CELLULAR AND HUMORAL ASPECTS OF IMMUNOMODULATION

这项建议的总体目标是汇集一批 具有互补专业知识的调查人员，其研究将解决 输血多学科领域的定义和相关领域 药 这个SCORE计划项目的总主题是研究 输血免疫调节的细胞和体液方面 药 免疫调节可能是由于同种异体血液 输血 这种改变的和“不需要的”免疫的表征 是开发特定治疗干预方法的关键。 或者，免疫调节可以是有意的，如在治疗 中心 后者属于同种异体输血治疗， 免疫活性细胞诱导移植物抗白血病。 总的来说，拟议的研究涉及独特的方法， 表征同种异体和自身免疫应答并进一步定义细胞 血型抗原靶标的生物学特征。 此外， SCOR计划将开发新的细胞疗法，并研究 其诱导的免疫调节作用的机制。 该计划包括5个主要研究项目。 项目1将访问 自然发生和致病性红细胞自身抗体的分子基础 关于它们的B细胞起源，抗原选择的作用， 与多克隆激活相反， 结构，这仍然是不明确的;项目2将调查反- 基因和血清水平的Rb同种免疫应答及其设计 抗Rb抗体- Rh抗原结合的抑制剂;项目3涉及 利用中国仓鼠血型抗原的生物学 卵巢细胞转染血型糖蛋白基因作为模型来研究两者 该复合膜抗原的生物化学和免疫学方面; 项目4将开发人类脐带血和血液收集、储存和 扩增程序，这是专为纠正纯合子镰刀 通过人脐带细胞移植治疗细胞性贫血;项目5将 开发与输血相关的体外和体内动物模型， 同种异体人T细胞作为免疫调节干预的新形式 在癌症治疗中。 这5个项目将采用互补的方法， 解决病理学相关问题的方法， 通过互动和沟通加速进步。 他们一起 将在遗传学和生物化学学科之间架起桥梁， 病理生理学 从这些研究中获得的信息和试剂 在设计输血治疗中的免疫调节剂时应该是有用的。

The overall objective of this proposal is to bring together a group of investigators with complementary expertise, whose research will address defined and related areas in the multi-disciplinary field of Transfusion Medicine. The general theme of this SCORE Program Project is t he study of cellular and humoral aspects on immunonomodulation in Transfusion medicine. Immunomodulation may occur as a result of allogeneic blood transfusion. The characterization of such altered and "unwanted", immunity is essential to developing approaches of specific therapeutic intervention. Alternatively, immunomodulation may e intentional as in the treatment of center. The later pertains to the transfusion therapy of allogeneic, immunocompetent cells to induce graft versus leukemia. Collectively, the proposed studies involve unique approaches to characterize allo-and auto-immune responses and further define cell biological features of blood group antigenic targets. In addition, athe SCOR Program will develop novel cellular therapies and examine the mechanisms of their induced immunomodulatory effects. The Program comprises 5 major research projects. Project 1 will access the molecular basis of naturally occurring and pathogenic RBC autoantibodies with respect to their B-cell origin, the role of selection by antigen as opposed to polyclonal activation, and the characterization the odontogenic structures, which remain ill-defined; Project 2 will investigate the anti- Rb alloimmune response at the genetic and serologic level and design inhibitors of anti-Rb antibody - Rh antigen binding; Project 3 pertains to the biology of blood group antigen glycophorus utilizing Chinese hamster ovary cells transfected with glycophorin genes as a model to study both biochemical and immunological aspects of this complex membrane antigen; Project 4 will develop a human umbilical and blood collection, banking and expansion program, which is tailored to the correction of homozygous Sickle Cell Anemia by human umbilical cord cell transplantation; Project 5 will develop in vitro and in vivo animal models relevant to the transfusion of allogeneic human T cells as a novel form of immunomodulatory intervention in cancer therapy. These 5 projects will use complementary approaches and different methodologies to address pathologically related questions, which will accelerate progress through interactions and communication. Together they will bridge disciplines of genetics and biochemistry with a basis in pathophysiology. The information and reagents derived from these studies should be useful in devising immunomodulators in transfusion therapy.