Question 1

Immunologic tolerance is defined as:&#10;A) The removal of an antigen, or the microbes expressing the antigen, by the immune system, so that the host can tolerate the infection&#10;B) Activation of only B cells, and not T cells, on exposure to an antigen&#10;C) Unresponsiveness of the immune system to an antigen, which is induced by previous exposure to that antigen&#10;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&#10;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 2

Matching
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 3

Matching
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 4

Failure of self-tolerance is the cause of which one of the following types of diseases?&#10;A) Allograft rejection&#10;B) Autoimmunity&#10;C) Atopy&#10;D) Anergy&#10;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 5

Matching
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 6

Matching
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 7

Matching
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

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⁺ IgD⁻ immature B cells are the most sensitive to tolerance induction.

Question 8

Matching
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 9

Matching
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 10

Which of the following statements about induction or maintenance of T cell tolerance is NOT true?&#10;A) Central tolerance is induced when immature developing T cells in bone marrow or thymus encounter self antigens.&#10;B) Peripheral T cell tolerance results when mature naive T cells recognize antigens without adequate B7-1- or B7-2-mediated costimulation.&#10;C) Peripheral T cell tolerance results when T cells recognize antigen in the setting of an innate immune response to the antigen.&#10;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.&#10;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.

Deck 16: Immunologic Tolerance