Answer Key Spring 2000 Immunology Exam #2
Chapters 5 - 7

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:
Here is the honor code
http://www.davidson.edu/student/redbook/honorgeneral.html#honorcode

"On my honor I have neither given nor received unauthorized information regarding this work, I have followed and will continue to observe all regulations regarding it, and I am unaware of any violation of the Honor Code by others."

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 - multienzyme complex that facilitates somatic recombination in both B and T cells.
2) instructive model (within T cell selection) - when bound to the appropriate MHC (II and I) each of the two coreceptors (CD4 and CD8) give different signals to the T cell to shut off the expression of the other coreceptor.
3) caspase * - protease family involved in apoptosis, e.g. effector caspase that cleaves I-CAD to activate CAD in DNA destruction.
4) double negative thymocyte - immature T cell CD3-, CD4-, CD8-, TCR- but called double negative because CD4-, CD8-.
5) primary focus of B cells - mature B cell in secondary lymphoid organ, activated by TH2's, cells divide and then craeate the primary focus inside T cell zone.
6) GEF * - Guanine-nucleotide Exchange Factor, catalyzes the exchange of the inhibitory GDP for an activating GTP for G proteins; e.g. SOS
7) nude mouse - no thymus or hair, Wnt transcription factor is missing in these mice; no (very few) T cells (interesting to note that web browsers that censor the content of pages will censor this page because of the word nude)
8) SH2 * - Src Homology 2 domain; bind to phosphorylated tyrosine residues in ITAM domains of receptor proteins. c-src has one.
9) differential signaling (within T cell selection) - hypothesis that says positive and negative selection are not signaled by the number of binding sites available, but that the TCR binding to MHC:peptide delivers a unique signal for the two kinds of selection.
10) allelic exclusion * - expression of a gene from one homologous chromosome, but not the other. e.g. the heavy and light chains of antibodies are expressed from only one chromosome each, but not both.

II. More thoughtful questions:
12 pts.
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.
In brief outline form:

  1. clustering - TCR bringing ITAMS and SH2 proteins into close proximity
  2. phosphorylation of ITAMs - syk phosphorylating B cell during activation
  3. IP3 signal pathway - PLC cleaves PIP2 to produce IP3 and DAG. IP3 produces a rise in cytoplasmic calcium concentration.
  4. adaptor proteins - proteins have two SH3 domains to bring two proteins into proximity (e.g. SOS and Ras) and they bind to phosphorylated ITAMs by their SH2 domains.
  5. G proteins - such as ras that activate kinases
  6. MAPK pathway - series of kinases that phosphorylate one another and lead to the production of activated transcription factors

6 pts.
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?

  1. Reduced number of T cells that survive negative selection (5% for each new alllele or 10% for each new locus).
  2. Need for a certain density of MHC:peptide to provide the critical number (100-200) to activate a T cell and the density for any given MHC:peptide would be reduced if two new MHC needed some space at the plasma membrane.

12 pts.
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.
.This answer had many extra possible good answers. However, there were four main areas I was looking for:

stage

event

location
proB heavy chain somatic recombination (V-DJ)  bone marrow
preB  light chain somatic recombination  bone marrow
 Immature B cell  selection  bone marrow
 Mature B cell  survival signal  secondary lymphoid tissue

20 pts.
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.
1) CD8+ (plus B cells and NK) 2) only immunity that does not require CD4+ cells, therefore limited.

b. MHCb mouse that has been irradiated and this mouse receives MHCa bone marrow that had been treated to destroy MHCa T cells.
1) CD4+ and CD8+ (plus B cells and NK) 2) autoimmune disease against MHCb; and APCa cells not recognized by MHCb-restricted T cells; thus no functional immunity

c. MHCa x b mouse that has both H2-M alleles (mouse homolog of HLA-DM) deleted from its genome.
1) CD4+ and CD8+ (plus B cells and NK) 2) normal function but not very good at MHC II presentation of pathogen peptides.

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.
1) no (very few TI) T cells ((plus B cells and NK) 2) B cell immunity for TI antigens only

e. MHCa x b mouse donates its T cell depleted bone marrow to a MHCa mouse that had been irradiated.
1) CD4+ and CD8+(plus B cells and NK) 2) Normal immune system with APC functioning via their MHCa haplotype

8 pts.
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.
See Diagrams in book, page 186.

6 pts.
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.
The only genes that are somatically recombined, are those that are available via unwinding of the DNA. It is believed that transcription, and thus the binding of transcription factors determines which genes will be rearranged. The transcription factors only bind to the appropriate enhancers and promotes for the Ig gene segments in B cells. It has also been reported that acetylation of histones play a role as well.

8 pts.
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.
Many good choices from Chapter 5 but you had to show how the signaling started at the plasma membrane.

2 pts.
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.
FLASH.

6 pts.
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.
In brief outline format:

  1. Proteins that are not expressed in the thymus could be targeted as self-reactive.
  2. Proteins that are expressed later in life (e.g. after puberty) could be targeted as self-reactive.
  3. T cells that have two TCRs on them might be able to respond to a self peptide if the other TCR has lead to the T cell's activation.

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