SPECIFICITY AND MODULATION OF VIRUS INDUCED MEMORY CELLS

我是一名医生，不仅对病人的护理有强烈的承诺，而且 致力于医学研究，这在我的护理历史中得到了很好的证明。我 在新南威尔士州哈利法克斯的达尔豪西大学获得医学硕士学位。在此期间，我 作为一名医科学生已经积极参与了内分泌研究 结果出版了3本书。我继续拿到了我的内科药物 在同一家机构进行培训，然后在 加拿大大学领先的加拿大中心的传染病 马尼托巴省，温尼伯，明尼苏达州加拿大医学研究委员会资助 我追求对人类免疫防御的兴趣，并获得了博士学位， 马尼托巴大学医学微生物学系。我的论文 工作重点是人类NK和Gammadelta T细胞对肿瘤的反应。我觉得 对病毒的免疫学反应的进一步培训将 补充我的临床和研究兴趣。因此，我加入了Dr。 马萨诸塞大学医学院病理学系雷蒙德·威尔什实验室 中心，3年前开始博士后培训。与威尔士博士合作，有 导致我做出了一些新奇的观察，这些观察不仅与病毒有关 免疫学只是对免疫学的基本理论。我已经证明了急性病毒 感染，产生细胞毒性T淋巴细胞(CTL)与 小鼠体内的异源病毒。异源病毒感染可引发 CTL应答并对第二种病毒提供一定的保护性免疫 感染，在第二次病毒感染后，记忆中的CTL 对第一种病毒的响应被部分删除。我设想了一个 记忆细胞的免疫网络，凭借有时遥远的 交叉反应，不断受到感染性病原体的调节 和环境抗原。我建议在这里使用几种病毒和 人工合成病毒多肽探索病毒诱导的特异性 多克隆CTL的活化及其意义的确定 交叉反应性CTL对感染和病毒诱导的天然抵抗力 免疫病理学。具体目标：#1将定义病毒的动力学 巨噬细胞病毒CTL应答的多肽特异性；#2分析CTL 不同病毒之间的交叉反应；#3测试模型系统 交叉反应的重要性。这是一种理想 实现我作为临床研究员的终极目标的环境。在 威尔士博士的实验室我可以继续发展强大的基础科学背景 在病毒免疫学领域，在一所拥有强大 病毒免疫学的跨部门项目。随着我工作的进展，我 有可能与哈里特博士 Robinson将我的模型应用到她的猕猴艾滋病毒系统中，并与Dr。 弗兰克·恩尼斯，研究人类感染病毒时的免疫调节 例如流感、艾滋病毒和EB病毒。

I am a physician with a strong commitment not only to patient care but also to medical research , which is well demonstrated by my carer history. I obtained m MD at Dalhousie University, Halifax, N.S.. During this time I was already actively involved as a medical student in endocrine research resulting in 3 publications. I went on to obtain my internal medicine training at the same institution., followed by subspecialty training in infectious diseases at the leading Canadian center at the University of Manitoba, Winnipeg, Mb.. With Medical Research Council of Canada funding I pursued my interest in human immune defenses and obtained a PhD, in the medical Microbiology Department at the University of Manitoba. My thesis work focused on human NK and gammadelta T cell responses to tumors. I felt that further training with immunological responses to viruses would complement both my clinical and research interests. I therefore joined Dr. Raymond Welsh's Lab, Pathology Dept., University of Massachusetts Medical Center, 3 years ago for postdoctoral training. Working with Dr. Welsh, has led to my making some novel observations which pertain not only to viral immunology but to basic immuno theory. I have shown that acute viral infections, generate cytotoxic T lymphocytes (CTL) cross-reactive with heterologous viruses in mice. A heterologous viral infection can prime a CTL response and provide some protective immunity to a second viral infection, and subsequent to the second viral infection, the memory CTL response to the first virus becomes partially deleted. I envision an immunological network of memory cells that, by virtue of sometimes remote cross-reactivities, are continually being modulated by infectious agents and environmental antigens. I propose here to use several viruses and synthetic viral peptides to explore the specificities of virus-induced polyclonal CTL activation and to determine the significance of crossreactive CTL in "natural" resistance to infection and virus-induced immunopathology. Specific Aims: #1 will define the kinetics of the viral peptide specificities of the CTL response to LCMV; #2 analyzes CTL responses crossreactive between different viruses; #3 tests model systems for the significance of the crossreactive responses. This is an ideal environment to achieve my ultimate goal of clinical investigator. Within Dr. Welsh's Lab I can continue to develop a strong basic science background in the field of viral immunology, at a school that has a strong interdepartmental program in viral immunology. As my work progresses I have the potential to form collaborative efforts with both Dr. Harriet Robinson, applying my models to her HIV system in macaques, and with Dr. Frank Ennis, looking at immune modulation in human infections with viruses such as influenza, HIV and EBV.