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1.
Changes in immune responses, resistance to reinfection, and pathological reactions were studied serially in mice that had been infected for four to 40 weeks with 150 larvae of Trichinella spiralis. Immediate footpad hypersensitivity reactions to antigens of Trichinella were present throughout the period of observation. Delayed hypersensitivity reactions 48 hr after injection of antigen were first seen in mice infected for 14 weeks and gradually increased in size thereafter. Intestinal adult worm burdens were determined one week after challenge with 5000 larvae. There was resistance to reinfection and accelerated expulsion of worms in animals challenged three weeks after the primary infection; this resistance waned at seven and 13 weeks but reappeared in mice infected for 20 weeks or longer. Counts of larvae in muscle were determined four weeks after challenge with 5000 larvae. Marked resistance was present four weeks after the primary infection and was maintained for the duration of the study.  相似文献   

2.
The immunoglobulin G (IgG) and IgA antibody responses to different Schistosoma mansoni antigens have been determined in chronically infected mice as well as in unisexually infected animals. With a panel of enzyme-linked immunosorbent assays (ELISAs), soluble antigens from furcocercariae, adult worms, and eggs were probed with sera collected at 3-week intervals. Bisexually infected animals developed significant IgG and IgA antibody responses to the antigens tested, which increased after egg deposition. In unisexual infections no significant differences were recorded in the IgG antibody profile for furocercaria and adult worm antigens, whereas the IgA antibody response was impaired. Both the IgA and IgG antibody responses toward egg antigens were reduced compared with those in a bisexual infection. Furthermore, a specific mucosal IgA antibody response was observed only in the bisexually infected animals. Histological analysis performed on bisexually infected mice led to the observation of eggs and granulomatous lesions within the Peyer's patch follicles, which are essential sites for the induction of mucosal immunity in the intestine. These data suggest a relationship between egg deposition and the induction of the IgA antibody response toward schistosomes.  相似文献   

3.
Rats immunized against Trichinella spiralis rejected larvae from a challenge infection within minutes. Infectivity of these once-rejected larvae for nonimmune rats following intestine-to-intestine transfer, infectivity for nonimmune mice following oral inoculation, and normal development in these mice indicated that the parasite did not sustain immediate or long term damage as a result of the host's immune response. Associated with rapid worm rejection was a change in host intestinal function - altered absorption. Uptake of a hexose, 14C-beta-methyl-D-glucoside, was studied in intestinal segments isolated from rats before and 30 min after primary and secondary infections. Larvae were administered intraintestinally. Absorption was measured using a tissue accumulation method, under conditions of substrate saturation (30 mMolar) and over a 5-min period. 3H-mannitol was used as a marker to measure extracellular water, hence, extracellular sugar. Following challenge infection of previously infected (immunized) hosts, there was a significant reduction (22%; P less than 0.05) in hexose absorption as compared to the uptake rate before challenge. In contrast, cellular uptake before and 30 min after primary infection was similar. These findings are presented in support of the hypothesis that the failure of T. spiralis larvae to infect immune hosts is the result, not of direct worm damage, but of functional changes in gut epithelium, the habitat of the parasite.  相似文献   

4.
In three experiments mice were given three intravenous injections of Trichinella spiralis newborn larvae produced in vitro. Following a challenge infection of newborn larvae the mice were shown to be on the average 85% resistant i.e., only 15% of the challenge larvae developed to encysted muscle stage larvae in these mice; when the challenge consisted of normal muscle larvae administered per os, the mice were 51% resistant. Neither the number nor longevity of adult worms in the intestines was affected by this immunization procedure.  相似文献   

5.
Effects of protective resistance on lymphatic lesions and granulomatous inflammation in infected jirds (Meriones unguiculatus). Experimental Parasitology 77, 395-404. The hypothesis that protective immune responses play a role in the induction of filarial-associated lymphatic lesions was tested in jirds immunized twice with 75 Brugia pahangi radiation-attenuated third-stage larvae. Lymphatic lesions and granulomatous reactivity were compared in immunized, infected, and naive jirds at both acute and chronic periods following challenge with 100 third-stage larvae. Challenge worm burdens were reduced in immunized jirds at both infection periods. The ratio of lymph thrombi to lymphatic worms, an indicator of lymphatic lesion severity, was significantly greater in immunized jirds than in nonimmunized-challenged jirds during acute but not chronic infections. Parasite-specific-granulomatous hypersensitivity was assessed by measurements of granuloma areas around B. pahangi-soluble adult worm antigen-coated sepharose beads embolized in the lungs prior to necropsy. Marked granulomatous inflammatory responses seen during the acute period in both immunized-challenged and nonimmunized-challenged jirds were significantly reduced in similar jirds during chronic periods. Jirds with existing B. pahangi infections were not resistant to homologous challenge infection and had fewer lymphatic lesions and reduced granulomatous inflammatory responses to soluble adult worm antigen compared to previously naive jirds at acute periods postchallenge. These data suggest that protective immune responses increase the severity of filariae-induced lymphatic inflammation. The subsequent modulation of these lesions is probably associated with parasites that survived the protective immune response.  相似文献   

6.
In order to study the role of eosinophils in the host defense against Trichinella spiralis infection, worm recovery after infection with T. spiralis was compared between interleukin-5 transgenic (IL-5 Tg) mice with a constant high level of peripheral eosinophils and nontransgenic C3H/HeN mice. No significant difference in the recovery of muscle larvae or adult worms in the small intestine, fecundity of female adult worms, or infectivity of newborn larvae was observed between nonimmunized C3H/HeN and IL-5 Tg mice or C3H/HeN and IL-5 Tg mice immunized with somatic antigen of T. spiralis. However, a significant difference was observed in the fecundity of female adult worms and recovery of muscle larvae between nonimmunized and immunized IL-5 Tg mice or C3H/HeN mice. These results demonstrate that having more eosinophils does not improve immunity against the various aspects of T. spiralis infection.  相似文献   

7.
BALB/c mice immunized with L3 of Brugia pahangi, irradiated at 45 kRad from a 137Caesium source, are strongly immune to challenge infection (75-100% reduction in the recovery of challenge infection larvae on day 6 post-challenge). The target of immunity appears to be the post-infective L3, as challenge infection larvae are killed within 5-6 days of infection. By immunoblot analysis, serum from immune animals recognizes a limited set of somatic antigens, the majority of which are shared between different life cycle stages. Serum from immune mice also strongly recognizes larval surface antigens by immunofluorescence, some of which may be stage specific. The larval surface determinants do not appear to be protein or glycoprotein by standard immunochemical analysis. A proportion of the antibody response of the BALB/c mouse is directed towards phosphorylcholine epitopes on filarial antigens, but the limited antigen recognition cannot be explained on the basis of the mouse strain used, as CBA/Ca mice recognize a similar limited set of antigens.  相似文献   

8.
Ixodes ticks are infected by Borrelia burgdorferi when larvae feed on spirochete-infected mice. We studied the acquisition of B. burgdorferi by larval ticks, characterized the production of outer surface protein A (OspA) by spirochetes entering larvae, and examined the effects of OspA antibodies on the establishment of B. burgdorferi infections in ticks. Most larvae were infected by spirochetes 24 to 48 h after placement on mice. OspA antibodies stained the first spirochetes observed in larvae, suggesting that OspA is synthesized early during the colonization of the vector. When OspA antibodies were administered to B. burgdorferi-infected mice and larvae were then placed on the animals, the severity of larval infection and the number of infected ticks (7 of 16) were decreased compared with that of controls (15 of 16). The inhibitory effects of OspA antibodies were observed with passive antibody transfer as well as active host-generated immunity. The lower larval infection rate observed in the presence of OspA antibodies was exacerbated after the larval molt since only 1 of 12 nymphs was infected, and none of the mice that were fed upon by these nymphs became infected with B. burgdorferi. Therefore, an OspA antibody response in mice altered the reservoir competence of the vertebrate host by inhibiting the movement of B. burgdorferi from the host to the vector.  相似文献   

9.
To assess the gamma delta TCR T cells in the control of the timing of the mucosal response to enteric parasitic infections, we used C57BL mice, orally infected with 200 viable T. spiralis larvae. The small intestine, spleens and Peyer's patches (PP) were excised on 1, 4, 7, 14, 21 and 29 postinfection days (p.i.) for immunophenotyping and histological studies. Uninfected mice served as control. Characterization of isolated lymphocytes of C57BL control mice, confirmed that T cell immunophenotype differs in spleen, PP and i-IEL. Practically all i-IEL were CD3+ cells (83%). In addition, most of the i-IEL expressed Ly-2 (65%). Among the i-IEL, the level of gamma delta TCR+ cells was significantly higher (29%) than that found in spleen (3%) and PP (3%). The expression was high on CD3+ and Ly-2+ (26 and 21%, respectively) and low on L3T4+ i-IEL (< 1%). During T. spiralis infection alpha beta TCR+ CD3+, gamma delta TCR+ CD3+ and gamma delta TCR+ Ly-2+ i-IEL increased on day 4 and 7. However, infected mice displayed a reduction in i-IEL number from 14 to 29 p.i. day. At the same time the proportion of gamma delta TCR on spleen Ly-2+ and on PP CD3+ and Ly-2+ cells increased on 14 and 21 p.i. day. Adult worms were expelled from the gut by day 14. Thus, the kinetics of gamma delta TCR+ i-IEL, but not spleen and PP gamma delta TCR, corresponded to the kinetics of worm expulsion in C57BL mice. Most murine i-IEL of the gamma delta T cell lineage tend to be cytolytic when activated. We speculated that gamma delta T cells of i-IEL during the early stages of infection recognize and eliminate damaged epithelial cells generated by parasite antigens, simultaneously accelerating the worm expulsion.  相似文献   

10.
Immune responses in resistant BALB/c mice infected with the murine nematode parasite Trichuris muris were examined. Following the establishment of infection, worm burdens of T. muris were expelled by BALB/c mice by day 21 postinfection (p.i.). Specific immunoglobulin G1 (IgG1) antibodies to T. muris excretory/secretory (E/S) antigens were detected in sera from infected mice, though specific IgG2a antibodies were not observed during infection. Ig-producing cells increased in the mesenteric lymph nodes (MLN) of infected mice on days 7, 14, and 21 p.i., with the greatest increase in numbers of IgG- and IgA-producing cells occurring on day 14. Marked increases in the relative percentages of B220+ and surface Ig+ (sIg+) cells were observed in the MLN of infected mice on days 14 and 21 p.i. Furthermore, cellular expansion of the MLN in infected mice resulted in an increase in the absolute numbers of B220+ and sIg+ cells. The levels of interleukin 2 (IL-2), IL-4, and interferon-gamma (IFN-gamma) detected in the supernatants from concanavalin A-stimulated MLN cells of infected mice were higher than those found in normal mice. Consequently, the expulsion of T. muris in resistant BALB/c mice was concomitant with cytokine production and B-cell activation in the MLN of infected mice. These results suggest the involvement of B-cell responses in protective immunity to T. muris infection.  相似文献   

11.
One of the current goals in vaccine development is the noninvasive administration of protective antigens via mucosal surfaces. In this context, the gut-associated lymphoid tissues have already been extensively explored. Vaccination via the nasal route has only recently been the focus of intensive investigation, and no live vector specifically designed for the respiratory mucosa is yet available. In this study we show that intranasal administration of the recombinant Bordetella pertussis BPGR60, producing the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm28GST) protective antigen fused to filamentous hemagglutinin, induces priming in mice for the production of serum antibodies. In addition to significant levels of anti-Sm28GST immunoglobulin A (IgA) antibodies, high levels of anti-Sm28GST serum antibodies were obtained after intranasal boost with the purified antigen or infection with S. mansoni following intranasal priming with BPGR60. These antibodies were of the IgG1, IgG2a, and IgG2b isotypes, suggesting a mixed immune response. No priming was observed in animals that had received nonrecombinant B. pertussis or purified Sm28GST, indicating specific priming by BPGR60. This priming was also evident in immune protection against S. mansoni challenge. Significant protection against worm burden and egg output was obtained in mice primed with BPGR60 and intranasally boosted with purified Sm28GST. A lower but still significant degree of protection against egg output was also obtained in mice infected with a single dose of BPGR60. These results indicate that intranasal administration of recombinant B. pertussis can prime for serum antibody responses against a foreign antigen and for heterologous protection.  相似文献   

12.
Although most strategies of vaccination require immunopotentiation to induce efficient immune responses, the development of new adjuvants for human vaccines is highly limited by safety problems. In order to overcome this problem, we developed a new vaccine formulation based on the covalent linkage of protein or peptide to synthetic microspheres. In previous experiments performed in mice, we demonstrated that these particulate antigens induce strong antigen-specific CD4+ T cell proliferative responses in the absence of adjuvant. In the present study, we analyzed the immunogenicity in primate Saimiri sciureus monkeys of two different proteins linked to synthetic microspheres. Immune responses induced by these particulate proteins administered without adjuvant were compared to those stimulated by the soluble antigens injected with alum. We currently demonstrated that, in monkeys, particulate antigens administered without adjuvant, induced good PBMC proliferative response and antibody production. Furthermore, the analysis of antibody responses using mAbs specific for different Saimiri sciureus immunoglobulins showed that the antibody response profiles were different in monkeys immunized with soluble versus particulate form of antigens. Results of this study demonstrate that particulate form of antigen may stimulate qualitatively different immune responses as compared to alum and therefore suggest that this new antigen formulation could be an attractive candidate for the development of vaccines.  相似文献   

13.
The eye is endowed with a number of mechanisms that protect it from immune-mediated injury. One such mechanism, termed anterior chamber-associated immune deviation (ACAID), evokes the antigen-specific, systemic down-regulation of Th1 responses to antigen inoculated into the anterior chamber of the eye. ACAID has been correlated with the selective production of IL-10 by the antigen-presenting cells (APC) and the development of a cross-regulatory Th2-like response. A small subset of antigens do not induce ACAID, but instead provoke IL-12 and normal Th1 immunity. Remarkably, all soluble antigens tested are capable of inducing ACAID; only cell-associated antigens do not induce ACAID. We hypothesized that the nature of antigen plays a decisive role in the resultant immune response. This hypothesis was tested with two well-characterized antigens, ovalbumin (OVA) and SV40 large T antigen (SV40 Lg T Ag). The soluble forms of OVA and SV40 Lg T Ag induced ACAID in both in vivo and in vitro models of the eye. In contrast, the particulate forms of these antigens, i.e. OVA passively absorbed onto inert latex beads (OVA-latex) and SV40 Lg T Ag expressed in two different cell lines, 99E1 and SV-T2, did not induce ACAID in either in vivo or in vitro models of the eye. In addition, the cytokine profiles of ocular APC pulsed with OVA or OVA-latex showed that soluble OVA induced the production of IL-10, whereas OVA-latex induced the production of IL-12. These data suggest that the nature of the antigen in the eye, whether soluble or particulate, is a crucial determinant in the resultant immune response. Moreover, they suggest a mechanism in which soluble antigens preferentially induce the release of ACAID-inducing IL-10 whereas particulate antigens preferentially induce the release of Th1-inducing IL-12 by responding APC.  相似文献   

14.
BACKGROUND & AIMS: Infection with Helicobacter induces a T helper type 1 response in mice and humans. Mice can be cured or protected from infection with Helicobacter by mucosal immunization with recombinant H. pylori urease B subunit (rUreB). This study characterizes the immune response of infected mice immunized with rUreB. METHODS: BALB/c mice were infected with H. felis. Two weeks later, they were orally immunized four times with rUreB and cholera toxin (CT) at weekly intervals. Controls were only infected or sham-immunized with CT. Animals were killed at various times after immunization. Splenic CD4(+) cells were obtained and cultured in vitro with rUreB to evaluate antigen-specific proliferation and induction of interferon gamma and interleukin 4 secretion. RESULTS: All rUreB-immunized mice (n = 8) were cured from infection 3 weeks after the fourth immunization. Immunization induced a proliferative response of splenic CD4(+) cells, a progressive decrease in interferon gamma secretion, and a concomitant increase in interleukin 4 secretion after each immunization. A simultaneous increase in rUreB specific serum immunoglobulin G1 levels was observed in infected/immunized mice. CONCLUSIONS: In BALB/c mice, therapeutic mucosal immunization with rUreB induces progressively a Th2 CD4(+) T cell response resulting in the elimination of the pathogen.  相似文献   

15.
The importance of in situ lymphocyte proliferation for net accumulation of lung lymphocytes during pulmonary immune responses and in immunologic lung diseases remains uncertain. Accordingly, we studied the experimental pulmonary immune response of antigen-primed C57BL/6 mice to intratracheal challenge with the particulate antigen sheep red blood cells. Uptake of nucleotide analogs (bromodeoxyuridine in vivo and tritiated thymidine in vitro), expression of the cell activation antigens CD25 and CD69 by flow cytometry, and response to the antimitotic agent hydroxyurea (in vivo) were measured. Although many lung lymphocytes and CD4+ T cells were CD25+ and CD69+, indicating recent activation, all techniques demonstrated that lung lymphocytes proliferated minimally in vivo. Blockade of cell division by hydroxyurea administration for 24 h did not significantly decrease lung lymphocyte accumulation on Day 3 after challenge. Lung lymphocytes also proliferated minimally in vitro (even on macrophage removal and despite addition of exogenous interleukin [IL]-2 or IL-4). However, lung lymphocytes responded vigorously to mitogens (immobilized anti-CD3, phytohemagglutinin, or concanavalin A), excluding global unresponsiveness to restimulation. Thus, in this model of pulmonary immunity, accumulation of lung lymphocytes does not require local T-cell proliferation and presumably depends instead on recruitment.  相似文献   

16.
Meningeal worm (Parelaphostrongylus tenuis) is a neurotropic nematode of ungulates in eastern North America. Lack of an effective diagnostic test increases the concern of translocating potentially infected ungulates into western North America, where P. tenuis does not occur naturally. In an attempt to identify serodiagnostic molecules, we determined (1) whether elk (Cervus elaphus) experimentally infected with P. tenuis produce antibodies against infective larvae or adult worms, and (2) if sera consistently recognize antigens that distinguish P. tenuis from a common nematode parasite of elk, the lungworm Dictyocaulus viviparus. Each of 10 elk were exposed to 15 or 300 infective P. tenuis larvae. Serum was collected (0, 41, and 83 days post-exposure and at necropsy) and monitored for antibodies using the enzyme-linked immunosorbent assay (ELISA) and immunoblot. When reactivity of sera with larval P. tenuis protein was compared (day 0 versus 83), ELISA values were significantly higher on day 83 for elk exposed to 15 or 300 parasites. Likewise, ELISA values using protein of adult P. tenuis were higher for elk exposed to 300 larvae. Immunoblots showed that sera from elk, with adult worms in the central nervous system, consistently recognized the 25-27, 28-30, and 34-36 kDa antigens of infective larvae after 83 days. However, many D. viviparus molecules were found to cross-react with antibodies formed against meningeal worm antigens. Use of adult worm proteins for serodiagnosis appears limited, because no protein was consistently recognized by sera collected from elk exposed to 15 larvae. We believe that development of a reliable diagnostic test for meningeal worm requires more research addressing cross-reactivity and detection of P. tenuis during the incubation stage.  相似文献   

17.
Comparison of the anthelmintic activity and pharmacokinetic profiles following albendazole (ABZ) and albendazole-sulphoxide (ricobendazole = RBZ) administration was made in a mouse model for helminthic infections. Swiss CD-1 mice were experimentally infected with Trichinella spiralis and treated with either ABZ or RBZ at 3 different stages of the parasite life-cycle: pre-adult (day 1 p.i.), migrating larvae (days 13, 14 and 15 p.i.) and encysted muscle larvae (days 34, 35 and 36 p.i.). Plasma concentrations of albendazole-sulphoxide (ABZSO) were measured in age matched non-infected mice by high performance liquid chromatography (HPLC), after administration of ABZ or RBZ dosed at 50 mg ABZ equivalent kg-1. ABZSO pharmacokinetic profiles following ABZ or RBZ administration were similar, although the Tmax (1.83 +/- 0.30 and 0.41 +/- 0.28, respectively) were significantly different (P < 0.01). Against pre-adult stages ABZ was significantly (P < 0.05) more effective than RBZ when administered at 10 mg kg-1 (96.5% and 78.0% reduction with respect to the control group). Migrating and encysted larvae were less sensitive to both compounds and dose rates had to be increased to 100 mg kg-1 to achieve significant efficacies. Against parenteral stages, ABZ was significantly more effective than RBZ when both were given at 100 mg kg-1 (64.0% and 44.2% reduction against migrating larvae and 94.7% and 65.5% reduction against encysted larvae, respectively). In conclusion, RBZ was not more effective than ABZ against enteral and parenteral stages of Trichinella spiralis.  相似文献   

18.
Naive CBA/Ca mice and mice vaccinated with gamma-irradiated cercariae of Schistosoma mansoni were challenged percutaneously with normal cercariae and depleted of L3T4+ T helper cells through the administration of a specific monoclonal antibody. Three regimes were utilized to target known phases of parasite migration. The in vivo depletion of L3T4+ cells resulted in a significant reduction in immunity (up to 65%) in vaccinated/challenged mice, provided the monoclonal antibody was targeted towards skin-resident schistosomula. When antibody was targeted towards lung phase challenge larvae, however, there was a significant reduction in worm recovery, but no correspondingly significant reduction in vaccine immunity. In contrast, the administration of monoclonal to naive mice, via all three treatment regimes, had no effect on the primary schistosome worm burden. Histopathological studies complemented these worm recovery data. Skin tissue biopsied from vaccinated/challenged mice treated with monoclonal to L3T4+ T cells rarely showed the inflammatory foci which normally characterize untreated vaccinated/challenged mice. This was true when antibody was given either before challenge, or just after challenge, and correlated with the recorded depression in vaccine immunity. Lung tissue collected from monoclonal-treated vaccinated/challenged mice (for all three treatment regimes) exhibited no changes in morphology compared to that from untreated vaccinated/challenged mice. This was not altogether surprising since in the NIMR vaccine mouse model, the lungs represent a poor site for challenge attrition and appear normal in morphology with the exception of a few, small inflammatory reactions. When the monoclonal was given to naive/infected mice, there was no change in the morphology of the pulmonary tissue, as compared to corresponding untreated cohorts. Immunohistochemical studies revealed that Thy-1+ cells dominated the subdermal inflammatory foci of vaccinated/challenged mice. Of the T cells identified, the T helper subset was the most common, with T suppressor cells being only weakly represented, and in some cases not at all. The proportion of macrophages (Mac-1+) varied between reactions.  相似文献   

19.
In order to characterize immunodominant components of T. spiralis a workshop was organized. In this the reactivity of monoclonal and polyclonal antibodies, provided by different research groups, towards total extracts from adult, new born larvae and muscle larvae as well as to excretory/secretory components of muscle larvae were tested by ELISA, Western blot and immunoprecipitation assays. As a result of this workshop T. spiralis ML antigens have been classified into eight groups (TSL-1-TSL-8) according to their recognition by monoclonal and polyclonal antibodies. Among them, TSL-1 antigens have been the most extensively characterized both biochemically and immunologically. These antigens are stage specific, originate in the muscle stichosome and are abundant in both E/S and on the larval cuticular surface. The TSL-1 antigens share an immunodominant carbohydrate epitope (tyvelose), which is unique for Trichinella and is not associated with phosphorylcholine. The data collected in this workshop has allowed both the unification of the nomenclature for T. spiralis antigens and their biochemical characterization. It also has provided a platform for further studies on the characterization of other T. spiralis antigens and indeed for other Trichinella species.  相似文献   

20.
Mice inoculated at 5, 21 and 28 days of age with 10(6) or 10(7) Cryptosporidium parvum oocysts became infected but did not exhibit any clinical signs of disease. Specific IgA antibodies were detected in faecal extracts from all infected mice by an indirect immunofluorescent assay. These antibodies first appeared between 11 and 37 days post-infection (dpi) and persisted until the end of the experiment at 55 dpl. They appeared earlier in older mice than in newborn mice. Reduction and resolution of oocyst shedding was not directly related, however, to IgA antibody levels in infected mice. Reactive C. parvum antigens were identified by immunoblotting techniques using faecal and serum samples from infected mice. IgA copro-antibodies reacted specifically with two antigens of 26 and 33 kDa, which were also identified by IgG antibodies in mouse serum. The role of these antibodies in the resolution of infections and the subsequent protection against challenge is unknown.  相似文献   

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