Many parasitic diseases are accompanied by an immunosuppression which may affect only parasite-specific responses in some infections or lead to a general dysfunction of the immune system in others. African trypanosomiasis causes a particularly severe disorder of the immune system and this serves as a model system for analysis of the cellular basis of a parasite-induced general immune dysfunction affecting nearly all T- or B-lymphoid cell subpopulations. The nature of the parasite products causing havoc in the immune system may well vary in different infections and still remains to be defined. Trypanosome membrane fractions are active in vitro or in vivo but we have no evidence for a direct action on B- or T-cells. In vitro, both in man and mouse, T-cells are stimulated, but only in the presence of accessory cells. This points to the importance of host-derived immunosuppressive factors in the immune dysfunction. We have evidence that macrophages, after uptake of parasites in the presence of antibodies, are at least one target cell for parasite action. They can mediate immunosuppression and undergo changes in phenotype and mediator release during the course of infection. The macrophages show all the characteristic signs of activation, which can also be induced by other means and other infective agents such as BCG. Thus, macrophage activation would provide a common pathway for induction of a general immunosuppression in different infections.

Chimaerocestos prudhoei gen. et sp. nov. from Rhinochimaera atlantica in the North Atlantic off north-eastern Scotland represents a new family, the Chimaerocestidae, of tetraphyllideans and is the first record of a strobilate tapeworm from a holocephalan. The main taxonomic features are described and figured along with aspects of the ecology and mode of attachment to the gut mucosa. The lobed annular ovary and distribution of the vitellarium in two fields are characteristic features. About 15 eggs are deposited together in capsules. C. prudhoei is discussed in relation to other unusual fish tapeworms and the evolutionary biology of tapeworms, and to our scant knowledge of the holocephalans.

The morphology of the mucosal surface of samples from the small intestine of young protein-deficient pigs was examined by scanning electron microscopy. Three pigs had been infected with Ascaris suum for at least 58 days while 1 had remained uninfected; all pigs were housed and maintained under the same conditions, at the same time. The tissue samples collected at post mortem examination from pigs which contained A. suum showed varying degrees of villous atrophy and fusion. In addition, unusual small craters and as yet unidentified objects were observed at the surfaces of the enterocytes of Ascaris-infected pigs. These changes in mucosal morphology were not seen in the tissue taken from the uninfected pig. The possible association between the mucosal lesions and lactose maldigestion in young, protein-deficient pigs infeceted with A. suum is discussed.

Purified eosinophil and neutrophil cationic proteins isolated from the lysosomal secretion granules of human leucocytes have been tested for cytotoxic capacity against lung-stage schistosomula of Schistosoma mansoni in vitro. Eosinophil cationic protein (ECP) caused paralysis but not death at high concentration; this effect was reversible and involved no gross pathological manifestations. Eosinophil protein X (EPX) and neutrophil cationic protein (NCP) were highly toxic at concentrations of 10−5 mol/1, and induced paralysis at sublethal concentrations. These two proteins exerted their cidal effect principally against the subtegumental musculature and internal tissues of the parasite rather than against the surface syncytium and tegumental outer membrane. ECP and NCP were shown to bind to lung worms at paralysing concentrations, but this binding occurred independently of the charge of the parasite surface. Of several control proteins tested, only protamine was capable of destroying lung-stage parasites; the manifestations of damage were different, however, from those induced by the granulocyte-derived proteins. Parallel assays demonstrated that EPX also possessed cytotoxic capacity against newly transformed schistosomula, but it was less efficient than ECP in this respect. The data are discussed in relation to potential post-skin mechanisms of challenge attrition in the immunized host.

Using groups of 4 baboons (Papio anubis), 21·0% of a trickle exposure of 480 Schistosoma mansoni cercariae/baboon (10/week for 48 weeks) were recovered as adult worms (Group A) compared with 72·6% from a single massive exposure of 2500 cercariae/baboon (Group C). Group B, exposed first to the trickle and then to the massive exposure simultaneously with Groups A and C, yielded a worm recovery of 54% which was slightly but significantly less than Group C. The trickle infection apparently induced a substantial resistance to light re-exposure, but only a partial, although significant, resistance to a massive re-exposure. In Group B, however, there was a marked reduction in the degree of gross pathology, despite high tissue egg production by the mature challenge worms. The parasitological results, in terms of resistance to reinfection by and development of pathology to a trickle infection, are not materially different from those obtained in studies using conventional heavy primary and challenge exposures with S. mansoni. The significance of these findings is discussed in relation to the epidemiology of human schistosomiasis mansoni in which heavy exposures are believed to be the exception rather than the rule.

The development of the tegument and cercomer of Paricterotaenia paradoxa polycephalic larvae was examined using electron microscopy. Larvae are formed by budding from the inner surface of the tegument of the degenerating hexacanth embryo. A new secondary tegument formed around the larvae is probably produced from the original hexacanth sub-tegumental cells. Microvilli covering the surface of young larvae are converted directly into microtriches, as the larvae develop, by addition of electron-dense material to the proximal part of the microvillus. Remnants of the original microvillus are visible at the distal surface of each new microthrix, but they eventually degenerate. The cercomer homologue is represented by scattered follicular cells, bearing microvilli, lying just within the containing cyst wall. The continuity of tegumentary tissue from one developmental stage to the next is discussed.

It is proposed that, for many species of parasites, evasion of the host immune response may be achieved passively through enhanced survival within host individuals that have a genetically determined low responsiveness to infection. Evasion by this means may contribute significantly to continued transmission of infection in man and domestic animals and influence the severity of pathology. Low responsiveness plays an important role in determining over-dispersion of parasites within host populations, and the common occurrence of this form of distribution is seen as supporting evidence for the proposition, although few of the examples available provide conclusive proof. The extensive individual and strain variation in response to parasitic infection in laboratory strains of mice is tak as a homologue of the natural situation and allows analysis of the mechanisms underlying low responsiveness. Two examples are considered in detail. In Leishmania infections both non-H-2 and H-2-linked genes influence resistance, but the primary expression of genetically determined low response is at the level of the macrophage. Genetic influences upon acquired immunity regulate macrophage–T-cell interactions. In Trichinella spiralis H-2-linked and non-H-2 genes influence development of the intestinal responses necessary for expulsion of the adult worm, the former through the response of helper T-cells to worm antigen and the amplification of this response through other T-cells, the latter through an effect upon the response of myeloid stem cells to T-cell signals. Modification of genetically determined low responsiveness is discussed in terms of (a) improving host responsiveness through vaccination or non-specific immunostimulation and (b) altering host genotype through selective breeding or the introduction of resistance alleles into a population.

The entire surface of the early developmental stages of the cysticercoid of Hymenolepis diminuta bears microvilli. Posteriad differentiation produces a microthrix-bearing surface on the presumptive scolex region, commencing before scolex retraction in cysticercoids in Tenebrio molitor kept at 26°C. During sucker development, the scolex syncytial cytoplasm possesses electron-dense discoidal bodies, aligned parallel to the surface. They become associated with the apical membrane, domes are formed and electron-dense spine-like profiles become apparent. Elevation on short shafts follows, and multilaminate baseplates are then discernible. Fewer microvilli are now present and vesicles with asymmetric membranes (denser inner leaflet) occur within the syncytial cytoplasm. Before scolex retraction, this differentiation extends to the level of the suckers; thus the neck, which becomes reflected on retraction, still possesses only microvilli. After retraction, differentiation proceeds rapidly with increased growth of existing microtriches, discoidal bodies possibly contributing to the shaft support material; the reflected neck develops microtriches and the microvilli are shed into the scolex retraction cavity. The ‘asymmetric’ vesicles increase numerically, some fusing with the apical membrane and releasing their contents. Concurrently, apical membrane asymmetry (denser outer leaflet) becomes apparent. The adult-type surface is formed by 3 days post-scolex retraction, coinciding with the earliest time that the metacestode is infective to the final host.

A method is described for the reproducible purification of greater than 1·0 × 108 sporozoites of Eimeria spp. by centrifugation on metrizamide density-gradients. The mean contamination of the purified sporozoite fraction by sporocysts and sporocyst debris was less than 6% and the recovered sporozoites were fully viable, infective and ultrastructurally intact.

The antibody response of the appropriate hosts (cattle) to Taenia saginata larvae was compared with that of an inappropriate host (Balb/c mice) using gel electrophoresis followed by immunoelectrotransfer blot techniques (Western blotting). Three groups of cattle were included, those known to be resistant to challenge infection because of repeated oral challenge with T. saginata eggs over a 1-year period, a previously infected but known susceptible group and a group of uninfected controls. Serum from the mice and the two groups of infected cattle contained antibodies recognizing different ‘target’ antigens, some of which may be related to host resistance. The potential value of the technique of Western blotting in dissecting the humoral response of a particular host species to parasitic infection and in the identification of those antigens suitable for the production of effective vaccines is discussed.

Incorporation of four amino acids into protein by stage V cysticercoids of Hymenolepis diminuta occurred in the order leucine > phenylalanine > alanine > proline. Leucine incorporation was apparently linear over a 5 h period in contrast to uptake which was non-linear over the same time. Pre-incubation in sugars did not affect protein synthesis but incorporation was inhibited by cycloheximide. Uptake and incorporation of leucine by stage III cysticercoids exceeded that of stage V metacestodes and the 10-day-old adult worm.

Variations in the general protein and 40 enzymes of the 8 European pathotypes of the potato cyst nematode Globodera rostochiensis and G. pallida have been examined by isoelectric focusing (IEF) and cluster analysis. Differences in the protein patterns were observed and the presence of a major band at pH 8·0 allowed the two species to be discriminated. Extra isozymed of peptidase (EC 3.4. 11.*) and esterase (EC 3. 1. 1. 1) were also found in G. rostochiensis. Intra-species variation was seen within G. rostochiensis for superoxide dismutase (EC 1. 15. 1. 1) and within G. pallida for phosphoglucomutase (EC 2. 7. 5. 1) and glucose phosphate isomerase (EC 5. 3. 1. 9). The results suggest that the two species are very similar and the prospect for recognizing their pathotypes by IEF is discussed.

The following brief survey considers various manoeuvres which can be applied to manipulate the immune response to parasitic infections in vivo. The examples quoted largely concern malaria, babesiosis, schistosomiasis and leishmaniasis, predominantly in inbred mouse strains. Since my own relevant research experience has been restricted to leishmaniasis, this will receive undue emphasis, although it does illustrate particularly well points I wish to stress. The types of intervention described do not all provide the precision of interpretation with which they are sometimes credited. Thus, effects of immunosuppression or T-cell depletion alone can usually only implicate the specific immune response (in its broad sense) in shaping the natural history and outcome of an infection or in underlying the effect of prophylactic immunization. Nevertheless, more precise delineation of lymphocyte subset involvement can be obtained by cell replacement studies in some of these models or by exclusion of antibody. The outcomes of these approaches have been (or are) predictable in most cases. More fascinating, however, are the various instances which will be stressed where totally unpredicted and contrary observations have been made which led (or may lead) to fresh insight into the disease. These serendipitous findings illustrate at the same time the value of applying the manoeuvres, even though they imply that the logical immunologist cannot yet always outsmart the parasite by design.

Fourth-stage larvae of Ascaris suum, recovered from piglets at 11–22 days post-infection (p.i.), were examined by light microscopy for changes in the somatic musculature. During this time the estimated total number of muscle cells in the body increases from approximately 600 to 21 000 cells. This non-eutelic development appears to occur by division of platymyarian muscle cells into coelomyarian cells, thereby increasing the number of muscle cells/quadrant from 5 to 85. The incompleteness of these divisions results in sarcoplasmic connections among muscle cells, and between muscle cells and nerve chords. At 11 days p.i., immediately after the 3rd moult, the variation in muscle cell length in a quadrant, with the longest cells being at the lateral chords, has been established. The average muscle cell length at this point is 0·101 mm, the longest is 0·164 mm. These values have increased to 0·365 mm and 1·122 mm, respectively, by 22 days p.i. At 18 days p.i. those cells in the posterior section of the larva are still the shortest in the body.

The initial infection and first-generation development of Eimeria tenella was quantified using a cloned MDBK (Madin-Darby Bovine Kidney) cell line, irradiated with gamma radiation prior to infection, as the host cell. Irradiated cell cultures were found to be more susceptible to infection and had a greater capacity to support parasite development than non-irradiated cultures. It was suggested that the larger proportion of cells in the G2 phase of the cell cycle, the larger individual cell size and the inhibition of cell division in the irradiated cultures were all factors contributing to the increased susceptibility to infection and capacity to support parasite growth and development. The application of this technique (host cell irradiation) to the cultivation of other intracellular, protozoan parasites is discussed.

Mice were infected per os with Trichinella spiralis and their lymphocytes were removed and fused with mouse myeloma cell line P3 × 63Ag8653P3 for the selection of monoclonal antibodies to biochemically defined, stage-specific surface antigens of 3 parasite developmental stages: muscle larvae, adults and newborn larvae. Two separate antibodies against a defined single surface antigen of each stage were isolated. In each separate case the pair of monoclonal antibodies precipitated the same component from detergent-solubilized surface antigen preparations, but only one was able to bind to the surface of the living worm. The other must therefore be directed against an antigenic epitope which is obscured in the intact worm surface. The latter type of antibody is unlikely to be involved in the initial phase of parasite rejection and hence is another example of a non-protective host antibody response. The stimulus for its synthesis may be release of surface antigen, which does occur in vitro. One surface antigen of the newborn larvae is only detected by antibody in the first 6 h after birth; thereafter its presence is obscured as other antigens appear. The major surface antigen of the infective larvae contains carbohydrate determinants which are not available at the parasite surface. In addition, it displays great molecular heterogeneity but all variants appear to be derived from a common polypeptide structure.

Trichinella spiralis infections may lead to the loss of behavioural dominance among male mice. Reversals of dominance order first appear at the time when newborn larvae are released into the circulation of the host. The duration of dominance reversals bears no relationship to the number of muscle larvae harboured.

In the preceding paper Howard (p. 665) has given a very elegant presentation on ways in which the host immune system may be manipulated to provide valuable information about immunoregulation of parasitic infection in vivo. In our laboratory we have used some of the same manoeuvres to study immunoregulation of genetically controlled responses to Leishmania donovani infection in inbred mouse strains (Ulczak & Blackwell, 1983; Crocker, Blackwell & Bradley, 1984). As has been Howard's experience, the results obtained have not always been as one might have predicted at the outset.

Mice infected with Nematospiroides dubius generate weaker immune responses to concurrently administered sheep red blood cells (SRBC), than non-infected controls. The experiments described in this paper demonstrate that both adult and larval stages of N. dubius cause non-specific immunodepression of the response to SRBC. Mice which had been infected with larvae exposed to 25 krad. of irradiation, which prevents development to the adult luminal stages, produced as weak haemagglutination responses to SRBC as mice infected with normal worms even when SRBC were administered 6 weeks after infection. The removal of adult N. dubius by treatment with pyrantel 9, 11 and 15 days after infection with normal larvae did not restore the host's ability to respond to SRBC given on day 14. It was only when the mice had been without worms for 17 days that their capacity to respond normally to SRBC was restored. Mice infected with 60 or 400 transplanted adult worms produced depressed haemagglutination and plaque-forming responses to concurrently injected SRBC when compared with normal or sham-operated controls. The significance of these results is discussed in relation to the possible role of non-specific immunodepression in facilitating the survival of N. dubius in the host.

DNA contents of individual stages of Isospora (Toxoplasma) gondii and other Eucoccida were measured after Feulgen-pararosaniline (SO2) staining either by direct microfluorometry or by scanning of microphotographic negatives. Frequency distributions were analysed using a computer program based on a mathematical model describing cell division. All stages of I. (T.) gondii, except fertilized macrogametes (2c), contained a haploid amount of DNA (1c), indicating that meiosis in I. (T.) gondii occurs during sporogony. Microgametes possessed 3·3% DNA in excess, presumably mitochondrial DNA. Nuclei of M2-and M3-merozoites differed in two characteristics: a small but distinct nucleolus was observed in almost 50% of the M2-merozoites but in none of the M3-merozoites; all M2 merozoites were strictly haploid, while all M3-merozoites were synthesizing DNA (17% above the haploid value). It may be concluded that all M2- and M3-merozoites are already sexually differentiated, i.e. are macro- and microgamontoblasts, respectively. DNA synthesis necessary for the development of the microgamont starts already in the microgamontoblast stage (M3-merozoite). M2-merozoites macrogametes, synthesize 11% extra DNA before fertilization, (after fertilization an extra amount of 12% of the diploid value was found), probably by amplification of genes for proteins which are needed for rapid maturation and later sporogony. Essentially parallel results have been found in Eimeria tenella and in crescent cystozoites of Sarcocystis cruzi. Absolute DNA values in representatives of the Eucoccida have been estimated as follows (10−15 g): I. (T.) gondii, 96; E. tenella and E. acervulina, both 75; S. cruzi, 216; Plasmodium berghei, 27. The value of the estimation of total haploid amounts as a tool in taxonomy of Eucoccida is discussed.