Etiology of yellow fever.: X.: Comparative immunological studies on leptospira icteroides and leptospira icterohæmorrhagle.
Etiology of yellow fever.: X.: Comparative immunological studies on leptospira icteroides and leptospira icterohæmorrhagle.
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DOI：
10.1084/jem.31.2.135
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发表时间：
1920-02-01
影响因子：
15.3
通讯作者：
Noguchi, H
中科院分区：
文献类型：
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作者：
Noguchi, H
以前曾有报道说，在瓜亚基尔，从黄热病患者的血液或器官中发现了一种属于钩端螺旋体属的可过滤微生物，这种被称为黄疸型钩端螺旋体的微生物在某些实验动物中引起了在被分离的病人身上观察到的特征性症状和病变。先前也已经表明，当将从瓜亚基尔的黄热病发作中恢复的患者的血清引入正常豚鼠的腹膜腔时，其具有凝集和溶解生物体的能力（Pfeiffer现象）。此外，尽管豚鼠在4至5天后表现出明确的发热反应，但它们一旦接种黄热病患者的血液而没有死于感染，却被发现对随后接种的黄疸型钩端螺旋体培养物无效。所有这些观察结果都指出，这种生物体可能与瓜亚基尔的黄热病有关。该病原体的可过滤性和美丽坚蝇可传播同一病原体的证据进一步加强了该病原体在黄热病中可能的病原学意义。确定黄疸型钩端螺旋体和黄疸出血型钩端螺旋体之间的关系决不是一个简单的问题。以前的一篇论文中报道的一个实验似乎证明了这两种钩端螺旋体密切相关但不完全相同的观点，但在确定它们之间的区别之前，有必要穷尽各种其他的分化模式。本论文将继续这一阶段的研究，并进一步详细讨论凝集现象、普发反应、补体结合、各种单价和多价免疫血清的保护特性以及主动免疫。作为与这些免疫现象有关的实验结果，提供了下列数据：在一只对黄疸型钩端螺旋体自然不敏感的动物中，通过多次连续注射制备的单价免疫血清，不仅对同源菌株，而且对所有其他被测的黄疸型菌株都具有体外凝集能力。另一方面，当这些免疫血清在体外与各种黄疸出血型钩端螺旋体菌株混合时，观察到轻微的效果，或根本没有效果。在单价抗黄疸出血型血清和各种黄疸型钩端螺旋体菌株之间也存在类似的关系;也就是说，在某些情况下，对黄疸型菌株有轻微的凝集作用，但这种凝集作用从来没有在抗黄疸出血型菌株试验中出现的那么强。法伊弗反应在两组之间提供了更明显的区别，因为在大多数情况下，这种现象是该组特有的。偶尔会出现可疑反应，但不足以将两组混淆，多价免疫血清（一种是特异性类囊黄疸，另一种是类囊黄疸出血症）对同源组的培养物显示出高滴度的中和力。然而，我们发现血清的作用并不是绝对特异的，因为注射足够量的抗黄疸血清可以明显防止豚鼠接种多个最小致死剂量的黄疸出血钩端螺旋体培养物而出现致死性结果，反之亦然。该血清的特异性仅在用于较小的肿瘤时才得到证实。
It has been previously reported that a filterable microorganism belonging to the genusLeptospirahas been recovered from the blood or organs of human beings suffering from the disease known as yellow fever in Guayaquil, and that the organism, which has been termedLeptospira icteroides, induces in certain experimental animals the characteristic symptoms and lesions observed in the patients from whom it was isolated. It has also been previously shown that the serum from patients recovering from an attack of yellow fever in Guayaquil had the power to agglutinate and dissolve the organism when introduced into the peritoneal cavity of a normal guinea pig (Pfeiffer phenomenon). Moreover, the guinea pigs which had once been inoculated with the blood of yellow fever patients without succumbing to the infection, notwithstanding the fact that they had shown a definite febrile reaction after 4 to 5 days, were found to be refractory to a subsequent inoculation of a culture ofLeptospira icteroidesAll these observations pointed to the possible relation of this organism to the disease known as yellow fever in Guayaquil. The demonstration of the filterability of the organism and the transmission of the infection with the same organism byStegomyia calopushave further strengthened the probable etiological significance of the organism in yellow fever.It was by no means a simple problem to determine the relation existing betweenLeptospira icteroidesandLeptospira icterohæmorrhagiæ. An experiment reported in a previous paper seemed to justify the view that the two leptospiras are closely related but not identical, yet it was necessary to exhaust various other modes of differentiation before the distinction between them was firmly established. The present paper continues this phase of the inquiry in further detail.There have been taken up here the phenomena of agglutination, the reaction of Pfeiffer, complement fixation, the protective properties of various monovalent and polyvalent immune sera, and active immunity. As the result of experiments in connection with these immunity phenomena the following data are presented.Monovalent immune sera prepared by several successive injections in an animal naturally refractory toLeptospira icteroidespossess the power to agglutinatein vitronot only the homologous strains, but also all other strains oficteroidestested. On the other hand, a slight effect, or none at all, has been observed when these immune sera have been mixedin vitrowith various strains ofLeptospira icterohæmorrhagiæ. A similar relation exists between the monovalent anti-icterohæmorrhagiæsera and the various strains ofLeptospira icteroides;that is, there is a slight agglutinating effect in some instances upon theicteroidesstrains, but it is never so strong as that occurring in tests against theicterohæhagiæstrains. The Pfeiffer reaction gave a sharper differentiation between the two groups, for in most instances the phenomenon was specific for the group. There were occasional doubtful reactions, but not enough to warrant a confusion of the two groups.Polyvalent immune sera, one specific foricteroides, and the other foricterohæmorrhagiæ, showed a high titer of neutralizing power for the cultures of the homologous groups. It was found, however, that the action of the sera is by no means absolutely specific, because the injection of a sufficient amount of the anti-icteroidesserum apparently prevented a fatal outcome in a guinea pig inoculated with multiple minimum lethal doses of a culture ofLeptospira icterohæmorrhagiæ, andvice versa. The specificity of the serum was demonstrated only when it was used in smaller …