Ch 11 Book Questions

Question 1

Which of the following is a property of exhausted CD8+ T cells?

a. Low expression of CTLA-4
b. High expressing of IL-4
c. High expression of PD-1
d. Low expression of class I MHC
e. High expression of interferon-γ

Answer 1

c. High expression of PD-1
Exhausted CD8+ CTL arise when there is persistent exposure to antigen, such as in the setting of chronic infections or cancers. Exhausted CTLs have high expression of the inhibitory receptor PD-1 and other inhibitory molecules such as CTLA-4. Exhausted T cells produce less interferon-γ than normal CTL. CTL do not express IL-4, and class I MHC expression is not typically altered.

Question 2

Which pair of molecules are found in cytotoxic T lymphocyte (CTL) granules and are important for CTL killing of target cells?

a. Perforin and Fas ligand
b. P-selectin and tumor necrosis factor
c. Major basic protein and granzyme B
d. C9 and interferon-γ
e. Perforin and granzyme B

Answer 2

e. Perforin and granzyme B
Perforin and granzyme B are the cytotoxic T lymphocyte (CTL) granule constituents of most importance in killing of target cells. CTL granules are emptied by exocytosis into the intercellular space between the CTL and target cell. Here perforin polymerizes and insert into the target cell plasma membrane and/or in the membranes of endocytic vesicles in the target cell. Granzyme B is a proteolytic enzyme that cleaves substrates in the cytoplasm of the target cell, leading to a cascade of enzyme activation that ends in apoptosis. Granzyme B enters the target cell via a perforin dependent mechanism. FasL is expressed on the surface of the CTL, not in granules. FasL binding to Fas on target cells may induce apoptosis of the target cells by a caspase-dependent pathway, but this is a minor mechanism of CTL killing relative to perforin- and granzyme B–dependent mechanisms. P-selectin is an endothelial adhesion molecule stored in cytoplasmic granules, and MBP is a cationic protein found in eosinophil granules. Although perforin is homologous to the complement protein C9, C9 is not present in CTL granules. CTLs do produce interferon-γ, but they do not store this cytokine in granules.

Question 3

CTLs are the major defense against which of the following class of organisms?

a. Extracellular bacteria
b. Fungi
c. Protozoans
d. Viruses
e. Helminths

Answer 3

d. Viruses
CTLs kill host cells with intracellular infections. All viruses must reproduce within host cells, and are eradicated by CTL killing of the cells they infect. CTLs have little capacity to kill extracellular microbes since they are activated by microbial-peptide self-class I MHC complexes. Thus CTLs do not kill extracellular bacteria. Most protozoans, fungi, and helminths are also extracellular.