QUANTITATIVE STUDIES ON TISSUE TRANSPLANTATION IMMUNITY .2. THE ORIGIN, STRENGTH AND DURATION OF ACTIVELY AND ADOPTIVELY ACQUIRED IMMUNITY
QUANTITATIVE STUDIES ON TISSUE TRANSPLANTATION IMMUNITY .2. THE ORIGIN, STRENGTH AND DURATION OF ACTIVELY AND ADOPTIVELY ACQUIRED IMMUNITY
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DOI：
10.1098/rspb.1954.0054
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发表时间：
1954-01-01
期刊：
影响因子：
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通讯作者：
MEDAWAR, PB
中科院分区：
文献类型：
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作者：
BILLINGHAM, RE;BRENT, L;MEDAWAR, PB
和其他动物一样，小鼠对同种皮肤移植的排斥会使宿主处于一种高度抵抗的状态，其结果是加速对来自同一供体或基因与第一次相似的供体的第二次皮肤移植的排斥。一线同种皮肤移植物移植到正常cbaa宿主的中位预期寿命为11.0 + 0.3天；第二次移植a系皮肤，在第一次移植后60天内移植，则缩短至6天或更短。免疫力在几个月内逐渐衰减，但在120天后仍明显有效。对第二阶段移植物的抗性增强具有继发性反应的特征。正常的宿主（“次生宿主”）接种了主动免疫的宿主（“初级宿主”）的某些组织，然后表现得好像它们自己已经被主动免疫了。原发宿主具有这种转移免疫能力的组织是局部淋巴结和较小程度的脾脏。因此，区域淋巴结被认为是对皮肤同种移植物反应的主要而不是唯一的场所。其他反应途径的有效性揭示了这样一个事实，即同种移植物回归后切除区域节点不会损害宿主产生二次反应的能力；在移植前切除局部淋巴结也不会显著降低原发反应的强度——这一结果不仅是由于其他预先存在的反应中心的参与，也是由于开辟了通向淋巴结的新途径，否则这些淋巴结就不会参与反应。死亡的淋巴结和皮下移植的淋巴结没有转移免疫的能力；大剂量的全血、白细胞或血清也没有。由于这些和其他原因，有人认为继代宿主获得的免疫不可能是由于预先形成的抗体的被动转移。也不可能是由于从原代宿主中提取的疫苗中含有的抗原物质对次级宿主进行了主动免疫，因为免疫可以转移到小鼠（“耐受小鼠”）身上，使其无法对原代宿主免疫的抗原作出反应。所有的实验发现都是基于这样一个假设：从主宿主转移过来的组织存活下来，并融入到次宿主中，在新的环境中表现得就像在原始环境中不受干扰时一样。以这种方式产生的免疫力被称为收养性获得。过继性免疫是被动的，因为它是二手来源的，但它是主动的，因为它取决于主动免疫细胞的引入和持续工作。过继免疫动物与被动免疫动物的不同之处在于能够产生二次反应，而与主动免疫动物的不同之处在于从未产生过一次反应。移植免疫可以通过而不是被动获得，这一事实支持其与结核菌素反应和延迟型致敏反应的相似性。
In mice, as in other animals, the rejection of a skin homograft leaves its host in a state of heightened resistance, the effect of which is to hasten the rejection of a skin homograft transplanted on a second occasion from the same donor or from a donor genetically similar to the first. The median expectation of life of a firstA-line skin homograft transplanted to a normalCBAhost is 11·0 + 0·3 days; that of a second graft ofA-line skin, transplanted within 60 days of the first graft, is reduced to 6 days or less. Immunity decays progressively over a period of months, but is still clearly in force after 120 days. The heightened resistance to second-stage grafts has the character of a secondary response. NormalCBAmice (‘secondary hosts’) which have been inoculated with certain tissues derived from actively immunizedCBAmice (‘primary hosts’) behave thereupon as if they themselves had been actively immunized. The tissues of the primary host which have this power to transfer immunity are the regional lymph nodes and to a lesser degree the spleen. The regional nodes are therefore held to be the principal but not the only seat of the reaction against skin homografts. The efficacy of other pathways of response is revealed by the fact that extirpation of the regional nodes after the regression of a homograft does not impair the host’s capacity to give a secondary response; nor does extirpation of the regional nodes before grafting significantly reduce the power of the primary response—a result shown to be due not merely to the participation of other pre-existing centres of response, but also to the opening up of new pathways leading to lymph nodes which would not otherwise have taken part in the reaction. Killed lymph nodes and nodes transplanted subcutaneously had no power to transfer immunity; nor had massive doses of whole blood, blood leucocytes or serum. For these and other reasons, it is argued that the immunity acquired by the secondary hosts could not be due to the passive transfer of preformed antibodies. Nor could it be due to an active immunization of the secondary hosts by antigenic matter contained within the inocula taken from the primary hosts, for immunity can be transferred toCBAmice (‘tolerant mice') rendered incapable of reacting on their own behalf against the antigens which immunized the primary hosts. All the experimental findings are accounted for by the assumption that tissue transferred from the primary hosts survives and becomes incorporated in the secondary hosts, behaving in its new environment much as it would have done if left undisturbed in its environment of origin. The immunity that arises in this way is said to beadoptively acquired. Adoptive immunity is passive in the sense that it is of second-hand origin but active in that it depends upon the introduction and continued working of actively immunized cells. Adoptively immunized animals differ from passively immunized animals in being capable of a secondary response, and from actively immunized animals in never having given a primary response. The fact that transplantation immunity can be adoptively but not passively acquired argues in favour of its similarity to the tuberculin reaction and to sensitization reactions of the delayed type.