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The acquisition of host antigens by Schistosoma mansoni was studied by evaluating the resistance of schistosomula to the complement attack mediated by lethal antibody. Schistosomula cultured for 24 hours with intact human erythrocytes (N-HuE) or ghosts of any type of ABO or Rh blood group, showed a marked resistance to complement damage. Sheep red blood cells, pronase-treated N-HuE or erythrocytes from patients with paroxysmal nocturnal hemoglobinuria, which are complement-sensitive cells, were unable to protect schistosomula. Schistosomula protected by N-HuE became again susceptible to complement killing after incubation with a monoclonal antibody anti-DAF. These results indicate that, in vitro, host DAF from N-HuE can be acquired by schistosomula surface in a biological active form that protects the parasite from the complement lesion.

Protein A-sepharose affinity chromatography was used to isolate IgG subclasses from the serum of CBA mice chronically infected with Schistosoma mansoni. The subclasses were tested for the presence of two antibodies which are responsible for the death of young schistosomula in vitro; 'lethal antibody' (LA), which kills schistosomula in co-operation with complement and 'eosinophil adherence antibody' (EAA) which causes the death of schistosomula by promoting the adherence of eosinophils to the parasite. LA and EAA were detected only in the IgG fraction of the serum. LA was concentrated in the IgG2a fraction and EAA in the IgG1 fraction. The development of IgG subclasses specific for schistosomula was followed in mice exposed to twenty cercariae by the fluorescent antibody technique. IgG1, IgG2a and IgG2b antibodies were detected 2 weeks after infection and their titres rose steadily to reach high levels by weeks 12 or 14. IgM antibody was not detected until week 6 and IgA until week 10; both were present at lower concentrations than the IgG1 antibodies.

The effect of different incubation media and of temperature on the induction of water sensitivity has been investigated in intact and tailless Schistosoma mansoni cercariae. Removal of the cercarial tail by vortex stirring and elevation of the temperature of the medium from 27 to 37 degrees C resulted in the rapid onset of permeability changes in the larvae. The rate of change was greater in water than in TC-199 or Hanks' BSS media. Lowering the pH of the medium or increasing the concentration of Ca2+ ions decreased the rate of permeability change: raising the pH of the medium or the addition of 10(-5) M EDTA enhanced the rate. Raising the temperature of the medium also increased the rate of permeability change in intact cercariae although the rates obtained varied with the different media tested, being greatest in TC-199. It is concluded that both temperature elevation and loss of the cercarial tail influence the onset and rate of permeability changes in cercarial bodies during the transformation to schistosomula.

Eosinophils from the peritoneal washings of normal rats adhered to live or formalin-fixed schistosomula of Schistosoma mansoni in vitro, in the presence of heat-inactivated serum from infected rats. Eosinophil adherence caused permeability changes in the schistosomula as revealed by 51Cr release and methylene blue uptake. The serum factor which mediated adherence resided in the 7S fraction after Sephadex G-200 gel filtration. Protein A from Staphylococcus aureus which binds specifically to the Fc piece of IgG inhibited adherence, thereby demonstrating that IgG was the antibody responsible for this reaction and that the Fc portion was the site of interaction between eosinophil and antibody; rat eosinophils were shown to possess Fc receptors. The antibody mediating adherence reached high titres in the sera of rats 5-8 weeks after exposure to 500 cercariae, but thereafter there was a gradual decline in titre. Surface membrane from adult S. mansoni inhibited adherence, indicating the presence of cross-reacting antigens in adult worms and schistosomula.

Schistosoma mansoni infected hosts produce an IgG that mediates the complement-dependent killing of schistosomula in vitro. In this study, we followed the levels of serum lethal antibody during infection of rats and mice. Rats presented detectable lethal activity early in the course of infection with a peak in the 6-8th week of infection. This activity declined to non-detectable levels within 2 weeks, remaining low up to the 20-26th week. In mice, lethal antibody was not detected before 7-12 weeks of infection, but raised to higher levels, as compared to non-infected animals, up to 20-24 weeks after infection. We correlate lethal antibody and protective immunity suggesting that the antibody-mediated complement-dependent cytotoxicity to schistosomula play a role in the immunity to reinfection.

The carrier effect, using TNP-labelled schistosomula was used to measure the helper T-cell activity against the schistosomula surface in CBA mice exposed to 30 cercariae of Schistosoma mansoni. After infection the helper T-cell activity reached a peak in 8--10 days, but by 6 weeks it had declined to background levels. Five x 10(7) spleen cells from chronically (12-week) infected mice when injected into 9-day infected mice caused a specific suppression of the helper T-cell response to schistosomula. Subsequent fractionation of the spleen cell population using a nylon wool column and specific depletion of T cells from the spleen cell population with anti-Thy 1.2 antisera and complement, showed that the suppressive activity was due to T cells. We conclude that during infection of mice with S. mansoni a population of suppressor T cells is generated which partially regulates antibody production against schistosome surface antigens.

Peripheral blood mononuclear cells (PBMN) from individuals with active or former intestinal schistosomiasis mansoni or splenocytes from patients with the hepatosplenic form of the disease were evaluated for their ability to generate chemotactic factors for neutrophils in response to schistosomal antigenic preparations derived from adult worms (SWAP), eggs (SEA), or phytohemagglutinin (PHA). When supernatants from cultures of stimulated PBMN from normal donors were assayed, only those obtained from cells which had been cultured in presence of PHA displayed chemotactic activity for neutrophils. In contrast, supernatants from cultures of SWAP or SEA stimulated PBMN from patients with intestinal or hepatosplenic schistosomiasis were shown to contain chemotactic activity for neutrophils from normal individuals. PBMN from persons who previously had been infected with Schistosoma mansoni but had received chemotherapy years before presented a pattern of response to SWAP or SEA similar to those from patients with active infections. The response of splenocytes from patients with hepatosplenic schistosomiasis was considerably different from PBMN from individuals with active or with treated schistosomiasis. Splenocytes from most of those patients with hepatosplenic disease failed to produce chemotactic factors for neutrophils in response to stimulation with at least 1 of the schistosome antigens tested. These results indicate that the lymphocytes from schistosomiasis mansoni patients are able to recognize and are stimulated by adult worm and egg antigens to produce chemotactic substances for neutrophils, and that this ability persists for many years after chemotherapy with schistosomicidal drugs. At the hepatosplenic stage, immunoregulatory mechanisms, which may prevent the production of chemotactic factors by splenocytes and/or their activity upon neutrophils in vitro, seem to occur.