適應(yīng)性免疫的起源與演化立項報告

摘 要：免疫學(xué)是當(dāng)今生命科學(xué)的前沿學(xué)科之一。近年來，基于多物種比較的演化免疫學(xué)發(fā)展迅速，既為諸多基礎(chǔ)科學(xué)問題提供了答案，也為農(nóng)牧副漁和醫(yī)療保健領(lǐng)域帶來了新思路與新技術(shù)。該研究圍繞天然免疫和適應(yīng)性免疫從文昌魚到人的交替演化過程，將研究的問題進一步凝練到適應(yīng)性免疫的起源上，擬解決如下關(guān)鍵科學(xué)問題：（1）目前并存的多種抗原受體多樣性形成機制如何起源與演化？是否還有未知的多樣性形成機制？（2）后口動物免疫信號通路的基本框架是什么？關(guān)鍵適應(yīng)性免疫信號通路是如何起源？其功能意義如何？（3）不同物種的免疫應(yīng)答尤其是適應(yīng)性免疫應(yīng)答的分子、細(xì)胞與組織器官基礎(chǔ)是什么？天然免疫和適應(yīng)性免疫如何交替演化？（4）哪些新發(fā)現(xiàn)的抗原受體與免疫分子具有那些潛在應(yīng)用價值？哪些免疫新機制與新策略將給病害防御帶來什么新思路和技術(shù)？該研究分為5個研究方向以中國文昌魚與七鰓鰻為主要研究對象，同時兼顧其他居于關(guān)鍵演化節(jié)點的物種，系統(tǒng)性地開展以下研究：（1）抗原受體多樣性的形成機制及其起源；（2）特異性免疫識別中結(jié)構(gòu)與功能的演化；（3）免疫信號轉(zhuǎn)導(dǎo)通路的起源與演化；（4）天然免疫與適應(yīng)性免疫應(yīng)答的協(xié)作與交替演化；（5）原始淋巴細(xì)胞系與淋巴器官的起源與演化。通過系統(tǒng)性比較研究，我們力圖闡明各種免疫抗原受體（Ig、TCR和VLR等）的多樣性形成機制及其起源演化歷程；揭示適應(yīng)性免疫特異識別和信號傳導(dǎo)的分子、細(xì)胞與器官基礎(chǔ)及起源演化；揭示各類新穎的免疫分子尤其是VLR等的特異性抗原受體的功能特性。

關(guān)鍵詞：適應(yīng)性免疫 起源 演化

Abstract： Immunology is one of leading research fields in life science. The interest and effort on evolution immunology study are growing fast in the last 20 years， and the discovery in the field provides not only answers to many basic scientific questions， but also new technologies and methods for farming， animal husbandry and health care. Our team members have made a significant progress in the study of amphioxus-based evolution immunology under the support of last 973 program named “The 100 million years ascend of the origin of the immune system”. Based on the previous experience and achievements， we will continue focus on the origin and evolution of adaptive immunity and try to investigate the following questions including： （1） where does the origin of the diversity of antigen receptors come from？ and is there any other procedure except V（D）J recombination to introduce high diversity of antigen receptors； （2） which molecules are the main players in signal transduction in the Deuterostomia immunity？ What kind of functions of these molecules server as？ （3） Which molecules， cells and tissues are the fundamental bases for the adaptive immunology？ To address these questions， five projects have been developed in this 973 program. We will systematically study （1） the origin and evolution of the diversity of antigen receptors； （2） the evolution of the structure and function of the specific immune recognition； （3） the origin and evolution of immune signal transduction； （4） the collaboration between innate immunity and adaptive immunity along with their evolution； （5） the origin and evolution of immune cells and organs. Through these studies， we will try to elucidate the key time points and mechanisms of the evolution of antigen receptors， e.g. Ig， TCR and BCR； reveal the molecular， cellular and tissue basis for immune recognition and immune signal transduction， and clarify the functions of the ancestor molecules in adaptive immune system.

Key Words： Adaptive immunity； Origin； Evolution

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