Immune Mechanisms of Red Cell Alloimmunization

描述 (申请者摘要)萨莉·坎贝尔·李博士是一位非裔美国医生 世卫组织已完成输血医学奖学金培训，并将成为 该奖项的首席调查员。保罗·尼斯博士和威廉·鲍德温博士， 约翰霍普金斯大学病理学系的两人都将担任共同导师 和主要导师。约翰斯的临床和研究项目 霍普金斯医疗机构提供了丰富的成长环境和 发展年轻的调查人员，拥有可供他们使用的许多资源。 坎贝尔-李博士的职业目标是成为一名独立调查员 专攻输血同种异体免疫的免疫机制 输血，除了担任一家医院的血液医学主任 银行和输血医疗服务。这一奖项将有助于实现这一目标 为Campbell-Lee博士提供额外的免疫学培训 研究方法，以及动物模型在研究心力衰竭发病机制中的应用 同种异体免疫，它的应用将提供对 输血医学中长期存在的问题，即免疫调节 输血接受者。 该研究项目将研究红细胞的免疫机制。 输血中的异体免疫。当红细胞(RBC)被输注时， 受体可能对外来红细胞抗原产生同种异体免疫。什么时候 同种异体免疫发生时，必须确定抗体的特异性， 而且必须找到缺乏该患者相应抗原的血液。 这是劳动密集型和成本高昂的，可能会导致显著的延迟 血液的可得性。为了开发对此的预防或治疗 问题是，调节抗体形成的免疫机制必须更好 已确认身份。我们将使用小鼠输血系统研究以下内容： 消除或修饰供体白血球靶向亚群的效果 血细胞对RBC抗原的同种异体免疫；包被RBC对 补体C3d对同种异体抗体形成的影响及对红细胞的影响 阻断修饰抗原提呈细胞形成同种异体抗体 CD28-B7与CTLA41g的共刺激通路。

DESCRIPTION (Applicant's abstract) Dr. Sally Campbell-Lee is an African-American physician who has completed fellowship training in Transfusion Medicine, and will be the principal investigator on this award. Drs. Paul Ness and William Baldwin, both of the Department of Pathology at Johns Hopkins, will serve as co-mentor and primary mentor, respectively. The clinical and research programs at Johns Hopkins Medical Institutions provide a rich environment for the growth and development of young investigators, with many resources at their disposal. Dr. Campbell-Lee's career goals are to become an independent investigator specializing in immune mechanisms of allo-immunization in transfusion in transfusion, in addition to serving as a medical director of a hospital blood bank and transfusion medicine service. This award will aid in reaching this goal by providing Dr. Campbell-Lee' with additional training in immunological research methods, and the use of animal models in examining mechanisms of alloimmunization, the application of which will provide insight into a longstanding problem in transfusion medicine, that of immune modulation in the transfusion recipient. The research project will investigate immune mechanisms of red cell alloimmunization in transfusion. When red blood cells (rbc) are transfused, the recipient may become alloimmunized to foreign red cell antigens. When alloimmunization occurs, the specificity of the antibody must be identified, and blood must be found that lacks the corresponding antigen for that patient. This is labor intensive and costly, and can cause a significant delay in the availability of blood. In order to develop prevention or treatment for this problem, immune mechanisms regulating antibody formation must be better identified. We will study the following using a murine transfusion system: the effects of eliminating or modifying targeted subpopulations of donor white blood cells alloimmunization to rbc antigens; the effect of coating rbc for transfusion with C3d on alloantibody formation, and the effect on red cell alloantibody formation of modifying antigen presenting cells by blockage of the CD28-B7 co-stimulatory pathway with CTLA41g.