Of all the laboratory models of intestinal nematode infection, Trichuris muris in the mouse is arguably the most powerful. This is largely due to the fact that the ability to expel this parasite is strain dependent. Thus, most mouse strains readily expel T. muris. However certain mouse strains, and indeed some individuals within particular mouse strains, are unable to mount a protective immune response and harbour long term chronic infections. This unique model thus presents an opportunity to examine the immune events underlying both resistance to infection and persistent infection within the same host species, and in some cases, the same host strain.

The host-protective immune response to infection with gastrointestinal (GI) nematodes involves a range of interacting processes that begin with recognition of the parasite's antigens and culminate in an inflammatory reaction in the intestinal mucosa. Precisely which immune effectors are responsible for the loss of specific worms is still not known although many candidate effectors have been proposed. However, it is now clear that many different genes regulate the response and that differences between hosts (fast or strong versus slow or weak responses) can be explained by allelic variation in crucial genes associated with the gene cascade that accompanies the immune response and/or genes encoding constitutively expressed receptor/signalling molecules. Major histocompatibility complex (MHC) genes have been recognized for some time as decisive in controlling immunity, and evidence that non-MHC genes are equally, if not more important in this respect has also been available for two decades. Nevertheless, whilst the former have been mapped in mice, only two candidate loci have been proposed for non-MHC genes and relatively little is known about their roles. Now, with the availability of microsatellite markers, it is possible to exploit linkage mapping techniques to identify quantitative trait loci (QTL) responsible for resistance to GI nematodes. Four QTL for resistance to Heligmosomoides polygyrus, and additional QTL affecting faecal egg production by the worms and the accompanying immune responses, have been identified. Fine mapping and eventually the identification of the genes (and their alleles) underlying QTL for resistance/susceptibility will permit informed searches for homologues in domestic animals, and human beings, through comparative genomic maps. This information in turn will facilitate targeted breeding to improve resistance in domestic animals and, in human beings, focused application of treatment and control strategies for GI nematodes.

At present, the genus Trichinella comprises seven species of which five have encapsulated muscle larvae (T. spiralis, T. nativa, T. britovi, T. nelsoni and T. murrelli) and two do not (T. pseudospiralis and T. papuae) plus three genotypes of non-specific status (T6, T8 and T9). The diagnostic characteristics of these species are based on biological, biochemical and genetic criteria. Of biological significance is variation observed among species and isolates in parameters such as infectivity and immunogenicity. Infectivity of Trichinella species or isolates is determined, among other considerations, by the immune status of the host in response to species- or isolate-specific antigens. Common and particular antigens determine the extent of protective responses against homologous or heterologous challenge. The kinetics of isotype, cytokine and inflammatory responses against T. spiralis infections are isolate-dependent. Trichinella spiralis and T. pseudospiralis induce different dose-dependent T-cell polarizations in the early host response, with T. spiralis initially preferentially promoting Th1-type responses before switching to Th2 and T. pseudospiralis driving Th2-type responses from the outset.

Comparisons were made of the immune and inflammatory responses of four strains of inbred mice to infection with the intestinal nematodes Trichinella spiralis and Nippostrongylus brasiliensis to determine whether genetically determined ‘high responsiveness’ to infection, seen most clearly in intestinal responses, is independent of the parasite concerned and necessarily correlated with protection. The time course of infection was followed by counting adult worms at intervals after infection. Mucosal mast cells and Paneth cell numbers were determined as indices of the intestinal inflammatory response. Levels of IgG2a and IgG1 antibodies and of the cytokines IFN-γ and IL-5 released from in vitro-stimulated mesenteric node lymphocytes were measured to assess type 1 and type 2 responses. NIH and CBA mice were the most resistant to T. spiralis and N. brasiliensis respectively, resistance in each case being correlated with the most intense intestinal inflammatory responses. C57BL/10 (B10) and B10.BR were the least resistant to T. spiralis, but were as resistant as CBA to N. brasiliensis, despite their intestinal inflammatory responses to both parasites being much lower than the other two strains. Mice infected with T. spiralis made the expected switch from a type 1 (IFN-γ) to a type 2 (IL-5) response between days 2 and 8, and there were no significant differences in levels of these cytokines between the strains. In contrast, when infected with N. brasiliensis, CBA showed an IFN-γ response at day 4, all strains switching to IL-5 by day 8 and NIH mice releasing the greatest amount of IL-5. The results indicate that the ‘high responder’ phenotype to intestinal nematode infection is in part determined by host characteristics, but is also determined by the parasite concerned – seen most clearly by the differences between NIH and CBA when infected with T. spiralis and N. brasiliensis. The fact that ‘low responder’ B10 background mice were more resistant to N. brasiliensis than ‘high responder’ NIH implies that each parasite elicits a particular pattern of protective host responses, rather than parasites being differentially susceptible to the same response profile.

In rodents, Trichinella spiralis and Nippostrongylus brasiliensis infect the small intestine and Trichuris muris resides in the colon. The intestinal host response in these animals is characterized by changes in mucosal architecture and inflammation and is associated with worm expulsion. The requirement of T cell-mediated host response in worm expulsion has been demonstrated over many years. Subsequent studies have shown that Th2-type, but not Th1-type, responses mediate resistance to the nematodes. Investigations using neutralizing antibodies and genetically manipulated mice have characterized the contribution of individual Th2-type cytokines in not only worm expulsion, but also specific cellular changes that occur in the mucosa, such as alterations in epithelial phenotype and smooth muscle. There is also increasing appreciation of the contribution of non-bone marrow-derived cells in innate and adaptive host responses in these models.

T helper cell (Th1 and Th2) associated responses were examined following a primary infection with the gastrointestinal nematode Heligmosomoides polygyrus in five inbred strains of mice with different resistance phenotypes. Levels of (i) mast cell protease, (ii) specific IgE, (iii) nitric oxide and (iv) specific IgG2a, as markers of Th2 and Th1 associated responses, respectively, were determined in sera and intestinal fluids and correlated with worm burdens. The ‘fast’ responder (resistant) strains SWR and SJL produced strong Th2 and Th1 associated responses respectively in a mutually exclusive fashion. The F1 hybrid (SWR×SJL) F1, showed rapid expulsion of the parasite and expressed both intense Th1 and Th2 responses, suggesting synergism between Th1 and Th2 activity in these mice. The results indicate that both Th2 and Th1 responses operate in mice following a primary infection with H. polygyrus and that each Th response may be involved to a greater or lesser degree within certain strains. Resistance to H. polygyrus was found to correlate only to the intensity of either the gut-associated mastocytosis or nitric oxide production in these strains but not to either specific IgE or IgG2a titres. Chronic infections in the ‘slow’ response phenotype mouse strains CBA and C57BL/10, were associated with both poor Th2 and poor Th1-associated responses attributed to a general parasite-mediated immunosuppression of the host immune response to infection.

Intestinal infection continues to be a problem worldwide and helminths, which currently infect billions of individuals, are primary culprits. The major burden of disease falls on the populations of developing countries, given that over the last four to five decades helminth infections are disappearing in industrialized societies. In developing countries, a major source of immunomodulatory signals in post-natal life are parasites, particularly helminths, which, unlike most bacteria and viruses, selectively stimulate Th2 function. Helminths and their eggs are probably the most potent stimulators of mucosal Th2 responses. Responses elicited by worms can modulate immune reactions to other parasites, bacterial, viral infections and several unrelated diseases. Bacterial and protozoal infections may also protect against atopy and asthma, through the induction of the Th1 regulatory responses. Today, people in developed countries often live in ultra-hygienic environments, avoiding exposure to viruses, bacteria, ectoparasites and endoparasites, particularly helminths. Perhaps failure to acquire worms and experience mucosal Th2 conditioning predisposes to unrelated diseases. In contrast to this hypothesis it has also been suggested that Th2 responses can make the host more susceptible to other important diseases and to contribute to the spread of them.

Mucosal mast cells (MMC) play an important role in the immune response against selected species of intestinal nematode. The kinetics with which different strains of inbred mice resolve infection with Trichinella spiralis correlates with their ability to mount MMC responses in the intestinal mucosa. Homologues of MMC that express and constitutively secrete abundant amounts of the granule chymase, mouse mast cell protease-1 (mMCP-1), can be generated in vitro from bone marrow cultures supplemented with interleukins-3 and -9, stem cell factor and transforming growth factor-β1. Using the enhanced growth characteristics of these MMC homologues, a novel limiting dilution assay for mast cell precursor (MCp) frequency has been developed. The assay is highly specific, in that cultures containing mast cells are identified with mMCP-1 specific antibody, and almost three-fold more sensitive than previously published systems. MCp frequencies were compared in BALB/c and C57/BL10 strains of mice that, respectively, respond rapidly and slowly to infection with T. spiralis. MCp frequency (1/378 bone marrow cells) was significantly greater (P<0.05) in BALB/c than C57/BL10 mice (frequency: 1/751). Similarly the rate of growth of MMC homologues and the production of mMCP-1 was significantly (P<0.05) greater in BALB/c than in C57/BL10 bone marrow cultures.

Larval stages of Anisakis spp. (Nematoda: Anisakidae) were found encapsulated or free in the viscera and abdominal cavity of the black-scabbard fish, Aphanopus carbo, chub mackerel, Scomber japonicus and oceanic horse mackerel, Trachurus picturatus in Madeiran waters. The prevalence of infection reached 97.2% (n=142) for A. carbo, 69.5% (n=154) for S. japonicus and 62.5% (n=40) for T. picturatus. Considerable differences in parasite intensities between A. carbo and both S. japonicus and T. picturatus were found, with mean intensities up to 69.6 in A. carbo, while in the other two fish hosts the intensity reached only a maximum of 2.6. These differences were probably due to different feeding behaviours of the hosts. Intensities of Anisakis sp. in A. carbo were high irrespective of sex and season. No relationship between host length and prevalence of infection was observed for A. carbo, while for S. japonicus a weak positive significant relationship was found.

Adult Ascaris suum were dissected to obtain different worm components (body wall, body fluid, ovaries, uterus and oesophagus) which were used as antigens when testing 95 sera of naturally A. suum-infected Iberian pigs by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB). Pigs with patent Ascaris infections had significantly lower ELISA optical density values than pigs without adult worms when using the body fluid and the body wall as antigens. A poor negative correlation was found between adult intestinal worm burden or eggs in faeces and specific antibody responses, measured by ELISA and WB using all antigens. By WB, the recognition of specific bands was variable, but three groups of bands with molecular weights of 97 kDa, 54–58 kDa and 42–44 kDa were generally recognized by sera from naturally infected pigs as well as from hyperimmunized pigs when using the five antigen extracts. The ELISA and WB techniques may be used for immunodiagnosis, using somatic adult worm antigens, to declare young pigs to be Ascaris-free but cannot be used for individual Ascaris-diagnosis in adult Iberian pigs.

The effect of pollutants on the intensity of infection of metazoan parasites in the Mayan catfish, Ariopsis assimilis was investigated. Data were collected on pollutants and metazoan parasites from 76 catfish from five localities in Chetumal Bay in October, 1996. Nineteen pollutants (pesticides, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs)) were found in the catfish livers. Heavy metal content was not determined. Nineteen metazoan parasite species were recovered. After controlling for fish length and sampling station, there was a significant negative linear relationship between the intensity of the larval digenean Mesostephanus appendiculatoides and 1,1,1,-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT) concentrations. This negative relationship may be explained either by the effect of the pesticide on the mortality of (i) free-living larval forms, (ii) metacercariae in the fish, (iii) infected fish or (iv) intermediate host snails. There were significant differences between fish parasitized and not parasitized with M. appendiculatoides with respect to their DDT concentrations. There were also significant differences between the variances of the mean Clark's coefficient of condition values between catfish parasitized and not parasitized by M. appendiculatoides, with the variance of non-parasitized catfish being significantly larger. The results provided statistical evidence that DDT has a detrimental effect on M. appendiculatoides infection intensity. Furthermore, the significantly larger variance value of Clark's coefficient for non-parasitized fish suggested that DDT affects both the parasite and general host condition.