MECHANISM OF IMMUNOLOGICAL FUNCTION IN SOFT CORAL

该项目的总体目标是增进对免疫识别和同种异体不相容的基础的了解，特别是从系统发育的角度。在具有代表性的珊瑚礁和软珊瑚物种中，已经证明存在高度区分的同种免疫反应。尽管低等动物的免疫反应性与哺乳动物的免疫反应惊人地相似，但其潜在的机制还没有被发现，目前也存在争议。虽然人类的免疫系统极其复杂，涉及众多细胞和因素的相互作用，但在这些更简单的动物中的基本发现可能会为理解更复杂的免疫学机制提供重要的见解。建议的研究将集中在柳珊瑚Swiftia exserta中的以下问题：1.免疫细胞的进一步特征及其功能。在伤口愈合和同种异体移植的实验条件下，将使用组织化学和电子显微镜来检查组织，以确定细胞的结构/功能关系，以及测试特定细胞的吞噬、黏附和凝集能力。2.细胞毒作用机制。细胞毒性将通过体外和体内实验进行测试，以(A)测试细胞毒性反应的特异性，(B)鉴定细胞毒性细胞并测试可溶细胞毒性因子的假说，(C)验证细胞凋亡与同种异体移植排斥反应有关的假说，以及(D)开始分离与同种异体移植排斥反应有关的基因。3.免疫记忆。实验将演示同种异体免疫记忆的持续时间，测试同种异体细胞作为刺激的持久性，并检查温度对记忆的影响。4.同种异体免疫的细胞方面。一系列实验将检查细胞识别、激活、运动和参与同种免疫反应的调节。5.组织亲和性遗传学。一大系列的同种异体移植将与基于微卫星的DNA指纹相结合，以测试Swiftia组织相容性的潜在遗传学符合Medawar的“个体独特性”概念的假设。

The overall objective of this project is an increased understanding of immunorecognition and the basis of allogeneic incompatibilities, especially from a phylogenetic perspective. Existence of a highly discriminating alloimmune reaction has been demonstrated in representative species of reef and soft corals. Although immune reactivity in thee "lower" animals is surprisingly similar to that found in mammals, the underlying mechanisms have not been discovered and are currently controversial. While the human immune system is exceedingly complex and involves interactions of numerous cells and factors, basic findings in these simpler animals could provide important insights in understanding more elaborate immunologic mechanisms. Proposed studies will focus on the following questions in Swiftia exserta, a gorgonian coral: 1. Further characterization of immunocytes and their function. Histochemistry and electron microscopy will be used to examine tissues under the experimental conditions of wound healing and allografting to determine the structure/function relationships of the cells as well as testing the capability of specific cells with regards to phagocytosis, adherence and agglutination. 2. Mechanisms of cytotoxicity. Cytotoxicity will be examined through in vitro and in vivo experiments to (a) test the specificity of the cytotoxic response, (b) identify the cytotoxic cell and test the hypothesis of a soluble cytotoxic factor, (c) test the hypothesis that apoptosis is involved in allograft rejection, and (d) start isolating the genes involved in the allograft rejection. 3. Immunological Memory. Experiment will demonstrate the duration of alloimmune memory, test for the persistence of allogeneic cells as a stimulus and examine the effects of temperature on memory. 4. Cellular aspects of alloimmunity. A series of experiments will examine cellular recognition, activation, movements and regulation involved in the alloimmune response. 5. Genetics of histocompatibility. A large series of allografts will be made in conjunction with microsatellite based DNA fingerprinting to test the hypothesis that the underlying genetics of Swiftia histocompatibility fits Medawar's concept of the "Uniqueness of the Individual."