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Previous studies have suggested that the suppression of IgM responses induced by different strains of trypanosomes can be related to the virulence of the parasite in a defined mouse strain (Sacks et al. 1980). This study has examined immunosuppression induced by Trypanosoma brucei NIM7 in two mouse strains (C3H/He and [CBA/H x C57B1/6]F1) which differ considerably in their ability to survive infections. The results confirm our previous studies in that mice were able to survive infection whilst they maintained at last a residue of their ability to mount an IgM response to DNP-Ficoll, a T-independent antigen. Complete abrogation of the IgM response coincided with fulminating parasitaemia, resulting in the death of the host.

This article examines the effectiveness of an innovative program aimed at training union activists to become mental health primary prevention agents and organizers in their workplaces. The three-year occupational stress training project is described and analyzed, and its successes and failures are examined in light of relevant theories of health education and community organization. The training program attempted to combine psychological theories of group dynamics and individual change with community organization and social change strategies. The project is viewed as successful to the extent that it included the trainees in the planning and implementation of strategies and activities in their own unions. It fell short, however, of its goal of "de-stigmatizing" mental health in the participating unions. The contradictions between training group facilitators and community organizers are examined. The experience of this union program points up the need for the continued development of practical and theoretical links between personal and political change.

A description of the different stages of Trypanosoma (M.) melophagium in different regions of the gut of the sheep ked (Melophagus ovinus) as observed by the SEM is presented. The extensive pile carpet or palisade colonization of the midgut and pylorus is described. The method of attachment and the relationship of the parasites to the microvilli in the midgut and the cuticle of the pylorus and ileum observed by other methods are confirmed. The micro-structure of the surfaces themselves in the regions of the gut to which parasites attach are described. The use of the technique for the study of other similar systems is discussed.

Levels of circulating filarial antigen, and humoral antibody to other defined antigenic targets, were measured over the course of experimental infection of three Presbytis cristatus monkeys with Wuchereria bancrofti. Circulating antigen levels, measured with an anti-phosphorylcholine monoclonal antibody, varied widely although all animals were positive for some period of the infection. Circulating antigen levels tended to be inversely related to the titre of anti-phosphorylcholine antibody, and this trend was maintained even following acid dissociation and inactivation of immune complexed host antibody. Other antibody specificities were measured by Western blotting against somatic proteins and immunoprecipitation of surface antigens. Amongst somatic antigens, targets between 14,000 and 200,000 daltons were recognised by monkey antibodies, but no correlation with infection status could be discerned. Likewise when measuring the response to the 29,000 dalton major adult surface glycoprotein, one animal produced a rapid response but the others did not recognise it until late in infection. In general, the experimental findings are characterised by wide variability between individuals, as may perhaps be expected in a primate host for a human spectral disease.

Brugia malayi, a lymphatic filarial parasite, secretes acetylcholinesterase during in vitro cultivation. A significant amount of enzyme activity was detected both in culture media and somatic extracts of adult and microfilarial stages of the parasite. The microfilarial stage produces three times more enzyme than adult parasites as a proportion of total protein. The enzyme has true acetylcholinesterase (AChE) activity as hydrolysis of acetylthiocholine is three times faster than butyrylthiocholine and is inhibited by eserine, a specific inhibitor of AChE. Secretory enzyme from adult female parasite excretory-secretory material (ES) was enriched 23 fold using copper chelating and concanavalin A (Con A) affinity chromatography. The Con A eluate showed a major protein band of 100 kDa and a minor 200 kDa component. The ES enzyme is antigenic and cross reacts with antibodies raised in mice against AChE from electric eel by enzyme-linked immunosorbent assay and immunoprecipitation. Immunoprecipitation of 125I-labelled microfilarial ES and adult ES with anti-electric eel AChE antibodies revealed three proteins of 30, 40 and 200 kDa in microfilariae and two proteins of 100 and 200 kDa in adult female ES. It appears that filarial secretory AChE exists in multiple molecular forms.

Previous reports have described profound effects on the function of the lymphoid system, especially the spleen, in mice infected with Trypanosoma brucei. This study provides further evidence of major change in the cell populations of the blood, peritoneum, and bone marrow, but shows that at least some of the stem cells of the bone marrow survive the damage caused by trypanosomes and retain their ability to repopulate the animal. In these infected mice the initial parasitemia was terminated by day 11 and was followed by a subpatent period of approximately 7 days before a final, lethal parasitemia occurred. Lymphopenia preceded the initial and final waves of parasites in the blood, and there was a marked increase in circulating neutrophils and large mononuclear cells for 1 week after the termination of the first wave of bloodstream parasitemia and during the final lethal parasitemia. Dividing macrophages were detected in the peritoneum only briefly during week 1 of infection, but the total number of peritoneal cells was increased from day 8 until the mice died. The bone marrow is severely stressed by the parasite infection. Total cell numbers and spleen colony-forming cells in the bone marrow were profoundly depleted during the resolution of the first parasitemia, but both these parameters largely recovered during the subpatent period before the mice were killed by the disease. Immune function was restored gradually after treatment with Berenil late in infection. We conclude that the progenitors of lymphocytes as well as the mature cells are affected by trypanosomes, but that some of the early bone marrow stem cells escape and rapidly repopulate the peripheral organs upon removal of the parasites.

Trypanosoma brucei gambiense differs from other T. brucei subspecies in the stability and conservation of its bloodstream form antigenic repertoire. Two variant surface glycoprotein (VSG) cDNA clones corresponding to the antigens U1 and L2 were isolated from T. b. gambiense bacteriophage lambda gt11 expression libraries and characterized. A third VSG cDNA clone, P1, was also examined. The L2 and U1 VSG genes are present in a large number of T. b. gambiense stocks isolated over a thirty-year period from different geographical areas of Africa, suggesting that they are stably maintained in the T. b. gambiense genome. These probes may be useful in epidemiological studies of Gambian sleeping sickness to differentiate between T. b. gambiense isolates.

We have examined the organization of genomic sequences homologous to the spliced leader of Trypanosoma brucei variant surface glycoprotein (VSG) mRNA, using a synthetic oligodeoxynucleotide probe. These sequences are highly reiterated in the trypanosome genome and most are located in 1.4 kb units arranged in a direct tandem repeat. However, some of the 1.4 kb sequences are dispersed from the cluster(s) of tandem repeats and are flanked by non-repeat DNA. The number and arrangement of these leader sequence orphons varies among different T. brucei stocks. Within the IsTat serodeme, the arrangement of three of four spliced leader orphons observed with Eco RV digestion was stable during a chronic infection and cyclic transmission through the insect vector. The fourth Eco RV orphon, however, undergoes rearrangement during antigenic variation and life-cycle differentiation.

Adult Brugia malayi nematode parasites possess a range of cuticular and epicuticular molecules which may be defined by various surface-labelling techniques. We present here evidence that at least two distinct antigens are associated with the surface, a glycoprotein of 29 kDa, and a complex of twelve components forming a regular series or 'ladder' between 17 and 200 kDa (17/200 kDa) which have not previously been described. Each of these products is antigenic in infected hosts, although responses in infected humans to the 17/200 kDa are relatively weak. Digestion of the 29 kDa antigen with proteases and endoglycosidases indicates that it is closely conserved between B. malayi and B. pahangi, and that it carries at least two N-linked oligosaccharide chains each of 1.5-2 kDa. By contrast, a smaller surface-labelled antigen of 15 kDa shows no glycosylation by either lectin adherence or endoglycosidase digestion assays. Trypsin treatment of intact, labelled parasites results in cleavage of 29 kDa molecules isolated 17/200 kDa 'ladder' to trypsin abolishes all bands except the 17 kDa base unit. Both the 29 kDa and 17/200 kDa antigens can be recovered as water-soluble molecules by homogenisation of the parasite in the absence of detergent, or by disruption of the cuticle with reducing agents such as 2-mercaptoethanol. In the presence of such agents, both the 17/200 kDa series and the 29 kDa glycoprotein are shed rapidly from intact parasites. Finally, two-dimensional electrophoretic analysis shows that while the 29 kDa glycoprotein is strongly basic and the 15 kDa acidic, the 17/200 kDa antigens form a related series of neutral pI.

The lymphatic filarial parasites, Brugia and Wuchereria, continue to present an immunological puzzle, particularly with respect to the development of natural resistance or damaging disease. We have approached this question by examining humoral responses to a few defined antigens of selected interest from these parasites, using sera from each category in the spectrum of filarial disease. Many antigens, such as the major adult surface protein of Mr 29,000 (29K), appear to be recognized at all stages of infection, but two components show interesting patterns of differential recognition. A triplet of proteins of Mr 65-75K associated with the microfilarial surface is preferentially bound by serum from patent microfilaraemic infections, whereas an unrelated 75K protein has been found to react only with antibody from amicrofilaraemic individuals. In general, however, the data obtained so far emphasize the importance of undertaking an antigenic analysis at the level of single epitopes. Such studies are now under way using recombinant proteins expressed in bacterial hosts.