D.B. Adams

Cross-immunity between Haemonchus contortus and Trichostrongylus colubriformis in sheep

Cross-protective immunity between the nematode parasites, Haemonchus contortus and Trichostrongylus colubriformis, was examined in sheep vaccinated with irradiated larvae of either species. Secondary immunological responsiveness stimulated in this manner protected only against challenge infection with the species used for vaccination. Significant cross-protective immunity was not observed. Titres of serum antibody to an extract of adult but not infective larval T. colubriformis reflected the specificity for protective immunity. Immediate hypersensitivity skin reactions to nematode extracts did not reflect the antigen-specificity for protective immunity.

Immunity acquired by sheep from an experimental infection with Haemonchus contortus.

Abstract Adams D.B. and Beh K.J. 1981. Immunity acquired by sheep from an experimental infection with Haemonchus contortus . International Journal for Parasitology 11 : 381–386. A primary infection of sheep with a single dose of Haemonchus contortus larvae was traced by faecal egg counts until it had substantially declined after 55 weeks. These primed sheep were then given a sequence of two reinfections with the parasite. Comparison of faecal egg counts in primed sheep and in two separate groups of previously worm-free sheep showed that primary infection conferred significant immunity. This, however, was not sufficiently protective to prevent the development of further anaemia and faecal egg counts indicative of clinical haemonchosis. It is suggested that an adaptation in the host-parasite relationship which promotes the longevity of primary infection with H. contortus may also moderate the induction of acquired immunity. The titre of haemagglutinating antibody specific for H. contortus rose in serum during the course of primary infection, but the two reinfections did not stimulate a rise in titre. Titres of haemagglutinating antibody before reinfection did not correlate with subsequent faecal egg counts.

Time of onset and target of immune reactions in sheep with acquired immunity against Haemonchus contortus

Abstract Adams D. B. 1982. Time of onset and target of immune reactions in sheep with acquired immunity against Haemonchus contortus . International Journal for Parasitology 12: 439–443. Nonimmune sheep and sheep rendered immune by infection with the abomasal nematode, Haemonchus contortus , were infected with the parasite and treated at various times with the glucocorticosteroid, dexamethasone. The results show that this immunosuppressant drug abolished acquired but not innate immunity to H. contortus and that acquired responses were not important in restraining the fecundity of adult worms during primary infection. By treating immune sheep with dexamethasone during reinfection, it was shown that the responses acting against the establishment of infection commence later than the fourth day after larval administration and are complete by the seventh day. H. contortus more advanced in development than the fourth-larval stage were relatively insusceptible to this manifestation of acquired immunity.

A preliminary evaluation of factors affecting an experimental system for vaccination-and-challenge with Haemonchus contortus in sheep

A preliminary evaluation of factors affecting an experimental system for vaccination-and-challenge with Haemonchus contortus in sheep. International Journal for Parasitology 19: 169-175. Studies were made with Haemonchus contortus in sheep to ascertain the influence of a range of factors in the domain of the host, the parasite or the vaccine on the formulation of protocols for vaccination-and-challenge to be used in identifying protective immunogens. The results corroborate earlier findings that protective immunity can follow vaccination with homogenates of parasites and show that initial processing of parasites for a vaccine leaves protective immunogen in a functional state. Sonicates of adult worms produced protective immunity and were identified as raw stock in which to prospect for candidate immunogens. By contrast, sonicates of infective larvae and exsheathing fluid invoked no significant protection and were not accredited for the same purpose. In an experiment unaccompanied by protective immunity, ewes contained lower worm burdens than castrate males indicating that vaccination experiments should be made with hosts of one sex only. Again in an experiment unaccompanied by protective immunity, Freunds complete adjuvant increased susceptibility to infection compared with Freunds incomplete adjuvant or no adjuvant implying a profound and persistent interference from killed mycobacteria on resistance against H. contortus.

Observations on the self-cure reaction and other forms of immunological responsiveness against Haemonchus contortus in sheep

Abstract Self-cure reactions and immunological responses preventing establishment of Haemonchus contortus in sheep may operate as separate entities. In one experiment, self-cure occurred when challenge infection with 5000 larvae was superimposed on an infection with 5000 larvae given to worm-free sheep 6 weeks previously. Resident worms were rejected and establishment of infection by incoming larvae was impeded. The latter effect was not observed in sheep treated similarly but with resident parasites removed by treatment with oxfendazole before challenge. In another experiment, younger worm-free sheep primed by three infections with 2000 larvae at intervals of 2 weeks or a single infection with 6000 larvae were challenged with 10,000 larvae 6 weeks after the first priming infection. Self-cure was not incited but establishment of infection was impeded in sheep primed with three divided doses of larvae whether or not priming infections had been removed by oxfendazole. Infection regimes used for priming did not influence numbers of arrested fourth-stage larvae derived from challenge infection. However, more arrested larvae were present when challenge was superimposed on extant infections, indicating that resident worms or a factor activated by their presence induced developmental arrest. In a third experiment, large burdens with H. contortus were established in sheep immunosuppressed with the corticosteroid, dexamethasone, at the time of infection. Self-cure was not triggered by a challenge infection given 32 days later either in these sheep, or in sheep with a smaller worm burden derived from infection given without immunosuppression. Faecal egg counts, however, indicated that development of the challenge infection was prevented in both groups of sheep. Investigation of self-cure is restricted by lack of a predictable system for reproducing the phenomenon. Self-cure was induced by a single infection with 5000 larvae in mature sheep but not with 6000 larvae in immature sheep. Three infections with 3000 larvae given at intervals of 2 weeks to mature sheep did not prime for self-cure. Procedures aimed at heightening immediate hypersensitivity, i.e. treatment with pertussis vaccine or concurrent infections with Ostertagia circumcincta , did not promote self-cure reactivity in the latter situation.

Enhanced resistance to infection with Haemonchus contortus in sheep treated with a corticosteroid

Abstract Adams D. B. and Davies H. I. 1982. Enhanced resistance to infection with Haemonchus contortus in sheep treated with a corticosteroid. International Journal for Parasitology 12 : 523–529. Fewer worms established from experimental infections with Haemonchus contortus in either immune or naive sheep or in sheep of undefined immune status given the corticosteroid, dexamethasone, around the time of challenge. In four experiments, the number of adult worms present in sheep treated with dexamethasone ranged from 32 to 36% of that in untreated animals. That the phenomenon did not stem from direct action of dexamethasone on the worms themselves was demonstrated by comparing continuous treatment with the drug from infection until patency with treatment given at infection and four days later. Sheep continuously treated with dexamethasone harboured similar numbers of worms as the infection controls whereas fewer parasites were found in sheep given dexamethasone around the time of infection. The results imply that active regulation of immunological unresponsiveness operates in sheep during infection with H. contortus and that disruption of immunoregulation by dexamethasone released protective responses thereby decreasing worm burdens. Because suppressor lymphocytes are implicated, cellular perturbations following treatment with dexamethasone were investigated. Dexamethasone did not cause marked lymphopenia. It, however, reduced blastogenic responses by lymphocytes to con A but not PHA. Comparison of responses to these mitogens in cells from blood and lymph demonstrates that con A and PHA-reactivity resides in identifiably different cell populations in sheep.

Infection with Haemonchus contortus in sheep and the role of adaptive immunity in selection of the parasite

Abstract Adams D. B. 1988. Infection with Haemonchus contortus in sheep and the role of adaptive immunity in selection of the parasite. International Journal for Parasitology18: 1071–1075. A series of infections with Haemonchus contortus in immune and non-immune sheep gave no indication that successive generations of the parasite were selected for the enhanced ability to cope with host-protective immunity. Separate subpopulations of the parasite were passaged through individual immune sheep and were compared at each generation with infections by the pooled populations in an additional panel of immune sheep. The experiment ceased when infections became too low to allow the production of sufficient infective larvae for reinfection. Results showed that H. contortus is unable to make adjustments to the immune status of a given sheep. Attention is thus diverted from the process through which host identifies self and non-self and from the histocompatibility system as the targets for possible antigen-mimicry by H. contortus.

Immunity to Haemonchus contortus and the cellular response to helminth antigens in the mammary gland of non-lactating sheep.

Cellular exudates induced by infusion with helminth antigens were examined in non-lactating mammary glands of ewes immune to infection with the abomasal nematode, Haemonchus contortus. Secondary immunological responsiveness was expressed in two ways. Firstly, antigens from adult H. contortus elicited larger eosinophil-rich cellular exudates in immune compared to non-immune ewes. In this situation, secondary responsiveness in the mammary gland must have been generated through abomasal infection with the parasite. Secondly, repeated infusion with the antigens from adult H. contortus increased the size of cellular exudates in both immune and non-immune ewes. Eosinophils predominated but numbers of macrophages and lymphocytes were also increased. In this second situation, secondary responsiveness must have been either supplemented in immune ewes or derived completely in non-immune ewes by contact with helminth antigens through the mammary gland. The helminth antigens which induce eosinophil exudates in the mammary gland may not be potently protective against H. contortus. Furthermore, eosinophil exudation may not be an in vivo correlate of immunity which is directly useful for discriminating protective antigens and applicable to vaccine development. Infusion with antigens from adult forms of either H. contortus or Trichostrongylus colubriformis elicited cellular exudates equally well in immune ewes primed by infusion with H. contortus adult antigens 7 days beforehand. In addition, antigens from infective larvae of H. contortus elicited cellular exudates more potently than antigens from adult worms. However, vaccination with irradiated larvae has shown that species-specific protective immunity for H. contortus is stronger than cross-protective immunity conferred by T. colubriformis.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental arrest of Haemonchus contortus in sheep treated with a corticosteroid

Abstract Adams D. B. 1986. Developmental arrest of Haemonchus contortus in sheep treated with a corticosteroid. International Journal for Parasitology 16: 659–664. Developmental arrest of the nematode, Haemonchus contortus , at the fourth larval stage within sheep appears to be controlled by a complex of signals and events in which both host-associated and parasite-associated factors are essential participants. Treatment of worm-free sheep with the corticosteroid, dexamethasone, during infection demonstrated the existence of an arrest-prone state in infective larvae and a host-associated influence actuating the phenomenon of arrest. Not all subpopulations of the parasite responded to the influence of dexamethasone and a selection experiment in which the parasite was passaged through immune and non-immune sheep showed that the arrest-prone state was largely determined by genetic factors. The host-associated factor initiating or actuating arrest and identified by dexamethasone-treatment could be ascribed more satisfactorily to a manifestation of immune responsiveness than to a direct effect of the corticosteroid.

The effect of dexamethasone on a single and a superimposed infection with Haemonchus contortus in sheep

Abstract Experiments of the same design were run with non-immune and immune sheep to highlight protective immunity against H. contortus . Sheep were given a single infection with H. contortus or were given a second infection 7 days later. In half the sheep dexamethasone treatment was given to coincide with either the initial or the second infection. In non-immune sheep there was no indication that the first infection with the parasite influenced the magnitude of the second infection. Immunosuppressive treatment showed that major protective responses reduced the size of both the first and second challenge infections in sheep made immune by previous exposure to infection. However, responses to the second challenge could be abolished despite their effective operation against the first challenge. Parasites of longer standing in the host than 7 days appear to be resistant to the major protective response. Arrested larvae were seen in the experiment with non-immune sheep but not in the one with immune sheep, a difference ascribed to the different times of year in which experiments were run and not to differences in the physiological status of sheep. Both corticosteroid treatment and superimposed infection triggered developmental arrest in arrest-prone larvae