摘要:

SummaryEpimastigote forms ofTrypanosoma cruziare readily lysed by complement via the alternative pathway. Neither fibroblast‐derived trypomastigotes nor blood‐form trypomastigotes are lysed by complement alone and few (less than 30% of the Brazil strain) are lysed in the presence of parasite‐specific antibody and complement. The mechanism by which trypomastigotes resist antibody‐dependent, complement‐mediated lysis is not clearly understood. In the present study, we have utilized flow cytometric analysis to examine the binding of parasite‐specific antibody to epimastigotes, fibroblast‐derived trypomastigotes and blood‐form trypomastigotes of a Brazil strain ofT. cruzi. We also determined the extent of lysis of these parasites in the presence of complement utilizing propidium iodide to determine cell death. It was found that all epimastigotes bind approximately the same amount of antibody but that there are subpopulations of trypomastigotes which bind antibody to varying degrees. When these subpopulations were sorted, and treated with complement, lysis was only minimally increased in the population of parasites which bound significantly greater amou

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00001.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryInfections byTrypanosoma lewisiare characterized by hyporesponsiveness of the immune system during the early phase of parasitaemia. Blastogenic response of normal rat spleen cells to amphiphilic and hydrophilic components of Triton X‐114 solubilized epimastigote forms ofT. lewisiwhich characterizes the early phase of infection showed that suppression of responses to mitogens Concanavalin A (Con‐A) and lipopolysaccharide (LPS) occurred exclusively with the amphiphilic fraction that consists of integral surface membrane constituents. The Con‐A‐induced suppression by the amphiphilic constituents was ablated by addition of exogenous IL‐2 or by the removal of the adherent cell population in the cultures. This suggests that the integral surface membrane components play an important regulatory role in infections withTrypanosoma lewisi, through complex mechanisms that probably involve the B cells and suppressor macrophages; the suppressor macrophages probably produce a suppressor factor that inhibits the proliferation of T helper cells and subsequently the production of inte

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00002.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryThe effect of nonimmune human serum onEntamoeba histolyticatrophozoites was studied: (a) using whole serum in the presence of Ca and Mg ions allowing complement activation via both the alternative and classical pathways or in the presence of MgEGTA permitting alternative pathway activation only; (b) using differentE. histolyticaisolates; (c) varying serum and trophozoite concentrations and the time of incubation; and (d) using three different methods to quantify lysis, i.e., microscopic inspection, flow cytometry and111In release. All three methods yielded similar results, with flow cytometry being most sensitive in identifying membrane damage and111In release being most valid in determining cell death. Microscopic analysis was reliable only when a chamber was used to calculate the number of complement treated cells in relation to the initial cell count.E. histolyticaisolates were classified into three groups according to their susceptibility to lysis by complement: (i) pathogenic isolates after long term cultivationin vitrowere susceptible; (ii) pathogenic isolates after recent in vivo passage were less susceptible; and (iii) nonpathogenic isolates were nearly unaffected by exposure to the alternative pathway alone. The extent of lysis of the various isolates correlated with the degree of complement consumption in the serum samples, suggesting that unlysed isolates did not activate complement under the conditions employed. In general, lysis of susceptible trophozoites increased with the serum concentration and with the time of incubation. However, when the trophozoite concentration was 106/ml or higher, lysis no longer reflected complement susceptibility because of exhaustion of the complement supply.

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00003.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryThe therapeutic potential of locally injected interleukin‐2 (IL‐2) or interleukin‐4 (IL‐4) was studied in the footpads ofLeishmania mexicanaorLeishmania majorinfected BALB/c mice. The disease state was measured both pathologically, by measuring lesion size, and parasitologically, by counting total parasite numbers from infected footpads. IL‐2 (0.5 μg/dose) or IL‐4 (0.1 μg/dose) was administered either early, 1 day and/or 15 days after infection, or late, after palpable lesions had developed. Results differed markedly depending on whichLeishmaniaspecies was used and at what time during the course of disease that therapy commenced. BothL. majorandL. mexicanainfections, as measured by footpad thickness and parasite number, were exacerbated if IL‐4 was injected into the infected footpads early, during the first two weeks of infection. Paradoxically, late intralesional injection (i.e.after measurable lesions had developed) of IL‐4 markedly inhibited both lesion size and parasite growth inL. major, though notL. mexicana, infected mice. IL‐2 had no measurable effect on the course ofL. majorinfections no matter when or how often, the infected footpads of mice were treated. However, early administration of IL‐2 did exacerbateL. mexicanalesion and parasite growth while late treatment had no effect. Generally, but not always, increases in footpad size correlated with increas

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00004.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryGolden hamsters (Mesocricetus auratus) infected withLeishmania donovanidevelop a disease similar to human kala‐azar. There is conspicuous hypergammaglobulinaemia and their T cells do not respond to stimulation by parasite antigens. The impairment of the cellular immune response seems to be restricted to parasite antigens since infected animals are able to develop a T cell response to the mitogen Concanavalin A (Con‐A) and, after sensitization, to the antigens keyhole limpet haemocyanin (KLH) and human serum albumin (DNP‐HSA). In the present investigations we studied the role played by infected macrophages in the development of the cellular unresponsiveness present in visceral leishmaniasis. Adherent spleen cells from infected hamsters were unable to presentL. donovaniantigens to antigen specific T cells, however they were able to present KLH. Conversely. T cells from infected animals did not respond to parasite antigens even when these antigens were presented by normal syngeneic macrophages. Interestingly, lymphocytes from inguinal lymph nodes of infected animals sensitized in their foot pad with parasite antigens proliferated well when stimulated in vitro withL. donovaniantigens. These results suggest that the defect in the cellular immune response of theL. donovaniinfected hamsters is a consequence of a selective inability of their antigen presenting cells to process and present parasite antigens to T

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00005.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryGenetic restrictions to the immune repertoire will be an important consideration in the development of anti‐nematode vaccines. It has already been established that the major histocompatibility complex (MHC) limits responsiveness to nematode antigens in infection, but little is known of whether this also applies under other routes of sensitization, such as with adjuvants. The specificity of the antibody response was, therefore, compared in infection and adjuvant‐assisted immunization using secreted and somatic antigens ofAscaris suumas a model system in mice and rats. The findings were, first, that the lack of responsiveness to certain antigens in infection was not circumvented by Freund's adjuvant‐based immunization, despite the fact that the latter generally elicited higher levels of response. Secondly, that adjuvant‐assisted immunization could elicit responses to parasite products which were not detectable in the context of infection. Conversely, some specificities were detectable in infection but absent under adjuvant immunization. Finally, immunization with a defined parasite allergen (ABA‐1) in Freund's adjuvant did not provoke an IgE response which would be anticipated if the molecule were to have an intrinsic allergenic property. These results are likely to be of general importance to the application of subunit or recombinant vaccines against nematodiases and to the hypersensitivity reactions which vaccination might engender

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00006.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryAntibodies to two peptides DDAAD and (NANP)40representing the repetitive sequence of circumsporozoite antigens (CS protein) ofP. vivaxandP. falciparumrespectively were measured in a cohort of 149 and 107 individuals respectively at four, 6 monthly blood surveys performed on residents of Kataragama, aP. vivaxmalaria endemic region in southern Sri Lanka. The prevalence of antibodies to the CS protein of both species was relatively low being less than 20% to either peptide in the population as a whole, this being consistent with the low entomological inoculation rates in the area. A marked age related prevalence pattern was evident, with the prevalence of antibodies increasing with age to reach between 25 to 30% in the 25–50 year age group in bothP. vivaxandP.falciparum. The population had had a life long exposure toP. vivaxmalaria but not toP.falciparum, an epidemic of which occurred in this region a few months prior to the beginning of this study. Nevertheless, the age‐related prevalence of these antibodies was identical with respect to the two species. This suggests that the age‐related prevalence pattern reflected differences in inoculation rates between the age groups due to differences in exposure to inoculation rather than an age acquired response resulting from a cumulative experience over several years. An analysis of antibody prevalence in individuals showed first, that sporozoite inoculations must have been clustered rather than homogeneously distributed in the population and secondly, that sero‐conversion did not correlate with malaria infections in these indi

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00007.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryIn recent studies with 63 and 122 volunteers vaccinated with the SPf 66 synthetic malaria vaccine, specific antibody patterns were classified as high or low responders. Using the Polymerase Chain Reaction (PCR), a specific and selective preference was shown for the Vβ arrangement of the T‐cell receptor in the high responder group involving the Vβ‐8 gene. The low responder group showed the rearrangement of a different set of genes, and a particular association with

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00008.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryThe synthetic malaria vaccine SPf 66 has been shown to be safe, immunogenic and effective in trials performed with controlled groups naturally and experimentally exposed to the disease. In order to continue the trials in open populations, it was necessary to standardize the vaccination characteristics. We have performed four field trials with soldier volunteers with the aim, among others, of defining the number of doses required, the intervals between applications, the protein concentration, and the adjuvant to be used. In these trials, the vaccinated individuals' immune responses were evaluated by assaying anti‐SPf 66 antibody titres, in vitro growth inhibition of theP. falciparumparasite, and the vaccinees' capacity to recognizeP. falciparumnative proteins. From these results we conclude that the best vaccination schedule, for adults, is three doses administered subcutaneously on days 0, 30 and 180, each containing 2 mg of the synthetic polymerized petide SPf 66 adsorbed to alum hydroxid

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00009.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryThe KEK (Lysine‐Glutamic acid‐Lysine) motif is frequently found in the primary structure of certain malaria proteins involved in invasion, and plays an important role in the interaction of these proteins with the erythrocyte. This motif is contained in a peptide which forms part of the polymeric synthetic malaria vaccine SPf 66, currently undergoing extensive human trials. Analysis of the antibody titres against the subunit peptides that comprise this vaccine has shown that protection is associated with high titres to the KEK‐containing peptide. In this paper we examine the fine recognition of this motif by polyclonal sera from protected vaccinated individuals, demonstrating the critical role played by the interacting ion pair formed between the amino terminal lysine (K) and glutamic acid (E), which act as contact residues for an important proportion of the antibody population directed against this vaccine. This ion pair in the KEK motif constitutes perhaps one of the most important malaria epitopes involved in protection, and could explain the mechanism through which protective immunity is acq

ISSN:0141-9838    

DOI:10.1111/j.1365-3024.1992.tb00010.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY