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The reaction of Balb/c mice to primary and secondary subcutaneous infection with Echinococcus granulosus protoscoleces (PSC) is described. From 3 to 14 days following primary exposure to PSC, draining lymph nodes increase in weight and there is expansion of T and B lymphocyte populations, enhancement of in vitro lymphocyte transformational responses and production of PSC-specific IgM and IgE antibodies. Despite the persistence of viable PSC in host tissues, lymphocyte responses decline to pre-infection values over the period 3-8 weeks post-infection. Secondary exposure to PSC immediately induces lymphoproliferation, enhancement of transformational responses, production of IgE antibody and encapsulation of PSC by inflammatory cells. Although specific antibody levels remain high until at least 8 weeks after challenge infection, lymphocyte activity begins to decline after 4 days and is profoundly suppressed by 10 days. Parasite viability appears to be significantly reduced in secondary, as opposed to primary, infection and is associated with the accumulation of large numbers of eosinophils, mast cells and macrophages in infected tissues.

SUMMARYIndividual susceptibility to malaria infection, disease and death is influenced by host genotype, parasite virulence and a number of environmental factors including malaria-specific immunity. Immune responses are themselves determined by a combination of host genes and environmental effects. The extent to which host genotype limits the spectrum of possible immune responses may influence the outcome of infection and has consequences for vaccine design. Associations have been observed between human major histocompatibility complex (MHC) genotype and susceptibility to severe malaria, but no similar associations have been observed for mild malarial disease or for specific antibody responses to defined malaria antigens. Epidemiological studies have shown that, in practice, neither T helper cell nor antibody responses to malaria parasites are limited by host MHC genotype, but have revealed that genes lying outside the MHC may influence T cell proliferative responses. These genes have yet to be identified, but possible candidates include T cell receptor (TcR) genes, and genes involved in TcR gene rearrangements. More importantly, perhaps, longitudinal epidemiological studies have shown that the anti-malarial antibody repertoire is selective and becomes fixed in malaria-immune individuals, but is independent of host genotype. These findings suggest that the antibody repertoire may be determined, at least in part, by stochastic events. The first of these is the generation of the T and B cell repertoire, which results from random gene recombinations and somatic mutation and is thus partially independent of germline genes. Secondly, of the profusion of immunogenic peptides which are processed and presented by antigen presenting cells, a few will, by chance, interact with T and B cell surface antigen receptors of particularly high affinity. These T and B cell clones will be selected, will expand and may come to dominate the immune response, preventing the recognition of variant epitopes presented by subsequent infections - a process known as original antigenic sin or clonal imprinting. The immune response of an individual thus reflects the balance between genetic and stochastic effects. This may have important consequences for subunit vaccine development.

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