Schistosome parasites, despite being multicellular organisms several millimetres in length, can survive in the bloodstream of mammalian hosts for decades. The remarkable and complex adaptation exemplified in the host–parasite relationship in schistosomiasis may include not only immune evasion by the parasite, but also immune exploitation. While the developmental and adult stages of the parasite are by and large invisible to the immune response, the parasite egg induces a granulomatous reaction which not only protects the host from a diffusible parasite toxin, but also is required for normal transmission of parasite eggs from the host to the external environment. Other possible mechanisms of immune exploitation by schistosomes are discussed including skewing of cytokine responses, effects of cytokines on worm fecundity, exploitation of endothelial cell adherence, and induction of IgE.

In spite of the vast distribution and considerable impact on human and animal health of Ascaris suum and A. lumbricoides, little is known of the sexual biology and reproductive capacity of these intestinal nematodes. By oral transfer of adult female worms to previously parasite-naive pigs we show that in the absence of males the egg production ceases after 2–3 weeks. Such females readily resume egg production a few days after oral transfer of male worms. These observations throw light on an important aspect of Ascaris biology, but also pave the way for possible experimental interbreeding between the human and pig Ascaris species.

The relationship between cell-mediated granulomatous inflammation and transmission of disease in schistosomiasis and tuberculosis has been explored. In 2 experiments involving Schistosoma mansoni-infected normal and T cell-deprived mice, and infected deprived mice that had been variously reconstituted with immune or normal lymphocytes or immune serum, there was a significant positive numerical correlation between mean liver granuloma diameters and faecal egg counts in individual animals. Lymphocytes from donors with recently patent infections were more active than cells from chronically infected or uninfected donors in reconstituting egg excretion rates in deprived recipients, and mesenteric lymph node (MLN) cells were more active than spleen cells. Modulation of granulomatous activity with increasing chronicity of infection in the donors, resulting in a decrease in granuloma size around freshly produced tissue-bound eggs, was paralleled by a waning of the capacity of transferred lymph node cells to reconstitute egg excretion in the recipients. Serum taken from chronically infected donor mice over the same period and transferred to infected deprived recipients became more active in enhancing egg excretion in the recipients as the cell-mediated activity declined. A recent study in Kenya has found that S. mansoni-infected patients with concurrent human immunodefficiency virus (HIV) infection excrete fewer eggs than patients exposed to the same levels of schistosome infection, but who are not HIV-infected, thus indicating that schistosome egg excretion in humans is also immune-dependent. Attention is drawn to an apparently parallel situation in human tuberculosis, another pathogen which induces a cell-mediated granulomatous immune response. Several studies have shown that patients with tuberculosis who are also HIV-seropositive tend to have fewer tubercle bacilli detectable in their saliva than those with tuberculosis, but who are HIV-negative. This discrepancy, associated with differences in lung pathology in HIV-positive patients, suggests that in tuberculosis immune cell-mediated granulomatous inflammation causes the destruction of host tissue in a manner which facilitates onward transmission of the bacterial pathogen.

A new method has been developed to investigate behavioural diapause in adult Rhipicephalus appendiculatus ticks. It is based on a system of gauze columns in which the activity of the ticks can be monitored in the laboratory. An experiment was conducted, involving different photoperiodic conditions during the nymph-to-adult moulting and pre-questing periods, with the aim of comparing the results obtained by the in vitro method with those of the standard in vivo method. Comparable results were obtained with both methods.

We describe a variety of restriction site polymorphisms in the introns of Ascaris nuclear genes and in the ribosomal DNA spacers. We use these markers, in addition to previously described mitochondrial variation, to clarify our understanding of the epidemiology of Ascaris in Guatemalan villages where humans and pigs occur in sympatry and to describe the genetic structure of host-associated Ascaris populations from world-wide locations. Intron sequences were amplified from individual worms and alleles defined by endonuclease digestion. Two loci were monomorphic, while 4 length variants and 22 point mutations were detected in the other 7 loci. Within sympatric Guatemalan populations no single locus from either the nuclear or mitochondrial genome was fixed for alternative alleles, although allele frequencies were significantly different at many loci. Phenograms constructed from multilocus nuclear genotypes of individual worms failed to reveal a single case of cross-infection, and demonstrate that divergent mtDNA genotypes are segregating within host-associated populations. On a world-wide scale, the data suggest that extant worm populations result from a single host shift, although characterization of genetic variation in additional loci will be necessary to confirm this. The direction and the geographical origin of the host shift were unresolved. Overall 65% of nuclear genetic variation was found within populations, host (human or pig) explained 18%, while geographical variation within host-associated populations explained 17%. The results (a) demonstrate the utility of introns for studying the epidemiology of parasites showing limited allozyme variation (b) suggest that programmes aiming to control Ascaris infection in the human population can safely ignore zoonotic infection from pigs and (c) illustrate the problems inherent in using single genetic markers to make inferences about the epidemiology of closely related parasite taxa.

To study population kinetics during primary Ascaris suum infections, 3 groups of 52 pigs each were inoculated with 100, 1000, or 10000 infective eggs. In all groups, the majority of larvae was found in the liver on day 3 post inoculation (p.i.) and in the lungs on day 7 p.i. Liver white spots, caused by migrating larvae, were most numerous at day 7 p.i., whereafter they gradually healed, and only low numbers of granulation-tissue type white spots and lymphonodular white spots persisted at days 21–56 p.i. Independent of dose level, 47–58% of the inoculated eggs were recovered as larvae in the small intestine on day 10 p.i., but most larvae were eliminated at days 17–21 p.i. This elimination started earlier and removed a higher percentage of the worms with increasing inoculation dose, resulting in small strongly aggregated worm populations by day 28 p.i. (k of the negative binomial distribution was low: 0·2–0·4) without significant differences between groups. Thus, overdispersion, which is a characteristic of both porcine and human ascarosis, is found here under experimental conditions where aggregation factors like host behaviour, transmission rate, host status etc have been partly or totally controlled.

Regional differences of Hymenolepis diminuta to immune lysis have been investigated by monitoring surface membrane fluidity utilizing fluorescence recovery after photobleaching (FRAP). Although the surface membrane of the newly excysted stage was completely immobile the molecular fluidity of the strobila membrane of 4-day-old parasites was greater than that associated with the scolex/neck region. Significant differences (P>0·001) occurred in the mobility of the strobila membrane of 4-day-old H. diminuta from 100-worm infections compared with 7- and 21-day-old parasites and 4-day-old individuals from 10-worm infections. Exposure to 50% normal rat serum and 1 mg/ml rat C reactive protein decreased or eliminated membrane fluidity. The significance of membrane mobility is discussed with reference to resistance to complement-mediated lysis and destrobilation.

A cDNA was isolated from a cDNA expression library using serum prepared against a high molecular mass fraction of Fasciola hepatica excretory–secretory products. The full-length cDNA encodes a member of the recently described peroxiredoxin antioxidant family. Peroxiredoxin could be the major hydrogen peroxide removing antioxidant in F. hepatica since this parasite does not express a catalase and expresses little glutathione peroxidase activity. This novel antioxidant may be involved in functions such as protection against reactive oxygen species (ROS) generated by metabolic processes and/or protection of the parasite against ROS released by immune effector cells.

The author has summarized the history of discovery, the mechanism and the clinical significance of antibody-dependent enhancement (ADE) of HIV infection. ADE has two major forms: (a) complement-mediated antibody-dependent enhancement (C-ADE) and (b) complement-independent Fc receptor-dependent ADE (FcR-ADE). The most important epitope responsible for the development of C-ADE-mediating antibodies is present in the immunodominant region of gp41 while antibodies mediating FcR-ADE react mainly with V3 loop of gp120. There are at least three fundamentally different hypotheses for the explanation of ADE in vitro: (a) increased adhesion of HIV-antibody-(complement) complexes to FcR or complement receptor carrying cells; (b) facilitation of HIV-target cell fusion by complement fragment deposited on the HIV-virions and (c) complement activation products may have a non-specific stimulatory effect on target cells resulting in enhanced virus production. FcR-ADE and C-ADE have been measured in vitro mostly by using FcR-carrying and complement receptor-carrying cell lines, respectively; no efforts have been made to standardize these methods. Several data support the possible clinical significance of FcR-ADE and C-ADE: (a) Cross-sectional and longitudinal studies indicate a correlation between the amounts of FcR-ADE and C-ADE-mediating antibodies and clinical, immunological and virological progression of the HIV-disease; (b) ADE may facilitate maternal–infant HIV-1 transmission; (c) According to experiments in animal models, ADE are present and may modify the course of SIV (simian immunodeficiency) infection as well. The author raises a new hypothesis on the mechanism of the in vivo effect of C-ADE. According to the hypothesis, C-ADE-mediating antibodies exert their effect through enhancement of HIV propagation and consequent facilitation of the progression of HIV disease. Finally, according to observations from animal experiments and human clinical trials it cannot be excluded that ADE-mediating antibodies may develop, diminish the beneficial effect or may be harmful in volunteers vaccinated with HIV-1 candidate vaccines.

Data on parasites of rodents, collected over an 18-year period on the Iberian peninsula, were used to find the determinants of parasite species richness. A total of 77 species of helminth parasites (nematodes, cestodes and digeneans) was identified among 16 species of rodents. Parasites were classified into groups according to their specificity towards their host and their life-cycle. A working phylogeny of the rodents was proposed on the basis of molecular and paleontological data and for each host the following parameters were recorded: sample size, weight, geographical range, longevity, and life-style. Two comparative methods were used, the independent comparisons method of Pagel (1992) and the distance matrix method of Legendre, Lapointe & Casgrain (1995). The second method has the advantage of measuring the relative contribution of phylogeny. Both methods gave similar results. Overall parasite species richness correlated only with host sample size. Host body size does not correlate with any subset of parasite species richness. However, host phylogeny is a good predicator of specific parasites and the species richness of digeneans correlates with host geographical range. A phylogenetic reconstruction of host relations was performed using the parasites belonging to subgroups in which richness is correlated with host phylogeny. These parasite species were treated as Dollo characters, i.e. we made the assumption that the loss of a parasite species is irreversible. The consensus tree obtained reflects the major phylogenetic divisions of the host group. Finally, this study illustrates the relative importance of processes acting at different temporal and spatial scales (evolutionary time and actual geographical range of hosts) in determining the structure of helminth parasite fauna.

The defensive glands of beetles, Tenebrio molitor, infected with metacestodes (cysticercoids) of Hymenolepis diminuta are everted less frequently upon stimulation, and contain less toluquinone (methylbenzoquinone) and m-cresol, than glands of uninfected controls. These differences, as shown in predation trials with wild rats, increase the likelihood that both cysticercoids and beetles will be ingested by the tapeworm's definitive host. This is the first documented case of a parasite inhibiting the chemical defence of an intermediate host, and one of only a few reports of parasite-induced manipulation of host biology supported by empirical evidence implicating facilitated parasite transmission between host species.

Breast cancer is a complex disease. Its aetiology is multifactorial, its period of development can span decades, and its clinical course is highly variable. Evaluation of the role of the immune response in either the development or control of breast cancer is also complex. Nevertheless, there is substantial information that in this disease, the immune response is not a host defence reaction and may even serve to facilitate cancer development. This evidence comes from a variety of sources including clinical–pathological investigations in women that show a correlation between the intensity of lymphocytic infiltration into the tumour mass with poor prognosis, studies in breast cancer patients that demonstrate a similar correlation between delayed hypersensitivity reactivity or in vitro assays of immune reactivity to tumour cell membranes or non-specific antigens and poor prognosis, and analyses of cancer incidence in chronically immunosuppressed, kidney transplant recipients who develop an unexpectedly low incidence of breast cancer. The overall conclusions from these human studies are corroborated by observations in mouse mammary tumour models that also demonstrate immune enhancement of breast cell proliferation in vitro and of breast cancer development in vivo. Potential mechanisms for these effects include production, by inflammatory cell infiltrates, of direct or indirect modulators of breast cell growth, e.g. cytokines, peptide or steroid hormones, enzymes involved in steroid metabolism, as well as of antibodies to growth factors or their receptors. These immune facilitatory mechanisms must be overcome if immune-based therapies are to be applied successfully in breast cancer.

We examine the evolution of microparasites in response to the immune system of vertebrate hosts. We first describe a simple model for an acute infection. This model suggests that the within-host dynamics of the microparasite will be a ‘race’ between parasite multiplication and a clonally expanding response by the host immune system, resulting either in immune-mediated clearance or host death. In this very simple model, in which there is only a single parasite and host genotype, maximum transmission is obtained by parasites with intermediate rates of growth (and virulence). We examine how these predictions depend on key assumptions about the parasite and the host, and consider how this model may be expanded to incorporate the effect of additional complexities such as host–parasite co-evolution, host polymorphism, and multiple infections.

Recent developments in parasite immune evasion and exploitation are reviewed with special reference to the papers presented in this volume. Parasites, broadly defined, of animals with good immune responses have evolved many strategies that adapt them to survive and reproduce. These strategies may be passive, or may involve active intervention with host immune regulation, and can be categorized as immune evasion, immune exploitation and molecular piracy. The concept of immune evasion began with Paul Ehrlich's demonstration of antigenic variation in African trypanosomes and was reinforced by later ideas on molecular mimicry. Molecular mimicry is updated in the light of recent discoveries about degeneracy and plasticity of TCR/MHC-peptide recognition. Possible connections between two of its postulated consequences, evasion and autoimmunity, are discussed. Another putative consequence of molecular mimicry, host antigenic polymorphism, is also updated. The concept of exploitation of host immune responses by parasites has been reinforced by new data on its first known examples, especially the immune dependence of schistosome egg excretion. Newer examples include use of host cytokines as parasite growth factors, virokines, viroreceptors and helminth pseudocytokines. Finally, questions of host gene capture by viruses and possible horizontal gene transfer between host and parasite mediated by retroviruses are examined. The latter is compared with molecular conservation as a source of molecular mimicry and other aspects of host–parasite coevolution.