Transfer of immunity to Nematospiroides dubius: co-operation between lymphoid cells and antibodies in mediating worm expulsion

The effect of transferring immune serum (IS) and immune mesenteric lymph node cells (IMLNC) either alone or in combination was studied in NIH mice infected with partially radiation attenuated (5 krad) N. dubius. It was demonstrated that immunity to N. dubius could be transferred with IS and with IMLNC. However, considerably greater protection was transferred to recipient mice when they received both IS + IMLNC. Animals treated in this way had fewer worms than either of the other groups from as early as day 9 onwards, suggesting that a substantial proportion of the worms in mice given IS + IMLNC was retained in the intestinal tissues. The few surviving worms which completed the tissue phase of their development were then rejected by the fourth week of infection. Dose response data showed that as few as 1 × 10⁷ IMLNC could cause a significant reduction in worm numbers when given in combination with IS. These experiments indicate that both antibodies (IS) and sensitized lymphoid cells (IMLNC) are required for effective resistance to N. dubius.     

Suppression of mucosal mastocytosis by Nematospiroides dubius results from an adult worm-mediated effect upon host lymphocytes

Infections with the nematode Nematospiroides dubius fail to elicit mucosal mast cell (MMC) responses in the intestines of host mice, and suppress MMC responses generated by heterologous infection. Larval N. dubius have the capacity to prime for mastocytosis, and to elicit this response in primed mice during a challenge, but only if adult worms are prevented from developing, either by anthelmintic treatment or by irradiation of the larvae themselves. The suppressive effect of the adult stage was confirmed in experiments where such worms were implanted directly into the intestines of mice primed by exposure to irradiated N. dubius larvae or concurrently infected with Trichinella spiralis. Data on the mechanisms underlying this suppressive effect were obtained from experiments involving the adoptive transfer of mastocytosis by mesenteric lymph node cells (MLNC) from T. spiralis infected mice. When MLNC were taken from mice infected concurrently with both T. spiralis and N. dubius no enhanced mastocytosis was seen in recipients after challenge with T. spiralis. Exposure of MLNC from T. spiralis infected donors to the presence of adult N. dubius after transfer did not reduce the adoptively transferred response. The response was also unaffected when MLNC from adult N. dubius infected mice were simultaneously transferred with MLNC from T. spiralis donors. It is concluded that the suppressive effect of adult N. dubius upon the expression of mucosal mastocytosis acts upon the generation of lymphocytes capable of promoting the development of MMC from precursor cells.     

Studies on chronic versus transient intestinal nematode infections in mice I. A comparison of responses to excretory/secretory (ES) products of Nippostrongylus brasiliensis and Nematospiroides dubius worms

Summary Previous reports have demonstrated that after implantation of intestinal worms or after exposure to infective third stage larvae, the duration of infection with Nematospiroides dubius is markedly prolonged in intact mice relative to infection with Nippostrongylus brasiliensis. The rapid rejection of N. brasiliensis adults appears T-cell dependent in that adults persist for longer periods in hypothymic nude mice than in intact mice. Excretory/secretory (ES) products harvested from N. dubius or N. brasiliensis intestinal worms did not differ obviously in the following characteristics: rate of production and degree of complexity of proteins, in vitro mitogenicity, allergenicity, or in their abilities to induce or elicit delayed type hypersensitivity reactions in naive and infected mice, respectively. Two differences between N. brasiliensis- and N. dubius-infected mice were an IgG₁ hypergammaglobulinaemia and readily detected anti-ES precipitating antibodies in the circulation; both responses were confined to the chronic N. dubius infection. One difference between N. brasiliensis and N. dubius ES products was that the former, but not the latter, induced protection against homologous infection when injected with Freund's complete adjuvant. By contrast, intraperitoneal implantation of either type of adult worm induced protection against homologous infection at least in female Balb/c mice. After intestinal implantation of both N. dubius and N. brasiliensis intestinal worms, the rejection of N. brasiliensis was not influenced by, nor did it alter, persistence of N. dubius adults. In support of conclusions drawn by others, the differences in persistence of infection between these two nematodes probably reflect differences in the ability to resist both specific and nonspecific components of the complex intestinal rejection process. The chronicity of N. dubius infection and nonpersistence of N. brasiliensis     

Genetic control of immunity to Nematospiroides dubius: a 9-day anthelmintic abbreviated immunizing regime which separates weak and strong responder strains of mice

Experiments were designed to re-examine the variables which influence the ability of single primary infections to elicit acquired immunity to Nematospiroides dubius, in particular the importance of the presence or absence of adult worms, as these are known to exert immunomodulatory effects. Briefly, anthelmintic abbreviated infections were considerably more effective at eliciting acquired immunity than longer infections in which adult worms were allowed to reside in the intestine. A 9-day anthelmintic abbreviated infection was extremely effective at stimulation of acquired immunity in NIH mice and very few immunising infection larvae were required. Immunity to subsequent reinfection developed rapidly after the primary infection worms had been eliminated; by day 21 post-infection, the mice were almost totally immune. Abbreviated infections were used to examine the capacity of a number of mouse strains to develop immunity to reinfection. Strains of mice were chosen to allow the effects of MHC linked and non-MHC linked (background) genes to be identified. CBA and C3H strains (both H-2k) were found to be weak responders to N. dubius. B10G (H-2q) mice responded better than C57Bl/10 (H-2b), although these strains have identical background genes. DBA/2 mice were stronger responders compared to BALB/c mice, both strains sharing a common MHC haplotype (H-2d). (NIH X B10G) F1 mice (H-2q) were better responders than either of the parental strains. Several mouse strains all sharing the H-2q haplotype were particularly effective at developing immunity to N. dubius, as were also SJL mice which were the sole representatives of the H-2s haplotype, in the present study. The results established that the response phenotype is influenced by both background and MHC genes and demonstrated gene complementation in the capacity of mice to acquire immunity to N. dubius.     

Immune-mediated damage is not essential for the expulsion of Nippostrongylus brasiliensis adult worms from the small intestine of mice

Nippostrongylus brasiliensis adult worms are expelled from the rat small intestine during a primary infection by two steps. First, host immune responses cause damage to the worms, and then a nonspecific inflammatory response initiates expulsion. We have tested the two-step expulsion hypothesis in mice infected with N. brasiliensis. After a primary infection in C57BL/6 mice, adult worms started to lay eggs on day 5 postinfection (p.i.) and were expelled around day 9-10 p.i. According to the rat system, 5 day- and 8-day-old worms were assumed to be 'normal' and 'damaged', respectively. When 5 day- and 8 day-old worms obtained from C57BL/6 mice were transferred surgically into the small intestine of naive C57BL/6 mice, both 5 day- and 8 day-old worms were almost simultaneously expelled by day 6 postworm implantation (p.w.i.). In contrast, when 5 day- and 8 day-old worms of mouse origin were implanted into naive Wistar rats, 8 day-old worms were expelled by day 5 p.w.i., while 5 day-old worms were expelled by day 8 p.w.i. Similar results were obtained when BALB/c mice were used. Therefore, mice can expel N. brasiliensis adult worms as rapidly as rats expel 'damaged' worms, regardless of the status of the worms ('normal' or 'damaged'). Stat6-deficient mice were unable to expel implanted 5 day-old worms up to day 10 p.w.i., suggesting that cellular mechanisms depending on Stat6-signalling system are necessary for the expulsion. When N. brasiliensis adult worms obtained from Stat6-deficient mice 5 and 15 days after a primary infection were implanted into Wistar rats, the former established in the recipient rats for approximately 1 week and were then expelled by day 10 p.w.i., whereas the latter were expelled by day 4 p.w.i. These results suggest that immune-mediated damage of N. brasiliensis adult worms (first step) is not a prerequisite for expulsion from the small intestine of mice, although adult worms are actually damaged by Stat6-independent immune mechanisms.     

Nematospiroides dubius in the mouse: evidence that adult worms depress the expression of homologous immunity

Summary Mice immunized by a single infection with irradiated (25 krad) larvae of N. dubius were very resistant to subsequent challenge. However, when normal larvae were administered together with irradiated larvae at immunization, the acquired immunity expressed against a challenge infection was markedly depressed. It was found that as few as 50 normal N. dubius larvae interfered with the immunity that would have otherwise been elicited by the concurrently administered irradiated larvae, but this depressed response was totally alleviated when the normal worms were removed after completing their development in the intestinal mucosa and before they reached adulthood. Adult TV. dubius were transplanted directly into the intestines of mice either 7 days before or after immunization by irradiated larvae; it was shown that the recipient mice were less resistant to challenge than mice which had been sham operated. Transplanted adult worms themselves stimulated very little resistance to challenge in recipient mice. These results established that adult parasites are capable of depressing the expression of homologous immunity in the mouse. The possible mechanisms by which JV. dubius might modulate the host's immunological activity at the intestinal level are discussed and it is proposed that this mechanism is of benefit to the parasite in preventing the host from eliminating the worms during a chronic primary function.     

Survival to patency of low level infections with Trichuris muris in mice concurrently infected with Nematospiroides dubius

Large, single-pulse laboratory infections with Trichuris muris are rejected by mice before patency, but low-level infections of fewer than 20 worms survive for long periods. Data are presented to show that the threshold at which an effective immune response takes place is significantly higher in mice concurrently infected with Nematospiroides dubius. In control CFLP mice trickle infections did not survive to maturity but in the slower responder C57 Bl10 mice egg production began on Day 35 and continued for a further seven weeks, with some mature worms present at autopsy. Concurrent infection with N. dubius resulted in trickle infections, T. muris surviving much better than in control mice, although these still showed some resistance to T. muris. It is suggested that the results support the hypothesis that T. muris elicits concomitant immunity in the host. Thus, the first worms to establish survive to patency at which time they can no longer be removed by the host, but once the immunological threshold has been exceeded incoming larvae are rejected by the host. Such a survival strategy would be very useful to T. muris in the wild.     

Suppression of muscosal mastocytosis by infection with the intestinal nematode Nematospiroides dubius

Mice exposed to primary infections with the parasite intestinal nematode Nematospiroides dubius failed to show the mucosal mast cell (MMC) response which is characteristic of infections with other species of intestinal nematode and which was readily induced in these mice by infections with Nippostrongylus brasiliensis or Trichinella spiralis. The failure to generate a mucosal mastocytosis was independent of host strain or sex. When infections with N. dubius were established before, or concurrently with, T. spiralis or N. brasiliensis, the MMC response elicited by these species was delayed and/or depressed as was expulsion of the worms themselves. Infection with N. dubius given when a MMC response was already established, by exposure to T. spiralis, had no effect on MMC numbers. The possibility that the effects of N. dubius upon MMC responses reflect a lack of mastocytopoietic potential, rather than an active interference, was excluded by showing that SJL mice, which expel primary infections with N. dubius and express strong immunity to reinfection, developed marked mastocytosis during secondary infections. The depression of MMC responses by N. dubius is discussed in relation to the known immunosuppressive properties of this parasite and in relation to the T cell mediated control of MMC development.     

Impaired natural defence of beige (Chediak-Higashi syndrome) mice against tissue-migrating larvae of Strongyloides ratti and its reconstitution by bone marrow cells

The susceptibility of C57BL/6-bgJ/bgJ mice, which exhibit a murine counterpart of the Chediak-Higashi syndrome, to infection with Strongyloides ratti was examined. After a primary infection, the peak of the daily larval output in faeces (LPG) of bgJ/bgJ mice was approximately twice as high as that of their littermate bgJ/+mice. The total number of tissue migrating larvae recovered from bgJ/bgJ mice at 36 h after infection was also approximately twice as high as that from bgJ/+mice. However, after a primary infection, bgJ/bgJ mice could completely expel adult worms in the intestine by day 14. When an equal number of tissue migrating larvae obtained from the head of +/+ mice were implanted into bgJ/bgJ and bgJ/+mice, the magnitude and the kinetics of LPG were comparable between them, indicating that in both groups implanted larvae established in the intestine to become adult worms and then they were expelled by day 13. Thus, immune mechanisms involved in worm expulsion of bgJ/bgJ mice were comparable to those of bgJ/+mice. The higher susceptibility of bgJ/bgJ mice could be reduced to the level of bgJ/+mice by bone marrow grafting from bgJ/+mice 6 weeks prior to infection. Furthermore, when lethally irradiated bgJ/bgJ mice or bgJ/+mice were reconstituted with either type of bone marrow cells, the mice given bgJ/bgJ bone marrow cells showed higher susceptibility to infection with S. ratti regardless of the genotype of the recipients. These results indicate that the impaired natural defence of bgJ/bgJ mice is predetermined at the level of haemopoietic stem cells.     

妊娠对小鼠旋毛虫感染免疫应答的影响

目的 研究妊娠对小鼠旋毛虫感染免疫应答的影响。 方法 6只孕鼠分别经口感染300条旋毛虫肌幼虫,ELISA检测感染后不同时间血清抗体水平。感染后6周剖杀,消化全身肌肉计算每克肌肉虫荷（lpg）。测定孕鼠感染后1～4周血清介导的抗体依赖细胞介导的细胞毒性作用（ADCC）对成囊前期幼虫（PEL）的杀伤作用。观察孕鼠感染旋毛虫后第6、8和12天的肠道虫荷及雌虫体外生殖力指数。对6只处女鼠肌肉注射孕酮,观察其感染旋毛虫后6周的血清抗体水平与肌肉虫荷。 结果 孕鼠感染旋毛虫后2周的血清抗体水平（A492=0.113）显著高于未孕鼠（A492=0.078）（F=21.390,P＜0.05）。孕鼠感染后6周的每克肌肉虫荷（1 251±450）明显低于未孕鼠（2 310±1 123）（t=2.419,P＜0.05）。孕鼠感染后2周血清介导的ADCC导致成囊前期幼虫的死亡率（42.6%）显著高于未孕鼠（26.9%）（F=1.195,P＜0.05）。孕鼠感染后第6、8和12天的肠道虫荷与未孕鼠相比差异均无统计学意义（Z6=-1.185,Z8=-0.149,Z12=-0.0289,P＞0.05）,感染后第6和8天孕鼠与未孕鼠的雌虫生殖力指数间的差异亦无统计学意义（Z6=-0.149,Z8=-1.043,P＞0.05）。孕酮注射处女鼠感染旋毛虫后6周的血清抗体水平（A492=0.299）显著高于对照组（A492=0.191）（t=2.955,P＜0.05）,但其每克肌肉虫荷（1 457±551）与对照组（1 235±439）相比差异无统计学意义（t=0.726,P＞0.05）。 结论 妊娠在小鼠抗旋毛虫感染的免疫应答中具有协同作用,其机制可能与孕鼠感染旋毛虫后早期血清抗体水平升高及其介导的ADCC对成囊前期幼虫的杀伤作用增强等有关。     

The development of resistance in different inbred strains of mice to infection with Nematospiroides dubius

Infection by the intestinal nematode parasite Nematospiroides dubius was studied in seven different inbred mouse strains. Although there was some minor variation in the susceptibility of the different strains to a primary infection there were marked differences in their ability to develop resistance to infection following repeated exposure to infective larvae. The strains of mice which developed the best resistance also expelled adult worms arising from the previous infections. The adult worms resulting from a primary infection were slowly eliminated in two inbred strains studied whereas no loss occurred from outbred LACA mice. Although males and females of two strains, C3H/HeJ and CBA/H were equally susceptible to a primary infection, the females developed better resistance than the male mice following two oral administrations of third stage larvae. Infected mice of every strain and both sexes contained high levels of IgG1 in the serum.     

SjAWMAg免疫血清和吡喹酮联用体内杀不同发育期血吸虫的实验研究

目的　观察日本血吸虫成虫表膜抗原(SjAWMAg)免疫血清与吡喹酮合用对不同发育期血吸虫的杀虫效果,探讨体液免疫在吡喹酮杀虫中的作用。　方法　提取 SjAWMAg,并用 SDS PAGE 对其进行鉴定,制备高滴度(1∶25 600)SjAWMAg抗血清,采用Western blot分析该血清与肺期童虫、肝期童虫及成虫抗原的反应性;将 SjAWMAg抗血清与吡喹酮合用治疗血吸虫感染后第2 d、第14 d和第35 d的小鼠,在感染后第49 d剖杀小鼠收获虫体,计算减虫率和减卵率。结果　Western blot分析表明,SjAWMAg抗血清与肺期及肝期童虫抗原存在交叉反应; 联合用药的 3 个治疗组(感染2、14、35 d)与单用吡喹酮组比较杀虫作用均有显著提高,减虫率分别提高了 38.79%、29.80%和 46.82%,其中以感染35 d治疗组提高最显著;减卵率分别提高了 62.04%,42.78%和 29.81%,以感染 2 d治疗组更为显著。结论抗SjAWMAg多克隆抗体与吡喹酮联合使用,均可提高吡喹酮对不同发育期血吸虫的杀灭效果,揭示体液免疫在吡喹酮杀血吸虫过程中具有重要作用,同时提示这种联合用药可能解决单用吡喹酮治疗血吸虫早期感染效果不佳的难题。     

Reduced infectivity of Nematospiroides dubius larvae after incubation in vitro with neutrophils or eosinophils from infected mice and a lack of effect by neutrophils from normal mice

Summary Neutrophils and eosinophils, isolated from the blood of mice infected with Nematospiroides dubius , were tested for their capacity to damage exsheathed third stage N. dubius larvae in vitro. In the presence of fresh serum from infected mice, both types of granulocyte caused a significant reduction in larval infectivity (up to 40–50%) whereas lymphocytes/monocytes prepared from the same blood samples were inactive. Neutrophils were at least as active as eosinophils, on a cell for cell basis. None of the cells exhibited larvicidal activity in the absence of serum and serum alone had no effect. The reduction in larval infectivity caused by neutrophils in the presence of fresh normal mouse serum (NMS) was only marginally less than that obtained using immune mouse serum (IMS), suggesting that complement, which is activated by the larvae via the alternative pathway and mediates the adherence of both cell types, was able to promote the larvicidal effect of these cells in vitro. In contrast to neutrophils, eosinophils were considerably less effective in NMS than in IMS. Both NMS and IMS were ineffective if they had been heat-inactivated or incubated with methylamine at pH 8.0 to destroy complement activity. The immunoglobulin fraction of IMS was also ineffective in promoting neutrophil or eosinophil-mediated larval damage. These results indicate that in this in vitro system antibodies are incapable of directing the activity of either cell type in the absence of complement. A novel finding of this study was that neutrophils from uninfected mice were unable to reduce larval infectivity in the presence of fresh NMS or IMS. 'Altered' neutrophils possessing larvicidal activity appeared in the blood of mice within 4 days of infection with N. dubius.     

不同免疫途径对Sj童虫细胞型免疫原诱生的保护性效果及抗体应答差异

目的比较研究小鼠经不同途径接种日本血吸虫(Schistosoma japonicum,Sj)童虫原代细胞(primary juvenile worm cells,pJCs)后所诱导的免疫保护效果,寻找其合适的免疫途径。方法将pJCs经皮下或静脉注射途径免疫昆明小鼠,间隔2w共免疫3次,末次免疫后第4w,与对照组同时经腹部皮肤感染尾蚴30±2尾/鼠,比较三组小鼠的肝脏虫卵数及虫卵肉芽肿的大小、成虫数、虫体大小。同时在第2、3次免疫前及攻击感染前1d,小鼠尾静脉采血,用ELISA法检测抗pJCs-IgG水平。结果 pJCs免疫小鼠后,与PBS对照组比,静脉免疫组的减虫率为48.53%、肝卵减少率为54.54%、虫体平均重量减少率为29.62%(P0.01)、虫卵肉芽肿面积减少率为36.8%,而皮下免疫组分别为41.28%、43.19%、23.08%、31.2%。IgG抗体水平也是静脉注射组高(PBS组,P0.01;皮下注射组,P0.05)。结论日本血吸虫童虫细胞免疫原通过皮下和静脉注射均可诱导小鼠产生对日本血吸虫的免疫保护力,其中静脉注射诱导的免疫保护效应最强,提示通过静脉注射日本血吸虫童虫细胞是可行有效的免疫途径。     

香菇多糖抗小鼠急性弓形虫感染免疫机制的初步探讨

目的从香菇多糖对弓形虫感染小鼠Th1／Th2免疫应答建立的影响及二者平衡维持的角度探讨香菇多糖抗小鼠急性弓形虫感染的免疫机制。方法RH株弓形虫速殖子腹腔感染小鼠前及感染后进行香菇多糖处理,观察各组小鼠的存活率,同时用ELISA法动态检测小鼠脾细胞培养液中Th1／Th2免疫反应关键细胞因子IFN—γ／IL-4水平及血清中IgG2a／IgG1抗体的含量。结果与对照组相比香菇多糖可以明显提高两处理组小鼠的存活率,香菇多糖处理组（LTN组）第10d全部死亡,而香菇多糖预处理组（pre-6dLTN组）第13d存活率仍达18．4％;pe-6dLTN组及LTN组在感染后第3d建立Th1型免疫应答,IFN-7含量分别为186．28pg／ml及117．07pg／mi,与对照组相比差异有统计学意义（P〈0．01）;IgG2a含量为0．332（A-490）及0．320（A-490）,与对照组相比差异有统计学意义（P〈0．01）,且于第7d达峰值。同时Th2型免疫应答开始建立,IL-4含量分别为121．28pg／ml及94．47pg／ml,与对照组相比差异有统计学意义（P〈0．01）;IgG1含量分别为0．382（A-490）及0．354（A-490）,与对照组相比差异有统计学意义（P〈0．05）,随后维持较高水平。结论香菇多糖能辅助小鼠建立Th1／Th2免疫应答,且能适时转化并维持二者平衡,避免因任何一种免疫反应过度表达而导致的免疫病理反应,从而增强小鼠抵抗弓形虫感染的能力。     

Schistosoma mansoni: enhanced efficacy of Praziquantel treatment in immune mice

Naive CBA/Ca mice and CBA/Ca mice vaccinated 4 weeks previously with radiation-attenuated cercariae of Schistosoma mansoni were challenged with normal cercariae and then treated with 500 mg/kg body weight of Praziquantel (Pzq). The drug was administered intramuscularly or intradermally on day 1, but intramuscularly only on day 6. The results show clearly that in naive mice skin-stage larvae were susceptible to Pzq provided the drug was given intradermally on day 1. Lung worms were susceptible to Pzq given intramuscularly on day 6. Drug efficacy in naive mice is thus dependent upon treatment being given at the correct time and via the optimal route. The efficiency of Pzq treatment was enhanced in vaccinated mice, but was again affected by the treatment regime. Analysis of the data revealed a highly significant synergistic effect between drug treatment and vaccination when Pzq was given intramuscularly on day 6. Synergy was detectable but only marginally significant when the drug was administered intradermally on day 1, and could not be demonstrated when Pzq was given via the intramuscular route on day 1. These findings are discussed in the light of known sites and mechanisms of vaccine resistance in mice, as well as in relation to the mode of action of Pzq against schistosome parasites.     

Immunological consequences of intestinal helminth infections. Humoral responses to ovalbumin

Humoral responses to ovalbumin (OA) administered i.p. with Al(OH)3 were depressed in C57BL mice immunized 5-13 days after infection with N. dubius, but not N. brasiliensis or T. muris. These two parasites induced elevated IgM responses, possibly as a result of systemic contact with parasite larvae or debris since i.v. administered N. dubius also increased IgM titres to OA. Depression of anti-OA IgG titres by N. dubius was also observed in infected BALB/c and CBA mice given OA-Al(OH)3 (i.p.), but not in C57BL mice given OA-Al(OH)3 (s.c.), OA-FCA (i.p. or s.c.), or OA-B, pertussis (i.p.). These findings suggest that local effects of N. dubius within the peritoneum reduce the adjuvanticity of Al(OH)3, resulting in depressed responses to OA-Al(OH)3.     

Effective therapy of the LP-BM5 murine retrovirus-induced lymphoproliferative immunodeficiency disease with diethyldithiocarbamate.

The effects of therapy with the immunomodulator diethyldithiocarbamate (DTC) on the manifestation and natural history of LP-BM5 murine retrovirus infection in adult C57 Black 6 mice was investigated. DTC itself, had limited effects on the spleen weight, serum IgM, or mitogen responses of the non-virus-infected control mice when evaluated over a 9-week period. The virus inoculum administered was such that there was approximately a twofold increase in serum IgM and a halving of phytohemagglutinin (PHA) and lipopolysaccharide (LPS) responses in about two weeks and death of all animals by about 26 weeks postinfection. Doses of DTC of 20 and 200 mg/kg weekly or 5 days per week (intraperitoneally) in mice with LP-BM5 infection did not alter the manifestations or course of the disease. Doses of 400 or 600 mg/kg given 5 days per week, starting either 2 weeks before or the day of virus inoculation significantly reduced hypergammaglobulinemia, spleen weight, lymphadenopathy, and also prolonged survival. A dose of 400 mg/kg started 2 weeks after virus inoculation resulted in partial prevention of hypergammaglobulinemia, splenomegaly, and lymphadenopathy as well as 100% survival compared with 12.5% in non-drug-treated controls at 23 weeks after virus inoculation. The 9 surviving animals in the treated group were then allocated to continue treatment or stop treatment. In the animals without further treatment, lymphadenopathy and mortality occurred starting within 6 weeks after cessation of therapy while the animals with continued treatment remained in good condition for 40 weeks. There was only a very limited and transient effect of DTC therapy on the decline of the proliferative responses to phytohemagglutinin or lipopolysaccharide in any of the treated groups in the above described experiments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibody-dependent neutrophil-mediated parasite killing in non-lethal rodent malaria

The effects of administrating recombinant human granulocyte colony-stimulating factor (rhG-CSF) and passively transferring immune serum on infection with an attenuated variant of Plasmodium berghei XAT (Pb XAT), in severe combined immunodeficiency (SCID) mice were examined. In immune competent (C.B-17) mice, the attenuated parasite infection was inevitably self-resolving and degenerating forms inside erythrocytes appeared, coinciding with the drop in parasitaemia, whereas SCID mice were unable to control parasite growth and all the mice died. Continuous administration with rhG-CSF caused neutrophilic granulocytosis in both SCID and C.B-17 mice. The effect of rhG-CSF on the infection in C.B-17 mice was to suppress the course of the parasitaemia at an early phase whereas it had no effect in SCID mice. When immune serum was transferred on the day of infection, the prepatent period was prolonged two days in both SCID and C.B-17 mice. When administration with rhG-CSF was combined with transfer of immune serum, SCID mice showed four days delay in patency and degenerating parasites were seen during the course of parasitaemia, although the infection was ultimately fatal. C.B-17 mice similarly treated showed a seven day delay in the onset of the patent parasitaemia which was of a lesser magnitude and shorter in duration compared with control mice. On the other hand, when C.B-17 mice were splenectomized three weeks before infection and then treated with rhG-CSF and immune serum, no degenerating parasites were seen during the infection and all mice died with high parasitaemias. These results show that antibody-dependent neutrophil-mediated parasite killing may occur in the spleen of mice infected with P. berghei XAT.     

日本血吸虫组织蛋白酶B核酸疫菌血清抗体与抗生殖免疫关系的初步研究

目的 探讨日本血吸虫组织蛋白酶B DNA疫苗（Sj31B1N）抗生殖免疫的可能机理。方法 用Sj31B1N免疫小鼠,每2周1次,每次免疫前均尾静脉采血1次,作血清抗体动态变化分析,免疫4次后尾蚴攻击感染,感染后45天,计数成虫负荷和肝、肠组织内虫卵数。结果 用Sj312B1N免疫小鼠后第2周部分小鼠血清中出现了抗体,随时间延长,出现抗体阳性组小鼠数量增多,抗体滴度增加。抗体阳性组小鼠与阴性组小鼠对比,成虫减少率40.6%,肝组织减卵率为48.0%,肠组织减卵率为45.4%。结论 核酸疫苗Sj31B1N可有效地诱导小鼠产生抗体,并且具有免疫保护作用。核酸疫苗Sj31B1N所诱导的体液免疫可能是抗日本血吸虫生殖免疫的机理之一。