Pathology

病理

基本信息

批准号：
8134128
负责人：
Robert B Colvin
金额：
$ 22.99万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8134128
关键词：
Acute Adhesions Adverse effects Allografting Animals Antibodies Apoptosis Autopsy Biopsy Cells Chronic Clinical Complement DNA Fragmentation Dendritic Cells Detection Electron Microscopy Event Fertilization Freezing Goals Graft Survival Heart Histology Image Immunofluorescence Immunologic Immunoglobulin Deposition Immunohistochemistry Immunoperoxidase Technics In Situ Nick-End Labeling Individual Infiltration Inflammation Inflammatory Injury Kidney Lasers Lesion Location Lung Lymphoid Measures Memory Molecular Nature Organ Organ Transplantation Paraffin Embedding Pathologist Pathology Patients Phenotype Protocols documentation Receptor Activation Regulatory T-Lymphocyte Role Sampling Slide Source Staining method Stains Techniques Therapeutic Tissue Banking Tissue Banks Tissues Toxic effect Transplantation allograft rejection cell injury cell type complement C4d cytokine digital digital imaging experience immunopathology insight intervention effect lymph nodes morphometry novel programs research study treatment strategy

项目摘要

Core B provides common facilities and expertise for mechanistic interpretation of pathological and immunopathological studies. The broad, long range objective of the Immunopathology Core B is to provide insights into the mechanism of action of the therapeutic manipulations used to induce grafts survival and tolerance. The insights from these studies will complement the interpretation of clinical samples in patients on similar protocols, as has been our experience. The other goal will identify and evaluate any toxicities and complications that may arise from these treatments. The primary role of the pathological analyses is to document and characterize the status of the graft (nature of infiltrate, presence of acute or chronic rejection, including a humoral component) and the systemic effects of the protocols (toxicity, complications). The mechanistic studies to be done on protocol biopsies include detection of Treg cells in grafts and lymphoid organs, measures of local inflammation in the graft and infiltration and activation of various cell types important in allograft rejection (T memory, dendritic cells) and antibody/complement effects. These are described in detail in the three projects, n addition full necropsies will be performed to determine the efficacy and adverse effects of the novel treatment strategies. The techniques that will be utilized include routine histology, immunohistochemistry, immunofluorescence with specialized techniques available as needed (electron microscopy, laser capture). Immunoperoxidase techniques with a panel of mAbs will distinguish the infiltrating cell types, adhesion and cytokine molecules and receptors, and activation markers quantitated using digital imaging of whole slides. Immunofluorescence will be used to localize the deposition of immunoglobulin and complement, as well as phenotyping cells with double/triple staining. C4d stains will be used to detect humoral rejection. We have a well-annotated tissue bank of frozen and paraffin embedded tissue available from our previous transplantation experiments (>6000 samples), which can be drawn upon to expand and refine our analysis.

核心B为病理和免疫病理学研究的机械解释提供了共同的设施和专业知识。免疫病理学核心B的广泛，远程目标是提供有关用于诱导移植物生存和耐受性的治疗操作的作用机理的见解。与我们的经验一样，这些研究的见解将补充类似方案中患者临床样本的解释。另一个目标将确定和评估这些治疗方法可能引起的任何毒性和并发症。病理分析的主要作用是记录和表征移植物的状态（浸润性的性质，急性或慢性排斥的存在，包括体液成分）以及方案的系统效应（毒性，并发症）。在协议活检中要进行的机理研究包括检测移植物和淋巴机构中的Treg细胞，在同种异体移植物排斥（T记忆，树突状细胞）中重要的各种细胞类型的局部炎症，浸润以及激活各种细胞类型以及抗体/补体效应。这些在这三个项目中详细描述了，将进行n个添加完整的死灵，以确定新型治疗策略的功效和不利影响。将要使用的技术包括常规的组织学，免疫组织化学，免疫荧光，并根据需要提供专门的技术（电子显微镜，激光捕获）。带有MAB面板的免疫过氧化物酶技术将区分浸润细胞类型，粘附和细胞因子分子和受体，以及使用使用激活标记来区分使用的激活标记。整个幻灯片的数字成像。免疫荧光将用于定位免疫球蛋白和补体的沉积，以及具有双重/三染色的表型细胞。 C4D污渍将用于检测体液排斥。我们有一个井井有条的组织库，由以前的移植实验（> 6000个样品）提供的冷冻和石蜡嵌入式组织可用，可以通过这些组织来扩展和完善我们的分析。