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Despite the plethora of evidence on the consequences of host nutrition on their immune responses to gastrointestinal parasites, the identity of molecules and mechanisms that drive the manifestations of immunity under nutrient abundance are not yet known. This is partly due to limitations of the methodologies employed to date that have failed to give comprehensive answers. The great advancements in the technological front over the past few years have opened a window of opportunity to identify these effector molecules, to explore both the mechanisms and cellular pathways and to evaluate their importance in the immune response to parasites. The aim of this paper is to present some of the novel, high-throughput technologies that are currently available in immunology and to explore their use in advancing our knowledge in interactions between nutrition and immunity to nematode parasites, with special reference to sheep. In the first part, we introduce the technologies and we discuss advantages and pitfalls of their use. We bring in successful examples of how their employment advanced knowledge and improved our understanding of the mechanisms that regulate immune responses to pathogens (both micro- and macroparasites). In the second part, we focus on the impact of nutrition on the immune response to parasites, and explore how these technologies can be used to advance our knowledge of immunonutritional interactions. We use as our starting point well-established models that have been successfully used to investigate the consequences of nutrition on the manifestations of immunity to parasites, which we further consider in the context of the novel technologies. We conclude by emphasizing the great potential of the described methodologies in unravelling the complex interactions between nutrition and immunity, but we also recommend caution when interpreting the outcomes. [ABSTRACT FROM AUTHOR]

The present paper reviews the available literature on the development of immunity to animal Schistosoma infections. The majority of the studies on animal schistosomiasis were performed in cattle and pigs and only Schistosoma mattheei , S. bovis and S. japonicum received particular attention, mainly because of their recognized veterinary significance or zoonotic aspect. Although it is an accepted fact that acquired resistance to Schistosoma is of major importance in the regulation of infection intensity in the field, almost nothing is yet known of either the nature of the antigens or of the immune mechanisms involved. The recent studies on immunity development focus in particular on the occurrence of maternal to foetal transfer of immunological substances related to animal Schistosoma infections and possible effects of these transfers on the immunity development of the foetus/newborn. Since congenital infections for Schistosoma species other than S. japonicum are extremely rare, the most plausible route for foetal contact is the transplacental or postnatal transfer of immunological substances. Prenatal transfers of specific antibodies and antigens via placental lesions and postnatal transfers via the colostrum were observed in cattle and pigs, and subsequent modifications of the immune response of the newborn were observed. Placental lesions induced by Schistosoma eggs could allow other pathogens to cross the placenta. [ABSTRACT FROM AUTHOR]

SUMMARY In an accompanying paper we show that antibodies in intestinal mucus that recognize a 35-kDa antigen from the surface of the L3 stage of the sheep intestinal nematode parasite, Trichostrongylus colubriformis, are strongly associated with immune rejection of L3 in a truncated infection model of immunity in sheep. Monoclonal antibody PAB-1 was used to immunopurify this antigen from T. colubriformis L3 . The antigen is resistant to digestion with a range of proteases including proteinase K and does not stain on gels or blots treated with protein-detecting reagents but does stain with carbohydrate-detecting reagents. The antigen is also resistant to degradation by the action of lipases and is not soluble in organic solvents, suggesting that lipid components are not present or not accessible. Treatment with glycosidases does not affect the antigen, indicating either that sialic acid and N-linked or O-linked sugars are not present or that they are not accessible to enzyme attack. The antigen is not destroyed by harsh alkaline degradation with up to 8 m NaOH with or without borohydride reducing agent, or by extensive hydrazinolysis. Strong acid hydrolysis with trifluoroacetic acid or boiling in hydrochloric acid for 20 min does destroy the antigen. The antigen migrates as a poorly defined high molecular weight complex on native electrophoresis gels, but is detected as a major band at 35 kDa on SDS PAGE either by carbohydrate staining or by immunoblotting with antibody from immune sheep intestinal mucus and with mAb PAB-1. Proteinase K digestion and alkaline degradation of extracts from L3 of 10 other parasitic nematode species revealed that L3 of each species contained a carbohydrate staining molecule which can be detected by mAb PAB-1 and by mucus antibody from immune sheep. Because antibodies in intestinal mucus are directed against these antigens and may be responsible for protective immunity, carbohydrate larval antigens (CarLA) could represent a new family... [ABSTRACT FROM AUTHOR]

In some central‐American countries, Leishmania (L.) infantum chagasi infection can cause non‐ulcerated or atypical cutaneous leishmaniasis (NUCL) in addition to the classic clinical form, visceral leishmaniasis (VL). Little is known about the host‐parasite relationship that can contribute to the determination of one or another clinical form. The present study had the objective to evaluate the humoral and cellular immunity in the sera of individuals affected by NUCL to improve the comprehension of this atypical host‐parasite interaction. Based on clinical and laboratory diagnosis, serum of 80 individuals was collected to evaluate the cytokines and immunoglobulins profile of NUCL (n = 47), VL patients (n = 5), and negative controls (n = 28). Cytokines were detected using Cytokine Bead Array (CBA) Human Th1/Th2/Th17 kit according to the manufacturer's instructions; class (IgG and IgM), and subclass of (IgG1 and IgG2) immunoglobulins was evaluated by ELISA using specific antigens. The concentration of TNF‐α, IFN‐γ, IL‐2 and IL‐4 cytokines in NUCL, VL and control was present below the detection threshold of CBA kit. IL‐6, IL‐10 and IL‐17A cytokines was lower in NUCL compared to LV patients. Regarding to immunoglobulins, NUCL patients produced 4.0 times more IgG than the control, while VL patients produced 6.6 times more; and IgM level was 1.6 times higher in NUCL and 2.6 times in VL patients compared to the control. Concerning the immunoglobulins subclass, only VL patients showed positive reaction for IgG1, and IgG2 did not show positive reaction among the groups. The results showed a weak cellular and humoral systemic immune response in NUCL patients. [ABSTRACT FROM AUTHOR]

The insect innate immune system comprises both humoral and cellular defence responses. In the laboratory, the insect immune system is well characterized. In the field, however, little is known about the role of constitutive insect immune function and how it varies within and between populations. Laboratory studies suggest that host nutrition has significant impact upon insect immune function. Thus, the rationale for this study was to sample natural populations of the Australian Plague Locust Chortoicetes terminifera to establish whether locust body condition (as determined by protein and lipid content) impacted their constitutive immune system and, as a result, has the potential to impact on their capacity to respond to a pathogenic challenge. We found that body condition varied greatly between individual female locusts within sites and that haemolymph protein levels, but not body lipid content, varied between sites. Moreover, our measures of immune function were correlated with the haemolymph levels of protein (in the case of haemocyte density), lipid (prophenoloxidase activity) or both (lysozyme-like antimicrobial activity). We discuss the implications of these findings for the role of biological pesticides in the control of locust populations. [ABSTRACT FROM AUTHOR]

In the face of rapid environmental change, anticipating shifts in microparasite and macroparasite dynamics, including emergence events, is an enormous challenge. We argue that immunological studies in natural populations are pivotal to meeting this challenge: many components of environmental change - shifts in biotic assemblages, altered climate patterns and reduced environmental predictability - may affect host immunity. We suggest that wild ungulates can serve as model systems aiding the discovery of immunological mechanisms that link environmental change with parasite transmission dynamics. Our review of eco-immunological studies in wild ungulates reveals progress in understanding how co-infections affect immunity and parasite transmission and how environmental and genetic factors interact to shape immunity. Changes in bioavailability of micronutrients have been linked to immunity and health in wild ungulates. Although physiological stress in response to environmental change has been assessed, downstream effects on immunity have not been studied. Moreover, the taxonomic range of ungulates studied is limited to bovids (bighorn sheep, Soay sheep, chamois, musk oxen, bison, African buffalo) and a few cervids (red deer, black-tailed deer). We discuss areas where future studies in ungulates could lead to significant contributions in understanding the patterns of immunity and infection in natural populations and across species. [ABSTRACT FROM AUTHOR]

There is good evidence for costs to both the uses of immune defences and their development and maintenance. The optimal defence will be a balance of these costs with the risk of infection and the virulence of the disease. It is therefore clear that the life-history characteristics of both host and parasite will impact the optimal level of defence, and that this may in part explain the variation in immune defence against different pathogens and parasites. For instance, it has traditionally been suggested that long-lived hosts should invest in immune memory. Ecological evolutionary theory can be used to examine in detail how different host characteristics will affect the optimal immune response that evolves. Here, we review theoretical studies on the impact of host lifespan on various immune defence characteristics including acquired immunity and highlight the importance of population-level epidemiological feedbacks on the outcome. In particular, we discuss when longer-lived hosts may invest less in acquired immunity and develop new theory to highlight the importance of the mechanism of host population regulation to the outcome. We finish by discussing where more theory is needed and how comparative and experimental studies may test the theory. [ABSTRACT FROM AUTHOR]

Interacting pathogens and hosts have evolved reciprocal adaptations whose function is to allow host exploitation (from the pathogen stand point) or minimize the cost of infection (from the host stand point). Once infected, two strategies are offered to the host: parasite clearing (resistance) and withstanding the infection while paying a low fitness cost (tolerance). In both cases, the immune system plays a central role. Interestingly, whatever the defence strategy adopted by the host, this is likely to have an effect on parasite evolution. Given their short generation time and large population size, parasites are expected to rapidly adapt to the environmental conditions provided by their hosts. The immune system can therefore represent a powerful engine of parasite evolution, with the direction of such evolutionary trajectory depending on, among other factors, (i) the type of mechanism involved (resistance or tolerance) and (ii) the damage induced by overreacting immune defences. In this article, I will discuss these different issues focusing on selected examples of recent work conducted on two bird pathogens, the protozoa responsible for avian malaria ( Plasmodium sp.) and the bacterium Mycoplasma gallisepticum. [ABSTRACT FROM AUTHOR]

Sustained research efforts over the last 50 years have revealed a considerable amount of information about immunity to taeniid cestode infections in the parasites’ intermediate hosts. As a product of this research, a series of effective recombinant vaccines have been developed which have no parallel in any other group of parasitic organisms. There are, however, many important aspects relating to immunity that remain to be elucidated. Some concepts have come to be firmly held as facts and yet the supportive data are either conflicting or unconfirmed. This review considers the phenomenon of immunity to re-infection with taeniid cestodes in their intermediate hosts, examining carefully the nature of the evidence that is available to support conclusions that have been drawn in this area. [ABSTRACT FROM AUTHOR]

Parasitic nematodes of the small-ruminant gastrointestinal tract pose a problem worldwide. The impact of these pathogens is worsened by the emergence of anthelmintic resistance to all three available classes of drugs. In addition to causing considerable economic loss, these parasites are detrimental to the health and welfare of sheep and goats. Vaccination offers an alternative approach to drug-based control and a great deal of investment has gone into the investigation of protective antigens for some of these nematode species. However, attempts at vaccination are hindered by a lack of understanding of how best to promote protective immunity to nematode species, such as Teladorsagia circumcincta, which inhabits the abomasum of sheep. This situation contrasts with that in murine models of gastrointestinal nematode infection, where the basis of protective immunity is increasingly well understood. In this review, we discuss the current knowledge of the immune effector mechanisms elicited by T. circumcincta and consider the probable role of dendritic cells in the initiation of both effector and regulatory responses in the abomasum. [ABSTRACT FROM AUTHOR]

The slow development of acquired immunity is thought to be responsible for the characteristic convex age–intensity curve seen in human schistosome infection, which peaks earlier in more heavily infected populations (this is described as a peak shift). Schistosomes are able to suppress protective host responses, and it is hypothesized that this suppression is responsible for the delayed development of protective responses. A deterministic mathematical model is used to describe levels of infection and immunity in an endemic population, incorporating protective immune responses which either reduce adult worm burden or reduce superinfection. Suppression, related to current worm burden, is also included and acts against one or both protective responses. If suppression acts against the entire protective response, it is able to delay the development of protective immunity, and the peak shift is predicted to be reversed at higher infection intensities, with removal of the peaks altogether at the highest levels of infection and/or suppression. If only the anti-adult worm protective immune response is vulnerable to suppression, while the anti-reinfection response remains intact, then suppression does not remove the peak in the age–intensity curve. These findings are discussed in the light of existing field and experimental data. [ABSTRACT FROM AUTHOR]

Host resistance to Trichuris muris is driven by Th2 responses. However, TNF-α has also been shown to play a role in protection. As TNF-α has a variety of actions, the exact role of TNF-α in immunity to T. muris is yet to be established. Here we demonstrate that although blocking TNF-α has been shown to abrogate resistance, rTNF-α treatment does not promote resistance. Further, we show that TNF-α functions to enhance the ongoing immune response. AKR animals that typically respond to infection with a polarized Th1 response produce greater levels of Th1 cytokines when treated with TNF-α and BALB/c animals that normally respond with a polarized Th2 response produce higher levels of Th2 cytokines. Crucially, blocking TNF-α in the strong Th2 responder strain BALB/c does not prevent expulsion of T. muris , thus supporting its role as a biological enhancer. TNF-α does increase transcription of both IFN-γ and IL-13 in vitro but can also act synergistically with IL-13 in vitro to promote production of RELMβ, which has also been shown to play a role in resistance to T. muris . Thus, this data demonstrates that TNF-α acts to enhance an ongoing immune response but is not necessary for a strong protective Th2 response. [ABSTRACT FROM AUTHOR]

Many studies on the role of merozoite surface protein 3 (MSP3) in immunity against malaria have focused on a conserved section of MSP3. New evidence suggests that polymorphic sequences within MSP3 are under immune selection. We report a detailed analysis of naturally-acquired antibodies to allele-specific and conserved parts of MSP3 in a Kenyan cohort. Indirect and competition ELISA to heterologous recombinant MSP3 proteins were used for antibody assays, and parasites were genotyped for msp3 alleles. Antibody reactivity to allele-specific and conserved epitopes of MSP3 was heterogenous between individuals. Overall, the prevalence of allele-specific antibody reactivity was significantly higher (3D7-specific 54%, K1-specific 41%) than that to a recombinant protein representing a conserved portion of C-terminal MSP3 (24%, P <  0·01). The most abundant IgG subclass was IgG3, followed by IgG1. Allele-specific reactivity to the K1-type of MSP3 was associated with a lower risk of clinical malaria episodes during a 6-month follow-up in individuals who were parasitized at the start of the malaria transmission season (Relative risk 0·41 with 95% confidence interval 0·20–0·81, P =  0·011). The potential importance of allele-specific immunity to MSP3 should be considered in addition to immunity to conserved epitopes, in the development of an MSP3 malaria vaccine. [ABSTRACT FROM AUTHOR]

That humans in endemic areas become immune to malaria offers encouragement to the idea of developing protective vaccines. However natural immunity is relatively inefficient, being bought at the cost of substantial childhood mortality, and current vaccines are only partially protective. Understanding potential targets and mechanisms of protective immunity is important in the development and evaluation of future vaccines. Some of the problems in identifying such targets and mechanisms in humans naturally exposed to malaria may stem from conceptual and methodological issues related to defining who in a population is susceptible, problems in defining immune responsiveness at single time points and issues related to antigenic polymorphism, as well as the failure of many current approaches to examine functional aspects of the immune response. Protective immune responses may be directed to the pre erythrocytic parasite, to the free merozoite of the blood stage parasite or to new antigens induced on the infected red cell surface. Tackling the methodological issues of defining protection and immune response, together with studies that combine functional assays with new approaches such as allelic exchange and gene knock out offer opportunities for better defining key targets and mechanisms. [ABSTRACT FROM AUTHOR]

APlasmodium falciparumcDNA expression clone,λPf9, had been identified earlier as a protective epitope, using anti-λPf9 antibodies and combinatorial phagotopes. A segment of the Pf9 gene showed homology withParameciumimmobilization surface antigens such as 51B, 51A and 156G. A synthetic Pf9-peptide was designed from this region, and specific antibodies were raised. Each of these anti-Pf9 antibodies and combinatorial reagents, as well as anti-Paramecium51B antibodies, recognized the Pf9-peptide on ELISA, and the same protein band in parasite immunoblots. TheP. falciparumprotein was released from the merozoite membrane fraction on treatment with PI-PLC, indicating the presence of a GPI anchor. Anti-Pf9-peptide antibodies specifically inhibited the growth ofP. falciparumin culture. Immunofluorescence assays showed the reactivity of anti-Pf9-peptide sera withP. falciparummerozoites and gametocytes, as well as on the surface ofParamecium tetraurelia. The Pf9-peptide was able to induce proliferation of splenic lymphocytes obtained from mice infected with the rodent malarial parasitesPlasmodium bergheiandPlasmodium yoelii.These results point towardsPlasmodiumPf9 as a conserved novel protective protein, sharing an epitope withParameciumsurface antigens. [ABSTRACT FROM AUTHOR]

Immunity to the sexual stages of Plasmodium falciparum can be induced during natural infections. Characterization of this immunity may facilitate the design of a transmission-blocking vaccine (TBV). This study aimed to assess the prevalence and serological correlates of functional transmission-blocking immunity in Gambian children (aged 1–4 years old) who were P. falciparum gametocyte carriers. Serological assays showed 100% response to fixed, whole parasites but only 42% to live gametes. Responses to the antigens Pfs230 and Pfs48/45 were 54.1% and 37.3%, respectively, in an IgG1 ELISA. 14/55 sera were capable of reducing the infectivity of laboratory isolate NF54 in a standard membrane-feeding assay (SMFA). This activity was strongly correlated with IgG1 responses to Pfs48/ 45 (r = 0.49, P < 0.001) and to a serological reaction with epitopes of the same molecule (r = 0.38, P = 0.003). A weaker correlation was observed with IgG1 to Pfs230 (r = 0.29, P = 0.03). In direct membrane feeding assays (DMFA) with autologous isolates, sera from 4/29 children showed transmission-blocking activity. There was no correlation with serological assays and the DMFA or between the SMFA and DMFA. This may be caused by variation in sexual stage antigens and/or alternative modes of transmission-blocking immunity, both of which have implications for vaccine implementation. [ABSTRACT FROM AUTHOR]

A novel pepsin-like aspartyl protease was identified as a component of Haemonchus galactose-containing glycoprotein (H-gal-GP), which is an integral membrane glycoprotein complex located on the intestinal cells of Haemonchus contortus, and a highly protective antigen for sheep. This molecule, designated HcPEP2, showed 50% sequence identity with a previously described aspartyl protease from H-gal-GP known as HcPEP1. Fractions of H-gal-GP, either containing both HcPEP1 and 2 or other lower molecular weight components of the complex, were evaluated as protective antigens in immunization – challenge trials in sheep. When separated from the rest of the complex by gel filtration in 8  m urea, the HcPEP1 and 2 fraction significantly reduced H. contortus egg counts by 48% and worm numbers by 36%, but the lower molecular weight components were not significantly protective. However, the HcPEP1 and 2 fraction did not protect if electro-eluted from SDS-dissociated H-gal-GP, nor did bacterially expressed recombinant HcPEP1, suggesting that conformational epitopes are important for inducing immunity. [ABSTRACT FROM AUTHOR]

Before the start of the schistosomiasis transmission season, 129 villagers resident on a Schistosoma japonicum-endemic island in Poyang Lake, Jiangxi Province, 64 of whom were stool-positive for S. japonicum eggs by the Kato method and 65 negative, were treated with praziquantel. Forty-five days later the 93 subjects who presented for follow-up were all stool-negative. Blood samples were collected from all 93 individuals. S. japonicum soluble worm antigen (SWAP) and soluble egg antigen (SEA) stimulated IL-4, IL-5 and IFN-γ production in whole-blood cultures were measured by ELISA. All the subjects were interviewed nine times during the subsequent transmission season to estimate the intensity of their contact with potentially infective snail habitats, and the subjects were all re-screened for S. japonicum by the Kato method at the end of the transmission season. Fourteen subjects were found to be infected at that time. There was some indication that the risk of infection might be associated with gender (with females being at higher risk) and with the intensity of water contact, and there was evidence that levels of SEA-induced IFN-γ production were associated with reduced risk of infection. [ABSTRACT FROM AUTHOR]

Sheep were sensitized by weekly infections with Teladorsagia circumcincta over a 9-week period. After a 12-week rest, sheep were divided into four groups and killed without challenge or 3, 5 and 10 days post challenge (DPC) with 50 000 L3. Recovery of challenge larvae from abomasal scrapings was highest at 3 DPC while no parasites were recovered by 10 DPC. Abomasal lymph nodes (ALN) of challenged sheep were significantly larger at 5 DPC, coinciding with an increase in the proportion of CD4 T cells and a decrease in CD21+ cells, probably reflecting the loss of CD21 from terminally differentiated antibody secreting cells. A significant increase was observed in γδ-TCR+ cells at 3 DPC in the ALN, while their number slightly decreased in the abomasal tissues throughout the challenge period. The number of tissue eosinophils was dramatically increased after challenge compared with the unchallenged controls, with a peak at 3 DPC, coinciding with the peak in larval recovery. CD4+ cells significantly increased in the abomasal tissues at 5 DPC, while no changes in globule leucocytes were observed until 10 DPC. Antibody-secreting cell probes (ASC-probes) generated from the ALN showed highest reactivity against larval antigens at 5 DPC. This reactivity was predominantly directed against regions between 90 and 100 kDa and 30–35 kDa in the L3 preparation and lower molecular weight antigens in the L4. No reactivity was observed against the adult extract. The 30–35 kDa antigen seemed to exist as a high molecular weight complex in L3 homogenate and was not susceptible to protease K treatment, suggesting it may be non-protein in nature. [ABSTRACT FROM AUTHOR]

SUMMARY Substantial protection against the economically important nematode Haemonchus contortus has been achieved by immunizing sheep with a glycoprotein fraction isolated from the intestinal membranes of this parasite. This fraction has been termed Haemonchus galactose-containing glycoprotein complex (H-gal-GP) since it was originally isolated through its selective binding to lectins with a specificity for N-acetylgalactosamine. A major component of this highly protective antigen complex is a family of four zinc metalloendopeptidases, designated MEPs 1–4. Various combinations of these MEPs were evaluated in immunization–challenge trials in sheep. In two experiments a combination of all four MEPs, separated from the rest of the complex by gel filtration in 8 m urea, significantly reduced H. contortus egg counts by 45 and 50%, an effect not significantly different from that conferred by 8 m urea treatment of H-gal-GP itself. Similarly, MEP3 alone or MEPs 1, 2 and 4 in combination, electroeluted from the complex following SDS gel electrophoresis, each reduced egg counts by some 33%. The MEPs are therefore protective components of H-gal-GP and from previously published findings, it appears that MEP3 is the most effective member of this metalloendopeptidase family. However, there was no significant protection when sheep were immunized with fully reduced and denatured H-gal-GP or with bacterially expressed recombinant forms of MEP 1 or the principal domains of MEP3, suggesting that conformational epitopes on the MEPs are required for immunity. [ABSTRACT FROM AUTHOR]

Sheep immunized with Toxoplasma gondii (Toxovax®) prior to pregnancy were tested for their ability to withstand a challenge at 90 days gestation with 10[sup 7] Neospora caninum (NC1) tachyzoites. The antibody responses in sheep following immunization with T. gondii were specific for T. gondii whereas peripheral blood mononuclear cells responded to both T. gondii and N. caninum antigen in vitro. This suggested that there was induction of crossreactive immune recognition in the sheep, at least at the cellular level. Following challenge of sheep at mid-gestation with N. caninum, no febrile responses were recorded in the group of sheep which had previously received Toxovax® while significant febrile responses were recorded in the group of sheep which received N. caninum challenge alone. Antibody responses to N. caninum developed in all sheep following N. caninum challenge and antibody responses to T. gondii were boosted in the group of sheep which had previously been immunized with Toxovax®. No antibodies to T. gondii were observed in the sheep which received the N. caninum challenge alone. Peripheral blood mononuclear cells from both groups of sheep responded to T. gondii and N. caninum antigen in vitro and interferon gamma was present in the cell-free supernatant from activated cells. However despite evidence of the induction of crossreactive immunity between T. gondii and N. caninum, this was not sufficient to prevent foetal death. The group of sheep which had received Toxovax® prior to pregnancy and the group of sheep which only received the N. caninum challenge experienced 100% foetal death compared with 0% in the unchallenged control group. Vaccination prior to pregnancy with Toxovax® did protect against foetal death following oral challenge at 90 days with 2000 T. gondii oocysts which caused 100% foetal death in a control challenge group. [ABSTRACT FROM AUTHOR]

The coccidian Cryptosporidium infects epithelial cells of a variety of vertebrate hosts and is the causative agent of cryptosporidiosis. In mammals, including humans and domestic animals, C. parvum infects the gastrointestinal tract producing an acute watery diarrhoea and weight loss. CD4+ T-cell-deficient hosts have increased susceptibility to infection with the parasite and may develop severe life-threatening complications. The host responses which induce protective immunity and contribute to pathogenesis are poorly understood. In the immunological control of infection, recent studies with murine infection models suggest that IFN-γ plays a key role in a partially protective innate immunity against infection identified in immunocompromised mice and also in the elimination of infection mediated by CD4+ T-cells. At the mucosal level, CD4+ intraepithelial lymphocytes are involved in the control of cryptosporidial infection, acting at least in part through production of IFN-γ which has a direct inhibitory effect on parasite development in enterocytes. Primary infection of ruminants induces an intestinal inflammatory response in which increased numbers of various T-cell subpopulations appear in the villi. In addition, infection results in increased intestinal expression of pro-inflammatory cytokines such as IL-12, IFN-γ and TNF-α. Because these cytokines appear to be important in the aetiology of inflammatory bowel disease, it is possible that they are involved in the mucosal pathogenesis of cryptosporidiosis. [ABSTRACT FROM AUTHOR]

The recognition of antigens from fourth-stage Ostertagia circumcincta by plasma IgA was studied in a group of 30, ten-month-old Scottish Blackface sheep which had been naturally, then deliberately infected. Western blotting revealed 49 bands that were recognized by antibody from one or more of the 30 sheep. There was a heterogeneous pattern of antigen recognition amongst the sheep. No individual recognized all the 49 bands and only one of the 49 bands was recognized by all sheep. Two antigens with approximate molecular weights 87 000 Da and 129 000 Da were significantly associated with a reduction in mean adult worm lengths. The observed variation in recognition of these two antigens on fourth-stage larval preparations accounted, in a statistical sense, for nearly 40% of the total variation in worm length. In addition to the variation in antibody mediated recognition of these two parasite molecules, three other components have been implicated in regulating worm length. They are a 37 000 Da band from adult worms, the amount of fourth-stage larval specific IgA in the abomasal mucosa and the density-dependent influence of adult worm burden. Together, these components and their interactions accounted for over 90% of the observed variation in worm length. These results indicate that the parasite-specific IgA response, or something extremely closely associated with it, is the major immunological mechanism controlling worm length. [ABSTRACT FROM AUTHOR]

Selected cytokine profiles of lymphocytes were assessed in BALB/c mice infected with protoscoleces of Echinococcus granulosus. Late stages of the infection (three months +) were characterized by more dominant Th2 activity with elevated IL-4 and IL-10 and reduced IFN-γ output by Con-A and antigen stimulated splenocytes. Circumparasitic leucocytes produced mainly IL-10 by five months post infection. A peak in IFN-γ production in the first month of infection may suggest Th1 or Th0 activity at this time and this may be correlated with initial protoscolex death. In addition, cytokine profiles from mice implanted with intact hydatid cysts were also assessed. At two weeks post implantation all cysts were still viable and cytokine production was characterized mainly by elevated IL-10 production. However, at four months post implantation, some of the cysts from two mice had been killed whilst all cysts in the remaining mouse remained viable. In the mice where dead cysts were present, elevated levels of IFN-γ were detected from splenocytes and circumparasitic cells. Elevated IL-4 was also evident with the splenocytes. In the mouse with viable cysts IFN-γ production was reduced. Results indicate that IFN-γ (Th1) activity may be correlated with killing of both protoscoleces and established cysts of E. granulosus. [ABSTRACT FROM AUTHOR]

The article presents an editorial regarding the significance of genetically modified parasites and the immune response. In doing so, investigations on the use of genetically modified parasites to probe their interaction with the host immune response are made. In addition, discussion on the use of this technology to study specific aspects of protozoan biology and immunity is presented.