Understanding the function of dendritic cells in the chicken - a species lacking lymph nodes.

点击翻译按钮获取中文摘要

The UK poultry industry faces increasing challenges in the 21st century. Many of the drugs used to control diseases in poultry are being withdrawn from use. At the same time, improving welfare standards mean that the industry is becoming more free-range. But the downside is that free-range chickens face higher rates of disease challenge, for example through contact with wild birds. One answer to this problem is to develop novel vaccines. To do this, we need to understand the bird's immunity to disease, so that we can identify ways to control that response. We already know that in birds and mammals the immune response can be divided into two arms - the innate response and the adaptive response. The latter is a very specific response, which hopefully leads to immune 'memory', in other words the ability to respond rapidly to subsequent infections with the same pathogen. This is how vaccination works. The innate immune response is a generalised response that recognises components of a wide range of pathogens, for example, specific types of molecules in a bacterial coat. It serves two roles - it limits infection until the adaptive immune response can kick in, and also provides signals that control the adaptive immune response. The main link between the two responses is a specialised cell type, the dendritic cell or DC. These cells are 'professional antigen presenting cells'. They present 'antigen' (little bits of the pathogen) from pathogens to cells of the adaptive immune response, so they can be recognised as foreign, and provide signals to the same cells to help them respond in the correct way. To date, the function of DC have only been understood for a small number of mammalian species. We are the first people to have been able to grow chicken DC in the lab, and now wish to begin to understand their function. If we can understand how chicken DC work, then we can begin to figure out how we can manipulate them to give better responses to vaccines. We propose to determine how chicken DC respond to different pathogens, how they move around the body from the site of infection to the site of antigen presentation (in other words, to where they talk directly to the cells of the adaptive response), and how they control the cells of the adaptive immune response. From this should come clues as to which molecules are able to influence the function of chicken DC, and therefore which have the potential to act as vaccine adjuvants, in other words to give a stronger response to existing and novel vaccines, to give better protection to the pathogen the vaccine is designed against.