摘要:

SummaryIn humans with lymphatic filariasis microfilaremia is associated with a parasite antigen‐specific hyporesponsive‐ness when assessed by cell proliferation and secretion of interleukin‐2 and interferon‐γ. Hyporesponsiveness in these individuals is not only parasite antigen‐specific but appears to be limited to Th1‐type responses. Th2 mediated responses such as IL‐5 secretion and IgE antibody production to parasite antigens are generally strong and usually no different than those seen in immunologically more reactive amicrofilaremic individuals with chronic lymphatic pathology. The mechanisms by which Th1 responses are inhibited have not yet been elucidated, but some studies suggest that down‐regulatory cytokines such as IL‐10 may be involved in this process. Mononuclear cells from microfilaremic individuals have been found to secrete greater quantities of IL‐10 spontaneously and in response to parasite antigens. In this review, mechanisms by which IL‐10 may be induced by the parasite and the mode by which IL‐10 may regulate parasite antigen‐specific Th1 responses in these

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00906.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryIn order to gain insights into the immune response in onchocerciasis during early infection, laboratory‐reared calves were infected with 1000 Onchocerca lienalis infective larvae and examined serologically over a period of 508 days. Levels of serum antibodies measured by ELISA against adult worm extract revealed a multiphasic response, characterized by a broadly similar profile of peaks in individual animals arising at 15–30, 79 and>266 days after infection. Timings of these changes in responsiveness closely mirrored parasite development, coinciding with larval moults and with the onset of a patent infection. The levels of individual antibody isotypes directed against parasite antigens was strongly skewed. The dominant response was of IgG1, although limited reactivities were also found for IgG2 and IgM: No parasite‐specific IgA antibodies were detected. Immuno‐blots of adult worms extracts revealed a pattern of antigen recognition over time that matched the results obtained by ELISA. Again, the IgGl response was strongest, although certain lgG2 and IgM specificities were well represented. In general, there was a steady increase in the number of individual antigens recognized as the infection progressed, with a striking expansion of antibody specificities from day 79 following the fourth larval moult. Antibodies to a 16kDa component were a prominent feature of the response following development of a patent infection. These data reveal the strong influence of parasite biology on the development of the immune response in onchoce

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00907.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryEncephalitozoon cuniculi (phylum microspora) is a protozoan parasite that can replicate within parasitophorous vacuoles in macrophages. Thioglycollate‐elicited BALBjc peritoneal macrophages treated with murine recombinant interferon‐γ (rIFN‐γ; 10u/ml) in combination with lipopolysaccharide (LPS; 10ng/ml) for 24 h killed E. cuniculi as determined by significant reductions in the number of parasites and percent of infected macrophages 48 h later compared with cultures treated with medium only. Treatment of the elicited macrophages with murine rIFN‐γ (10u/ml or 100u/ml) only, resulted in microbistatic activity. Significantly higher levels of nitrite (NO2) were detected in supernatants from macrophage cultures treated with rIFN‐γ (10 u/ml or 100 u/ml) which induced microbistatic macrophage activity as well as from macrophage cultures treated with LPS + rIFN‐ when compared with levels of nitrite detected in supernatants of infected macrophages treated with medium only. Addition of the L‐ariginine analogue, N3monomethyl‐L‐arginine (NMMA) at concentrations of 50, 100 or 250 uM significantly inhibited nitrite synthesis and prevented microsporidia killing. Addition of exogenous L‐arginine at concentrations of 5mM or 10 mM reversed the NMMA‐induced inhibition of parasite killing. These results indicate that reactive nitrogen intermediates contribute to the killing of E. cuniculi by LPS + rIFN‐γ‐activated murine p

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00908.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryVγ9+ T cells from malaria non‐exposed donors make proliferative responses to Plasmodium falciparum on in vitro stimulation. Vγ9+ cells are strongly activated by components of the schizont stage of the parasite and by antigens released into the culture upon schizogony, while CD4+ Vγ9‐cells are stimulated by the earlier stages of the parasite. Using reverse transcriptase‐polymerase chain reaction (RT‐PCR) we determined mRNA expression for 14 cytokines in highly purified Vγ9+ cells enriched by positive selection after in vitro stimulation with P. falciparum schizont antigens. Interferon‐γ (IFN‐γ) and Tumor Necrosis Factor‐α (TNF‐α) were detected in all samples tested. The majority of samples also expressed TNF‐β, transforming growth factor‐β (TGF‐β) and Interleukin‐8 (IL‐8). Only occasional samples expressed IL‐2, IL‐5 and IL‐10. Using the ELISPOT assay we found that a large fraction of the reactive Vγ9+ cells produced IFN‐γ and that γδ T cells are the major producers of IFN‐γ in cultures stimulated with schizont antigens. The majority of Vγ9+ cells in these cultures also express the membrane‐bound form of TNF‐α. Expression of these cytokines speaks for a cytolytic and/or inflammatory role of γδ

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00909.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryWe have reported previously that immunization with a bacterial recombinant protein containing the two epidermal growth factor (EGF)‐like modules of Plasmodium yoelii Merozoite Surface Protein‐1 (MSP‐1) protected miced against challenge with this malaria parasite. Bacterial plasmids containing sequences coding for the individual modules fused to glutathione S‐transferase (GST) have now been made. The fusion protein containing the combined EGF‐like modules was recognized by anti‐parasite antibodies and was immunogenic, producing high litre anti‐parasite and anti‐GST antibodies. In contrast, fusion proteins containing the two individual EGF‐like modules reacted poorly with the natural antibodies and their proteins, as well as a simple mixture of them, induced low levels of anti‐parasite antibodies despite producing high levels of anti‐GST antibody. Antibodies raised to the recombinant proteins recognized the 230 kDa MSP‐1. Groups of mice immunized with the different recombinant proteins were challenged with parasites: protection was observed in the group which had received the recombinant protein containing both modules but not in those groups immunized with the individual modules, either alone or as a mixture. These results suggest that there are important structural determinants formed by the two modules together, which are not present in either of the individual domains alone, and which are responsible for the immunogenicity of the protein or are the target o

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00910.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryMice were infected with 200 untreated or vaccinated with 500 ultraviolet‐attenuated cercariae of either Schistosoma japonicum or S. mansoni. For three weeks, cell numbers in axillary and mediastinal lymphnodes were counted and cell populations typed by cytofluorometry. In the axillary lymphnodes, numbers of B‐cells and CD3+CD4+ T‐cells but not CD3+CD8+ T‐cells increased. Following vaccination with either species, parasite migration was apparently delayed in the skin and interrupted at the lungs, the lymphnodes gained weight, and cell numbers of axillary lymph nodes increased more than after infection. In mediastinal lymphnodes, only immunization with S. japonicum but not S. mansoni cercariae led to an increase of CD3+CD4+ T‐cells. Following infection, both schistosome species induced higher CD3+CD4+, but not CD3+CD8+ T‐cells in mediastinal nodes, and the peak was earlier with S. japonicum (about seven days after infection) than with S. mansoni (about 10 days). In analogy to T‐cell observations by others using a gamma‐attenuated cercarial vaccine in S. mansoni, the present results suggest that CD3+CD4+ cells also play a role in the ultraviolet‐attenuated vaccine aga

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00911.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryA pilot safety and immunogenicity trial of the malaria vaccine SPf66 has been undertaken in 150 Gambian infants. No significant systemic side effects were recorded but modest local reactions were seen after the administration of a third 1.0 mg dose. SPf66 produced in Colombia was more immunogenic than SPf66 produced in the USA and a 1.0 mg dose of each vaccine gave higher antibody levels than a 0.5 mg dose. However, antibody levels fell rapidly after administration of the third dose of vaccine and showed little change over the following malaria transmission season. The incidence of clinical malaria was higher among children who received SPf66 than among children who received inactivated polio vaccine, the effect being most marked among children who received 1.0 mg Colombian SPf66. As the trial was not designed to measure the effect of SPf66 on morbidity from malaria, the significance of this finding is uncertain.

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1995.tb00912.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY