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Regulation of mucosal antibody production

English title Regulation of mucosal antibody production
Applicant Harris Nicola
Number 116498
Funding scheme Project funding (Div. I-III)
Research institution Global Health Institute EPFL SV-DO
Institution of higher education ETH Zurich - ETHZ
Main discipline Immunology, Immunopathology
Start/End 01.04.2007 - 28.02.2011
Approved amount 260'000.00
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Keywords (3)

mucosal immunology; infectious disease; humoral immunity

Lay Summary (English)

Lead
Lay summary
The gastrointestinal tract functions as a site for digestion and water exchange, and for this reason is composed of a large surface area with a thin epithelium. Yet the intestinal tract is constantly exposed to a wide variety of environmental microbes (commensal bacteria) and pathogens, some of which can easily traverse this thin epithelium to enter the body. Thus, the intestinal immune system is faced with the difficult task of knowing how to respond to those pathogens which pose a threat, whilst maintaining non-responsiveness against harmless commesal bacteria and thereby avoiding the onset of inflammatory bowel disease. As such the intestine has evolved an intricate and tightly regulated system of immune defense which is still poorly understood. Our laboratory aims to gain a better understanding of intestinal immunology with the hope that this increased knowledge will lead to better vaccine design and improved therapeutics for inflammatory bowel disease. Landmark studies have already shown that intestinal pathogens preferentially promote the production of mucosal IgA and that IgA producing cells and activated CD4+ T cells migrate to the intestinal lamina propria to provide a barrier against commensal penentration and invasive pathogens. Recent evidence has additionally indicated a central role for intestinal dendritic cells in the regulation of this process. We are now using novel cell culture systems and genetically manipulated animals to study intestinal T and B cell activation and migration. These studies can be broadly separated into three projects. In the first project we are investigating the relative roles of various lymphoid organs associated with the intestine to determine which organs are necessary for IgA production. In the second project we have developed a novel tissue culture assay whereby intestinal dendritic cells and B cells are cultured together leading to IgA production. This system is now being used to identify those factors associated with dendritic cells which regulate IgA production. In the final project we aim to establish a new model of intestinal viral infection to investigate the migration and function of CD4+ T cells and B cells genetically modified to respond specifically to the employed virus. Such cells can easily be identified by existing technologies and the model will be used to further our understanding of the role of T cells and specific antigen on IgA plasmablast retention and differentiation in the intestinal lamina propria.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
133104 Role of antibodies in protective immunity against helminth parasites 01.06.2011 Project funding (Div. I-III)
133104 Role of antibodies in protective immunity against helminth parasites 01.06.2011 Project funding (Div. I-III)

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