Publisher Summary This chapter discusses the immunology of schistosomiasis. The only developments relating to innate immunity refer to the death of cercariae in the skin. Concomitant immunity has been shown to operate in a number of experimental systems, and there are encouraging reports that it may operate in human infections. A good deal of circumstantial evidence implicates host antigens as playing a role in concomitant immunity, but more direct evidence is needed to show that they indeed serve to protect the mature parasite from immune attack. The use of small animals, particularly those where syngeneic strains are available and in vitro cultivation, has increased the understanding of the immune mechanisms. In particular, a number of in vitro systems have been described in which antibodies and cells combine to damage and kill young schistosomules. It is essential to determine whether the differences described for these several systems truly reflect a multiplicity of host responses or merely represent differences in technical approach to a single system. Much work has concerned the immunopathology of the disease, particularly granuloma formation. Although the granuloma contributes significantly to the pathology, it does seem to protect the host liver from the toxic secretion of the egg. A number of approaches for the immunological control of schistosomiasis are currently under investigation, including the use of live cercariae and schistosomules and the use of more or less purified antigens.

The immunology of schistosomiasis.

Trichobilharzia is the largest genus within the family Schistosomatidae, covering over 40 species of avian parasites To clarify the existing confusion in the systematics of the genus, we recommend combining knowledge of life cycles and developmental stages, snail/bird hosts, cytogenetical and molecular data together with morphological criteria for the characterization of particular species The high specificity of Trichobilharzia for the intermediate host is a likely reflection of the ability to avoid the internal defence of specific snails The spectrum of final hosts (birds) seems to be much wider The infection of birds--trichobilharziasis--may lead to considerable tissue injuries, caused by eggs of the parasite or migration of immature/mature worms through the body Most Trichobilharzia (visceral species) migrate through the viscera of the host, but nasal species display a neurotropic mode of migration Due to a low specificity of penetrating cercariae, mammals (including humans) can be attacked This leads to cercarial dermatitis, predominantly in sensitized hosts Experimental infections indicate that Trichobilharzia never mature in an incompatible (mammalian) host However, not all cercariae and schistosomula are necessarily trapped and eliminated in the skin, and parasites may migrate throughout the viscera and the nervous system of mammals These findings suggest that the pathogenicity of Trichobilharzia may have been underestimated in the past and health risks associated with trichobilharziasis need to be studied further

Biology of the schistosome genus Trichobilharzia.

A comparison was made of the ultrastructure, development and antigenic nature of the surfaces and of the viability of three types of Schistosoma mansoni: schistosomula formed after cercariae had penetrated isolated skin (SS) schistosomula produced after mechanical separation of cercarial tails from bodies (MS), and schistosomula transformed from cercariae after incubation in fresh rat serum (RS). Within 2h of transformation, the surface membranes of all three types of schistosomula had changed from trilaminate to heptalaminate structures and SS and MS had lost their cercarial glycocalyx. Initially a dense amorphous material was demonstrated on the surfaces of RS, which was thought to be the result of an interaction between a factor in rat serum and the glycocalyx; this material was greatly reduced within 2 h of transformation. The pre-acetabular glands of SS were emptied while those of MS and RS retained their contents. Immunofluorescent studies showed that all schistosomula bound serum from mice immune to S. mansoni, but the binding was stronger with MS and RS. The mixed agglutination reaction demonstrated the presence of human A and B blood group-like antigenic determinants on approximately 30% of 3h old SS; these determinants were not detected on MS or RS. In vitro, the development of MS and RS was similar to SS; the first schistosomula reached the "gut-closed" stage by day 10; 50-70% of SS reached this stage by day 12, in contrast to only 25-50% of MS and RS. Between 28 and 45% of all schistosomula developed to maturity when injected intravenously into mice. It was concluded that the two types of artificially prepared schistosomula fulfil the main criteria of transformation from cercaria to schistosomulum. Further, it is suggested that MS are the most appropriate source of material for immunochemical and physiological studies.

Schistosoma mansoni: a comparative study of artificially transformed schistosomula and schistosomula recovered after cercarial penetration of isolated skin.

A large percentage of the cercariae of Schistosoma mansoni die while penetrating the abdominal skin of rats or mice but relatively few cercariae die in the skin of hamsters.Comparison of hamsters and mice infected from the same pool of cercariae showed that the higher percentage of cercariae recovered as adult worms from hamsters than from mice was due to the lower percentage of cercariae which died during penetration of hamster skin.In similar comparisons of rats with mice the lower percentage of adult worms recovered from rats was not entirely accounted for by the higher percentage of cercariae which died in rat skin. Losses of schistosomula at later stages of development are apparently higher in rats than in mice.Cercariae die within 10 min after beginning to penetrate the skin of mice. At this stage the cercariae, which are now termed schistosomula, are attempting to penetrate the Malpighian layer of the epidermis. Five minutes later many schistosomula have entered the dermis.The cause of death of cercariae has not been determined. It is not related to the development of sensitivity to water which accompanies the transition from cercaria to schistosomulum. Sensitivity to water appears much sooner after penetration in some cercariae than in others; even after 30 min in the skin some cercariae can tolerate a return to water.In rats, hyper-immunized by a series of infections with cercariae through the abdominal skin, the percentage of challenging cercariae which die in the abdominal skin shows a slight increase over controls. No further mortality of schistosomula occurs during the next 24 h.Age resistance to infection with S. mansoni could not be demonstrated in comparisons of young mice (1 month) with old mice (1 year) of the Parkes and CBA strain.We should like to thank Dr F. Hawking for performing the skin biopsies on the dogs and Mrs P. Clark and Miss J. Marsh for their excellent technical assistance.

Death of schistosome cercariae during penetration of the skin. II. Penetration of mammalian skin by Schistosoma mansoni.

Schistosomes infect the mammalian host by direct penetration of the skin and must then undergo a protracted migration to the site of parasitization, for Schistosoma mansoni the hepatic portal vasculature. This article reviews the work published roughly between 1976 and 1986 that clarified our understanding of the process in the laboratory mouse. A combination of histopathology, larval injection experiments and autoradiographic tracking revealed that migration involved one to several circuits of the pulmonary-systemic vasculature before chance delivery in cardiac output to splanchnic arteries that lead indirectly to the portal tract. The kinetics of migration through different capillary beds was established, with the lungs of naive mice not the skin proving the greatest obstacle; a proportion of schistosomula entered the alveoli from where they did not recover. The ‘immunity’ displayed by mice with a chronic infection was shown to be an artefact of a ‘leaky’ hepatic portal system, generated as a result of egg-induced hepatic pathology. The blockade of pulmonary migration was exacerbated in mice vaccinated with irradiated cercariae by immune-mediated inflammatory foci that developed around lung schistosomula thus decreasing the proportion that matured, but parasite elimination was a prolonged process, not an acute cytolytic ‘hit.’

The saga of schistosome migration and attrition.

The seagull, a natural host of Austrobilharzia terrigalensis, was infected with cercariae through a small area of breast skin; 40% of the schistosomula recovered from the skin shortly afterwards were dead. In budgerigar skin 29% of the schistosomula were dead, but mortality in the skin of ducklings was much higher (85%). The budgerigar is a useful laboratory host for this schistosome, but ducklings are completely resistant to experimental infection mainly because of the barrier effect of the skin.Rapid recovery of schistosomula from budgerigar skin established that the majority of deaths occurred during the first 15 min after application of cercariae. In sections of skin fixed after 10 min nearly all the schistosomula were in the epidermis between the narrow stratum corneum and the living cells of the Malpighian layer. In seagull and budgerigar skin most schistosomula succeeded in crossing the Malpighian layer in the next 5 min, but in ducklings nearly all schistosomula completely failed to penetrate this layer.In vitro experiments in which cercariae were allowed to penetrate through several layers of dead epidermis, isolated from dried budgerigar skin, into balanced saline, showed that schistosomula are not killed by host cells or a soluble toxic substance. The possibility that the epidermis contains an insoluble toxic substance could not be excluded.The proportion of schistosomula which died during penetration of dead epidermis was related to the number of layers in the barrier, suggesting that schistosomula may die owing to exhaustion caused by the intense activity of penetration.About 30% of the glycogen reserves of cercariae were utilized during penetration of budgerigar skin. In dead schistosomula the glycogen reserve had been reduced by 80%, but the significance of this observation is uncertain because much of the glycogen may have been autolysed after death of the schistosomula. Exposure of cercariae to glucose before penetration did not affect the proportion which died in the skin.Schistosomula adapt to the osmotic pressure in the skin, which is one-third that of sea water, and 30 min after penetration they are rapidly killed if returned to sea water. This process of adaptation is not related to mortality of schistosomula during penetration of the skin.We wish to acknowledge the expert technical assistance of Mrs J. Morgan. This investigation was supported in part by research grant AI-04707 from the National Institute of Allergy and Infectious Diseases, United States Public Health Service.

S. L. Rai

Papers

Death of schistosome cercariae during penetration of the skin: I. Penetration of bird skin by Austrobilharzia terrigalensis