Shirai A, Catanzaro P J, Phillips S M, Osterman J V
Infect Immun. 1976 Jul;14(1):39-46. doi: 10.1128/iai.14.1.39-46.1976.
The relative contributions of cellular and humoral immunity in scrub typhus infections were studied in inbred mice employing paired strains of Rickettsia tsutsugamushi differing in virulence. An infectious dose (100 MID50) of the less virulent Gilliam strain resulted in heterologous immune protection against an otherwise lethal challenge (1,000 MLD50) of the virulent Karp strain. Partial heterologous protection against lethal Karp challenge was observed in animals preimmunized with the Gilliam strain as early as 3 days prior to challenge, whereas complete protection against illness and death existed in animals immunized at least 7 days prior to challenge. In the heterologous protection provided by prior Gilliam infection, the role of humoral immunity was not of primary importance for the following reasons: (i) significant levels of complement-fixing antibody against R. tsutsugamushi were not detectable until long after animals were solidly immune; (ii) antibody eventually appearing after Gilliam immunization exhibited a consistently low complement-fixing titer against the immunizing homologous (Gilliam) strain and contained no detectable activity against the heterologous challenge (Karp) strain; and (iii) passive transfer of large quantities of serum from Gilliam immune mice, themselves immune to Karp challenge, failed to protect recipients against a similar challenge. However, protection was afforded by the passive transfer of serum containing antibody against Karp, suggesting a major role for antibody in protection against homologous infection. This heterologous challenge system was particularly useful because it minimized the role of humoral immunity, at least early in the course of infection, and allowed a definitive examination of the cellular response. Cell-mediated immunity played a major role in the heterologous protection observed after Gilliam immunization. This was evidenced by the significant protection against Karp challenge afforded by the passive transfer of spleen cells from animals immunized with Gilliam 7 to 63 days previously. Of the immune spleen cells, only those which were nonadherent, presumably lymphocytes, were capable of transferring passive heterologous protection. This protective effect of nonadherent cells could be ablated by depleting the cell population of thymus-derived or T cells with anti-theta serum and complement prior to transfer but not by use of anti-immunoglobulin serum and complement, which selectively removes bone marrow-derived or B cells. These results suggested that the cell in immune spleens capable of conferring heterologous protection was a T lymphocyte.
利用毒力不同的成对恙虫病立克次体菌株，在近交系小鼠中研究了细胞免疫和体液免疫在恙虫病感染中的相对作用。低毒力的吉列姆菌株的感染剂量（100个半数感染剂量）可产生异源免疫保护，抵抗强毒力的卡尔普菌株的致死性攻击（1000个半数致死剂量）。早在攻击前3天用吉列姆菌株预免疫的动物，对卡尔普菌株的致死性攻击有部分异源保护作用，而在攻击前至少7天免疫的动物则完全抵抗疾病和死亡。在先前吉列姆感染提供的异源保护中，体液免疫的作用并非至关重要，原因如下：（i）直到动物获得稳固免疫力很久之后，才检测到针对恙虫病立克次体的显著水平的补体结合抗体；（ii）吉列姆免疫后最终出现的抗体，对免疫同源（吉列姆）菌株的补体结合滴度始终较低，且对异源攻击（卡尔普）菌株无检测到的活性；（iii）将大量来自对卡尔普攻击具有免疫力的吉列姆免疫小鼠的血清被动转移，未能保护受体抵抗类似攻击。然而，含有针对卡尔普抗体的血清的被动转移提供了保护，表明抗体在抵抗同源感染的保护中起主要作用。这种异源攻击系统特别有用，因为它至少在感染过程早期将体液免疫的作用降至最低，并允许对细胞反应进行明确检查。细胞介导的免疫在吉列姆免疫后观察到的异源保护中起主要作用。这一点通过将7至63天前用吉列姆免疫的动物的脾细胞被动转移，对卡尔普攻击提供的显著保护得到证明。在免疫脾细胞中，只有那些不黏附的细胞，大概是淋巴细胞，能够转移被动异源保护。在转移前用抗θ血清和补体耗尽胸腺来源或T细胞的细胞群体，可消除不黏附细胞的这种保护作用，但使用抗免疫球蛋白血清和补体则不能，后者选择性地去除骨髓来源或B细胞。这些结果表明，免疫脾中能够赋予异源保护的细胞是T淋巴细胞。
