Final06_1_3ANS

Final06_1_3ANS - NAME_KEY_ You have two strains of mice,...

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NAME___KEY______________________ You have two strains of mice, one is normal and the other is an IL-15 knockout. When you vaccinate these animals against cytomegalovirus (CMV) and then challenge them with live virus 3 months later, only the normal mouse survives. Intrigued you perform several studies on lymph node derived cells. Initially you stain for CD3, CD4 and CD8. Here is what you see. What do these data suggest about T cell numbers and subsets? ( 5 points ) T cell profiles look identical. No apparent differences so far. You perform additional studies, where you isolate T cells, and stain for CD62L and CCR7. What does this tell you about why the IL-15 Knockout mice do not survive when re-challenged with virus? ( 10 points ) IL-15 KO animals have a deficient CCR7+/CD62L hi subset compared to normal mice. This is typically the central memory cell population. IL-15 thus appears to be required for maintenance of the central memory cell population. Is this consistent with the vaccination data? Explain. ( 15 points ). YES. Without central memory cells, long-term (3 month) memory responses to vaccine would dwindle. While the vaccinated normal mice clear the viral infection, you now notice that they have difficulty walking and look sickly, despite being free of virus. If you treat these mice with acyclovir (an anti-viral agent) a day or two after infection, they do not demonstrate this phenomenon, nor do acyclovir treated infected IL-15 knockout mice, which survive on the drug. Why do you think the normal mice exhibit this phenotype following infection with CMV? Explain why you think this happens (i.e propose a mechanism). ( 20 points ) The normal mice respond to the virus, but somehow viral epitopes must cross-react with some self antigen. Elimination of the virus before it can replicate and increase antigen dose prevents this. Somehow the presence of viral antigen breaks a peripheral tolerance mechanism, leading to an autoimmune disorder.
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You also have four different knock-out strains. They are deficient in the following: No RAG No IL-6 No Ig α No AID You hire a new person to clean your mouse colony. To your horror you find that they have removed all of the tags from the cages. Your laboratory assistant, a recent graduate of M185 says, “Don’t worry. I’ll find out which strain is in each cage. She analyzes bone marrow, spleen and thymus using anti-CD4, anti-CD8, anti-CD43, and B220, anti-IgM, and anti-PC-1; PC-1 is an antigen present on plasma cells. She obtains the following results: Spleen Bone Marrow Thymus anti-B220 anti-IgM Spleen anti-CD4 anti-CD8 anti-CD8 anti-CD8 anti-CD8 anti-IgM anti-IgM anti-IgM anti-CD43 anti-CD43 anti-CD43 anti-CD43 anti-PC-1 anti-IgM anti-IgM anti-IgM anti-IgM Mouse 1 Mouse 2 Mouse 3 Mouse 4 Identify the defect in each mouse explaining your reasoning:
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Final06_1_3ANS - NAME_KEY_ You have two strains of mice,...

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