHC and blocks it ability to bind peptides.
D)CTLA-4 binds IL-2,preventing IL-2 binding to the IL-2 receptor.
E)CTLA-4 binds to IgG,preventing IgG biding to antigens.

Accepted Answer

CTLA-4 expressed on the surface of regulatory T cells,or on recently activated naïve T cells competitively binds the B7 proteins on dendritic cells,and prevents B7 proteins from binding to CD28.Therefore the naïve T cells are not co-stimulated,leading to anergy or death of the T cells.CTLA-4 does not bind CD28,MHC proteins,IL-2,or IgG.

Question 10

For each feature of self-tolerance described in questions ,choose the term (letters A-K)that most closely matches it.
-Mechanism of peripheral tolerance of B cells and T cells
A)Immature (IgM+IgD-)
B)Thymic cortex
C)Bone marrow
D)Antigen recognition without T cell help
E)Receptor editing
F)Activation-induced cell death
G)Regulatory T cell-mediated suppression
H)Antigen recognition with costimulation
I)Double positive (CD4+CD8+)
J)Anergy
K)Thymic medulla

Accepted Answer

Anergy,which is a block in signaling that prevents full activation of lymphocytes,is a mechanism of peripheral tolerance for both B and T lymphocytes.

Question 11

For each feature of self-tolerance described in questions ,choose the term (letters A-K)that most closely matches it.
-Mechanism of central tolerance of B cells
A)Immature (IgM+IgD-)
B)Thymic cortex
C)Bone marrow
D)Antigen recognition without T cell help
E)Receptor editing
F)Activation-induced cell death
G)Regulatory T cell-mediated suppression
H)Antigen recognition with costimulation
I)Double positive (CD4+CD8+)
J)Anergy
K)Thymic medulla

Accepted Answer

If an immature B cell in the bone marrow recognizes self-antigen,RAG gene expression may be induced and additional Ig light chain V(D)J recombination events may occur.This will change the antigen specificity of the expressed Ig.

Question 12

Which of the following sets of proteins (among others)are typically expressed by most regulatory T cells ( Treg)?
A)CD8,CD3,Perforin,IL-2,T-bet
B)CD4,PD-1,IL-2,FoxP3
C)CD4,CD3,CD25 (IL-2 receptor),FoxP3
D)CD4,CD3,CLTA4,AIRE,
E)CD4,TGF-b,CD25 (IL-2 receptor),IL-2

Accepted Answer

Treg express the transcription factor FoxP3,which is essential for their development and function.They express the high affinity IL-2 receptor chain CD25,but not IL-2,and are dependent on IL-2 from other sources for growth and survival.Treg are mostly CD4 positive,and express a class II MHC-restricted T cell receptor,with associated CD3 and zeta chain signaling molecules.Most Treg do express PD-1 and CTLA-4,but not express perforin,T-bet,or AIRE.
Matching

Question 13

For each feature of self-tolerance described in questions ,choose the term (letters A-K)that most closely matches it.
-Tolerance-sensitive stage of B cell maturation
A)Immature (IgM+IgD-)
B)Thymic cortex
C)Bone marrow
D)Antigen recognition without T cell help
E)Receptor editing
F)Activation-induced cell death
G)Regulatory T cell-mediated suppression
H)Antigen recognition with costimulation
I)Double positive (CD4+CD8+)
J)Anergy
K)Thymic medulla

Accepted Answer

Tolerance induction of B cells and T cells requires antigen receptor expression,but it occurs most readily before full maturation is completed.For B cells,IgM+ IgDF1F1F1S1F1F1F10 immature B cells are the most sensitive to tolerance induction.

Quiz 3: Tolerance

Which of the following statements about induction or maintenance of T cell tolerance is NOT true?

For each feature of self-tolerance described in questions ,choose the term (letters A-K) that most closely matches it. -Tolerance-sensitive stage of T cell maturation

Failure of self-tolerance is the cause of which one of the following types of diseases?

For each feature of self-tolerance described in questions ,choose the term (letters A-K) that most closely matches it. -Mechanism of peripheral tolerance induction of B cells but not T cells

The AIRE protein is expressed by thymic medullary epithelial cells and is required for tolerance to many self-antigens.Which one of the following statements about how AIRE functions is correct?

Immunologic tolerance is defined as:

For each feature of self-tolerance described in questions ,choose the term (letters A-K) that most closely matches it. -Site of central T cell tolerance induction

For each feature of self-tolerance described in questions ,choose the term (letters A-K) that most closely matches it. -Mechanism of peripheral tolerance for T cells but not B cells

CTLA-4,expressed by regulatory T cells and activated effector T cells,is crucial for self-tolerance as well as regulation of T cell responses of foreign antigens.Which of the following is a property of CTLA-4 that is important for its function?

For each feature of self-tolerance described in questions ,choose the term (letters A-K) that most closely matches it. -Mechanism of peripheral tolerance of B cells and T cells

For each feature of self-tolerance described in questions ,choose the term (letters A-K) that most closely matches it. -Mechanism of central tolerance of B cells

Which of the following sets of proteins (among others) are typically expressed by most regulatory T cells ( Treg) ?

For each feature of self-tolerance described in questions ,choose the term (letters A-K) that most closely matches it. -Tolerance-sensitive stage of B cell maturation