scholarly journals Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): dose-dependent expulsion of adult worms

Parasitology ◽  
1989 ◽  
Vol 98 (1) ◽  
pp. 115-124 ◽  
Author(s):  
M. Robinson ◽  
F. Wahid ◽  
J. M. Behnke ◽  
F. S. Gilbert
Keyword(s):  
Primary Infection ◽  
Dependent Manner ◽  
Heligmosomoides Polygyrus ◽  
Data Set ◽  
High Infection ◽  
Parasite Survival ◽  
Nematospiroides Dubius ◽  
Parasite Loss ◽  
Dose Dependent ◽  
Marked Dependence

SummaryThe survival of Heligmosomoides polygyrus was monitored during primary infections in female C57Bl10, NIH and BALB/c mice at low and high intensities of infection. Survivorship curves were fitted for each data set and analysed. C57Bl10 mice, given either low or high intensities of infection, harboured parasites for 28–37 weeks, heavier infections surviving marginally but significantly longer. Essentially the survivorship curves of H. polygyrus in C57Bl10 mice could be accounted for by senility, the increased probability of worms with a longer life-span occurring at high infection intensities and, possibly, by a contribution from host-protective immune mechanisms in the terminal stages of infection. The pattern of survivorship was different in NIH and BALB/c mice. NIH mice showed weak but significant density-dependent suppression of parasite loss and infections in this strain did not exceed 27·5 weeks in duration. Primary infections in BALB/c mice were briefer still and showed marked dependence on parasite density. Thus low-level infections lasted 10–15 weeks whereas heavier infections survived for 21–34 weeks. The data suggested that both strains developed host-protective responses to adult H. polygyrus and that parasite survival was curtailed earlier than would be expected if senility alone was involved. The hybrid strains (C57Bl10 × NIH)F1 and (B10G × NIH)F1 both expelled H. polygyrus in a dose-dependent manner, worm loss commencing within 10 weeks of infection. In some experiments worm loss was clearly evident by weeks 4 and 6. These hybrid strains showed gene complementation in that adult worms were cleared considerably earlier than in parental strains.

Immunological realtionships during primary infection with Heligmosomides polygyrus (Nematospiroides dubius): expulsion of adult worms from fast responder syngeneic and hybrid strains of mice

Parasitology ◽  
1989 ◽  
Vol 98 (3) ◽  
pp. 459-469 ◽  
Author(s):  
F. N. Wahid ◽  
M. Robinson ◽  
J. M Behnke
Keyword(s):  
High Intensity ◽  
Primary Infection ◽  
Time Course ◽  
The Other ◽  
Mouse Strains ◽  
Heligmosomoides Polygyrus ◽  
Worm Expulsion ◽  
Nematospiroides Dubius ◽  
The One ◽  
Identical Gene

SUMMARYThe time-course of low and high intensity primary infections with Heligmosomoides polygyrus was monitored in SJL and SWR mice, both of which usually expel worms within 7 weeks of larval administration. Worm expulsion in these strains was not dependent on the intensity of infection, with low and high intensity worm burdens being lost within the same period of time. The ability to expel worms rapidly was inherited in a dominant manner in F1 offspring of SJL or SWR mice mated with C57Bl10 mice; the latter being a strain in which no loss of worms was evident within 10 weeks of infection. However, neither (SJL × C57Bl10)F1 nor (SWR × C57Bl10)F1 mice expelled worms as rapidly as the parental SJL and SWR strains. (SWR × B10G)F1 [H-2q] mice eliminated worms faster than (SWR × C57Bl10)F1 [H-2bq], suggesting that the b haplotype had a moderating influence on the expulsion process. In fact (SWR × B10G)F1 mice showed a significant reduction in worm burdens by week 4 but by weeks 6–8 the rate of worm loss had slowed considerably. In contrast, SJL and SWR mice, whilst initiating rejection slightly later, (after week 4) expelled all worms within the following 2 weeks. Thus two distinct patterns of response were observed among the fast responder strains as exemplified by SWR and SJL mice on the one hand and (SWR × B10G)F1 on the other. Our results support the hypothesis that the course of a primary infection with H. polygyrus is influenced by multiple host gene loci, some of which are encoded within the MHC. SJL and SWR mice probably have similar if not identical gene combinations at loci which determine a fast responder phenotype, distinguishing them from the other mouse strains which have been studied.

scholarly journals Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): the capacity of adult worms to survive following transplantation to recipient mice

Parasitology ◽  
1987 ◽  
Vol 95 (3) ◽  
pp. 569-581 ◽  
Author(s):  
J. M. Behnke ◽  
Diane J. Williams ◽  
J. Hannah ◽  
D. I. Pritchard
Keyword(s):  
Host Resistance ◽  
Post Infection ◽  
Primary Infection ◽  
Worm Burden ◽  
Egg Production ◽  
Heligmosomoides Polygyrus ◽  
Duration Of Infection ◽  
Nematospiroides Dubius ◽  
Single Worm

SUMMARYChronic primary infections with Heligmosomoides polygyrus (Nematospiroides dubius) are still relatively poorly documented, particularly in relation to the role of host resistance in limiting worm survival. In the present work the duration of infection with H. polygyrus was studied in CFLP mice given doses of infective larvae ranging from 50 to 500 L3. The least heavily infected (50 L3) group ceased egg production earliest (week 36) whereas eggs were still detected in the faeces of mice given 500 larvae in week 42. At autopsy (week 42) mice given 50 larvae had virtually lost their entire worm burden with 5 out of 11 mice still harbouring a single worm each. However, all the mice in the group given 500 larvae were still infected, the highest worm burden being 93. The concentration of serum IgGl and specific antibody was highest in mice given 500 larvae, but sera taken from mice with declining worm burdens 19–38 weeks post-infection did not contain detectable host-protective antibody. During the course of infection in CFLP mice, H, polygyrus sustained irreversible changes in its capacity for subsequent survival. Thus, adult worms transferred to naive mice 2, 7, 14, 30 or 36 weeks post-infection did not live longer than worms of a comparable age in the respective donor group. In contrast, primary infection worms taken from jirds in which expulsion is usually completed by 6 weeks post-infection, re-established in mice and survived considerably longer than in the group of donor jirds. These results were discussed in relation to the possible interactions between parasite senility and immunomodulation, and host resistance in limiting primary infections with H. polygyrus in mice and jirds.

Chloride influx in human leucocytes: A triple-isotope technique for the assessment of chloride transporters

1991 ◽  
Vol 81 (3) ◽  
pp. 405-412 ◽  
Author(s):  
M. Hogg ◽  
L. L. Ng ◽  
J. E. Davies
Keyword(s):  
Intracellular Ph ◽  
Autologous Serum ◽  
Dependent Manner ◽  
Tetradecanoyl Phorbol Acetate ◽  
Uptake Rates ◽  
Internal Ph ◽  
Isotope Technique ◽  
Disulphonic Acid ◽  
Dose Dependent ◽  
Marked Dependence

1. A novel triple-isotope method using 3H2O, [14C]-sucrose and 36Cl− for measuring initial Cl− uptake rates in human leucocytes that had been preincubated in 10% (v/v) autologous serum is described. 2. There was a marked dependence of Cl− influx on intracellular pH, the flux at an intracellular pH of 7.20 being about 11.2% of that at an intracellular pH of 7.56. 3. This Cl− influx was inhibited by 4,4-di-isothiocyanatostilbene-2,2-disulphonic acid in a dose-dependent manner. Half-maximal inhibition by 4,4-diisothiocyanatostilbene-2,2-disulphonic acid at an internal pH of 7.56 in the presence or absence of HCO−3 was 0.30 or 0.35 mmol/l, respectively. 4. Depletion of intracellular Cl− resulted in a 70.7% decrease in Cl− influx, whereas depletion of cellular ATP led to a 37.7% decrease in Cl− influx. 5. The phorbol ester 12-O-tetradecanoyl phorbol acetate at a concentration of 0.1 μmol/l reduced Cl− influx, especially the 4,4-di-isothiocyanatostilbene-2,2-disulphonic acid-sensitive component. This effect was independent of intracellular pH changes or Na+/H+ anti-port activity.

Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): H-2 linked genes determine worm survival

Parasitology ◽  
1991 ◽  
Vol 103 (1) ◽  
pp. 157-164 ◽  
Author(s):  
J. M. Behnke ◽  
F. N. Wahid
Keyword(s):  
Primary Infection ◽  
Congenic Mouse ◽  
Mouse Strains ◽  
Gene Products ◽  
Heligmosomoides Polygyrus ◽  
Duration Of Infection ◽  
Response Phenotype ◽  
Nematospiroides Dubius ◽  
Resistance To Infection ◽  
Congenic Mouse Strains

The course of primary infection was studied in BALB and B10 H-2 congenic mouse strains. The duration of infection, as assessed with regular faecal egg counts and worm burdens, was shorter in mice carrying the H-2s, H-2d or H-2q haplotypes when compared to mice with H-2b. Strains with H-2k were intermediate. An experiment was carried out to test the hypothesis proposed by Wassom, Krco & David (1987) predicting that the progeny of I–E+ve mouse strains crossed with I–E-ve strains, would show susceptibility rather than resistance to infection. This hypothesis was not substantiated by our data and we conclude that it does not apply to primary infections with Heligmosomoides polygyrus. It is proposed that the gene products of at least two loci within the H-2 (associated with the H-2b and H-2k haplotypes) are crucial in determining the response phenotype of mice to primary infection with H. polygyrus. One allele, (associated with the H-2b haplotype) may be preferentially affected by parasite-mediated immunosuppression.

Heligmosomoides polygyrus (Nematoda): the dynamics of primary and repeated infection in outbred mice

1986 ◽  
Vol 229 (1254) ◽  
pp. 47-67 ◽  
Keyword(s):  
Population Dynamics ◽  
Primary Infection ◽  
Female Worm ◽  
Parasite Population ◽  
Detectable Effect ◽  
Heligmosomoides Polygyrus ◽  
Male And Female ◽  
Repeated Infection ◽  
Parasite Survival ◽  
The Impact

The population dynamics of Heligmosomoides polygyrus were studied in outbred male MF1 mice subject either to primary or repeated experimental infection. Little variability in susceptibility was observed between mice, but heterogeneity increased with both duration and intensity of primary infection; this result indicates that there are differences in parasite survival between hosts. The rate of parasite-induced host mortality was 4 x 10 -4 per parasite per host per parasite lifespan. The mortality rates of male and female larvae during their development in the intestinal wall were estimated as 0.033 and 0.021 per parasite per day respectively, and estimates of the expected lifespans of the adult male and female parasites in primary infection of 11.22 and 9.92 weeks were obtained. Approximately 40% of female worms were observed in copula at any one time, although this proportion was significantly depressed in hosts harbouring fewer than 50 parasites and during the first four weeks of infection. Parasite fecundity was markedly age-dependent; each female worm produced approximately 31000 eggs during its lifespan. No density dependence in either worm survival or fecundity in primary infection was apparent. The only detectable effect of worm density was in association with spatial distribution in the intestine; high levels of infection were associated with a posterior shift in the location of a proportion of the parasite population. Characterization of the dynamics of primary infection allowed predictions to be made about the expected dynamics of repeated infection. The comparison of predicted results and observed data revealed unequivocal epidemiological evidence for the density-dependent regulation of parasite population growth during repeated infection, affecting both parasite survival and parasite fecundity. The results also demonstrated the existence of two types of host individual in which the dynamics of repeated infection were markedly different. It is concluded that immunological differences between mice (possibly under genetic control) may be responsible for the observed effects; approximately 25% of MF1 mice seem unable to generate any protective immunity against H. polygyrus, whereas 75% become almost completely refractory to reinfection. This experimental system could be used for quantitative investigation of the impact of acquired immunity and genetic heterogeneity on helminth population dynamics. Both are of obvious relevance with respect to the control of infections of medical and veterinary significance.

scholarly journals Immunity to adult Heligmosomoides polygyrus (Nematospiroides dubius): survival or rejection of adult worms following transplantation to mice refractory to larval challenge

1988 ◽  
Vol 62 (3) ◽  
pp. 221-231 ◽  
Author(s):  
M. Robinson ◽  
J. M. Behnke ◽  
D.J.L. Williams
Keyword(s):  
Adult Worm ◽  
Primary Infection ◽  
Heligmosomoides Polygyrus ◽  
Delicate Balance ◽  
Specific Immunity ◽  
Nematospiroides Dubius ◽  
Genetically Determined

ABSTRACTExperiments were carried out to explore the survival of 14-day adult H. polygyrus following transplantation to mice of four strains, immunized by various protocols. Adult worm establishment and survival was unimpaired in CFLP mice which were totally refractory to larval challenge. Transplanted adult worms were also successful in NIH mice immunized by the 9-day abbreviated infection regime. However, NIH mice exposed to irradiated larvae or subjected to the divided primary infection, expelled transplanted adults. The 9-day abbreviated infection was further examined in SJL and (C57 Bl10 X NIH) F1 mice which expel adult worms during a primary infection and although this regime was unsuccessful in causing NIH mice to reject adult worms, expulsion of adult worms was accelerated in SJL and F1 mice. The survival of adult H. polygyrus was discussed in the context of stage-specific immunity and the delicate balance between the immunogenic stimuli from developing larvae, the immunomodulatory activities of adult stages and the host's genetically determined capacity to respond to these opposing signals.

Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

1990 ◽  
Vol 63 (03) ◽  
pp. 505-509 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaar
Keyword(s):  
Molecular Weight ◽  
Bone Mineral ◽  
Low Molecular Weight Heparin ◽  
Zinc Content ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Bone Mineral Mass ◽  
Bone Ash ◽  
Dose Dependent ◽  
Mineral Mass

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

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