The interaction between host and infecting organism plays an important role in the survival of both of these components. The mechanisms whereby survival of one, or both, is achieved can be considered at various anatomical levels and degrees of complexity; those involving whole tissues together with events occurring at the cellular and subcellular levels. The involvement of sequestration, or the ‘standing apart’ of an invading organism from the host, as a mechanism of survival can also be examined at these various levels.

The parasitic protozoan Trypanosoma diemyctyli has a life-cycle that involves a vertebrate host, the red-spotted newt Notophthalmus viridescens, and an invertebrate host, the amphibian leech Batrachobdella picta. A study of the distribution and dynamics of this parasite in newts of known adult age and history of breeding in montane ponds in Virginia revealed a pattern of: (1) moderate prevalences of infection in post-metamorphic juvenile and adult stages, (2) rapid increases in numbers of trypanosomes in newts during their first year of maturity, (3) significant differences in the numbers of trypanosomes in male and female newts in mid-summer, (4) sustained high levels of infection in the first two years of newt adulthood, (5) significantly lower levels of infection in newts by the fourth and subsequent years of adulthood and (6) annual oscillations in the intensity of infection in older adult newts from spring and autumn lows to mid-summer peak levels. Newts with a history of skipping breeding seasons had higher levels of infection than those newts which returned to the pond for every breeding season. Newts brought to the laboratory and maintained under leech-free conditions failed to develop infection levels comparable to those in the field. The dynamics of infrapopulation sizes of trypanosomes in newts depend on multi plication rates of the trypanosomes, variable transmission rates from the invertebrate host and the development of resistance in older adult newts.

The reproduction of Eimeria vermiformis in different strains of phenotypically normal mice and in mice with various immunological characteristics or defects was compared. In some strains of phenotypically normal mice there were marked differences in oocyst production, both in terms of numbers and in the duration of patency, allowing the strains to be classified as resistant or susceptible to infection with E. vermiformis. These differences were apparent only in primary infections; both types of strain were equally resistant to reinfection. Amongst the strains of mice with immunological deficiencies, reproduction of the parasite was greatest in the athymic (nu/nu) mutants and these mice were completely susceptible to reinfection. Strains of mice with lowered or defective antibody production, or with defective neutrophils and low NK cell activity (bg/bg) were more susceptible than the relevant controls to primary infection but all developed substantial immunity to reinfection. Asplenic (Dh/+) mutants were remarkably resistant to infection.

Conventional mice and congenitally athymic, nude mice were infected with 20 metacercariae of the intestinal trematode Echinostoma revolutum. The sequential events in the pathological changes in the intestine were studied at different intervals post-infection. By day 11 onwards the conventional mice displayed dilatation of the region of the intestine which harboured the parasites. The mucosa in the dilated region showed marked crypt hyperplasia, villous atrophy and subepithelial fibrosis as the most conspicuous features which, together with a hypertrophy of the muscular layers, made the wall of the gut in the dilated region thicker than normal. The changes were thymus-independent as they were found to be as severe in the athymic, nude mice as in the conventional mice. The main histological features observed in the mice are discussed in relation to other conditions with similar changes, such as coeliac disease, nippostrongyliasis and trichinellosis. It is concluded that the present results support the view that there may be more than one effector mechanism of the change.

Y strain parasites (Wellcome stock) were cloned as epimastigotes by limiting dilution and one clone, Wel Tryp A2 was used to infect cell cultures and irradiated mice. The fibrosarcoma line, M4, was susceptible to infection with Wel Tryp A2 trypomastigotes but, after the first round of intracellular infection, proliferation and differentiation, failed to support parasite growth in long-term continuous culture. In contrast, a muscle-derived cell line, S2, produced regular waves of extracellular trypomastigotes and amastigotes during 80 days of continuous culture reported here. These infected S2 cultures have remained in continuous culture for up to 18 months over a 5-year period and have yielded in excess of 108 parasites/20 ml culture at 4–6 day intervals. Extracellular amastigotes produced in these cultures have a close morphological, immunological and biochemical analogy to intracellular parasites derived from rodents, and have maintained an absolute dependence on host cells for their growth and proliferation. These amastigotes produced low-grade chronic infections in normal CBA/T6 mice but produced acute, fatal infections with high parasitaemia in mice of the same inbred strain given 900 rad. whole-body irradiation prior to infection. Although present findings relate to a single parasite clone, the parent stock from which the clone was derived showed similar growth characteristics when co-cultured with S2 cells.

We have performed restriction endonuclease digestion of nuclear DNAs, combined with gel electrophoresis and molecular hybridization to characterize different Trypanosoma brucei brucei stocks and to identify trypanosome species. Cloned DNA complementary to the messenger RNAs (mRNAs) for different variable surface glycoproteins (VSGs) of T. b. brucei stock LUMP 227 was used to examine differences in genomic DNAs from T. b. brucei stocks and from various other trypanosome species. These cDNA reagents differentiated the stocks of T. b. brucei and also distinguished the trypanosome species. Our data also show that a T. b. brucei nuclear DNA fragment used as a probe in molecular hybridization analysis provides an appropriate marker in determining trypanosome species. We have extended our analysis of trypanosome nuclear DNA by developing a simple and rapid spot test, for the identification of trypanosome species, which can be carried out using crude materials such as isolated parasites, infected whole blood and tsetse saliva. The procedure is species-specific, sensitive to the level of 104 organisms and is suitable for use under field conditions. Thus, with appropriate sequences for hybridization, the procedure has obvious applications for the diagnosis of African trypanosomiasis.

It is now well established that animal parasites elicit vigorous immune responses in their hosts and that the resistance to reinfection thus acquired is mediated through conventional humoral and/or cellular effector mechanisms. It is also recognized, however, that some parasites exhibit extreme longevity in the face of a potentially hostile or lethal environment, and it may be assumed therefore that such organisms possess a repertoire of highly sophisticated and successful evasive strategies. Of all the survival mechanisms thus far proposed, the concept of antigen sharing, or disguise, is probably the most contentious. Arguments have arisen over the nature and origin of the shared determinants and over the validity of their role in ensuring parasite survival within the fully immunocompetent host. This presentation reviews published data concerning the existence of a disguise stratagem amongst medically important parasites and evaluates experiments designed to investigate the functional importance of disguise in immune evasion.

The tegumental mitochondria from the anterior, mid-ventral and mid-dorsal regions of the body surface of Corrigia vitta have been analysed using stereological and statistical methods. Mitochondria from the ventral tegument were more numerous and contained a greater density of cristae than either the anterior or dorsal tegumental mitochondria. A close association between the size and numbers of mitochondria in the anterior regions of tegument appears to be important in maintaining a relatively constant mitochondrial volume fraction. Results are discussed with respect to worm surface function in the intact host-parasite system.

Following inoculation of Trypanosoma brucei into large mammals by the tsetse fly a local skin reaction, the ‘chancre’, develops due to trypanosome proliferation. We have cannulated the afferent and efferent lymphatics of the draining lymph node in goats and examined the onset of a cellular reaction, the emigration of the parasite from the chancre and the development of both antigenic variation and the specific immune response. The chancre first became detectable by day 3 post-infection, peaked by day 6 and then subsided. Lymphocyte output increased 6- to 8-fold by day 10 and the number of lymphoblasts increased 50-fold in this period. Both then declined. Trypanosomes were detected in lymph 1–2 days before the chancre, peaked by days 5–6, declined during development of the chancre and then peaked again. The bloodstream population appeared by days 4–5 and displayed different kinetics from that in lymph. Recirculation of parasites through the lymphatics ensued. Lymph-borne trypanosome populations were highly pleomorphic. Parasites in lymph expressed firstly a mixture of the Variable Antigen Types (VATs) which are found characteristically in the tsetse fly, this being followed by a mixture of other VATs. The two groups overlapped in appearance. In the bloodstream the same sequence of events occurred although 2 or 3 days later. The specific antibody response, as measured by radioimmunoassay and agglutination, arose within a few days of the first detection of each VAT. Activities appeared first in the lymph and then in plasma.

Populations of Fasciola hepatica infecting sheep are regulated by at least 3 density-dependent processes. Parasite deaths due to parasite-induced primary host mortality, fluke fecundity and asexual multiplication in the intermediate snail host, Lymnaea truncatula, vary according to the intensity of infection. Empirical and theoretical evidence is used to assess the extent to which each of these processes in turn affects parasite population numbers.

Antigenic variation is a powerful survival strategy adapted by certain species of parasitic protozoa to allow them to survive in the immunized host. It is exemplified by the African trypanosomes, which provide far and away the best characterized and most studied system of this kind. Why have the trypanosomes developed antigenic variation to such a sophisticated level? Because the trypanosome lives its life in the bloodstream of its mammalian host and is therefore in continuous conflict with the host's immune system. Antigenic variation represents its whole survival strategy, with some help provided by its ability to immunosuppress the host. The importance of antigenic variation to the trypanosome is underscored by the estimate that up to 10% of the trypanosome genome may be devoted to variant antigen genes (Van der Ploeg et al. 1982). Most other parasitic protozoa prefer a less confrontational existence and usually adopt an intracellular home for at least a part of their life-cycle within the mammalian host. That being the case, do other parasitic protozoa need antigenic variation within their armorarium ? The answer seems to be yes, although the reasons why are by no means clear. For example, the stages in the life-cycle which exhibit antigenic variation might be expected to be those which are released free into the bloodstream – in malaria, sporozoites and merozoites, for example. Yet there seems to be no evidence for phenotypic variation at all in these stages. Rather, it is the intracellular stages which, in both Plasmodium and Babesia, seem to elaborate molecules which are expressed at the surface of the parasitized cell, and which are capable of both eliciting an immune response and of avoiding the con- sequences of such a response by phenotypic antigenic variation. Why are such antigens expressed, and what is their functional significance?

When jirds were infected with a single inoculum of 25–50 infective larvae of Brugia pahangi an overall mean recovery of adult worms of 44·5% (n = 41) was obtained. There was no difference in recoveries between male and female jirds. If jirds were repeatedly inoculated with larvae into the peritoneal cavity yields were only slightly reduced. Yields were 30·5% for 5 infections (n = 10), 26·7% for 10 infections (n = 8), 34·4% for 15 infections (n = 10) and 28·5% for 20 infections (n = 7). Twice as many worms were recovered from intraperitoneally inoculated jirds than from subcutaneously inoculated jirds.

Fibronectin determinants were revealed in a soluble extract of Schistosoma mansoni adult worms by standard immunodiffusion and immunoelectrophoresis techniques. The same target molecules were demonstrated on the parasite's surface using a binding assay with [125I] anti-fibronectin. The use of fluorescein- and peroxidase-conjugated antibodies confirmed the above observations and provided a fairly precise means for locating the cross-reacting antigen on the worm surface. An in vitro cytotoxic assay using inactivated (56°C, 2 h) anti-fibronectin rabbit immune serum and guinea-pig serum as a source of complement was developed. In these conditions, anti-fibronectin exerted cytotoxic activity against lung schistosomula and adult worms but not skin schistosomula. The ultrastructural damage induced by anti-fibronectin in the presence of complement was studied using transmission electron microscopy. The results suggest a close association between fibronectin determinants and S. mansoni membrane.

Infective larvae, adults and newborn larvae of Trichinella spiralis were surface labelled with radioactive iodine, and the surface material was solubilized in the mild detergent sodium deoxycholate. The radio-isotope labelled products were stage-specific glycoproteins that were few in number (2–4 components) and antigenic in infected mice and rats. Antibodies synthesized in infected animals against these biochemically defined surface antigens may or may not interact with the surface of the living worm. The latter type of antibody is unlikely to be involved in the initial phase of parasite rejection and is therefore another example of a non-protective host antibody response. The stimulus for its synthesis must be the observed release of surface antigen. A monoclonal antibody to a surface glycoprotein of newborn larvae protected against infection, and also promoted eosinophil killing in vitro. This observation emphasizes the importance of surface antigens in protection against infection, suggests a role for granulocytes in vivo, and provides encouragement for the possible use of nematode surface antigens in protection. An example of regional specialization of the nematode cuticle was given by a monoclonal antibody reactive with only the surface of the male intromittent organ and not the female or remainder of the male. The same stages were labelled in vitro with radioactive methionine, and the secreted proteins were also found to be stage-specific. Some, but not all, were antigenic in infected mice. The total concanavalin A-binding somatic glycoproteins of each stage exhibited considerable individuality, and hence stage specificity, when resolved by two-dimensional gel electrophoresis. These results extend our knowledge of stage-specific components of T. spiralis, and allow a rational approach towards protection and the construction of diagnostic procedures.

Rats harbouring a 35-day-old primary infection of Moniliformis dubius were inoculated with constant doses of Nippostrongylus brasiliensis and 10 days later, after post mortem examination, rats with concurrent infections harboured significantly fewer Nippostrongylus than rats with single infections. Similar infections of Moniliformis were carried out, but with post mortem taking place on days 8,9, 12 and 14 of the Nippostrongylus infections. On days 8 and 9 of infection, rats with concurrent infections did not harbour significantly fewer Nippostrongylus compared with single infections. Both single and concurrent infections of 12-and 14-day-old Nippostrongylus were found to harbour lower numbers of worms. In the single infection this corresponds to the timing of the typical immune expulsion of a primary single infection which takes place on approximately day 12 of infection. The Moniliformis population was not significantly affected, in terms of numbers, dry weight and length, although each parasite population did show a slight shift in site in the presence of the other. A significant reduction in egg production by Nippostrongylus was detected throughout concurrent infection. The possible role of non-reciprocal cross-immunity is discussed as an explanation for the apparent early expulsion of the Nippostrongylus population in the presence of Moniliformis.

The pattern of DNA synthesis in male and female Schistosoma mansoni from mixed and single-sex infections in mice has been determined biochemically and autoradiographically using the incorporation of [3H]-thymidine as a specific marker of DNA synthesis. During early development (up to 35 days post-infection (p.i.)) adult males and females from mixed infections had a comparable specific activity of DNA. In males, from 35 days p.i. onwards, the specific activity of DNA decreased rapidly to become significantly different from that observed in females. In single-sex infections DNA synthesis in females was depressed compared to that observed in males from single-sex infections and was also significantly different (P ≼ 0·01) from DNA synthesis in females from mixed infections. There was no significant difference in DNA synthesis between males from single or mixed infections. DNA synthesis in both sexes was found to be sensitive to hydroxyurea treatment, the inhibition in sexually mature females being approximately 75% and in males approximately 45%. Autoradiography using both light microscope and electron microscope techniques revealed that the testes and ovary had labelled cells. In male schistosomes the only other labelled cells were small undifferentiated cells found scattered through the tissues. In females the vitelline gland had large numbers of densely labelled nuclei within Stage 1 vitelline cells, as well as numerous small undifferentiated cells.

Volume conducted potentials were recorded from schistosomula of Schistosoma mansoni transformed mechanically (MS) and by skin penetration (SS). The spontaneous electrical activity recorded consisted of bi and triphasic transients ranging from 20 to 200 μV in amplitude and 10 to 300 msec in duration. Low amplitude potentials occurred at a much greater frequency than large amplitude potentials, which appeared to correlate with peristaltic-like contractions of the schistosomulum's musculature. Electrical activity in the schistosomulum was highly sensitive to a number of agents believed to affect metabolic pathways, the neuromuscular system or the host/parasite interface of adult schistosomes. Among the most reactive substances were potassium antimony tartrate, eserine, poly-L-arginine and potassium cyanide. Over a wide range of experimental treatments, electrophysiological responses in schistosomula transformed from cercariae by mechanical decaudation and skin penetration were remarkably similar, supporting the notion that MS are suitable material for in vitro immunochemical, biochemical and physiological study. Some treatments, however, were more or less effective in altering electrophysiological activity and motility in the schistosomulum than in adult S. mansoni. This suggests that significant physiological alterations may occur during development from skin stage to adult parasites concomitant with immunochemical and morphological changes already known to occur.

In common with a number of parasite surface antigens about which we have heard, the influenza haemagglutinin is a membrane glycoprotein which varies in antigenicity.

A question which often arises concerns the contribution of the carbohydrate side-chains to antigenicity, and we have recently observed that a number of monoclonal antibodies are able to discriminate between glycosylated and nonglycosylated haemagglutinin molecules. Specifically these antibodies select antigenic variants with haemagglutinins which contain asparagine substitutions in the sequence asparagine–cysteine–threonine and the asparagine is glycosylated. By infecting cells incubated in medium containing tunicamycin non-glycosylated variant haemagglutinin can be obtained, and it is possible to show that such molecules are precipitated by the antibodies used to select the variant. These results directly indicate that carbohydrate side-chains can modulate the antigenic properties of glycoproteins and may be involved in antigenic variation.

Experimental studies on the survival of Fasciola hepatica miracidia show no evidence that miracidial mortality varies with the pH of the medium, at least in the range 6·0–8·0. On the other hand, miracidial mortality is shown to vary with both the temperature of the medium and the age of the larvae. The mean expected life-span of the miracidium decreases from about 35 h at 6°C to about 6° h at 25° C. The Gompertz survival function provides a good description of the miracidial survivorship curves over the range of temperatures used, and we describe, a maximum likelihood method of estimating the mean values of the parameters of this function, together with their approximate 95% confidence limits.

An analysis of the frequency distribution of numbers of Moniliformis dubius in rats of an outbred strain of Wistar origin (CFHB) and feeding ad libitum on Oxoid 41B diet, showed that over-dispersion occurred regardless of the age and sex of the rats and the infective dose given (12, 20 or 40 cystacanths/rat). Over-dispersion was also shown to be independent of variability in the age and sex of the cystacanths given. The analysis demonstrated that the over-dispersion declined as the course of the infection proceeded. As expected, parasite survival was found to be age-dependent with female worms living longer, on average, than males, and both male and female worms living longer in rats given 12 as opposed to 20 cystacanths. Possible mechanisms for generating the over-dispersion observed during this work are discussed and a tentative hypothesis, invoking host heterogeneity with regard to carbohydrate availability in the small intestine, is proposed for further experimental investigation.