Download Exam Key 3 2008

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Biology 347
Exam 3 April 24, 2008
NOTE: Turn off all electronic devises.
Name________________________________
Please cover your exam at all times.
I. True/False: [Circle T (true) or F (false) 1 point each, 10 points total]
__F___1. IL-4 decreases IgE production by B cells.
__T___2. Both eosinophils and mast cells are important mediators of allergic responses.
__F___3. Most pollen allergens contain a single allergenic component.
__T___4. Transfusion reactions are a manifestation of type II hypersensitivity.
___T__5. The initial step in the process of mast-cell degranulation is cross-linking of Fc receptors.
___T__6. Th1 cells have been associated with development of autoimmunity.
___T__7. A defect in the gene encoding Fas can reduce programmed cell death by apoptosis.
___F__8. Hereditary retinoblastoma results from over-expression of a cellular oncogene.
___T__9. Translocation of c-myc gene is found in many patients with Burkitt's lymphoma.
___T--10. Viral integration into the cellular genome may convert a proto-oncogene into a transforming
oncogene.
II. Fill in the blanks (2 points/blank, 22 points total)
1. A type I hypersensitivity reaction is mediated by _____IgE _____________________
2. A type III hypersensitivity reaction is mediated by the formation of ____immune
complexes______________ and the ensuing activation of ___complement___________________.
3. A type IV hypersensitivity reaction involves the activation of Th1 cells may also include macrophages.
4. To prevent antibody production to Rh antigens, an Rh negative woman who has given birth to a Rh positive
baby can be given an injection of ______RHOGAM____ .
5. Human autoimmunity can be divided into ____organ specific and __systemic diseases.
6. Which CD 4 positive T cell ____T helper 1______is expressed in higher levels in females than in males?
7. Tumor suppressor gene p53 is mutated in approximately ____50% of most cancers, especially lung cancer.
The carcinogen ___Benzo(A)pyrene____from cigarette (tobacco) induces "hot spot" mutations in
the p53 ___________DNA binding domain____give partial credit if give codons 157, 248, 269,
273__________domain.
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III. List the three molecular manipulations utilized by Dr. Robert Weinberg to convert normal cells into cancer
cells. Briefly describe how each contributed to the development of the cancer phenotype (2 points each, 6
points total)
a. polyoma SV40 large T antigen--inhibits tumor suppressor genes Rb and P53 give credit if they
include E6 and E7
b. Ras oncogene--activates proliferation/survival pathway
c. telomerase--immortality, cell proliferation
IV. Compatible and incompatible blood transfusions: Fill in the blanks ( 2 points each, 10 points total)
1. A blood type O individual could successfully receive whole blood from blood type ___0__ individual(s).
2. A blood type AB individual could safely give whole blood to individual(s) of blood type __AB____.
3. A blood type A individual could safely receive plasma from person(s) of blood type _A and AB____.
4. Individuals with blood type _____AB_______ are referred to as a universal donors of blood plasma (serum).
5. Individuals with blood type ____O__________ are referred to as a universal donors of red blood cells.
V. List the autoimmune diseases that are identified by the following descriptions (2 points each, 12 points
total).
1. ________Pernicious anemia___________Auto-antibodies to intrinsic factor block vitamin B12 absorption.
2. ________thyroiditis__(Hashimoto's thyroiditis)_______________TH1-cell reaction to thyroid antigens
3. _______multiple sclerosis__________________ T-cell destruction of myelin basic protein
4. ______rheumatoid arthritis____________________Autoantibody to IgG
5. _________lupus_________________Auto-antibodies to DNA and DNA associated protein
6. _______scleroderma___________________Build-up of calcium in tissues and organs
VI. Short Answers (Total number of points = 40). (Be concise and answer in space provided)
1. Describe an Acute Arthus Reaction, include in your answer the events that trigger/mediate the Arthus
Reaction, a description of the symptoms and indicate which class of hypersensitivity reaction is involved.
page 392 in text. Type III localized immune reaction that occurs when injection of an antigen, usually
intradermally or subcutaneousl that occurs within 4-8 hours. Reaction is mediated by antigen-antibody
mediated complement activation, producing complement intermediates that mediate mast-cell degranulation,
attract neutrophils, and cause release of lytic enzymes from neutrophils.
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2. Diagram the events leading to the activation of tissue mast cells and the release of cellular content in an
allergic response.
Figure 15-2 on page 373. Some students may start with B cells receiving Thelp undergoing class switching to
IgE. If so, give them credit, if not, don't take away credit. Start with allergen specific IgE binds to FC
receptor (FcR1) on mast cells (some students may include basophils) resulting in sensitized mast cell. Second
exposure to the allergen leads to cross-linking of the bound IgE, triggering the release of pharmacologically
active mediators (vasoactive amines, prostaglandins, leukotrienes, histamines as some examples students may
give ) from mast cells.
3. Describe the role of T helper 1 and T helper 17 cells in autoimmune inflammatory bowel disease
Both T helper 1 and T helper 17 have been implicated in autoimmune inflammatory bowel disease. If one
depletes T helper 1 cells, the disease becomes more severe suggesting that although T helper 1 is involved in the
disease, it also dampers down the disease. T17 cells are activated by IL-6 produced by stroma cells. T helper 1
cells secrete IL-27 that inhibits stroma cells from making IL-6, thereby blocking T17 cells. When T helper 1
cells are removed, strma cells make IL-6 which activates Thelper 17 cells to secrete IL-17, a very toxic
inflammatory cytokine. Blocking antibodies to IL-17 the disease is less severe.
4. Give a description (explain or diagram) of the disease/disorder progression in the (NZBXNZW)F1 mouse
model for human lupus (5 points).
From Dr. Jolly lecture (don't know for sure what all he presented). also on page 412 of text . Mice
spontaneously develop autoimmune diseases that closely resemble syustemic lupus erythemastosus. Mice
spontaneoously develop lautoimmune hemolytic anemia between 2 and 4 months of age, at which time various
auto-antibodies can be detected, including antibodies to erythrocytes, nuclear proteins, DNA, and T
lymphocytes. The F1 hybrid mice develop glomerulonephritis from immune complex deposits in the kidney
and die prematurely by 18 months.
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5. What is EMT? Describe the significance of EMT in metastatic cancer
Breast cancers are epithelial in origin. Epithelial cells lack the ability to move. Epithelial cells in epithelial
tumors (cancers) can undergo a transition from epithelial to mesenchymal (fibroblast like) where they downregulate epithelial markers and upregulate mesenchymal genes. As mesenchymal cells, they can move from
primary site to secondary sites (metastasis). Thus, the mesenchymal cells are the ones that contribute to
metastases. Once the mesenchymal cells are established in a new site, they can undergo a MET transition from
mesenchymal to epithelial (don't count this against students who do not include it since I did not ask for this).
6. (a) How would one demonstrate that intra-tumoral T regulatory cells (TRegs in a tumor) are capable of
blocking cytotoxic T cell (Tc) killing of the cancer cells by apoptosis. (b) What will be the effects of depleting
(reducing numbers) TReg cells in non-cancer individuals or cancer patients?
Remove the tumor, isolate Tc, TReg, and cancer cells. Culture cancer cells in presence of Tc cells and measure
cell death. If one cultures the cancer cells with TRegs then no cell death. If in the culture of Tc cells and
cancer cells if one adds back TRegs then no cancer death. Both, Tc + tumor cells giving killing and blocking
this with TRegs show TRegs block cytotoxic T cells from killing tumors.
7. What is p16, and describe the significance of p16 in tumor development?
p16 is a tumor suppressor gene. p16 is silenced by DNA methylation of a small number of normal mammary
cells in culture. Loss of p16 gives the cell proliferative ability that gives rise to high numbers of cells. p16
also inhibits COX 2, as highly inflammatory cytokine. So, in the absence of p16 there is high levels of COX 2
(as well as other genes), contributing to the growth and expansion of cells with p16 silenced. (students may
point out that as cells proliferate, there is disruption of centrosomes, giving rise to high levels of proliferation
that is equal to high levels of apoptosis, providing environment for selection of cancer cells that are capable of
surviving in adverse environment)
8. What effect does co-stimulation B7/CD28 or B7/CTLA-4 have on the activation/function of cytotoxic T
cells?
Non activated Tc cell expresses CD28. During activation of Tc cells, B7 on APC binds to CD28 on Tc cells
and serves as a co-stimulation (along with MHC class 1 and TCR/CD3 complex). Activated Tc cells xpress
CTLA4 which binds to B7 thereby inducing anergy (non-activated Tc cells).
(some students may point out
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that if ne uses antibodies that block CTLA-4 then Tc cells will remain activated, resulting in accumulation of
Tc cells that contributes to lymphoproliferative diseases.