Speaker: Madeleine W. Cunningham, PhD

Topic:

"Molecular Mimicry, Autoimmunity and Infection "

The mechanisms by which autoimmune diseases develop may be a result of previous exposure to a pathogenic
microorganism. Infection may lead to immune responses which neutralize the pathogen, but antibodies or T cells may
develop which are crossreactive with host tissues and may lead to postinfectious autoimmune sequelae. These diseases
may provide important clues to how infection may break tolerance and subsequently lead to chronic autoimmune
inflammatory disease. Examples of post-infectious autoimmune sequelae include rheumatic heart disease, Sydenham
chorea and autoimmune myocarditis which will be used to illustrate how mimicry between host and microorganism or
between host proteins may lead to autoimmune inflammatory disease. In rheumatic heart disease, crossreactive antibodies may react with valve endothelium and lead to infiltration of the valve by mimicking T cells recognizing group A
streptococcal M protein and cardiac myosin. In Sydenham chorea, autoantibody responses against the brain react with the
neuronal cell surface, streptococcal carbohydrate, lysoganglioside and intracellular tubulin. The anti-neuronal antibodies
trigger calcium-calmodulin dependent protein kinase II signaling and eventual dopamine release by the neuronal cells
leading to the movement disorder. A third example is autoimmune myocarditis where mimicry between cardiac myosin
and the beta adrenergic receptor may lead to apoptosis in the heart which may lead to development of dilated
cardiomyopathy. The mechanisms leading to pathogenic autoantibody production and expansion of pathogenic T cells
displaying mimicry/degeneracy may be due to molecular mimicry and promiscuity at the B and T cell receptors as well as
in innate immune mechanisms involving Toll-like receptors.

When:

Monday, February 26, 2007
12:00PM – 1:00PM
 

Location:

Baldwin Auditorium
Robert H. Lurie Medical Research Center
303 East Superior Street, 1st floor
  

Hosted by Dr. David Engman

Li, Y., J.S. Heuser, S. D. Kosanke, M.W. Cunningham. 2006. Mimicry and antibody-mediated cell signaling in autoimmune myocarditis. J Immunol. 177:8234-40

Christine A. Kirvan, Susan E. Swedo, Lisa A. Snider, Madeleine W. Cunningham. Antibody-mediatedneuronal cell signaling in behavior and movement disorders. J. Neuroimmunol. 179:173-9

Fae, Kellwen, C.D. Diefenbach da Silva, S.E. Oshiro, A.C. Tanaka, P.M.A. Pomerantzeff, C. Douay, D. Charron, A. Toubert, M.W. Cunningham, J. Kalil, and L. Guilherme. 2006. Mimicry in recognition of cardiac myosin peptides by heart-intralesional T cell clones from rheumatic heart disease. J. Immunol. 176: 5662-5670

Ellis, N. M. W Hildebrand, V.A. Fischetti and M. W. Cunningham. 2005. T Cell Mimicry and Epitope Specificity of Human T Cell Clones from Rheumatic Heart Disease. J Immunol 175: 5448-5456.

Li, J S Heause, S D Kosanke, M Hemric and M.W. Cunningham. 2004. Cryptic Epitope indentified in rat and human cardiac myosin S2 region induces myocarditis in the Lewis rat. J. Immunol. 172: 3225-3234.

Kiryan, C.A., J.S. Heauser, and M.W. Cunningham. 2003. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nature Medicine 9: 914-920.