Studies on malaria immunology

用两种啮齿动物疟原虫（一种是强毒的伯氏疟原虫，另一种是减毒的突变疟原虫）在小鼠中研究了对疟疾的免疫力。毒力强的伯氏单胞菌对小鼠的感染是致命的。抗cd8 ^+或抗ifn - γ治疗延迟了感染小鼠的死亡率，尽管它不影响寄生虫的生长。在感染后期，肝脏中T细胞，特别是CD8^+ T细胞数量增加，而脾脏中CD8^+ T细胞数量减少。从肝脏分离的CD8 + T细胞等单核细胞在培养中释放ifn - γ和tnf - α。这些结果提示这些免疫反应产生的细胞因子可能与疟疾的发病机制有关。伯氏杆菌的减毒突变体在小鼠中引起了溶解性感染。在感染寄生虫的小鼠中，CD4^+ T细胞在保护性免疫中起着至关重要的作用。CD4^+ T细胞产生的inf - γ是保护…更多免疫的关键分子。注射人重组G-CSF的小鼠血液中中性粒细胞计数增加。G-CSF对减毒的伯氏杆菌感染有抑制作用，但抗inf γ干扰了这种作用。结果提示中性粒细胞可能是效应细胞之一，inf - γ可能参与了保护作用。抗inf - γ治疗可抑制感染小鼠抗疟原虫IgG2a的产生。从免疫血清中被动转移IgG2a片段能够转移保护。结果表明，保护性IgG2a抗体的产生可能依赖于inf - γ。综上所述，受疟疾抗原刺激的T细胞在保护和发病过程中发挥着重要的作用，这取决于它们的亚群；CD8^+ T细胞在发病机制和CD4^+ T细胞在保护性免疫。这些明显矛盾的反应可能是由相同的细胞因子介导的，inf - γ。少

Immunity to malaria was investigated in mice using two strains of rodent plasmodia, one was virulent Plasmodium berghei and another one was an attenuated mutant strain.The infection of mice with virulent P. berghei was always lethal. The treatment with anti-CD8^+ or anti-IFN-gamma delayed the mortality of the infected mice, although it did not affect the parasite growth. In the late stage of the infection, T cells, especially CD8^+ T cells, were increased in number in the liver at the expense of splenic CD8^+ T cells. The mononuclear cells including CD8^+ T cells isolated from the liver released IFN-gamma and TNF-alpha in culture. These results suggest that these cytokines produced by the immune response may be responsible for pathogenesis of malaria.An attenuated mutant of P. berghei caused a resolving infection in mice. In mice infected with the parasites, CD4^+ T cells had a crucial role in protective immunity. INF-gamma produced from CD4^+ T cells was the key molecule in protective … More immunity. Mice injected with human recombinant G-CSF showed increased neutrophil count in the blood. Effect of the treatment with G-CSF on the attenuated P. berghei infection was suppressive, but anti-INF-gamma interfered with the effect. The results suggest neutrophils may be one of effector cells and INF-gamma may be involved in protection. Development of anti-plasmodial IgG2a in infected mice was suppressed by the treatment with anti-INF-gamma. Passive transfer of an IgG2a fraction from immune serum was capable of transferring protection. The results indicate that production of protective IgG2a antibodies may be dependent on INF-gamma.In conclusion, T cells stimulated with malaria antigen play important rolesIn conclusion, T cells stimulated with malaria antigen play important roles both in protection and pathogenesis depending upon their subsets; CD8^+ T cells in pathogenesis and CD4^+ T cells in protective immunity. These apparently contradictory responses may be mediated by the same cytokine, INF-gamma. Less