Localization dose and time of antigens determine immune reactivity.
Localization dose and time of antigens determine immune reactivity.
复制标题
抗原的定位剂量和时间决定免疫反应性。
DOI：
--
复制
发表时间：
2000
影响因子：
7.8
通讯作者：
R. Zinkernagel
中科院分区：
文献类型：
--
作者：
R. Zinkernagel
比较了两种解释T细胞和B细胞免疫反应模式的模型：双信号理论和抗原定位-剂量-时间和结构概念。双信号理论认为，信号1（即抗原单独通过特定的T细胞或B细胞受体发出信号）关闭T细胞和B细胞，信号1加上共刺激信号2诱导它们。我们的模型采用免疫反应性抗原参数，即定位-剂量-时间动力学和抗原结构来确定T细胞和B细胞的反应性。这两个概念的共同之处在于，免疫反应是机体习得的，而不是种系定义的，抗原结构本身没有什么独特之处可以区分自身抗原和非自身抗原。虽然双信号理论基于体内任何地方存在或不存在共刺激信号来确定阳性或阴性反应性，但我们的替代模型提出，除了抗原结构、剂量和时间外，抗原的定位（对-à-vis有组织的淋巴组织）决定了反应性模式如下。首先，抗原不能以最低剂量或足够长的时间到达次级淋巴器官，在免疫学上被忽略。其次，通常存在于淋巴系统或到达淋巴系统并长期过量存在的抗原会清除T细胞。第三，足够（但不过量）的抗原被转运到次级淋巴器官，并在足够的时间内（但不持续）诱导有效的免疫反应。B细胞反应也只在淋巴组织中被诱导。针对与细菌脂多糖相关的抗原或针对高度重复和严格有序的抗原，B细胞的短期反应与T无关；因此，B细胞是模式识别器（通常B细胞可获得的单体抗原通常可能是自身抗原）。严格有序的重复抗原实际上根据定义是感染因子)。长期（开关）B细胞对单抗原和多态抗原的反应依赖于T细胞，受时间剂量和抗原定位的调节。
Two models to explain patterns of immune reactivity of T and B cells are compared: the two-signal theories and the antigen-localization-dose-time and structure concept. The two-signal theory states that signal 1 (= antigen alone signalling via specific T or B cell receptor) turns T and B cells off, signal 1 plus co-stimulatory signals 2 induces them. Our model employs immuno-reactivity antigen parameters, i.e. localization-dose-time kinetics and structure of antigen in determining T and B cell reactivity. Both concepts have in common that immune reactivity is somatically learned and not germline defined and that there is nothing unique to the antigenic structure itself that could distinguish self from nonself antigens. While two-signal theories base positive versus negative reactivity on the presence or absence of co-stimulatory signals anywhere in the body, our alternative model proposes that besides antigen structure, dose and time it is the localization of antigen--vis-à-vis the organized lymphoid tissues--that determines reactivity patterns as follows. First, antigen that does not reach secondary lymphoid organs in minimum doses or for sufficiently long time periods, is immunologically ignored. Second, antigen that either usually exists in the lymphoid system or reaches it and persists in excessive amounts for long periods deletes T cells. Third, antigen that is transported to secondary lymphoid organs in sufficient (but not excessive) amounts and for a sufficient time period (but does not persist) induces an effective immune response. B cell responses are also induced exclusively in lymphoid tissues. Short-term B cell responses are T independent against antigens linked to bacterial lipopolysaccharides or against highly repetitive and strictly ordered antigens; thus, B cells are pattern recognizers (monomeric antigens usually accessible to B cells are in general likely to be self-antigens. Strictly ordered repetitive antigens are virtually by definition infectious agents). Long-term (switched) B cell responses against mono- and polymorphic antigens are T cell dependent regulated by time dose and localization of antigen.
影响因子：
4.4
作者：
R. Dintzis;M. Okajima;M. Middleton;G. Greene;H. Dintzis
通讯作者：
R. Dintzis;M. Okajima;M. Middleton;G. Greene;H. Dintzis