Search for Origin of Vertebrate Adaptive Immunity in The Sea Lamprey

虽然所有生物都使用先天免疫机制来防御外来入侵，但只有颌类脊椎动物具有特定的适应性免疫，其基本要素包括抗原、抗体和主要组织相容性(MHC)基因的T细胞受体。获得性免疫系统大约在5亿年前进化，以提供免疫记忆和保护，防止相同病原体的反复感染。为了更好地了解先天免疫和适应性免疫是如何协同工作的，该项目试图确定七鳃鳗适应性免疫的构成要素，七鳃鳗是无颌脊椎动物的两个现存代表之一。这些实验将识别由七鳃鳗淋巴细胞和吞噬细胞表达的基因，七鳃鳗淋巴细胞是高等脊椎动物中负责适应性免疫反应的细胞类型，吞噬细胞是天然免疫反应的关键细胞类型。在这些七鳃鳗细胞类型中选择性表达的基因将与高等脊椎动物中参与先天和/或获得性免疫的基因进行比较。目标是阐述先天免疫系统的特征，可能还有让七鳗鱼在过去5亿年里存活的获得性免疫系统。这些研究将深入了解适应性免疫系统如何与先天免疫协同进化，以使包括人类在内的高等脊椎动物能够在各种传染性微生物和毒素的持续入侵下生存下来。这些信息还可能有助于设计生物控制捕食性七鳃鳗的手段，这种捕食性七鳃鳗已经摧毁了北美五大湖的鱼类种群。这项研究工作将在阿拉巴马大学伯明翰分校的知识环境中进行，并将为本科生和研究生以及社区中对比较免疫学重要领域感兴趣的其他人提供讲座、研讨会和研究培训。

While all living beings use innate immune mechanisms to defend themselves against foreign invaders, only jawed vertebrates possess specific adaptive immunity, the cardinal elements of which include T cell receptors for antigens, antibodies, and major histocompatability (MHC) genes. The adaptive immune system evolved around 500 million years ago to provide immunological memory and protection against recurrent infection with the same agent. To understand better how innate and adaptive immunity work together, the project seeks to identify the building blocks for adaptive immunity in sea lamprey, one of two living representatives of jawless vertebrates. These experiments will identify genes that are selectively expressed by lamprey lymphocytes, the cell type responsible for adaptive immune responses in higher vertebrates, and genes expressed by phagocytic cells, key types of cells for innate immune responses. Genes selectively expressed in these lamprey cell types will be compared with genes in higher vertebrates that are known to participate in innate and/or adaptive immunity.The goal is to elaborate features of innate and, possibly, the adaptive immune systems that have allowed lampreys to survive for the last 500 million years. These studies will provide insight into how the adaptive immune system evolved in concert with innate immunity to allow higher vertebrates, including humans, to survive constant invasion by a variety of infectious microorganisms and toxins. The information could also be helpful in devising means for biological control of predator sea lamprey that have devastated fish populations in the Great Lakes of North America. This research effort will be conducted in the intellectual environment of the University of Alabama at Birmingham and will offer lectures, seminars, and research training to undergraduate and graduate students and others in the community who are interested in the important field of comparative immunology.