Modulation of dendritic cells and initiation of cell-mediated immune responses in the chicken
Tuesday 5 May 2009
Dr Ir. Lonneke Vervelde
Most diseases in poultry are caused by intracellular pathogens (viruses and bacteria). Cell-mediated immune responses are required to eliminate infected cells, but the cytotoxic T lymphocytes needed for this are not induced with the current vaccination strategies. Current vaccines are potent inducers of antibodies, however, as soon as the pathogen is located intracellularly these antibodies will not be able to clear the infection anymore.
In this project we study the initiation and modulation of the cell-mediated immune responses in order to be able to improve vaccine design. We focus especially on respiratory viruses such as influenza avian pneumovirus and infectious bronchitis virus. The ultimate goal is to develop vaccine components that will selectively drive the immune system towards a cytotoxic response against the pathogen.
The response can be subdivided in 3 phases:
1. Activation and modulation of the dendritic cells (DC)
2. Priming of the naive T cells by the dendritic cells
3. Maturation of the naïve T cells into effector or memory T cells
In the first project bone marrow derived DCs are cultured and functionally characterized after activation through different stimuli (viral, bacterial); phagocytic capacity, matrution and cytokine production.
In the second and third project co-cultures will be set up to measure the capacity of DCs to activate T cells. Tools will be developed to distinguish naïve, effector and memory T cells in the chicken. Activation and maturation of T cells will be measured in experimental infection models using various techniques (qPCR, FACS analysis, histology-microscopical)
Student project can focus on one or more aspects of these 3 steps.
Various techniques are being developed and used: cell culture, cell isolation (MACS and FACS based), FACS analysis, (Q-)PCR, proliferation assays, cytotoxicity assays, histology, elispot, elisa, cloning techniques
6 or 9 months
Dr Ir. Lonneke Vervelde, L.Vervelde@uu.nl, 030 - 2531872