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The evolution of the adaptive immune system.

机译:适应性免疫系统的演变。

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摘要

Models proposed for the molecular evolution of the immune system are based on comparative studies of living species. Sharks are critical in this regard since they belong to an ancient clade (chrondrichthyans) that can be traced in the fossil record to the time of the earliest vertebrates. Approximately 450 million years ago, the gnathostomes diverged into two groups, the chondrichthyans (sharks and rays) and the osteichthyans (line leading to modern teleosts and tetrapods). It can be concluded that the molecular components of the immune system are ancient and arose prior to this divergence. This follows from studies showing that all the defining elements of the immune system, antibodies, T cell receptors (TCRs), MHC products and recombination activator genes (RAG), are present in chondrichthyes (4, 5). Thus, continued studies of sharks and rays, the most distant living relatives of mammals with a vertebrate type (VDJ-C recombination) immune system, should provide insights into the molecular origins and evolution of the immune system.;In this research, (1) I report the sequence of the sandbar shark TCR gamma chain genomic locus and confirm that it has a prototypical translocon arrangement. (2) I also show that in the sandbar shark TCR gammaV regions undergo somatic hypermutation, in addition to DNA recombination and junction addition and deletion, to generate TCR diversity. (3) I report the sequence of the sandbar shark beta-2 microglobulin (beta2m)genomic locus.;These findings certainly have functional implications for gamma/delta T cells, beta2m and MHCs in sharks, and may have phylogenetic significance for understanding the evolutionary origins of diversity in the immune system.
机译:为免疫系统的分子进化提出的模型是基于对生物物种的比较研究。鲨鱼在这方面至关重要,因为它们属于古老的进化枝(chrondrichthyans),在化石记录中可以追溯到最早的脊椎动物时代。大约4.5亿年前,棘足动物分为两组,即软骨鱼类(鲨鱼和rays鱼)和骨鱼类(导致现代硬骨鱼和四足动物的线)。可以得出结论,免疫系统的分子成分是古老的,并且在这种分歧之前就已经出现了。研究表明,软骨鱼类中存在着免疫系统的所有定义要素,抗体,T细胞受体(TCR),MHC产物和重组激活基因(RAG)(4,5)。因此,继续研究鲨鱼和rays鱼是具有脊椎动物类型(VDJ-C重组)免疫系统的哺乳动物的最远处的近亲,应该提供对免疫系统的分子起源和进化的见解。(1) )我报告了沙洲鲨TCRγ链基因组位点的序列,并确认它具有原型跨位排列。 (2)我还表明,在沙bar鲨中,TCR gammaV区域除了进行DNA重组以及连接处的添加和缺失外,还会发生体细胞超突变,从而产生TCR多样性。 (3)我报告了沙洲鲨鱼beta-2微球蛋白(beta2m)基因组位点的序列;这些发现对鲨鱼中的γ/δT细胞,beta2m和MHCs具有一定的功能意义,并且对于理解进化过程可能具有系统发育意义。免疫系统多样性的起源。

著录项

  • 作者

    Chen, Hao.;

  • 作者单位

    The University of Arizona.;

  • 授予单位 The University of Arizona.;
  • 学科 Biology Genetics.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 150 p.
  • 总页数 150
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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