MODELING OF IMMUNE RESPONSES IN INFECTIOUS DISEASES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。最近有许多实验室技术的发展，可以量化对感染的免疫反应。反过来，这些新的定量数据的可用性使得开发新的理论定量模型来帮助解释它们成为可能，而且确实是必要的。在这个建议中，我们正在开发针对病毒感染的免疫反应模型。我们特别针对两种重要的感染，乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染。这两种病毒都感染肝细胞，并可能导致慢性感染和严重的肝脏疾病，这被认为主要是由于免疫反应。相反，最初的免疫反应对于决定感染的结果至关重要——一个人是根除感染还是成为慢性感染。然而，在这些病毒中，早期免疫反应的动态和质量是不同的。我们正在根据现有的新数据开发数学模型，这些模型将用于帮助解释数据，并可能计划新的实验。我们的模型包括病毒和免疫细胞群的动力学，最初是基于用于研究人类免疫缺陷病毒（HIV）的非常成功的方法。对具有相似但不完全相同病理的病毒的免疫反应的比较建模，有越来越多的实验数据，将帮助我们不仅更好地了解这些疾病，而且了解对一般病毒的免疫。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There have been many recent developments of laboratory techniques that allow the quantification of immune responses against infections. In turn, the availability of these new quantitative data makes possible, and indeed necessitates, the development of new theoretical quantitative models to help interpret them. In this proposal, we are developing models of immune responses against viral infections. We specifically address two important infections, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both these viruses infect liver cells, and may lead to chronic infection and serious liver disease, which is thought to be mostly due to the immune response. Conversely, the initial immune response is crucial in determining the outcome of infection - whether an individual eradicates infection or becomes chronically infected. However, the dynamics and quality of the early immune response are different in these viruses. We are developing mathematical models informed by the new data available, which will be used to help interpret the data and, potentially, to plan new experiments. Our models include the dynamics of the virus and immune cell populations, and initially are based on very successful approach used to study human immunodeficiency virus (HIV). Comparative modeling of the immune responses against viruses with similar, but not identical, pathologies, for which there is a growing amount of experimental data, will help us understand not only these diseases better, but also immunity against viruses in general.