Download The Case of the Virulent Virus

The Case of the Virulent Virus
Nan and Ned really enjoyed their late summer holiday backpacking in the Colorado
Rockies. At 10,000 feet elevation, the nights were chilly, but the days were mild and
the scent of the pines was refreshing after the city smog. They camped near a glacial
lake, enjoying the solitude and the numerous birds congregating in the area and
congratulating themselves on having found such a perfect campsite. The only
downside was the hordes of of mosquitos that plagued them at dusk as they relaxed
near their fire. Nan covered herself with mosquito repellent and a long-sleeved shirt
and jeans, but Ned stubbornly refused the repellent and sat watching the last of the
sunset in his T-shirt and walking shorts. For once his asthma was not so bad, and he
could breathe without using his inhaler. The hiking trails in the area were excellent, and
Nan and Ned stayed there for the whole last week of their vacation.
A week after they returned to school, Ned thought he was coming down with the flu. He
had a fever, felt very tired, and his muscles ached. He had a headache and the lymph
nodes in his neck and armpits were enlarged. A few days later Nan experienced similar
but less severe symptoms. When Ned began complaining of feeling too weak to move
and having trouble breathing, Nan took him to Student Health Services. After
completing a history and hearing about the mosquito bites, the physician had Ned
admitted to the University Medical Center, where his cerebrospinal fluid (CSF) was
tested for IgM antibodies to West Nile Virus. The test was positive, and Ned remained
hospitalized for treatment until the symptoms regressed. Nancy recovered without
becoming severely ill.
West Nile Virus (WNV) is a Flavivirus, consisting of a single-stranded (+) RNA genome,
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an icosahedral protein capsid, and a host-derived lipid envelope. The envelope
E-glycoprotein allows the virus to bind to host cells and is the antigen to which
neutralizing antibody is made. Antibodies made to WNV E-glycoprotein often also bind
glycoproteins from other flaviviruses, for example Japanese encephalitis virus (Asia),
St. Louis encephalitis virus (the Americas), and Murray Valley encephalitis virus
(Australia). WNV is a virus of bird that is transmitted by mosquitos; humans are
accidental hosts for the virus. Most people who are infected have minor or no
symptoms; serious disease occurs mostly in people over 50 and those with weakened
immune system.
Activation of T Cells
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QUESTIONS:
1. Outline (bullets) what steps in innate immunity will deal with the West Nile Virus as it
enters the skin.
2. Compare and contrast how B cells and cytotoxic (CD8+) T cells will see/bind WNV
E-glycoprotein. Include in your answer the nature of the antigens recognized and the
antigen-recognition molecules involved for each cell type.
3. How is it that neutralizing antibodies to E-glycoproteins from WNV can cross-react
with antibodies made to other Flavivirus E glycoproteins.?
4. Why are dendritic cells such good professional APC? Why are they better than
macrophages and B cells for activating Tc to viruses?
5. Do dendritic cells need to be infected with virus in order to present it to CD8 T cells?
5. Explain the role of vaccine adjuvants in stimulating immune responses.
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7. Describe co-stimulation of T cells and explain why this requirement is important in
regulating T cell activity.
8. Are the Th and Tc above binding to the same peptide? Does it matter?
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9. What is the role of IL-2 in T cell activation? What is autocrine function of cytokines?
9. How do T cells "find" the APC presenting the WNV antigen? How do they "find" the
WNV-infected cells?
Cytotoxic T Cell and Th1 Cell Functions
10. Describe the functions of effector Tc, Th1, and Th2 cells. Be able to sketch the
interactions with target cells and describe the functions of the effector molecules shown
in Janeway Fig 8.31 (above).
11. Explain how effector T cell functions are localized to specific target cells; for
example, how do WNV-specific Tc kill only cells infected with WNV?
12. Give specific examples of pathogens which elicit effector Tc, Th1, or Th2 cells.
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13. What are the functions of perforin and granzymes? of IFN-γ and TNF-α and β?
What is apoptosis?
14.In addition to the IgM-anti WNV E glycoprotein in Ned's CSF, what other
measurable changes would you expect to find in their blood following WNV infection?
How could you measure these changes?
Functions of Th1 Cells
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Helpful Reading:
Mukhopadhyay, S., B.-S. Kim, P. R. Chipman, M. G. Rossmann, and R. J. Kuhn.
Structure of West Nile Virus. Science 302 (10 October): 248, 2003.
Petersen, L. R., and A. A. Martin. wwest Nile Virus: A Primer for the Clinician. Annals
of Internal medicine 137: E173-E179, 2002.
www.cdc.gov
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