Deck 10: Immunological Tolerance and Autoimmunity

Question 1

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

Answer 1

Autoimmunity

Question 2

Which of the following molecules does NOT promote lymphocyte apoptosis?

A)Bid
B)Caspase-8
C)FADD
D)FLIP
E)Glucocorticoid

Answer 2

FLIP

Question 3

All of the following describe features of apoptosis EXCEPT:

A)Caspase activation
B)Membrane blebbing
C)Inflammation
D)Nuclear fragmentation
E)DNA cleavage

Answer 3

Inflammation

Question 4

Transgenic mouse lines have been very useful for the study of mechanisms of self-tolerance.In one such line,transgenes were introduced encoding a T cell receptor (TCR)specific for the H-Y antigen,which is a protein expressed by many cell types only in male mice.When these transgenic mice were analyzed,researchers found that T cells expressing the H-Y-specific TCR developed normally in female mice but not in male mice.This finding illustrates which of the following mechanism of self tolerance?

A)Peripheral anergy
B)Central (thymic)deletion
C)Clonal ignorance
D)Regulatory T cell-mediated suppression
E)Peripheral deletion

Question 5

A genetic deficiency in the ability to produce which of the following molecules results in autoimmunity?

A)B7-1
B)CD28
C)CD40L
D)Interferon- $\gamma$
E)Interleukin-2

Question 6

Which of the following factors generally favors stimulation of an adaptive immune response to an antigen,and not tolerance?

A)Intravenous portal of entry of antigen
B)Presence of antigen in generative lymphoid organs
C)Absence of costimulatory molecules on antigen-presenting cells
D)Innate immune response to the antigen
E)Presence of antigen during the neonatal period

Question 7

Which of the following is NOT a property of regulatory T cells?

A)Interleukin-2 receptor (CD25)expression
B)Secretion of transforming growth factor- $\beta$
C)Maturation in the thymus
D)Secretion of interferon- $\gamma$
E)Inhibition of function of other T cells

Question 8

The adaptive immune system has mechanisms of homeostasis that serve to terminate immune responses and return the immune system to a basal resting state.Which of the following is LEAST likely to be involved in lymphocyte homeostasis?

A)CTLA-4
B)Fas ligand
C)CD28
D)B cell Ig Fc receptors
E)Anti-idiotypic antibodies

Question 9

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

Question 10

Many tumors are found to overexpress bcl-2,which favors survival of the transformed cells.Which of the following best describes the function of bcl-2?

A)Direct inhibition of caspase-8
B)Direct inhibition of caspase-9
C)Up-regulates expression of DNA repair enzymes
D)Reduces the leakiness of the mitochondrial membrane
E)Inhibits the activity of granzymes released from cytotoxic T lymphocytes

Question 11

Which one of the following factors generally favors tolerance to an antigen and not stimulation of an immune response?

A)High doses of antigen
B)Short-lived persistence of antigen
C)Cutaneous portal of entry
D)Presence of adjuvant
E)Costimulator expression on antigen-presenting cells

Question 12

Which of the following terms best describes the mechanism by which effector T cells are deleted by repeated stimulation by persistent antigen?

A)Passive cell death
B)Central tolerance
C)Peripheral tolerance
D)Death by neglect
E)Activation-induced cell death

Question 13

Which one of the following statements regarding positive and negative selection of T cells is NOT true?

A)Thymic epithelial cells present self-peptide-MHC to developing T cells undergoing the selection process.
B)T cells that do not recognize self-peptide-MHC die by neglect.
C)T cells that bind too strongly to self-peptide-MHC die by Fas ligand-mediated apoptosis.
D)During positive selection,developing T cells express higher levels of anti-apoptotic proteins such as bcl-2.
E)A breakdown in negative selection may result in the development of some autoimmune diseases.

Question 14

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)is a rare disease in which there is autoimmune destruction of several endocrine organs.This disease is caused by mutations in the autoimmune regulator gene called AIRE.AIRE is normally expressed primarily in the thymus and serves as a transcription factor in thymic epithelial cells.A failure to produce AIRE leads to a failure in tolerance to several self-proteins.Which ONE of the following statements best explains the influence of AIRE on self tolerance?

A)AIRE up-regulates expression of proteins that induce proliferation of thymic epithelial cells,allowing greater self antigen presentation to T cells.
B)AIRE up-regulates expression of cytokines that inhibit activation of T cells.
C)AIRE up-regulates expression of MHC proteins,allowing for greater self antigen presentation to developing T cells.
D)AIRE up-regulates expression of proteins usually expressed only in peripheral organs,allowing presentation of the proteins to developing T cells.
E)AIRE up-regulates expression of Fas ligand on thymic epithelial cells to induce apoptosis in self-reactive T cells.

Question 15

Which one of the following is NOT a mechanism of T cell tolerance?

A)Inhibition of T cell activation by interleukin-12 from regulatory T cells.
B)Apoptosis induced by Fas ligand binding to Fas.
C)Anergy induced by B7-1 or B7-2 binding to CTLA-4.
D)Anergy induced by peptide-major histocompatibility complex (MHC)binding to T cell receptors (TCRs)without B7-1 or B7-2 binding to CD28.
E)TCR-mediated up-regulation of Bim or similar pro-apoptotic proteins.

Question 16

Which of the following statements about B cell tolerance is NOT true?

A)Negative signaling induced by monovalent antigens is a mechanism of central B cell tolerance.
B)Exclusion of B cells from follicles is a mechanism of peripheral B cell tolerance.
C)Functional anergy is a mechanism of peripheral B cell tolerance.
D)Receptor editing is a mechanism of central B cell tolerance.
E)Down-regulation of antigen receptor expression is a mechanism of central B cell tolerancE.

Question 17

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.