eBriefing

Immunity's Two-Edged Sword: Balancing Therapeutic Good with Adverse Effects in the CNS

Immunity's Two-Edged Sword
Reported by
Jill U. Adams

Posted February 01, 2008

Presented By

Neuroimmunology Discussion Group

Overview

Manipulating immunity for therapeutic ends is a delicate situation. In multiple sclerosis, for example, if you can stop immune cells from infiltrating the central nervous system, you can reduce the amount of inflammation of nervous tissue and improve patient outcomes. However, you also expose patients to attack from opportunistic viruses. In diabetes and neurodegeneration, both of which have an inflammatory component, the receptor for advanced glycation products (RAGE) can both protect and exacerbate disease processes. And when viruses infect the brain, toll-like receptors cause the release of inflammatory cytokines, which play their part in the immune response to infection. However, those cytokines can cause their own untoward effects, including mortality.

Scenarios like these illustrate the delicate balance governing the process through which the immune system responds to infection and injury. At a December 5, 2007, meeting of the Academy's Neuroimmunology Discussion Group three researchers spoke to the theme that the immune system can be both instigator and remediator of neurological disease.

Use the tabs above to find a meeting report and multimedia from this event.

Journal Articles

Michael Racke

Frohman EM, Racke MK, Raine CS. 2006. Multiple sclerosis: the plaque and its pathogenesis. N. Engl. J. Med. 354: 942-955.

Gocke AR, Cravens PD, Ben LH, et al. 2007. T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity. J. Immunol. 178: 1341-1348.

Stuve O, Marra CM, Bar-Or A, et al. 2006. Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. Arch. Neurol. 63: 1383-1387. FULL TEXT

Stüve O, Marra C, Cravens PD, et al. 2007. Potential risk of progressive multifocal leukoencephalopathy with natalizumab therapy: possible interventions. Arch. Neurol. 64: 169–176.

Stüve O, Marra CM, Jerome KR, et al. 2006. Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann. Neurol. 59: 743-747.

Ann Marie Schmidt

Herold K, Moser B, Chen Y, et al. 2007. Receptor for advanced glycation end products (RAGE) in a dash to the rescue: inflammatory signals gone awry in the primal response to stress. J. Leukoc. Biol. 82: 204-212.

Hudson BI, Schmidt AM. 2004. RAGE: a novel target for drug intervention in diabetic vascular disease. Pharmaceutical Research 21: 1079-1086.

Moser B, Desai DD, Downie MP, et al. 2007. Receptor for advanced glycation end products expression on T cells contributes to antigen-specific cellular expansion in vivo. J. Immunol. 179: 8051-8058.

Pichiule P, Chavez JC, Schmidt AM, Vannucci SJ. 2007. Hypoxia-inducible factor-1 mediates neuronal expression of the receptor for advanced glycation end products following hypoxia/ischemia. J. Biol. Chem. 282: 36330-36340.

Robert Finberg

Finberg RW, Knipe DM, Kurt-Jones EA. 2005. Herpes simplex virus and toll-like receptors. Viral Immunol. 18: 457-465.

Finberg RW, Wang JP, Kurt-Jones EA. 2007. Toll like receptors and viruses. Rev. Med. Virol. 17: 35-43.

Szomolanyi-Tsuda E, Liang X, Welsh RM, et al. 2006. Role for TLR2 in NK cell-mediated control of murine cytomegalovirus in vivo. J. Virol. 80: 4286-4291. FULL TEXT

Wang JP, Kurt-Jones EA, Finberg RW. 2007. Innate immunity to respiratory viruses. Cell. Microbiol. 9: 1641–1646.

Speakers

Michael Racke, MD

The Ohio State University Medical Center
e-mail | web site | publications

Michael Racke is an associate professor in the Department of Neurology and the Center for Immunology at Ohio State University. His research interests are in neuroimmunology in general and multiple sclerosis in particular. Racke received his MD from the University of Medicine and Dentistry of New Jersey and did his residency at Emory University. He did postdoctoral work at the NIH and was on the faculty of the University of Texas Southwestern before moving to Ohio State this year.

Ann Marie Schmidt, MD

Columbia University College of Physicians & Surgeons
e-mail | web site | publications

Ann Marie Schmidt is professor and chief of surgical science at Columbia University. Her research interests span basic and translational research: RAGE and mechanisms linked to diabetes, cancer, inflammation and nuerodegerative diseases. Schmidt received her MD at New York University School of Medicine and did both residency and research fellowships at NYU's Bellevue Hospital Center. She did postdoctoral studies in physiology and cellular biophysics at Columbia University.

Robert Finberg, MD

University of Massachusetts Medical Center
e-mail | web site | publications

Robert Finberg is a professor in the Department of Medicine, Infectious Disease and Immunology, and the Department of Molecular Genetics and Microbiology at the University of Massachusetts. His laboratory works on the relationships between host cell surface proteins and viruses and bacteria, and the basis of cellular activation mediated by cell surface proteins. Finberg received his MD from Albert Einstein College of Medicine. He did his residency at Bellevue Hospital in New York, then research and clinical fellowships at Harvard Medical School and Peter Bent Brigham Hospital in Boston, MA.


Jill U. Adams

Jill U. Adams is a scientist-turned-science-writer based in Albany, New York.