Site potential for challenge attrition in mice, rats and guinea pigs vaccinated with irradiated cercariae of <i>Schistosoma mansoni</i>

A histopathological and ultrastructural study was made of schistosomula and associated inflammatory reactions in the lungs of normal mice, and mice previously vaccinated with irradiated cercariae. In normal mice at day 7 post-infection all schistosomula were located in blood vessels. From day 11 onwards an increasing proportion of schistosomula were intra-alveolar (80% from day 20). No cellular reactions were evident around intravascular parasites in normal mice but at later sampling times large compact foci were associated with alveolar parasites. Initial reactions, probably in response to non-specific tissue damage, were approximately 50% polymorphonuclear, and 50% mononuclear. Mononuclear cells predominated at later times. In spite of inflammation, no damage to the schistosomula was observed. There was no evidence for re-entry of schistosomula into blood vessels, and it was assumed entry into alveoli occurred accidentally as parasites attempted to traverse pulmonary blood vessels. The pattern of localization of schistosomula in vaccinated mice was similar to that in normal mice, the proportion in alveoli increasing with time (64% from day 20). The most significant difference was that intravascular schistosomula attracted foci of host leucocytes which were always 85% or more mononuclear, containing both lymphocytes and macrophages. The infiltrating cells enlarged the intersititium, separating the vascular endothelium from the alveolar epithelium. Fibrous protein was also deposited in the interstitial region. In some instances the complete blood-air barrier was destroyed by the infiltrates. Unusual paracrystalline inclusions were observed in alveolar macrophages and giant cells. The differences in cellular responses in vaccinated and normal mice suggest that challenge schistosomula stimulated an anamnestic immune response. The resulting inflammation, by impeding movement through the vasculature, terminated migration in the lungs, and accounted for the observed resistance to reinfection. The reactions in vaccinated mice have many of the features of a delayed hypersensitivity response implying that lung phase resistance in vaccinated mice may be T-cell rather than antibody-mediated.

Section: Vaccinated Micesupporting

confidence: 53%

The role of pulmonary cellular reactions in the resistance of vaccinated mice to Schistosoma mansoni

Crabtree

Wilson

1986

“…The parasites were then washed three times and examined on a Leitz fluorescence microscope. Fluorescence was quantified using a fluorimeter as described previously (Pearce et al 1985).…”

Section: Immunofluorescencementioning

confidence: 99%

“…While parasitological studies indicate that skin stage schistosomula are vulnerable to resistance mechanisms in immunized mice (Miller & Smithers 1980, Smithers & Gammage 1980, McLaren Pearce & Smithers 1985, recent experiments utilizing autoradiography or histology (Mastin, Bickle & Wilson 1983) to track the migration of individual parasites of a challenge infection within the immunized host suggest that lung and or post-lung, pre-adult stages of the parasite may be the major targets of the protective immune response in uiuo. However such a premise is not compatible with data derived from in uitro studies which have shown that soon after penetrating the skin, schistosomula acquire several mechanisms for evading the immune response (McLaren 1984).…”

Section: Introductionmentioning

confidence: 99%

Post lung‐stage schistosomula of Schistosoma mansoni exhibit transient susceptibility to macrophage‐mediated cytotoxicity in vitro that may relate to late phase killing in vivo

Pearce

James

1986

Studies of protective immunity against Schistosoma mansoni in immunized mice suggest that a proportion of challenge parasites may be eliminated after they have passed through the lungs of the host several days after infection; however, no potential immune effector mechanism of resistance against this stage of the parasite has yet been identified, since schistosomes have been shown to rapidly become resistant to antibody-dependent killing mechanisms. In this study, different development stages of S. mansoni were examined for their susceptibility to in vitro cytotoxicity by lymphokine-activated macrophages. As previously shown, newly transformed larvae were readily killed by lymphokine-treated peritoneal macrophages or the macrophage cell line IC-21 (80% mortality over 48 h in vitro), whereas 7 and 10 day old lung-stage parasites had become refractory to macrophage effects. However, after 2 to 2 1/2 weeks of development in vivo, juvenile parasites recovered from the liver were again susceptible to activated macrophage-mediated cytotoxicity (25-65% mortality). Ultrastructural studies of 2 1/2 week old parasites co-cultured with activated IC-21 cells revealed that damage was largely restricted to the areas beneath the parasite surface and gut syncitia; surface membrane disruption was not evident. This late stage of susceptibility was transient and by 4 to 6 weeks liver-stage worms had again become refractory to macrophage killing. The interaction of post lung-stage parasites with activated macrophages was antibody independent. Furthermore, schistosomes isolated from the portal circulation 2 1/2 weeks after infection showed no evidence of surface-bound immunoglobulin in a quantitative immunofluorescence assay, nor did antisera from chronically infected mice (CIS) or mice vaccinated with irradiated cercariae (VS) react with the surface of these parasites in vitro, making the possibility of direct antibody-dependent killing mechanisms unlikely. However, both CIS and VS did recognize excretory/secretory proteins synthesized by 2 1/2 week old liver-stage schistosomes, including a major antigen of approximate Mr (X 10(-3] 220 (220K). It is therefore possible that such antigens might participate in protective immunity, for example via immune complex formation or activation of sensitized T cells. These observations support the role of macrophages as immune effector cells in mice immunized against Schistosoma mansoni, and provide the first physiologically relevant mechanism whereby the immune system might recognize and kill post-lung stage schistosomes.

“…It is now well established that laboratory rodents vaccinated with highly irradiated cercariae of Schistosoma mansoni develop significant protection against a challenge population of worms, and that resistance depends upon specific immunological mechanisms (Smithers & Doenhoff 1982, Dean, Bukowsky & Clark 1981, James, Labine & Sher 198 1, Sher et al 1982, Ford et al 1984, McLaren, Pearce & Smithers 1985. The rat and mouse models of vaccine-induced immunity have without doubt, received most attention with respect to dissection of the sites and mechanisms of challenge elimination, but the reintroduction of the guinea-pig as an alternative laboratory system (Pearce & McLaren 1983 a,b), has now revealed that challenge attrition does not necessarily occur at the same point along the migratory pathway of the parasite in every laboratory rodent .…”

Section: Introductionmentioning

confidence: 99%

Schistosoma mansoni: liver phase challenge attrition is a stage‐dependent phenomenon in guinea‐pigs vaccinated with highly irradiated cercariae

McLaren¹,

Rogers²

1986

Self Cite

Guinea-pigs vaccinated with highly irradiated cercariae of Schistosoma mansoni have been examined for their ability to kill challenge parasites at the level of the liver. Skin and lung phase attrition were eliminated by surgical introduction of 4/5 day old schistosomula, or 2, 3 or 6 week schistosomes into the mesenteric vasculature of vaccinated and naive animals. These experiments showed consistently that lung schistosomula and 2 week old parasites were killed preferentially by sensitized animals, but that older worms were refractory. Liver phase immune elimination would therefore seem to be a stage-dependent phenomenon in the vaccinated guinea pig model of schistosomiasis.