Ch 15 Book Questions Flashcards
Which one of the following statements about immunological tolerance to self is correct?
a. Self tolerance of B cells but not T cells is acquired early during their development, before antigen receptor expression
b. Self tolerance of T cells but not B cells is acquired early during their development, before antigen receptor expression
c. Self tolerance of both T and B cells is acquired early during their development, before antigen receptor expression
d. Self tolerance of both T and B cells is acquired late in development but independent of exposure to antigens
e. Self tolerance of both T and B cells is acquired late in development and is dependent on exposure to self antigens
e. Self tolerance of both T and B cells is acquired late in development and is dependent on exposure to self antigens
Lymphocyte self tolerance is actively induced by exposure to self antigens, and recognition of these antigens via functional antigen receptors on the lymphocytes.
Which of the following is NOT a consequence of recognition of self antigens by developing lymphocytes
a. Apoptosis (clonal deletion) of T cells in the thymus
b. Apoptosis (clonal deletion) of B cells in the bone marrow
c. Differentiation of TH2 cells
d. Receptor editing in immature B cells
e. Development of regulatory T cells
c. Differentiation of TH2 cells
TH2 cells are a type of effector T cell that differentiates from naïve T cells in peripheral lymphoid tissues, in response to foreign antigens. All the other choices are mechanisms of central tolerance that occur in bone marrow (for B cells) or thymus (for T cells).
A young girl has a history of persistent oral and skin fungal infections, and bouts of hypotension and hypoglycemia. Further workup shows evidence of parathyroid, adrenal and pancreatic dysfunction. Genetic work up reveals homozygous mutations in the AIRE gene, and she is diagnosed with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also called autoimmune polyendocrine syndrome type 1 (APS-1). In this disorder, there is autoimmune destruction of various endocrine organs. Which of the following is the reason for the autoimmune phenotype?
a. Failure to anergize self reactive T cells because AIRE normally suppresses costimulatory molecule expression in resting dendritic cells
b. Failure to develop central B cell tolerance because AIRE normally induces expression of RAG1 in immature B cells
c. Failure to delete self reactive T cells because AIRE normally induces expression of caspases required for T cell apoptosis
d. Failure to develop central T cell tolerance because AIRE normally induces expression of peripheral tissue antigens in thymic medullary epithelial cells
e. Failure to develop peripheral T cell tolerance because AIRE normally induces expression FoxP3 in mature T cells
d. Failure to develop central T cell tolerance because AIRE normally induces expression of peripheral tissue antigens in thymic medullary epithelial cells
AIRE is a transcription factor that induces medullary thymic epithelial cell (MTEC) expression of peripheral tissue antigens, including those usually only expressed in endocrine organs. MTEC present these antigens to developing T cells, and those cells that are recognize the self antigens are deleted.
Which of the following is NOT a property of regulatory T cells (Treg)?
a. Interleukin-2 receptor (CD25) expression
b. Secretion of interferon-γ
c. FoxP3 expression
d. Secretion of transforming growth factor-β
e. Inhibition of activation of effector T cells
b. Secretion of interferon-γ
Most Teg are CD4+CD25+ T cells that express the FoxP3 transcription factor, and secrete TFGβ. Interferon γ is an inflammatory cytokine secreted by effector T cells, including TH1 cells and cytotoxic T lymphocytes.
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
a. High doses of antigen
High doses of antigens, especially administered without adjuvants, favor peripheral tolerance, often by the induction of anergy or apoptosis. Antigens that induce immune responses are typically present for short durations, and are associated with adjuvants that enhance antigen presentation and costimulatory molecule expression.
Which of the following statements about B cell tolerance is NOT true?
a. Somatic mutation of Ig genes 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.
a. Somatic mutation of Ig genes is a mechanism of central B cell tolerance.
Somatic mutation of Ig genes occurs during B cell responses to antigens, e.g. in germinal centers, and is not a mechanism of central tolerance. Strong recognition of self antigen in the bone marrow may result in B cell apoptosis, antigen receptor down-regulation, or receptor editing, whereby V(D)J recombination is reinitiated and light chain gene usage is altered; all these are mechanisms of central B cell tolerance. In peripheral B cell tolerance, B cells may become anergic or they may be excluded from entry into follicles, owing in part to failure of expression of CCR5 chemokine receptors.
It has been postulated that regulatory T cells reduce available B7 costimulators on APCs, and this is one possible mechanism by which the Tregs inhibit immune responses. Which of the following molecules is expressed on regulatory T cells (Treg) and functions to block B7-mediated costimulation
a. PD-1
b. CTLA-4
c. CD28
d. CC127 (IL-7 receptor)
e. Fas ligand
b. CTLA-4
Treg express CTLA-4, and CTLA-4 is a high affinity receptor for B7-1 and B7-2. Treg function depends on CTLA-4, and it is likely that one mechanism of Trge suppression of effector T cell responses is to competitively bind B7-1 and B7-2 on dendritic cells presenting self antigens to naïve T cells, or remove B7 molecules from these APCs. This results in reduced costimulation, which would prevent the induction of effective immune responses.
Among the genes that are associated with common autoimmune diseases, the strongest associations are with which of the following?
a. Cytokine genes
b. Autophagy genes
c. Apoptosis genes
d. MHC genes
e. Antigen receptor signaling genes
d. MHC genes
MHC genes, mainly class II MHC genes, are the most strongly associated with autoimmune diseases.
