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At least 19 recordsLinked to original sources
PubMed1984

Primary infection sera and IgG1 do not block host-protective immunity to Nematospiroides dubius.

IgG1 immunoglobulin purified from sera 3 weeks following primary infection with 400 L3 larvae of Nematospiroides dubius was shown to be protective against challenge infection as assessed by worm recovery and worm length. No evidence was seen of blocking activity either using primary infection sera or IgG1 purified from primary infection sera in a variety of assay systems both in vivo and in vitro. In addition, immune complexes precipitated from primary infection sera by polyethylene glycol failed to inhibit the capacity of immune mesenteric lymph node cells to transfer immunity. It is concluded that an explanation for the prolonged survival of Nematospiroides dubius must be sought in mechanisms other than circulating blocking factors.

Animals↗
PubMed1985

Hymenolepis citelli (Cestoda) and Nematospiroides dubius (Nematoda): interspecific interaction in mice.

In mice concurrently infected with Hymenolepis citelli and Nematospiroides dubius, survival of the tapeworm was prolonged, and there was an impairment of the efferent arm of the response to the cestode. The immunological rejection of a six cysticercoid primary H. citelli infection was delayed by the N. dubius infection. The growth of the cestode was poorer in concurrently infected mice, and this effect was rapid, being evident within 4 days of the N. dubius infection. Maximum biomass in the controls was reached on Day 20, whereas in the concurrently infected mice it was reached on Day 25. The induction of acquired immunity to homologous H. citelli infection was suppressed, although the expression of a secondary response against homologous challenge was not abrogated in doubly infected mice. The results are discussed with reference to the immunodepressive effects the nematode is known to have on heterologous antigenic stimulation.

Animals↗
PubMed1986

Nematospiroides dubius: direct and correlated responses to selection for high and low immune responsiveness in mice.

High and low immune responder lines of mice were bred selectively from an allogeneic stock over 10 generations, based on their fecal parasite egg count assayed 3 weeks after reinfection with 100 Nematospiroides dubius larvae. By generation 10, (F10), the low immune response mice voided about 10 times as many fecal N. dubius eggs as the high immune response mice. Realized heritability for the selected trait, fecal egg count after secondary infection (= protective immunity), was 0.35 at F7. F7 was considered the selection limit. Selection for change in fecal egg count did not significantly influence the conformational nor reproductive characteristics of these mice. Significant phenotypic and genetic correlations were evident between the selected character and innate immunity to N. dubius, humoral antibody response to N. dubius infection, and establishment, growth, and reproduction of N. dubius in the selected mice.

Animals↗
PubMed1987

Nematospiroides dubius and Nippostrongylus brasiliensis: delayed type hypersensitivity responses to ovalbumin in the infected mouse.

Mice (C57BL) infected with the intestinal nematode Nematospiroides dubius showed depressed delayed type hypersensitivity responses to ovalbumin administered subcutaneously in Freund's complete adjuvant. IgG and IgM responses to this inoculum were unaffected. It is unlikely that the depression arose from impairment of the ear test response because responses to an extract of the adult parasite were measurable and ear testing with lipopolysaccharide yielded normal responses in infected mice. Furthermore, mice immunized on the day of infection responded normally, whilst long term infected mice ear challenged with antigen pulsed macrophages gave depressed responses. The in vitro proliferative responses of cells from the spleens and from the lymph nodes draining the site of immunization were enhanced marginally by N. dubius infection. Furthermore, these cells induced normal or elevated adoptive delayed-type hypersensitivity and IgG responses in irradiated recipients. These findings suggest that N. dubius does not compromise the development of ovalbumin specific T cells involved in a delayed type hypersensitivity response. Evidence for the induction of suppressor cells by N. dubius is discussed, and the findings are compared with results obtained with Nippostrongylus brasiliensis, a parasite which is rejected rapidly from the mouse.

Animals↗
PubMed1988

Nematospiroides dubius: genetic control of immunity to infections of mice.

Inbred strains of mice differ in their susceptibility and resistance to challenge infections with Nematospiroides dubius. In our studies, F1 hybrid mice from resistant SJL and susceptible CBA parents were resistant to N. dubius challenge infections. Only 22% of backcrosses to SJL were susceptible while backcrosses to CBA had a wide range of susceptibility. Male mice were more susceptible than female mice. In another experiment, inbred strains of mice were compared in their ability to resist N. dubius challenge infection: SJL and A.SW (H-2s) mice became resistant after one immunizing infection, A, A/He (both H-2a), as well as BALB/c and DBA/2 (both H-2d) mice became resistant after two immunizing infections, while C57BL/6 (H-2b), C3H/He, CBA, and AKR (H-2k) mice remained susceptible. The resistance to reinfections was characterized by reduction of worm burdens between Days 6 and 14 postinfection. It was concluded that (1) resistance to N. dubius challenge infections is inherited in a dominant fashion and that multiple genes may influence such response, which in turn might be modulated by the Y chromosome; (2) both MHC and non-MHC genes may influence, in conjunction with the number of exposures to parasite antigens, the resistance to challenge infections.

Animals↗
PubMed1988

Nematospiroides dubius: passive transfer of protective immunity to mice with monoclonal antibodies.

Nine hybridoma cell lines secreting monoclonal antibodies specific for Nematospiroides dubius were produced by fusion of the mouse myeloma cell line NS-1 to either spleen cells or mesenteric lymph node cells from mice repeatedly infected with N. dubius. Seven of the antibodies were identified as IgM and two as IgG1. Each monoclonal antibody bound to polypeptide epitopes on both infective larvae (L3) and adult worms. However, five antibodies bound preferentially to L3 and three to adult worms. All nine antibodies reacted with high molecular weight protein antigens. Passive protective immunity in Balb/c mice was demonstrated with monoclonal antibodies Nd2 and Nd3 in ascites fluid which stunted both male and female worms and reduced parasite fecundity.

Animals↗
PubMed1988

Nematospiroides dubius: two H-2-linked genes influence levels of resistance to infection in mice.

Strains of mice sharing common H-2 haplotypes but different genetic backgrounds, and H-2 congenic strains of mice differing only at H-2 genes were studied to assess the role of H-2 and non-H-2 genes in immunity to challenge infections with the nematode parasite Nematospiroides dubius. Strains of mice sharing the H-2k haplotype were uniformly more susceptible to challenge than strains expressing H-2q alleles, regardless of genetic background. However, in some cases strains of mice sharing the k or q haplotypes differed significantly in levels of resistance. Therefore, non-H-2 genes must influence the response observed. H-2 cogenic strains of mice differed markedly in their ability to resist challenge infections. Mice sharing the C57BL/10 background but expressing k alleles were very susceptible to challenge, while the H-2q, H-2f, and H-2s, haplotypes were associated with resistance. Studies of H-2 congenic recombinant strains of mice suggested that two H-2 genes influence the antiparasite response. One of these genes maps to the left of E alpha and the other to the D-end of the H-2 complex. It is concluded also that the unique configuration of H-2 genes in F1 hybrids contributes to increased resistance to challange.

Alleles↗
PubMed1989

Nematospiroides dubius: influence of adjuvants on immunity in mice vaccinated with antigens isolated by affinity chromatography from adult worms.

Five adjuvants were examined for their ability to potentiate the immune response of mice to soluble antigens from adult Nematospiroides dubius prepared by affinity chromatography against antibodies from repeatedly infected mice as ligands (IMIgAg). Immunized mice were better protected against N. dubius by IMIgAg injected intraperitoneally with either pertussigen (75%) or aluminium hydroxide (Alum) (67%) as adjuvants than with Freud's complete (54%) or incomplete adjuvants (31%). Protection was correlated with elevated specific antibody values and with cellular responses. Quil A was toxic to recipient mice at the concentration used. Alum may be a more practical adjuvant than pertussigen, which may activate protective immunity only in specific recipient genotypes and oil-based adjuvants which appear to be less efficient, to vaccinate mice with soluble parasite antigens.

Adjuvants, Immunologic↗
PubMed1989

Suppression of heterologous immunity by Nematospiroides dubius antigens in vitro.

The direct effect of the soluble antigens in the homogenate of adult Nematospiroides dubius (AH) on spleen cells from uninfected NIH mice was investigated using a Mishell-Dutton culture system. Parasite antigens were shown to reduce the plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in a dose-dependent manner in vitro. A population of suppressor cells was demonstrated in the spleens of infected mice. Furthermore naive spleen cells cultured in the presence of AH gave rise to cells which depressed the PFC response of naive cells when subsequently cultured together in vitro. Treatment of these cell populations with anti-thy 1.2 plus complement did not impair suppressor activity, and it was concluded that cells expressing the T-cell phenotype were not involved.

Animals↗
PubMed1989

Immunity in mice vaccinated with a molecular weight 60,000 glycoprotein secreted by adult Nematospiroides dubius.

A mol. wt 60,000 glycoprotein was purified from adult Nematospiroides dubius excretory-secretory products (ES) by polyacrylamide gel electrophoresis and electroelution and used to vaccinate BCF1 mice. This molecule is also released from the surface of the parasite and can be cleaved by pepsin. Mice immunized twice with ES 60,000 in Alum adjuvant harboured similar numbers of N. dubius as did control mice but voided 40% fewer parasite eggs in their faeces. The mol. wt 60,000 component in ES and from the surface of the parasite appears to influence how the parasite reproduces and may be important to its survival.

Animals↗
PubMed1989

Low molecular weight immunosuppressors secreted by adult Nematospiroides dubius.

Adult Nematospiroides dubius excretory-secretory products (ES) were collected from worms cultured in vitro, separated by sodium dodecyl sulphate--polyacrylamide gel electrophoresis (SDS-PAGE) into four fractions (FI-IV), electroeluted and assessed for their ability to inhibit the proliferation of mouse lymphocytes stimulated by mitogens in vitro. The proliferation of mitogen- and ES-stimulated mouse spleen lymphocytes from normal and infected mice was inhibited by low mol. wt ES F-IV (less than 26,000).

Animals↗
PubMed1989

Proteolytic enzymes in excretory-secretory products from adult Nematospiroides dubius.

Excretory-secretory products (ES), collected from in vitro cultures of adult Nematospiroides dubius, were examined for proteolytic enzyme activity. ES enzymes had a pH optimum of 8.0 and their activity was sensitive to serine-proteinase inhibitors. Three SDS-resistant proteases were identified in ES at molecular weight (mol. wt) 200,000, 105,000 and 48,000 by incorporating substrates into the matrices of sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE) gels.

Animals↗
PubMed1985

The suppression of homologous immunity by soluble adult antigens of Nematospiroides dubius.

An established adult infection of Nematospiroides dubius was unaffected by the administration of immune lymphocytes and immune sera whereas an incoming larval infection was expelled. Past experiments have shown that the immune inoculum at least had the ability to recognize adult stages, leading to the hypothesis that adult stages secrete or excrete an immunomodulatory shield around themselves in the gastrointestinal tract. This hypothesis was given further credence by the demonstration that soluble antigens derived from adults abolished the generation of homologous immunity to this parasite. Modulation of immunity was reflected by increased fecundity, increased worm size, and increased survival time in the gut.

Animals↗
PubMed1986

Inheritance of immunity in mice to challenge infection with Nematospiroides dubius.

Two lines of mice (Mus musculus) were selectively reared over 10 generations for high (H) and low (L) levels of immune response to Nematospiroides dubius, an enteric nematode parasite. Filial and backcross families were derived from the two parent lines. The mode of inheritance of the trait, immune response to challenge infection with N. dubius, was analysed by comparing the levels of infection in the parental, filial and backcross (BC) families of mice. The immunity of the F1 mice was found to be dissimilar to both parents, but was closer to the H value than to the level of immunity in the L mice. The backcross to H progeny showed levels of immunity approaching that of the H mice, whereas only two of four backcross to L families were low immune responders. Analysis of these results indicated that the inheritance of immunity in these mice to challenge infection with N. dubius was quantitative, partially dominant for high immune response, and additive, in nature.

Animals↗
PubMed1985

Vaccination against Nematospiroides dubius in mice using adult worm extracts as antigens.

Various preparations of somatic Nematospiroides dubius antigens were emulsified in Freund's complete adjuvant and assayed in Quackenbush mice for efficacy as vaccines against homologous infection. Soluble and particulate fractions were given by two different routes. Only minimal protection was induced by vaccination with either soluble or particulate parasite fractions used independently when compared with the adjuvant control. Fewer and smaller worms were recovered from, and significantly fewer parasite eggs were voided by, mice which had been treated previously with both soluble somatic protein (15 micrograms N. dubius per mouse) by the intraperitoneal route and particulate antigen by subcutaneous injection. These mice showed higher antibody titres in comparison with other mice treated with either fraction alone. Further, treatment with both antigen fractions together appeared to exert a synergistic effect in comparison with either fraction administered alone.

Animals↗
PubMed1985

Suppression of early immunity to Nematospiroides dubius in mice by selective depletion of neutrophils with monoclonal antibody.

The role of neutrophils and eosinophils in the acquired resistance of mice to infection with the helminth Nematospiroides dubius has been investigated in vivo by testing infected mice for their resistance to a challenge dose of larvae following treatment with monoclonal rat antibodies (MAbs) specific for mouse granulocytes. Treatment of normal and infected mice with NIMP-R10 MAb reduced the number of neutrophils in the peripheral blood and peritoneal cavity during the ensuing 2-5 days without affecting macrophage or eosinophil levels. The effect of this MAb on immunity depended on the immune status of the mice tested. The partial resistance of mice receiving a primary 'immunising' infection, followed by passive transfer of immune serum and challenge at 4 days, was completely suppressed by NIMP-R10 MAb. The acquired resistance of mice challenged 10 days after being given a single 'immunising' infection was halved by NIMP-R10 treatment, while that of 'twice-immunised' mice (infected on days 0 and 14, challenged on day 24) was unaffected. Treatment of twice-infected mice with the eosinophil-specific MAb NIMP-R6 reduced the number of eosinophils in the blood and peritoneal cavity by 40-60%, but caused no significant loss of immunity. The data indicate that after infection of mice with N. dubius, neutrophils play a predominant role in early resistance to reinfection, but they become progressively less essential as activated macrophages and (following a second infection) eosinophils become prevalent. The lack of effect of NIMP-R6 MAb treatment on the immunity of twice-infected mice may have been due to an insufficient reduction in eosinophil numbers; however, it seems likely that the neutrophils and macrophages present in these mice would have provided adequate protection even in the absence of eosinophils.

Animals↗
PubMed1987

Mice vaccinated against Nematospiroides dubius with antigens isolated by affinity chromatography from adult worms.

A crude soluble extract (AWH) obtained from homogenized adult Nematospiroides dubius worms was fractionated into normal (NMIgAg) and immune (IMIgAg) antigens by sequential passage through Sepharose 4B, and CNBr-activated Sepharose 4B to which immunoglobulins from normal (NMIg) and N. dubius-infected mouse serum (IMIg) had been coupled. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions showed that MNIgAg and IMIgAg contained several proteins with molecular weights (MW) between 20,000 and 200,000. IMIgAg contained 2 polypeptides, MW 24,000 and 55,000, which reacted strongly in western blot analysis against IMIg; the larger molecule related to a cuticular component of the worm. Protective high MW AWH G-200 filtrates shared 5 polypeptides with IMIgAg (MW 85,000-200,000) together with several smaller molecules (MW 30,000-less than 10,000). The MW 55,000 and 24,000 components concentrated in IMIgAg were restricted to non-protective low MW AWH gel filtrates. BCF1 mice vaccinated with IMIgAg were protected against N. dubius. Worm numbers, size and fecundity were reduced to an extent commensurate with that obtained in mice vaccinated with AWH. Mice vaccinated with NMIgAg showed partial resistance. The role of surface and dominant parasite immunogens in immunity is discussed.

Animals↗
PubMed1987

Surface and excretory/secretory antigens of Nematospiroides dubius.

Sera from mice immunized by repeated anthelmintic-terminated infections (IMS) or by a single primary infection (PMS) of Nematospiroides dubius were assayed for antibodies reactive with N. dubius antigens. The surface proteins of adult worms, the excretory/secretory (ES) proteins of adult worms and soluble extracts from lysates of both adult (AWH) and larval (LWH) N. dubius were used in an immunoprecipitation assay. A 60,000 MW protein was the major radiolabelled surface and ES protein. This antigen was dominant in precipitates by IMS from AWH, ES and surface-labelled worms but was not precipitated by PMS from any antigen source. Minor antigens of 20,000, 33,000, 36,000, 45,000, 50,000 and 66,000 MW were precipitated from AWH by both PMS and IMS but not from ES or surface-labelled worms. The dominant antigen precipitated from LWH by IMS was 20,000 MW. This antigen was not precipitated by PMS but larval antigens of 65,000 and 96,000 MW were precipitated by both PMS and IMS. The major antigens precipitated by IMS were adult (60,000 MW) and larvae (20,000 MW) stage-specific but some minor antigens (33,000, 45,000, 50,000 MW) were common to both stages. Our results show that the dominant antigen precipitated by serum immunoglobulin from mice immunized by repeated anthelmintic-terminated infections are proteins present on both the cuticle surface and in the ES.

Animals↗