There is no time limit on this test, though I have tried to design one that you should be able to complete within 3 hours, except for typing. You are not allowed to use your notes, or any books, any electronic sources, nor are you allowed to discuss the test with anyone until all exams are turned in at 9:30 am on Monday March 20, 2000. EXAMS ARE DUE AT CLASS TIME ON MONDAY MARCH 20. You may use a calculator and/or ruler. The answers to the questions must be typed on a separate sheet of paper unless the question specifically says to write the answer in the space provided. If you do not write your answers on the appropriate pages, I may not find them unless you have indicated where the answers are.
-3 pts if you do not follow this direction.
Please do not write or type your name on any page other than this cover page. Staple all your pages (INCLUDING THE TEST PAGES) together when finished with the exam.
Name (please print here):
Write out the full pledge and sign:
How long did this exam take you to complete (excluding typing)?
I. Define these terms - 2 pts each. When the term is followed by an asterisk (*), provide a specific example to further demonstrate your knowledge. These terms can be define succinctly so using a lot of words is not the best way to demonstrate your fluency with these terms. However, do not leave out important information that you assume the reader knows. Be sure to avoid the word "it".
1) V(D)J recombinase
2) instructive model (within T cell selection)
3) caspase *
4) double negative thymocyte
5) primary focus of B cells
6) GEF *
7) nude mouse
8) SH2 *
9) differential signaling (within T cell selection)
10) allelic exclusion *
II. More thoughtful questions:
1) In class, we discussed six major themes or principles in signal transduction that is used by lymphocytes.
a. List these six major cellular communication principles.
b. Give a specific example for each principle.
2) Give two reasons why people think natural selection has "settled on" the number of MHC loci present in humans and mice. In other words, why don't individuals have more loci encoding for a greater variety of MHC proteins per cell?
3) Cells that will differentiate into B cells are meant to die, unless something unusual happens.
Please create a table that has two columns:
1) ways to die and
2) where #1 happens.
Please use this table to list all the different ways B cells can die starting with pro-B cells.
4) Describe the immune system that would result under these experimental conditions. Specifically, for each condition, make sure you describe: 1) the lymphocytes in circulation and why this is so; 2) the degree of normal function of these lymphocytes and why this is so.
a. MHCa mouse with targeted deletion of all loci encoding MHC class II from cortical epithelial cells but not APCs.
b. MHCb mouse that has been irradiated and this mouse receives MHCa bone marrow that had been treated to destroy MHCa T cells.
c. MHCa x b mouse that has both H2-M alleles (mouse homolog of HLA-DM) deleted from its genome.
d. MHCa x b mouse has been given a transgene that encodes one TCR that is specific for MHCa class I and an ovalbumin peptide. Furthermore, the dendritic cells are engineered to express ovalbumin.
e. MHCa x b mouse donates its T cell depleted bone marrow to a MHCa mouse that had been irradiated.
5) Draw a diagram that shows the major steps and proteins in the Fas-FasL signal that induces apoptosis. You must label all the parts you want me to understand and write neatly.
6) One of the great mysteries in biology is how some genes can be activated while others are left undisturbed inside the same cell. Please explain what you know about how B cells manage to rearrange only their immunoglobulin genes but not their TCR genes, even though B cells are expressing RAG1 and RAG2.
7) Four different and specific pathways were illustrated in the chapter on signal transduction used in lymphocytes to activate transcription. Choose your favorite one and illustrate the steps and proteins involved. Make sure your drawing has good labels which are written neatly.
8) It has been known for a long time that mice were a great model system. Although the immune system of mice and (hu)man are not identical, they are similar enough to be instructed. What was the name of the first mouse that was used in an immunological study. The mouse was discussed on Friday before the break.
9) The final question is designed to see if you have thought about the possible consequences of a single positive thymocyte leaving the thymus. Give three specific examples that illustrate potential problems with positive and negative selection in a normal human. I do not want you to tell me how selection can go wrong, or what might happen in weird experimental or bone marrow transplantation situations. I want you to tell me what might happen to a person after normal positive and negative selection in the thymus that could present a problem later. The three potential problems usually do not happen due to other factors outside the thymus but selection in the thymus alone does not address these situations which could happen in some people.
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