MCB 5255 Cellular and Molecular Immunology
SYLLABUS
SPRING 2012
Course topic: The biochemistry and genetics of immune-related disease
Meeting times: Wednesdays 4-6 pm BPB 201
Instructor: Michael Lynes; office phone 486-4350; email michael.lynes@uconn.edu
Course Goals
This course will explore the genetic and biochemical mechanisms that potentiate and initiate immune
related disease. We will begin with an overview of regulatory mechanisms, and then explore the diseases
that ensue from abnormal genetic or biochemical regulation. Interspersed will be discussions of diagnosis,
and therapeutic interventions currently under investigation.
Student responsibilities
This graduate level course will focus not only on the informational content described above, but will
also involve extensive student participation. Students will be responsible for (1) participation in
discussions of the primary literature readings, (2) a presentation of a specific research theme to the class,
and (3) a written grant proposal. Some classroom time will be dedicated to the organization and
presentation of student proposals, and to the mechanisms associated with the writing and reviewing of an
NIH style grant proposal.
Student topic selection There is a list of potential topics listed at the bottom of page 2 of this syllabus.
These topics have been chosen for their relevance to the specific theme at hand: "the biochemistry and
genetics of immune-related disease". Selection of assigned topics for each student will be made on
January 25th in class. If a student has a specific topic in mind that might be relevant to the to the course
theme, they should consult with Dr. Lynes. Dates for presentations will be assigned based on the topics
selected (to put them in a logical order).
Course schedule
January 18
no class; assigned reading for general discussion on 1/25 (come prepared on 1/25
to discuss the first pair of assigned papers!)
January 25
Introductory overview, group discussion of assigned papers (papers 1, 2)
Selection/Assignment of Student presentation topics
February 1
Grantsmanship, group discussion of assigned papers (papers 3-6)
February 8
Group discussion of assigned papers (papers 7,8)
February 15 Group discussion of assigned papers (papers 9,10)
Discussion of what a specific aim is designed to express in a grant proposal
February 22 Transcriptional regulation of CD4 and CD8 cells
Guest Presenters: Sara Colpitts, Ph.D. and Courtney Plumlee,
Ph.D. (Postdoctoral Fellows; Department of Immunology, University of Connecticut
Health Center): Topic: "Genetic control of CD4 and CD8 fate"
assigned papers 13,14
February 29 Guest Presenter: Maureen Sherry Lynes, Ph.D., Postdoctoral fellow, Stem Cell Center,
Harvard University. Topic: "Stat 3 and inflammatory disease"
assigned papers 11,12
March 7
Specific aims discussion (come with your grant specific aim thought out and written
down; email of this aim due to Dr Lynes by 5pm of March 6th
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MCB 5255 Cellular and Molecular Immunology
SYLLABUS
March 14
March 21
March 28
April 4
April 11
April 18
April 25
May 2-7
SPRING 2012
Student presenters #1,2
SPRING BREAK (3/11-3/17) Be working on your grant proposal
Student presenters #3,4
Student presenters #5,6
Student presenters #7,8
Student presenters #9,10
Student Grant Proposals are due today; reviewer assignments will be distributed
Grant review panel meeting
Final exam period
Scheduled presenters/Assigned papers
1. Michael Lynes
a. Papers: Overview of IR
i. What has happened in the last decade? (1)
ii. Is TH17 an appropriate target for cancer immunotherapy? (2)
b. Papers plus grantsmanship advice
i. grantsmanship (3) (4)
ii. chemokine antagonists as anti-inflammatory agents (5) (6)
c. Papers: microRNAs and immune regulation (7) (8)
d. Papers: therapeutic interventions with biologics (9) (10)
2. Maureen Sherry
a. Papers: Stat 3 and inflammatory disease (11, 12)
3. Sara Colpitts Courtney Plumlee
a. Papers 11,12: Genetic control of CD4 and CD8 fate (13, 14)
Potential Student Topics with article suggestions for getting into the literature
1. Epigenetic regulation of immune responses (15) (16) (17) (18)
2. Psychoneuroimmunology; the interaction between the nervous system and the immune system (19)
(20)
3. Obesity-induced activation of the NLrp3 inflammasome and insulin resistance (21, 22) (23)
4. Reactive oxygen and immune regulation (24) (25)
5. Ubiquitin as a regulator of chemotactic responses (26-28)
6. Myeloid derived suppressor cells and their role in carcinogenesis (29-31)
7. Myeloid derived suppressor cells and their role in autoimmune disease (32) (33, 34)
8. pharmacologic manipulation of the immune response with biologic agents; CTLA4Ig (35-38)
9. Genome wide associational studies and the identification of Rheumatoid arthritis susceptibility loci
(39-42)
10. Metallothionein and immune regulation (43-48)
11. Inflammasome regulation and microbial infections (49) (50)
12. mTOR as a central regulator of immunity (51, 52)
13. catastrophic dysregulation of the immune response; the cytokine storm hemophagocytic syndrome
and multi-organ failure in sepsis (53-57)
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MCB 5255 Cellular and Molecular Immunology
SYLLABUS
SPRING 2012
Citations and Readings
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Highlights of 10 years of immunology in Nature Reviews Immunology. Nat Rev Immunol 11:693702.
Middleton, G. W., N. E. Annels, and H. S. Pandha. Are we ready to start studies of Th17 cell
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Feigenbaum, D. C. Palmer, P. A. Antony, C. C. Chan, A. Laurence, R. L. Danner, L. Gattinoni,
and N. P. Restifo. Th17 Cells Are Long Lived and Retain a Stem Cell-like Molecular Signature.
Immunity 35:972-985.
Yang, C. Y., J. A. Best, J. Knell, E. Yang, A. D. Sheridan, A. K. Jesionek, H. S. Li, R. R. Rivera,
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12:1221-1229.
Carson, W. F., K. A. Cavassani, Y. Dou, and S. L. Kunkel. Epigenetic regulation of immune cell
functions during post-septic immunosuppression. Epigenetics 6:273-283.
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Bajramovic, J. J. Regulation of innate immune responses in the central nervous system. CNS
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SYLLABUS
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SPRING 2012
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Karlsson, E. A., and M. A. Beck. The burden of obesity on infectious disease. Exp Biol Med
(Maywood) 235:1412-1424.
Karlsson, E. A., P. A. Sheridan, and M. A. Beck. Diet-induced obesity in mice reduces the
maintenance of influenza-specific CD8+ memory T cells. J Nutr 140:1691-1697.
Vandanmagsar, B., Y. H. Youm, A. Ravussin, J. E. Galgani, K. Stadler, R. L. Mynatt, E. Ravussin,
J. M. Stephens, and V. D. Dixit. The NLRP3 inflammasome instigates obesity-induced
inflammation and insulin resistance. Nat Med 17:179-188.
Hurd, T. R., M. Degennaro, and R. Lehmann. Redox regulation of cell migration and adhesion.
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Goitre, L., B. Pergolizzi, E. Ferro, L. Trabalzini, and S. F. Retta. Molecular Crosstalk between
Integrins and Cadherins: Do Reactive Oxygen Species Set the Talk? J Signal Transduct
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Saini, V., D. M. Staren, J. J. Ziarek, Z. N. Nashaat, E. M. Campbell, B. F. Volkman, A. Marchese,
and M. Majetschak. The CXC chemokine receptor 4 ligands ubiquitin and stromal cell-derived
factor-1alpha function through distinct receptor interactions. J Biol Chem 286:33466-33477.
Mines, M. A., J. S. Goodwin, L. E. Limbird, F. F. Cui, and G. H. Fan. 2009. Deubiquitination of
CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but
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Nikolaou, Y. Morias, P. De Baetselier, and J. A. Van Ginderachter. Mononuclear phagocyte
heterogeneity in cancer: different subsets and activation states reaching out at the tumor site.
Immunobiology 216:1192-1202.
Zamarron, B. F., and W. Chen. Dual roles of immune cells and their factors in cancer development
and progression. Int J Biol Sci 7:651-658.
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induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice.
Cancer Cell 14:408-419.
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Plaitakis, A. Sharpe, D. Boumpas, and P. Verginis. Crucial Role of Granulocytic Myeloid-Derived
Suppressor Cells in the Regulation of Central Nervous System Autoimmune Disease. J Immunol.
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Winkels, E. Traggiai, A. Casati, F. Grassi, and V. Bronte. Hierarchy of immunosuppressive
strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. Eur J
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Jansson, A., and S. J. Davis. Quantitative analysis predicts the relative therapeutic efficacy of
different forms of CTLA4Ig. Mol Immunol 49:527-536.
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SYLLABUS
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in Lyn-/- mice. J Immunol 184:757-763.
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in rheumatoid arthritis and multiple sclerosis. FEBS Lett 585:3627-3632.
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Kunz, M., and S. M. Ibrahim. Non-major histocompatibility complex rheumatoid arthritis
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Kossenkov, C. Nicols, M. Yousef, K. Mounzer, J. Shull, J. Kostman, L. Showe, and L. J.
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55.
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and D. Y. Li. Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and
influenza. Sci Transl Med 2:23ra19.
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