Protective immunity to malaria: studies with cloned lines of Plasmodium chabaudi and P. berghei in CBA/Ca mice. I. The effectiveness and inter-and intra-species specificity of immunity induced by infection

CBA/Ca mice were immunized by infection with cloned lines of Plasmodium berghei (isolates ANKA, KSP-11). Plasmodium chabaudi chabaudi (AS, CB) or Plasmodium chabaudi adami (DS) and then challenged with either homologous or heterologous parasites. Protective responses were assessed in immune mice relative to the controls by their ability to (i) extend the time taken for the mean parasitaemia to reach a predetermined level (1% or 0.1%) (ii) reduce peak parasitaemia (iii) resolve the parasitaemia sooner and/or (iv) control or eliminate recrudescences. At both the inter- and intra-species level, immunity appeared largely specific for the cloned line inducing it. At the interspecies level marginally effective cross-immunity was sometimes evident, thus P. berghei KSP-11 immune mice displayed some immunity against P.c. chabaudi AS, although immunity to this parasite was relatively ineffective against P. berghei ANKA or KSP-11. Cross-immunity was more apparent between the subspecies P.c. adami and P.c. chabaudi and between cloned lines of the latter parasite derived from the AS and CB isolates. These data reflect considerable inter- and intra-species structural and immunogenic differences in certain antigens of parasitized erythrocytes and merozoites, which have been identified in a number of murine malarias and associated with protective immunity. Similar differences recently identified in the equivalent antigens of the human parasite P. falciparum may therefore have important implications for protective immunity in man.     

Site potential for challenge attrition in mice, rats and guinea pigs vaccinated with irradiated cercariae of Schistosoma mansoni

The potential sites of attrition of a challenge population of schistosomes have been investigated in mice, rats and guinea pigs vaccinated with irradiated cercariae of Schistosoma mansoni, by the use of challenge regimens that permit sequential site elimination. Vaccinated mice showed significant immunity to a percutaneous cercarial challenge, but were only marginally resistant to an i.v. challenge with healthy lung stage worms. Vaccinated rats and guinea pigs differed from mice, in that they were able to mediate significant challenge attrition at post-skin sites. Healthy lung worms were subject to immune elimination by rats in the lungs, or perhaps en route to the liver, but not in the liver itself. In contrast, guinea pigs had the capacity to kill challenge lung worms injected into either the lungs or the liver. Interestingly, lung worms harvested by extended incubation were shown to be sub-optimal in terms of viability, since they were eliminated in significant numbers when injected i.v. into vaccinated mice. These data show that different hosts vaccinated in essentially the same manner differ in terms of their site potential for challenge attrition. It is emphasised however, that sites implicated by these experiments as having the capacity to mediate immune elimination are not necessarily the sites at which challenge attrition occurs under normal circumstances.     

The genetic control of host responses to Dipetalonema viteae (Filarioidea) infections in mice

Dipetalonema viteae (Filarioidea) infections were established in inbred strains of mice by the s.c. implantation of adult female worms and the resulting microfilaraemia and adult worm survival monitored. BALB/c mice were the most susceptible strain examined, showing a high level microfilaraemia of approximately 6 month's duration. C57Bl/10, CBA/Ca and C3H/He mice were all equally resistant to infection, showing a low level of microfilaraemia of approximately 1 month's duration. The response of NIH mice was intermediate. Relatively little strain difference was seen in adult worm survival although worms lived slightly longer in C57Bl/10 mice than in BALB/c mice. The adult females became depleted of microfilariae over a period of approximately 1 month before becoming encapsulated in host tissue. Challenge infections given to mice previously implanted with worms resulted in lower level, shorter lasting microfilaraemias than those seen in the initial primary infections. All strains showed immunity when challenged. High responsiveness (resistance) was inherited as a dominant trait in F1 hybrids produced by crossing high and low responder strains. Genes linked with the major histocompatibility complex (H-2) were found to have no effect on the response phenotype as demonstrated by the similar responses of H-2 congenic mice on the BALB/c or C57bl/10 backgrounds. The response phenotype of radiation chimaeras was determined by the phenotype of the donor from which bone marrow (BM) cells were taken for reconstitution. Susceptible BALB/c mice reconstituted with resistant B10D2/n BM behaved identically to the donor strain, indicating that the genetic variation which exists between mouse strains in their responses to D. viteae is expressed through a population of BM derived cells and is not simply a consequence of host structure or physiology.     

早期梅毒皮损组织CD3、CD20和CD68的表达

为探讨一，二期梅毒皮损组织细胞免疫应答过程及机制，采用免疫组织化学及计算机图像分析的探讨，对一，二期梅毒病损组织中的CD3，CD20，CD68表达进行定性定量分析研究。结果显示，43例一，二期梅毒标本中CD3，CD20，CD68表达均阳性，表达水平病期发展，皮肤损害加重而逐渐升高。CD68表达水平高于CD3，CD20，尤其在血管周围表达明显增高，CD20表达较低。研究表明，T细胞，B细胞，特别是巨噬细胞在清除早期梅毒组织内感染的梅毒螺旋体过程中起着重要的细胞免疫调节作用，但作用不完全。     

Toll‐Like Receptor 3 and 7/8 Function Is Impaired in Hepatitis C Rapid Fibrosis Progression Post‐Liver Transplantation

Recurrence of hepatitis C (HCV) postliver transplant is universal, with a subgroup developing rapid hepatic fibrosis. Toll‐like receptors (TLRs) are critical to innate antiviral responses and HCV alters TLR function to evade immune clearance. Whether TLRs play a role in rapid HCV recurrence posttransplant is unknown. We stimulated peripheral blood mononuclear cells (PBMCs) from 70 patients with HCV postliver transplant with TLR subclass‐specific ligands and measured cytokine production, TLR expression and NK cell function. Rate of fibrosis progression was calculated using posttransplant liver biopsies graded by Metavir scoring (F0–4; R = fibrosis stage/year posttransplant; rapid fibrosis defined as >0.4 units/year). Thirty of 70 (43%) patients had rapid fibrosis progression. PBMCs from HCV rapid‐fibrosers produced less IFNα with TLR7/8 stimulation (p = 0.039), less IL‐6 at baseline (p = 0.027) and with TLR3 stimulation (p = 0.008) and had lower TLR3‐mediated monocyte IL‐6 production (p = 0.028) compared with HCV slow fibrosers. TLR7/8‐mediated NKCD56 dim cell secretion of IFNγ was impaired in HCV rapid fibrosis (p = 0.006) independently of IFNα secretion and TLR7/8 expression, while cytotoxicity remained preserved. Impaired TLR3 and TLR7/8‐mediated cytokine responses may contribute to aggressive HCV recurrence postliver transplantation through impaired immune control of HCV and subsequent activation of fibrogenesis.     

Caspase家族与固有免疫关系研究进展

Caspases是一组存在于胞质溶胶中的结构上相关的半胱氨酸蛋白酶,它们的一个重要共同点是活性位点都含有半胱氨酸,并可特异性地断开天冬氨酸残基后的肽键。根据其功能特点,该家族主要分为炎性Caspases和凋亡Caspases。炎性Caspases包括Caspase-1、Caspase-4/5/11和Caspase-12,在固有免疫防御过程中发挥重要作用。凋亡相关的Caspase-2/3/6/7/8/9/10主要调控免疫沉默的细胞凋亡过程,但近年来研究发现,Caspase-8也可通过多种途径介导细胞和机体的免疫反应。越来越多研究表明,Caspases在多种免疫相关疾病的发生发展进程中充当重要角色,因此本文主要对Caspases家族中与固有免疫相关的Caspase-1/4/5/11/8/12的活性调控及免疫介导机制进行综述,以期阐释Caspases与固有免疫的关系,同时为多种疾病的治疗提供一定的科学依据和理论参考。     

Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

原发性小肝癌微波消融治疗前后外周血播散癌细胞及免疫功能变化

目的研究微波消融治疗原发性小肝癌（≤5cm）对外周血播散癌细胞及细胞免疫功能影响。方法微波消融治疗19例小肝癌病人，手术切除治疗21例。于术前、术后30min、1d及7d采外周静脉血，巢式RT—PCR检测AFP mRNA，监测CD3、CD4、CD8及CD4／CD8。结果巢式RT—PCR检测外周血AFP mRNA，两组40例病人术前阳性率为40％（16／40）；微波组和手术组均有3例病人治疗前AFP mRNA阴性，术后30min转为阳性，两组之间比较无差异；微波组术后7d内外周血细胞免疫功能无明显变化，手术组降低。随访1～16个月，4例肝内复发或远处转移病人治疗前后AFP mRNA均阳性。结论与手术切除相比，微波消融治疗原发性小肝癌也可同样程度地造成癌细胞脱落人血，对外周血细胞免疫功能（7d内）无明显影响，有其自身特点；治疗前后外周血AFP mRNA均呈阳性表达（7d内）者，复发／转移的可能性增大。     

PI control based on parameter space approach supported metaheuristic optimization algorithms and ANFIS in a natural gas combined cycle power plant

In this article, proportional-integral (PI) control to ensure stable operation of a steam turbine in a natural gas combined cycle power plant is investigated, since active power control is very important due to the constantly changing power flow differences between supply and demand in power systems. For this purpose, an approach combining stability and optimization in PI control of a steam turbine in a natural gas combined cycle power plant is proposed. First, the regions of the PI controller, which will stabilize this power plant system in closed loop, are obtained by parameter space approach method. In the next step of this article, it is aimed to find the best parameter values of the PI controller, which stabilizes the system in the parameter space, with artificial intelligence-based control and metaheuristic optimization. Through parameter space approach, the proposed optimization algorithms limit the search space to a stable region. The controller parameters are examined with Particle Swarm Optimization based PI, artificial bee colony based PI, genetic algorithm based PI, gray wolf optimization based PI, equilibrium optimization based PI, atom search optimization based PI, coronavirus herd immunity optimization based PI, and adaptive neuro-fuzzy inference system based PI (ANFIS-PI) algorithms. The optimized PI controller parameters are applied to the system model, and the transient responses performances of the system output signals are compared. Comparison results of all these methods based on parameter space approach that guarantee stability for this power plant system are presented. According to the results, ANFIS- PI controller is better than other methods.     

Innate Immunity and Organ Transplantation: The Potential Role of Toll-like Receptors

Traditionally, the recognition and tolerance of transplanted grafts has been considered to be within the realm of the adaptive immune system. Innate immunity, on the other hand, as the first line of host defense, plays a role in fighting against invading microorganisms. Recently, with the discovery of the Toll-like receptors (TLRs), the role of innate immune responses in the control of adaptive immunity has become a new area of interest. Emerging evidence suggests that in addition to responding to pathogen-associated molecular patterns of microorganisms, TLRs can be activated by endogenous ligands, expressed by mammalian cells. These 'danger signals' may participate in ischemia-reperfusion related organ damage and subsequently influence function and survival of transplanted grafts. Furthermore, it has been suggested that adaptive immune responses can enhance the acute inflammatory responses controlled by innate immunity in organ transplantation. This review addresses the potential involvement of TLRs in different stages of organ transplantation. Intriguing and controversial findings are presented and discussed in order to stimulate more attention to this emerging and potentially important area of research in organ transplantation.