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Figure 2 Pattern of immune responses on an oncosphere of a taeniid cestode such as Taenia solium during initial penetration of the hatched oncosphere (initiating 'early immunity') and its subsequent migration to, and establishment in, its definitive site, where it is subject to 'late immunity'. The exact site of hatching in humans is unknown but most eggs probably hatch in the upper duodenum. (After Smyth and McManus (1989), with permission.)

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Figure 2 Pattern of immune responses on an oncosphere of a taeniid cestode such as Taenia solium during initial penetration of the hatched oncosphere (initiating 'early immunity') and its subsequent migration to, and establishment in, its definitive site, where it is subject to 'late immunity'. The exact site of hatching in humans is unknown but most eggs probably hatch in the upper duodenum. (After Smyth and McManus (1989), with permission.)

bodies to more easily reach the invading site. Eosinophils may accumulate around invading oncospheres, but there is no evidence that these cells actually damage oncospheres or postoncospheral stages. The role of macrophages or neutrophils, which may accumulate at the site of dying oncospheres, remains unknown.

When newly hatched oncospheres reach their site of establishment, they become transformed from a stage of being highly susceptible to attack to one of almost complete insusceptibility. The cellular and humoral response in T. solium cysticercosis is heterogeneous in humans and pigs. IgG represents almost 90% of the serum antibody detectable by ELISA but some patients show no antibody or cellular response whatsoever. Cysticerci of T. solium elicit a chronic granulomatous reaction in pig muscle. There is extensive eosinophil infiltration and degranulation on to the parasite surface but no apparent damage ensues. As in T. solium, eosinophilic response to T. taeniaeformis is antibody dependent. Eosinophils have been shown to adhere to and damage T. taeniaeformis in vitro but it is not clear if this occurs in vivo.

Little is known of T cell immunity to larval ces-todes, although CD4+ T helper cells have been implicated in the early phase of resistance to infection with T. taeniaeformis in mice. Such cells may be activated by parasite to produce cytokines involved in maturation and activation of eosinophils. Alternatively they may mediate interaction between hepa-tocytes and the parasite, thereby causing an alteration in the lipid metabolism of the former, resulting in the production of an eosinophilic chemotactic factor. Much work remains to be done in this important area.

Evasive strategies

The ability of tissue parasites, such as the larval taeniids, to survive in an immunologically hostile environment represents a phenomenon of special interest and controversy.

Blocking antibodies

In larval cestodes, host proteins have been demonstrated on the surface, including antibodies, these being referred to as 'blocking' antibodies. Thus, on the surface of the cysticerci of T. solium, a number of immunoglobulin isotypes have been found. In the case of T. crassiceps larvae, the predominating immunoglobulins appear to be IgM and IgG but, with this species, complete protection against immune attack may not be provided.

Molecular mimicry

The theory of molecular mimicry proposes that

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parasites disguise themselves as host (i.e. self) tissues by synthesizing host-like antigens on their surface, with the result that they are not recognized as foreign (i.e. nonself) by the host. There has been much controversy as to whether larval cestodes are capable of synthesizing such antigens or whether they have simply been absorbed from the host. Some evidence suggests that parasites can synthesize receptors or binding proteins capable of associating with host molecules. For example, an IgG (Fcy)-binding protein has been identified and purified from T. crassiceps.

There is evidence that the fact that the postonco-spheral stages rapidly outgrow their susceptibility to attack may be due to development of stage-specific antigens related to profound alterations in the surface structure of the developing larva. Thus, a strong immune response is generated against T. taeniaeformis in the liver, and larvae become insusceptible by 8 days - a time that coincides with the surface replacement of microvilli by microtriches.

Secretory products

Some larvae (e.g. T. pisiformis, T. taeniaeformis) release substances which inhibit proteolytic enzymes such as trypsin and chymotrypsin. Taeniaestatin, a 19.5 kDa secretory protein from T. taeniaeformis, in addition to inhibiting these enzymes, also inhibits neutrophil chemotaxis, the alternative and classical complement pathways, and interleukin 2 stimulation of T-cell proliferation. Antigen B (AgB) of T. solium, a secretory protein which has the ability to bind collagen, can inhibit, in vitro, the classical pathway of complement through inhibition of CI function and may play a role as a modulator of the host immune response in cysticercosis. Interestingly, AgB has immunologic and sequence homology with the invertebrate muscle protein paramyosin. Whether secretory products of other species can potentially modify the host cellular responses in a similar fashion remains to be established.

Immunosuppression

There are several reports that some cestode iarvae can induce immunosuppression in their hosts. For example, the sera of rabbits heavily infected with T. pisiformis have an inhibitory effect on the lectin-mediated blast transformation of lymphocytes. Furthermore, polyclonal B cell activation has been suggested as an immunosuppressive mechanism in human T. solium infections, while mice infected with T. crassiceps have impaired ability to make antibodies against sheep red blood cells.

Vaccines

The development of successful vaccines against the highly pathogenic larvae of T. solium (in humans and pigs) and those of economic importance, such as T. saginata (in cattle) and T. ovis and T. multiceps (in sheep) would clearly revolutionize the control of these important parasites. Studies with T. saginata, T. ovis and other taeniid species have shown that vaccination with living eggs, the parasite-free supernatant from in vitro culture of hatched and activated oncospheres, or detergent solubilized oncospheral antigens can induce complete protection against challenge infection. A major difficulty has been the limited supply of eggs, which has prevented the development of a practical vaccine.

Recently, recombinant DNA techniques have been applied to the problem of large-scale production of taeniid vaccine antigens, and the expression in Escherichia coli of cDNAs encoding taeniid antigens has been achieved. In particular, a highly effective recombinant antigen vaccine against T. ovis has been developed. Vaccination of sheep with this molecule, expressed as a soluble glutathione 5-transferase fusion protein (GST-45W), stimulated 94% protection against challenge infection with T. ovis. Initial trials with the 45W clone as a /3-galactosidase fusion protein proved unsuccessful. The antigen was stabilized subsequently by modification of the original

Table 1 Results of a pilot field trial showing numbers of Taenia ovis cysts found in the carcasses of vaccinated lambs naturally (field) or artificially Infected with T. ovis eggs

Group

Number

Range of cysts

Mean

Protection (%)*

Controls - field infection

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