Ch 9 Book Questions Flashcards
Most naïve T cell activation occurs where and in response to what?
a. In the skin in response to cytokines
b. In the infected tissues in response to antigen presentation by macrophages
c. In the blood in response to antigen presentation by monocytes
d. In the thymus in response to antigen presentation by thymic medullary epithelial cells
e. In secondary lymphoid organs in response to antigen presentation by dendritic cells
e. In secondary lymphoid organs in response to antigen presentation by dendritic cells
Naive T cells home to lymph nodes, and dendritic cells (DCs) carrying antigens from sites of infection drain into lymph nodes. The chemokine CCR7 directs the co-localization of both cell types. Other types of antigen presenting cell do not activate naive T cells efficiently because they do not migrate to where naïve T cells are, and/or they do not express the costimulatory molecules required for naïve T cell activation.
The most important costimulators for naïve T cell activation are which of the following?
a. ICOS Ligand
b. B7-1 and B7-2
c. PD-L1 and PD-L2
d. OX40 -Ligand
e. FAS Ligand
b. B7-1 and B7-2
B7-1 (CD80) and B7-2 (CD86) are the major costimulators required for naïve T cell activation. They are expressed on mature myeloid DCs, and bind to CD28 on the T cells. ICOS-Ligand and OX40 ligand are costimulators for previously activated T cells; their receptors are not expressed on naïve T cells. PD-L1 and PD-L2 bind to PD-1 on T cells, which inhibits T cell activation. FAS Ligand binds to FAS on T cells, and induces apoptotic cell death.
CTLA-4-Ig is a soluble recombinant protein containing the ligand binding portion of CTLA-4 fused to the Fc portion of IgG. It is an approved drug used to treat autoimmune diseases. How does it work?
a. Binds to CTLA-4 on T cells and induces inhibitory signals
b. Binds to CTLA-4 and blocks its ability to bind to B7-1 and B7-2
c. Binds to B7-1 and B7-2 on antigen presenting cells, and blocks their ability to bind to CD28 on T cells
d. Binds to inhibitory Fc receptors on B cells and inhibits the production of autoantibodies
e. Binds to cytotoxic T lymphocytes and blocks their ability to kill other cells
b. Binds to CTLA-4 and blocks its ability to bind to B7-1 and B7-2
CTLA-4-Ig is a costimulatory blocker. It has high affinity for B7-1 and B7-2, and therefore blocks costimulation by these molecules, which is required for naïve T cell activation. CTLA-4-Ig is not anti-CTLA-4 and does not bind to CTLA-4. The Ig Fc portion of the drug prolongs half-life, but is not involved in the immune inhibitory function of the drug.
The combination of TCR and costimulatory signals induces naïve T cells to express IL-2 and high affinity IL-2 receptors. This results in which of the following functional responses by the T cell?
a. Clonal expansion
b. Interferon γ expression
c. CD40 ligand expression
d. Granule exocytosis
e. Migration out of a lymph node
a. Clonal expansion
IL-2 is the major autocrine growth factor for T cells. Naïve T cells express two chains of the IL-2 receptor which bind IL-2 with low affinity. Antigen and costimulatory signals induce IL-2 production and expression of a third chain (CD25) of the receptor, which increases the affinity for IL-2. The T cell thus enters the cell cycle in response to IL-2 signals, and undergoes several rounds of proliferation, thereby expanding the clone of T cells specific for the inciting antigen.
At the peak of a CD8+ T cell response to a new microbe, what is the fold increase in the number of microbe-specific T cells in an individual compared to the number of naïve CD8+ T cells specific for the microbe before infection?
a. ~100
b. ~1000
c. ~10000
d. ~100,000
d. ~100,000
CD8+ T cells undergo tremendous clonal expansion in response to antigen stimulation. CD4+ clonal expansion is less, on the order of 1000 to 10,000 fold.
TH2 cells are defined in part by production of which of the following cytokines?
a. TNF
b. IL-1
c. IL-2
d. IL-4
e. IFNγ
d. IL-4
TH1 cells are defined by production of IFNγ. TH2 cells are defined by production of IL-4, IL-5, and IL-13. TH17 cells are defined by production of IL-17A, IL-17F, and IL-22. Many T cells produce combinations of various cytokines, and polarized cells expressing restricted cytokine profiles tend to develop upon chronic or repeated stimulation.
The differentiation of each major CD4+ T cell subset is controlled by a subset defining transcription factor. Which of the following correctly pairs each subset with its transcription factor?
a. TH1:T-bet; TH2:GATA3; TH17:RORγT
b. TH1:GATA3; TH2:T-bet; TH17:RORγT
c. TH1:T-bet; TH2: RORγT; TH17: GATA3
d. TH1: RORγT; TH2:GATA3; TH17: T-bet
e. TH1: GATA3; TH2:RORγT; TH17: T-bet
a. TH1:T-bet; TH2:GATA3; TH17:RORγT
T-bet, GATA3, and RORγT are sometimes called “master regulators”, and they are required for differentiation and function of the differentiated T cells. In each case the transcription of the subset defining cytokine genes is regulated by the subset defining transcription factors. Other transcription factors are also required for the differentiation of each subset.
