Immune Mechanisms of Red Cell Alloimmunization

描述 （申请人摘要）萨莉·坎贝尔-李博士是一位非裔美国医生 他已经完成了输血医学的奖学金培训， 这个奖项的主要研究者。 保罗·内斯和威廉·鲍德温博士 约翰霍普金斯病理学系的两位教授将担任共同导师 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一个丰富的环境， 青年调查员的发展，有许多资源可供他们支配。 坎贝尔-李博士的职业目标是成为一名独立调查员 专门研究输血中同种免疫的免疫机制， 输血，除了担任医院血液的医疗主任 银行和输血医疗服务。 该奖项将有助于实现这一目标 通过为Campbell-Lee博士提供免疫学方面的额外培训， 研究方法，以及使用动物模型来检查 同种异体免疫，其应用将提供洞察 长期存在的问题，输血医学，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 输血中的同种免疫。 当输注红细胞时， 接受者可能对外来红细胞抗原产生同种免疫。 当 发生同种免疫时，必须鉴定抗体的特异性， 并且必须找到缺乏该患者的相应抗原的血液。 这是劳动密集型的并且成本高，并且可能导致在制造过程中的显著延迟。 血液的可用性。 为了预防或治疗这种疾病， 问题，调节抗体形成的免疫机制必须更好 鉴定 我们将使用鼠输血系统研究以下内容： 消除或修饰供体白色的靶向亚群的影响 血细胞对红细胞抗原的同种免疫;包被红细胞对 C3 d对同种抗体形成及红细胞功能的影响 通过阻断抗原递呈细胞来修饰抗原递呈细胞的同种抗体形成 CD 28-B7与CTLA 41 g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.