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

英国家禽业在21世纪面临着越来越多的挑战。许多用于控制家禽疾病的药物正在停止使用。与此同时，福利标准的提高意味着该行业正变得更加自由。但缺点是，自由放养的鸡面临着更高的疾病挑战，例如通过与野生鸟类接触。解决这个问题的一个办法是开发新型疫苗。要做到这一点，我们需要了解鸟类对疾病的免疫力，这样我们就能找到控制这种反应的方法。我们已经知道，鸟类和哺乳动物的免疫反应可以分为两部分——先天反应和适应性反应。后者是一种非常特殊的反应，有望导致免疫“记忆”，换句话说，能够对同一病原体的后续感染做出快速反应。这就是疫苗接种的原理。先天免疫反应是一种广义的反应，可以识别各种病原体的成分，例如，细菌外壳中特定类型的分子。它有两个作用——在适应性免疫反应启动之前限制感染，并提供控制适应性免疫反应的信号。这两种反应之间的主要联系是一种特殊的细胞类型，树突状细胞或DC。这些细胞是“专业抗原呈递细胞”。它们将病原体的“抗原”（病原体的一小部分）呈现给适应性免疫反应的细胞，因此它们可以被识别为外源，并向相同的细胞提供信号，以帮助它们以正确的方式做出反应。迄今为止，DC的功能仅在少数哺乳动物物种中被了解。我们是第一批能够在实验室中培养鸡DC的人，现在希望开始了解它们的功能。如果我们能理解鸡的DC是如何工作的，那么我们就能开始弄清楚我们如何操纵它们来对疫苗做出更好的反应。我们建议确定鸡DC如何对不同的病原体做出反应，它们如何在体内从感染部位移动到抗原呈递部位（换句话说，它们如何直接与适应性免疫反应细胞对话），以及它们如何控制适应性免疫反应细胞。由此可以得到一些线索，了解哪些分子能够影响鸡DC的功能，因此哪些分子有可能充当疫苗佐剂，换句话说，对现有和新型疫苗产生更强的反应，更好地保护疫苗所针对的病原体。

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 Many of the drugs used to control diseases in poultry are being withdrawn from use.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.