Modulation of cytokine production and response phenotypes in murine trichuriasis

BALB/K mice are usually resistant to infection with the intestinal nematode parasite Trichuris muris and exhibit a Th2 dominated (IL-5, IL-9) response. Conversely in B10.BR mice, which are unable to expel T. muris, Th1 type (IFN-gamma producing) cells predominate. We have manipulated the course of infection in these two strains of mice such that the period of host-parasite contact is extended in the former and curtailed in the latter. Extension of host-parasite contact in BALB/K mice beyond normal (day 21) resulted in the modulation of cytokines produced by in vitro concanavalin A (Con-A) stimulated MLNC away from IL-5 and IL-9 (Th2-type cytokines) in favour of the Th1-type cytokine IFN-gamma. Curtailment of host parasite contact in B10.BR mice to less than 21 days resulted in elevated production of IL-5 and IL-9 by MLNC in the absence of elevated IFN-gamma levels. Thus modulation of expulsion phenotype also modulates cytokine production by T-cells in the MLN draining the site of infection, with a Th2 response being associated with resistance and a Th1 type response with the inability to expel the parasite. Mechanisms by which the modulated cytokine profiles arise are discussed.     

Murine schistosomiasis mansoni: coordinate cytokine regulation and differences in cellular immune responses of granuloma cells and splenocytes to endogenous and exogenous schistosome egg antigens

To better understand the cellular immune mechanisms that regulate granulomatous inflammation to Schistosoma mansoni ova, we examined the dynamics of lymphocyte proliferation and cytokine expression by granuloma cells and splenocytes to endogenous and exogenous schistosome egg antigen (SEA) 6-19 weeks postinfection. Compared to splenocytes, granuloma cells (partially CD4+ cells) which are at the site of antigen release were highly activated by endogenous SEA and terminally differentiated as indicated by the more than 10-fold greater frequency of ex vivo interleukin (IL)-4, IL-5 and interferon (IFN)-gamma -secreting cells, greater levels of constitutive cytokine production and failure to proliferate to either endogenous or exogenous SEA. Endogenous cytokine production by granuloma cells was coordinately regulated, enhanced little by exogenous SEA, and temporally correlated with granulomatous inflammation. By contrast, CD4+ splenocytes produced comparatively little cytokine release by endogenous antigen, whereas exogenous SEA strongly induced IL-4, IL-5, IL-10 and IFN-gamma production and lymphocyte proliferation that correlated poorly with the dynamics of granulomatous inflammation. These results show that cytokine responses to endogenous SEA correlated better with granulomatous inflammation than responses to exogenous SEA. Furthermore, granuloma cells and splenocytes demonstrated strikingly different proliferative responses and dynamics of cytokine expression, suggesting that how SEA reactive lymphocytes traffic between lymphoid tissues and the granuloma is critical to a better understanding of the mechanisms of granulomatous inflammation and its modulation.     

Humoral immune responses in human infection with the whipworm Trichuris trichiura

The humoral immune response to infection with Trichuris trichirua was investigated by ELISA and immunoblotting using human sera from the Caribbean island of St Lucia. Immunoblot analysis of the degree of cross-reactivity with the related trichuroid Trichinella spiralis and with the other commonly co-existent nematodes, Ascaris lumbricoides and Toxocara canis, was carried out using selected sera. The IgM, IgA, IgE, and IgG subclass antibody levels were measured in ELISA using a detergent solubilized extract of adult T. trichiura. The IgG and IgE responses were highly Trichuris specific. Anti-T. trichiura IgM responses were totally cross-reactive with A. lumbricoides and were completely ablated by pre-incubation of sera with Ascaris antigen. The IgG response was predominantly of the IgG1 subclass with a minimal IgG3 response. Only 1 person out of 130 tested had a detectable IgG3 response. The IgG2 response appeared to be directed primarily against carbohydrate or polysaccharide antigens as pre-treatment of the ELISA plates with poly-L-lysine was necessary before a response could be detected. These data are the first demonstration of human isotypic responses to infection with T. trichiura.     

Cellular immune responses of a Senegalese community recently exposed to Schistosoma mansoni: correlations of infection level with age and inflammatory cytokine production by soluble egg antigen-specific cells

A recently reported epidemic of Schistosoma mansoni infection in Senegal provided an opportunity to study the dynamics of the development of immunity to human schistosomiasis. We report here on the cell-mediated immune response in a population of 99 females and 95 males, with particular emphasis on the relationship between intensity of infection and age. We found that the intensity of infection correlated negatively with age in females but not in males. In men and women, both Th1- and Th2-type cytokines were detected upon in vitro stimulation of PBMCs with soluble egg antigen (SEA) or soluble adult worm antigens (SWAP). In the female group, SEA-induced PBMC proliferation was associated with the production of IFN-gamma, IL-2 and IL-5, all of which correlated negatively with intensity of infection. Most cytokine production correlated positively with age. Spontaneous production of TNF-alpha, IL-6 and IL-10 was higher in the infected population than in an uninfected control group. Our results suggest that immunity to infection could be more pronounced in the female population and associated with a Th0/1 + 2 pattern of cytokine secretion mediated by soluble egg antigen (SEA).     

Age-dependency of infection status and serum antibody levels in human whipworm (Trichuris trichiura) infection

This study examines the age-dependency of the relationships between human infection with whipworm (Trichuris trichiura) and parasite-specific antibody level measured by ELISA against an extract of adult worms after preincubation of the sera with Ascaris lumbricoides adult worm extract. The convex age-profile of parasite infection intensity is shown to be mirrored by an age-dependent change in age-class mean levels of IgG (all subclasses except IgG3), IgA, IgM and IgE. Mean antibody levels rise with increasing acquisition of infection in childhood and decline as the intensity of infection falls in adulthood. Immunoblot analysis of selected sera from different age-classes indicates that antigen recognition is similarly dependent on infection intensity. In individual children, antibody levels correlate positively with acquisition of infection, consistent with a simple model of antigen dosage specifying the magnitude of the humoral immune response. In adults, IgG4 correlates positively and IgA negatively with intensity of infection, suggesting involvement of these isotypes in functional roles of immune blockade or effector mechanisms, respectively.     

Reversal in microfilarial density and T cell responses in human lymphatic filariasis

This study reports reversals in microfilarial density and the accompanying changes in cellular immune responses to filarial antigens of 39 individuals (11 microfilaria-positives, 22 microfilaria-negatives and six converters) living in an area endemic for brugian filariasis. Microfilarial counts decreased from April, the end of the rainy season to July, middle of the dry season (g.m. 88 mf/ml and 38 mf/ml, respectively; P = 0.001) and subsequently increased in November, the beginning of the rainy season (P = 0.088). Whereas the proliferative responses remained low throughout the study period in microfilaraemic individuals, in amicrofilaraemics these responses changed in the opposite direction to that of microfilarial densities. In three converters, proliferation changed in the opposite direction to the presence or absence of microfilariae. Cytokine analysis in the converters revealed that interferon-gamma was most affected by the shifts in microfilarial densities. In contrast, interleukin-4 responses showed little correlation with changes in parasite densities.     

Cellular immune responses to recombinant Plasmodium vivax tryptophan-rich antigen (PvTRAg) among individuals exposed to vivax malaria

Plasmodium vivax , the most widespread species of human malaria parasite responsible for 70–80 million cases each year requires a vaccine. In recent years, many potential vaccine candidate antigens have been identified from P. vivax including PvTRAg. We describe here cellular immune response to recombinant PvTRAg expressed in Escherichia coli . The in vitro stimulation of PBMCs derived from P. vivax -exposed individuals ( n  = 16) showed strong proliferative response (SI > 2·2) to PvTRAg as compared to PBMCs from normal healthy controls ( n  = 8). Although both Th1 (IFN-γ, TNF-α and IL-12) and Th2 (IL-4 and IL-10) cytokines were secreted by the PBMCs of the P. vivax -exposed individuals in response to PvTRAg, the overall response was more inclined towards Th2. In conclusion, recombinant PvTRAg was found to elicit strong cellular immune response among the P. vivax -exposed individuals.     

Different Th1/Th2 responses to Anisakis simplex are related to distinct clinical manifestations in sensitized patients

Anisakis simplex is a fish parasite capable of inducing inflammatory and allergic reactions in humans who eat raw or undercooked fish. The aim of this study was to characterize the T helper type 1 (Th1)/Th2 immune response to parasite crude (CE) and thermostable (TsE) extracts in A. simplex-sensitized patients. Cytokines were quantified by a multiplex flow cytometric method in short-term whole blood cultures. Higher concentrations of IL-2, IL-4 and IL-5, measured with the CE and TsE, were found in patients than in controls. Patients showing urticaria-angio-oedema or anaphylaxis (UA/A) had higher total and specific IgE levels than those with gastrointestinal symptoms (GI). The UA/A group showed high levels of IL-5 and IL-4 and low expression of IFN-γ than the GI group. The GI group had significantly higher IFN-γ/IL4 ratio than the UA/A group. Four patients with severe GI symptoms reporting a delayed skin test reaction had very low values of specific IgE to A. simplex and higher IFN-γ/IL4 ratios than that observed in other patients belonging to the GI group. This short-term whole blood test can be useful for immune response characterization in Anisakis infection and showed that heated parasite antigens are still capable of inducing cellular immune response in sensitized patients.     

Cytomegalovirus-specific humoral and cellular immune responses in human pregnancy

Cytomegalovirus (CMV)-specific humoral and cellular immunity was evaluated prospectively during and after 19 normal human pregnancies. Seropositive pregnant subjects had lymphocyte proliferative responses to purified CMV antigen that were markedly depressed by the end of the third trimester of pregnancy despite persistent levels of complement-fixing and immunofluorescent antibodies to CMV. These reduced lymphocyte proliferative responses returned to levels detected early in pregnancy by one year after delivery. None of the subjects excreted CMV during the study period. General parameters of cellular immunity, including thymus derived-cell counts as determined by formation of erythrocyte rosettes and mitogen-induced lymphocyte proliferation, were unaffected. Reactivation of latent CMV during pregnancy might be related to transient depression of CMV-specific cellular immunity.     

Genetic variation in the humoral immune responses of mice to the nematode Trichuris muris

Genetically based differences in the antibody responses to the large intestinal nematode Trichuris muris were studied in two groups of H-2 congenic strains of mice that differed in their relative resistance to infection with this parasite. The primary antibody response to parasite excretory/secretory (E/S) antigen was predominantly an IgG response with the strains forming two distinct groups, defined by their genetic background. The more susceptible B10 genetic background mice had strikingly higher antibody levels than mice of the BALB genetic background. Superimposed upon these background effects were clearly defined influences attributable to H-2-linked genes, strains which differed genetically only at H-2 loci exhibiting differences in the kinetics of the antibody response. Only B10.G and B10.BR mice showed any great increase in IgM levels post-infection. No IgA specific to E/S antigen was detected in the peripheral circulation of any strain at any time post-infection. Antibody responses to a 40-43 kD antigen revealed clear H-2-linked gene effects, with mice sharing the H-2k haplotype (B10.BR, BALB/K) exhibiting considerably higher total antibody levels than strains expressing other haplotypes; mice of the H-2d haplotype (BALB/c, B10.D2/n) responded very weakly to this antigen. A Western blot analysis of antigen recognition by antibody revealed similarities between the mouse strains in their total antibody responses to T. muris E/S antigen. However, immunoprecipitation studies showed that in general the more susceptible B10 congenic strains had wider spectra of antigen recognition than the BALB congenics. Strains sharing the same H-2 haplotype had dissimilar antigen recognition profiles, but strains sharing the H-2b haplotype (B10, BALB/B) recognized a low mol. wt antigen (20-23 kD) not recognized by any other strain, suggesting an exclusively H-2b restriction in the recognition of this antigen. These results support the conclusion that both H-2-linked and background genes play important roles in controlling the humoral immune response to T. muris infection.     

Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia

BACKGROUND/AIMS: Most patients infected with hepatitis C virus (HCV) develop chronic infection and persistent viraemia. The immune mechanisms responsible for resolution of viraemia remain poorly understood. HCV specific humoral and cellular immune responses in patients with and without viraemia were investigated. METHODS: In vitro T helper (TH) lymphocyte responses to structural and non-structural HCV proteins were determined by means of proliferative response and cytokine production in 35 anti-HCV positive/HCV RNA negative patients and in 31 patients with chronic HCV infection and persistent viraemia. Humoral responses were determined by measuring HCV specific antibody quantity and specificity. RESULTS: A TH response to two or more HCV proteins was present in 18 of 35 patients with serological viral clearance compared with just one of 31 viraemic patients (p = 0.00001). HCV specific interferon-gamma production was increased only in the former group. In contrast, the antibody levels were significantly lower and directed at fewer HCV antigens in patients with undetectable HCV RNA. CONCLUSIONS: Patients without viraemia after HCV infection frequently have strong TH lymphocyte responses of the TH1 type to multiple HCV antigens many years after the onset of infection, whereas antibody responses are less marked. These results suggest that control of HCV replication may depend on effective TH lymphocyte activation.     

Age-dependency of serum isotype responses and antigen recognition in human whipworm (Trichuris trichiura) infection

The present study examines the age-dependency of parasite-specific isotype responses and antigen recognition profiles of individuals within a Trichuris trichiura endemic community, in order to evaluate the significance of serum antibodies as determinants of observed age-related patterns of infection intensity. A high degree of individual heterogeneity is observed in isotype responses to separated T. trichiura antigens by Western blot. Recognition by IgG₁ antibodies exhibits marked age-dependency. The age-profiles of IgG₁ responses to selected antigens of 16–17 kDa and 90 kDa molecular weight reflect the age-related changes in current infection intensity at the population level. Similarly, mean age patterns of IgG₂ responses to a 90 kDa antigen, and mean IgG₄ responses to a 16–17 kDa antigen reflect mean infection levels. IgG₃ responses are negligible, and for methodological reasons, both IgE and IgM specificities are not presented. IgA responses to separated antigens of 16–17 kDa and 90 kDa, exhibit age-profiles which may suggest the development of an IgA-mediated acquired resistance to T. trichiura with age. IgA levels remain elevated throughout early adulthood, when infection intensity levels markedly decrease, supporting the hypothesis that IgA antibodies may be significant in generating the convex nature of the age-infection profile of T. trichiura.     

成人急性HBV感染后免疫指标的变化及不同转归的比较

目的 观察成人急性HBV感染后免疫指标的变化并进行不同转归比较。方法 选择29例急性乙肝患者和20例正常对照者，采用双抗体酶联分析法检测外周血细胞因子IL-2、IFN-γ、IL-4、IL-10和IL-12的水平；通过流式细胞仪观察外周血T淋巴细胞亚群变化；采用抗人T淋巴细胞单克隆抗体间接免疫荧光法观察外周血T淋巴细胞膜IFN-γ和IL-4的表达。结果29例HBeAg全部转阴，8例HBsAg未转阴。在HBsAg转阴组，病程早期和中期血清IL-2、IFN-γ、IL4及IL-12水平增高与正常组比P〈0．05，中期IL-4下降与早期比P〈0．05，晚期IL-2、IFN-γ、IL-4及IL-12下降与中期比P〈0．05；未转阴组各期IL-4水平增高与正常组比P〈0．05。转阴组早期Th1／Th2降低与对照组比P〈0．05，未转阴组各期，Th1／Th2降低与对照组比P〈0．05。未转阴组中5例入院时HBV-DNA〈10^3且IFN-γ水平明显低。两组CD4^＋／CD8^＋变化趋势不同。转阴组早期和中期IL-4膜表达高于正常对照组，中期IL-4表达低于早期，晚期IL-4表达低于中期，P值均〈0．05。未转阴组各期IL-4表达高于正常对照组，P〈0．05，各期之间IL-4表达无统计学差异。结论 IFN-γ升高与疾病恢复相关。持续高水平的IL-4表达易致慢性化。恢复Th1／Th2细胞的平衡可能是控制乙型肝炎慢性化的一条途径。CD4^＋／CD8^＋失调可能影响机体清除病毒的能力，导致感染的持续。     

Zinc deficiency and energy restriction modify immune responses in mice during both primary and challenge infection with Heligmosomoides polygyrus (Nematoda)

This study characterized the consequences of zinc-sufficient (Zn+, 60 mg zinc/kg diet, ad libitum ), zinc-deficient (Zn−, 0.75 mg zinc/kg diet, ad libitum ) and energy-restricted (ER, 60 mg zinc/kg diet which was restricted to match food intake of Zn− mice) diets on the in vivo and in vitro immune response of BALB/c mice during both primary and challenge infection with Heligmosomoides polygyrus . In Zn+ mice, both primary and challenge infection with H. polygyrus induced not only a strong Th2 response (IgE, IgG1, eosinophilia, IL-4, IL-5, IL-10), but also elements of a Th1 response (IgG3, IFN-γ). Zinc deficiency significantly depressed Th2-dependent antibody production during both primary and challenge infection, and reduced mitogen and antigen-induced T cell proliferation during the challenge infection. Th2 cytokine production was reduced by zinc deficiency (IL-4), energy restriction (IL-5) and by zinc deficiency possibly in combination with energy restriction (IL-10) during the primary infection whereas Th1 cytokine production (IFN-γ) was depressed during the challenge infection by zinc deficiency, possibly together with energy restriction. Both zinc deficiency and energy restriction reduced eosinophilia with the more profound effect being exerted by zinc deficiency. Thus, both zinc deficiency and its concurrent energy restriction modify immune responses in the mice during primary and challenge infection with H. polygyrus.     

Echinococcus granulosus-specific T-cell lines derived from patients at various clinical stages of cystic echinococcosis

To investigate the role of T lymphocytes in the immune response to Echinococcus granulosus, using sheep hydatid fluid (SHF) and antigen B (AgB), we generated T-cell lines from patients with active, transitional and inactive hydatid cysts. We established 16 T-cell lines, eight specific to SHF and eight specific to AgB. At surface phenotyping 88-98% of cells displayed the helper/inducer CD4 antigen. In all patients, at all clinical stages of hydatid cyst disease, T-cell stimulation with SHF and AgB invariably amplified a large number of almost identical Vbeta subfamily fragments. Irrespective of antigen-specificity, the two cell lines from the patient with an inactive cyst had a Th1 profile, because they exclusively expressed and produced IFN-gamma. Conversely, the T-cell lines derived from the seven patients with active and transitional hydatid cysts had mixed Th1/Th2 and Th0 clones. The functional characteristics of the 16 T-cell lines differed markedly in the various clinical stages of cystic echinococcosis, thus providing new in vitro evidence that Th1 lymphocytes contribute decisively to the inactive stage of hydatid disease, Th2 lymphocytes in the active and transitional stages. The parasite-specific T-cell lines, especially the two Th1 lines from the patient with an inactive cyst, may help identify Th1 protective epitopes on SHF and AgB.     

慢性HBV感染患者外周血T淋巴细胞免疫应答及其临床意义

目的探讨Th1／Th2、Tc1／Tc2亚群比例在慢性HBV感染的临床分型中的变化,以及在慢性HBV感染免疫病理损伤中的作用。方法用PMA、Ionomycin作为刺激剂,采用流式细胞仪（FACS）胞内细胞因子法对慢性HBV感染者外周血CD3＋CD8＋T细胞和CD3＋CD8-T细胞内IFN～y和IL-4的表达进行分析,比较慢性肝炎、肝炎肝硬化（活动性）、慢性重症肝炎各组Th1／Th2、Tc1／Tc2亚群比例变化。结果慢性肝炎、肝炎肝硬化（活动性）、慢性重症肝炎患者的Th1、Tc1细胞均高于正常对照组。慢性重症肝炎组Th1、Tc1显著高于慢性肝炎、正常对照组（P〈0．01）,慢性重症肝炎组Tc1显著高于活动性肝炎后肝硬化组（P〈0．05）。肝炎肝硬化（活动性）组Tc1显著高于正常对照组（P〈0．05）。Th1、Tc1细胞随着慢性乙型肝炎肝脏炎症活动的加剧而增高。而Th2、Tc2细胞则在各组中均无显著性差异（P〉0．05）。慢性重症肝炎患者恢复期Th1和Tc1细胞显著低于治疗前水平（P〈0．01）。结论在慢性HBV感染中,机体免疫平衡偏向Th1类反应,Th1、Tc1细胞与肝脏炎症活动严重程度呈正相关。提示Th1和Tc1细胞在慢性乙型肝炎肝脏病理发生中可能起了重要作用。     

Toso controls encephalitogenic immune responses by dendritic cells and regulatory T cells

The ability to mount a strong immune response against pathogens is crucial for mammalian survival. However, excessive and uncontrolled immune reactions can lead to autoimmunity. Unraveling how the reactive versus tolerogenic state is controlled might point toward novel therapeutic strategies to treat autoimmune diseases. The surface receptor Toso/Faim3 has been linked to apoptosis, IgM binding, and innate immune responses. In this study, we used Toso-deficient mice to investigate the importance of Toso in tolerance and autoimmunity. We found that Toso^−/− mice do not develop severe experimental autoimmune encephalomyelitis (EAE), a mouse model for the human disease multiple sclerosis. Toso^−/− dendritic cells were less sensitive to Toll-like receptor stimulation and induced significantly lower levels of disease-associated inflammatory T-cell responses. Consistent with this observation, the transfer of Toso^−/− dendritic cells did not induce autoimmune diabetes, indicating their tolerogenic potential. In Toso^−/− mice subjected to EAE induction, we found increased numbers of regulatory T cells and decreased encephalitogenic cellular infiltrates in the brain. Finally, inhibition of Toso activity in vivo at either an early or late stage of EAE induction prevented further disease progression. Taken together, our data identify Toso as a unique regulator of inflammatory autoimmune responses and an attractive target for therapeutic intervention.More than 5% of the populations of Western countries suffer from inflammatory autoimmune diseases (1). In all cases, a hyperactivated immune system is responsible for the initiation of autoimmunity. In the periphery, inflammatory T cells such as IL-17–producing Th (Th17) and IFN-γ–producing Th1 cells are controlled by suppressive regulatory T (Treg) cells (2). Numeric or functional imbalance of these various T-cell populations can result in autoimmunity or immunodeficiency. How the immune system limits self-reactive inflammatory responses in healthy individuals, and how these mechanisms fail in patients, is still under intensive investigation.The transmembrane receptor Toso belongs to the Ig superfamily, and its cytoplasmic domain shows homology to Fas-activated serine/threonine kinase (3). Toso has been implicated in the regulation of CD95 (Fas/Apo1)- and TNF receptor (TNFR)-dependent T-cell apoptosis, and is highly overexpressed in apoptosis-resistant B-cell lymphomas (3–6). Toso also functions as an Fc receptor for IgM, and so may be important for B-cell development (7–10). Recently, Toso expression was detected on granulocytes and monocytes and Toso was linked to the homeostasis and activation of the innate immune system (11–13). However, the precise physiological relevance of Toso’s multifaceted functionality is still unknown.In this study, we investigated the impact of loss of Toso on inflammatory autoimmune responses. Toso-deficient (Toso^−/−) mice were less susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). Disease resistance was dependent on Toso’s function in dendritic cells (DCs). DCs from Toso^−/− mice initiated less intense inflammatory CD4⁺ and CD8⁺ T-cell responses that were associated with reduced immunopathology. Toso^−/− DCs induced more Tregs than controls. Finally, interference with Toso activity in vivo significantly decreased the burden of EAE disease following induction. Our findings indicate that Toso is a crucial mediator of inflammatory autoimmune responses in vivo.     

Filaria/Wolbachia activation of dendritic cells and development of Th1-associated responses is dependent on Toll-like receptor 2 in a mouse model of ocular onchocerciasis (river blindness)

Toll-like receptors (TLRs) regulate dendritic cell function and activate signals that mediate the nature of the adaptive immune response. The current study examined the role of TLRs in dendritic cell activation and in regulating T cell and antibody responses to antigens from the filarial parasites Onchocerca volvulus and Brugia malayi, which cause river blindness and lymphatic filariasis, respectively. Bone-marrow-derived CD11c(+) cells from C57BL/6 and TLR4(-/-) mice produced high levels of IL-6 and RANTES, and showed elevated surface CD40 expression, whereas CD11c(+) cells from myeloid differentiation factor 88(-/-) (MyD88(-/-)), TLR2(-/-) and TLR2/4(-/-) mice were not activated. Similarly, IFN-gamma production by splenocytes from immunized TLR2(-/-) mice was significantly impaired compared with splenocytes from C57BL/6 and TLR4(-/-) mice. In contrast, there was no difference among these strains in Th2-associated responses including IL-5 production by splenocytes from immunized animals, serum IgE and IgG(1), or eosinophil infiltration into the corneal stroma. Neutrophil recruitment to the cornea and CXC chemokine production was inhibited in immunized TLR2(-/-) mice compared with C57BL/6 and TLR4(-/-) mice. Taken together, these findings demonstrate an essential role for TLR2 in filaria-induced dendritic cell activation, IFN-gamma production and neutrophil migration to the cornea, but does not affect filaria-induced Th2-associated responses.     

减毒猪流感病毒与灭活猪流感病毒的体液免疫及细胞免疫效果的观察

摘要：目的 研究减毒A/California/07/2009ca流感病毒及A/California/07/2009灭活流感病毒之间的体液免疫及细胞免疫效果的差异。方法 蔗糖密度梯度离心纯化减毒A/California/07/2009ca流感病毒经滴鼻途径免疫BALB/c小鼠,以灭活病毒肌肉注射组为对照。应用ELISA的方法检测小鼠血清中IgG1、IgG2a及脾淋巴细胞上清液中的IL-6、IL-4和IFN-γ的效价。结果 通过对小鼠血清中IgG1、IgG2a及脾淋巴细胞上清液中的IL-6、IL-4及IFN-γ细胞因子的检测,结果显示,灭活流感病毒的IgG1/IgG2a高于减毒流感病毒,同时灭活病毒产生的IL-6和IL-4高于减毒病毒,但IFN-γ低于减毒病毒。结论 A/California/07/2009灭活病毒能够刺激小鼠机体产生较好的体液免疫,但细胞免疫较差,而减毒A/California/07/2009ca流感病毒能够较好激发小鼠体内的体液免疫和细胞免疫反应。通过这些数据我们可以初步断定,A/California/07/2009ca减毒病毒具有较全面的免疫效果,这为流感喷鼻疫苗的研制提供了理论数据参考。     

Comparative studies on immune responses to infection in susceptible B10.BR mice infected with different strains of the murine nematode parasite Trichuris muris

A comparison of immune responses to infection between groups of B10.BR mice infected with different strains of T. muris , S strain (isolated in Sobreda, Portugal), E strain (isolated in Edinburgh), and E-J strain (originally E strain, which has been maintained in our laboratory, Japan), was performed. In mice infected with E and E-J strains, most of the worms were expelled by day 32 after infection, though the expulsion was faster in E-J strain-infected mice. In contrast, no expulsion was observed in S strain-infected mice by day 32 and egg production occurred on day 32. IL-4 production occurred in concanavalin A (Con-A)-stimulated mesenteric lymph node cells (MLNC) from B10.BR mice infected with E and E-J strains, whereas no IL-4 production was observed in S strain-infected mice. IL-4 production did not occur in normal mice. In comparison with normal mice, high levels of IFN-γ production by Con A-stimulated MLNC were detected in mice infected with every strain of  T. muris . IFN-γ production in S strain-infected mice was greater, occurred earlier and was more persistent than in mice infected with E and E-J strains. IgG1 and IgG2a antibodies to T. muris excretory/secretory antigens were observed in B10.BR mice infected with every strain of T. muris . Antibody production showed similar kinetics. These differences in the expulsion kinetics and IL-4 production in B10.BR mice infected with S, E, and E-J strains suggest the involvement of IL-4 in protection against T. muris infection, and confirm the previous conclusion by Else et al . (1994).