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Immunity to schistosomes, helminth worms that infect 200 million people, is targeted to invading larvae (concomitant immunity). In vitro studies have revealed the role of T cells and of particular antibody isotypes in immune defense: IgE antibody cooperates with mononuclear phagocytes, eosinophils, and platelets to kill schistosome larvae. IgE antibody appears as an essential component of acquired resistance in rats. The role of IgE antibody has recently been confirmed by epidemiological studies demonstrating a positive correlation between the acquisition of resistance to reinfection by schistosomes and the level of IgE antibody to the parasite. A negative correlation found in these studies with the levels of IgM, IgG2, or IgG4 antibodies could be related to the development of a blocking antibody response. Antigens involved in protective immunity are expressed transiently at the surface of schistosomes. Sm28, a glutathione-S-transferase, induces significant protection against schistosome infection in rodents and nonhuman primates. In addition, this vaccine reduces the size of egg granulomas and egg output. Besides allowing the definition of a vaccine strategy against a major disease, studies on immunology of schistosomiasis have unraveled unsuspected antigenic mimicry between schistosomes and HIV regulatory proteins and have led to the demonstration that IgE antibody, a protective isotype against helminths, may also activate Fc epsilon-RII-bearing mononuclear phagocytes, eosinophils, and platelets in allergic disease.

We have recently demonstrated in Schistosoma mansoni infection that rat and human platelets could very efficiently kill parasite larvae, both in vivo and in vitro. The study of this IgE-dependent platelet effector function has led us to several subsequent findings. They concern: (1) the existence of a specific receptor for IgE on the platelet surface; (2) its close association with a platelet membrane glycoprotein of essential functional importance, the GPIIb-IIIa complex; (3) the observation, in extrinsic allergic asthma, of an allergen-specific IgE-dependent platelet activation; (4) the identification, in aspirin-sensitive asthma, of a similar, but non-IgE-dependent, platelet activation selectively induced by cyclo-oxygenase inhibitors, and prevented by salicylate. Beyond their implication in anti-parasite immunity, these findings provide a basis for new insights on the participation of platelets in disease.

INTRODUCTIONParasitic diseases represent a significant burden for health and for socioeconomical development in many tropical countries. The immuno prophylaxy of these infections would be a major advance, and this certainly justifies the important investments made at national and international levels in the search for a vaccine against the major human parasites. It should be stressed, however, that despite remarkable and sometimes spectacular progress, this goal still remains far out of reach. Parasites are, in general, of very ancient lineage; schistosomes for instance evolved from blood flukes during the Permian era, which means that they have had something on the order of 250 million years to perfect survival tactics appropriate to their coexistence with their vertebrate host immune system. For evolutionary reasons, in comparison with other infectious agents, they represent by their structure and the complexity of their life cycle a highly elaborate model of host-parasite interplay. Not surprisingly therefore, when immunologists started to study the immune response to parasites, they discovered that the adaptation of the parasite to its host was the result of a complex, refined, and dynamic balance between host effector mechan isms and parasite escape strategy. At the same time, they were struck by the fact that some entirely novel mechanisms were involved in antiparasite immunity, almost allowing researchers to rewrite some chapters of immunology textbooks. 455 0732-0582/85/0410-0455$02.00' Annu. Rev. Immunol. 1985.3:455-476. Downloaded from www.annualreviews.org Access provided by University of Utah -Marriot Library on 11/29/14. For personal use only. Quick links to online content Further ANNUAL REVIEWS 456 CAPRON & DESSAINTThe purpose of this review is to give an account of the immunology we have learned from parasites. The general message is that the understanding of these mechanisms appears indispensable for possible development of antiparasite vaccines and, more generally, provides new and fascinating insights into many areas of human pathology.Among the parasites used as models, schistosomes probably have been employed in the broadest experimental approach. They have illustrated the existence of novel effector and regulatory mechanisms among the im munological components of the specific response to metazoan parasites.An infection that affects 300 million people in the world, schistosomiasis is characterized by the presence of adult worms in the portal and mesenteric veins of humans and of various other mammalian species, as part of a complex migratory cycle initiated by cutaneous penetration of aquatic infective cercariae. These transform into schistosomula under the skin of appropriate hosts. It is generally agreed that pathological reactions to schistosome infection are related to the deposition of numerous parasite eggs in host tissues (106). STUDY MODELSAlthough clinical studies have made possible the investigation of several immune mechanisms operating in man (17, 78), most of the information is de...

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The demonstration of a specific receptor for IgE on nonmast cell or basophil leukocytes, such as mononuclear phagocytes, eosinophils, and platelets, suggests that these cells may participate directly in immunological disorders of allergy. Thus, a full understanding of the mode of action of antiallergic or antiasthma drugs must take into account their activity on these nonmast cell leukocytes. Consequently, inhibition by nedocromil sodium of IgE-dependent activation of human alveolar macrophages, blood monocytes and platelets, was investigated. This compound induced an inhibition of the IgE-mediated generation of cytotoxic molecules from monocytes and platelets, together with a concomitant inhibition of their oxidative metabolism, measured by chemiluminescence, and a reduction of the potential ability of alveolar macrophages to synthesize and release mediators, estimated by lysosomal beta-glucuronidase activity. These observations confirm the hypothesis that nedocromil sodium acts on a cell compartment other than the classical mast cell population, in IgE-dependent allergy and, more particularly, in asthma.

The isolation of 2 genomic clones has allowed us to further characterize a Schistosoma mansoni serine protease designated SmSP1. The deduced amino acid sequence (248aa) considered as a 'light chain' encoding the active site, presents significant homologies with mouse plasma kallikrein and human factor I light chain. The secondary structure of SmSP1 'light chain' is correctly predicted and may be sufficient by itself to constitute an active enzyme. The biological function of SmSP1 is unknown, however, the homology with 2 serine proteases suggests that SmSP1 may play a role in the evasion of the host immune response. This is supported by the presence of the native protein corresponding to SmSP1 particularly in schistosomula released products (SRP) and in male dorsal spines. The expression of this enzyme is differentially regulated throughout the parasite life-cycle. However, infected animals with S. mansoni did not produce specific antibodies to recombinant SmSP1. The lack of such response could be advantageous to the parasite by protecting itself from host effector mechanisms.

In this review the authors analyze the effector and regulatory mechanisms in the immune response to schistosomiasis. To study these mechanisms two animal models were used, mouse and rat. The mouse totally permissive host like human, show prominent-T cell control in the acquisition of resistance. But other mechanisms like antibody mediated cytotoxicity (ADCC) involving eosinophils and IgG antibodies described in humans, are observed in rats. Also in this animal, it is observed specific IgE antibody high production and blood and tissue eosinophilia. Using the rat model and schistosomula as target, some ADCC features have emerged: the cellular population involved are bone marrow derived inflammatory cell (mononuclear phagocytes, eosinophils and platelets), interacting with IgE through IgE Fc receptors. Immunization has been attempted using the recombinant protein Sm28/GST. Protection has been observed in rodents with significant decrease of parasite fecundity and egg viability affecting the number, size and volume of liver egg granulomas. The association of praziquantel and immunization with Sm28/GST increases the resistance to infection and decreases egg viability. The authors suggest the possibility of the establishment of a future vaccine against Schistosoma mansoni.