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The ability of filarial parasites to persist in an immunological competent host, has led to the suggestion that they have evolved specific measures to counter immune defences. Filarial nematodes produce and secrete excretory-secretory (ES) products, some of which have been described to have a potential role in immune evasion. As part of these ES products, two homologues of the mammalian cytokine macrophage-migration inhibitory factor (MIF) have been described from the filarial nematode Brugia malayi, Bm-MIF-1 and Bm-MIF-2. Mammalian MIF is a widely distributed protein constitutively expressed in many immune and non-immune cell types. Although firstly characterised by its ability to stop migration of peritoneal macrophages, it has now been shown to play an important role during different inflammation processes. The main aim of this study is to elucidate the role of Brugia MIF homologues and their relation with the mammalian cytokine. This thesis studies the effect of both filarial and host MIF homologues on two major immune cell types, macrophages and dendritic cells (DC). We found that both Brugia and mouse-MIF synergise with IL-4 to activate macrophages to an alternative phenotype, by enhancing expression of IL-4-induced alternative activation markers Arginase-1, Ym-1 and the macrophage Mannose Receptor. MIF also synergises with IL-4 to render macrophages suppressive, an important outcome during filarial infection. Additionally we found that MIF homologues induce IL-4Ra expression, suggesting a mechanism by which MIF enhances IL-4 activation. We showed that filarial and mouse MIF homologues differ in their capacity to activate bone marrow-derived immature dendritic cells. Mouse-MIF up-regulates MHC-II and CD40 expression and induces pro-inflammatory cytokine production after overnight treatment. On the other hand Bm-MIF-2 induces low levels of cytokine production but does not up-regulate activation markers, and Bm-MIF-1 failed to activate DC. Furthermore, we demonstrate that filarial MIF homologues impair DC differentiation from bone marrow precursors. While bone marrow cells cultured in the presence of GM-CSF, with or without mouse-MIF, differentiate into CD11c+ DC, addition of Bm-MIF-2 to the culture media impairs differentiation arresting the cells in an undifferentiated phenotype characterised by the expression of myeloid and granulocyte markers CD11b and GR1. Finally, using an in vivo model where we implant Brugia malayi parasites in the peritoneal cavity of mice, we observed that host MIF does not play an essential role in the activation of macrophages by adult parasites as macrophages form MIF deficient mice present the same phenotype as their wild type counterparts.

The literature on Ichthyobodo necator is reviewed. The prevalence and intensity of Ichthyobodo infestations on farmed salmonids was investigated on three farms over a period of two years. The infestations were found to be markedly age dependent. Peak infestations and related mortalities occurred in the first eight weeks after first feeding. Both mortalities and infestations declined to zero shortly after this period with no chemotherapy. Ichthyobodo reappeared on 0+ and appeared for the first time on I+ fish after a drop of water temperatures to less than 10*C. Many of the 1+ fish had started to mature. It is suggested that some form of host defence mechanism operates which limits the Ichthyobodo infestations in farmed salmonids. The sequential pathology of Ichthyobodo infestations of the skin of 0+ and 1+ salmon and rainbow trout was studied. Areas of greatest shelter from water currents were found to be most commonly infested and no parasites were found attached to the epidermis on the head of the fish. The parasite caused hyperplasia of the malphigian cells and exhaustion of the goblet cells below infestations, followed by spongiosis of the underlying epidermis. The epidermal plaque then sloughed off leaving a single layer of cells attached to the basement membrane. Cell kinetic studies showed that Ichthyobodo caused the cells immediately below infestations to divide, a markedly different pattern from that of normal teleost epidermal cell proliferation. The possibility that the parasite secretes some form of digestive enzyme is postulated. In areas where sloughing had occurred, the remaining malphigian cells were seen to be in the process of division. Various endocrinological aspects of Ichthyobodo infestations were investigated. Three corticosteroids and one androgen were injected or implanted into 1 year old rainbow trout. Implantations of hydrocortisone led to very heavy ichthyobodo infestations. Radio immune assays showed that the level of cortisol and testosterone in the serum of implanted fish was similar to that which would occur when salmonids mature. There appears to be a clear link between cortisol levels in the serum and Ichthyobodo infestation. The host response to Ichthyobodo is discussed and it is concluded that cortisol may suppress the host's defence mechanism to Ichthyobodo.

This study examines ultrastructural changes occurring in seven- and fourteen-day populations of Trypanosorfa lewisi when 60 mg sodium salicylate is administered to the host. These changes were related to the host-immune response. Seven-day trypanosomes showed approximately 10 posterior volutin granules. Seven-day trypanosomes whose host had received salicylate exhibited. 30 to 40 volutin granules, and their posterior tip exhibited volutin granules in high numbers sometimes excluding other cellular elements. Fourteen-day trypanosones showed fewer volutin granules than seven-day, salicylate-treated ones. Salicylate treatment caused no additional ultrastructural alterations. Thus the volutin granules are not linked to the reproduction inhibiting antibody (ablast in) but may be involved in the formation of the trypanocidal antibodies.

The occurrence of human Onchocerciasis has not previously been reported from the Anglo-Egyptian Sudan. It is my intention to show that the nematode Onchocerca Volvulus (Leuckart 1893) has a wide distribution in the southern Sudan, and that it, with its microfilariae, give rise to a variety of pathological conditions including grave ocular troubles, and that it is a parasite of serious economic importance, and not merely of academic interest. For the past six years I have been engaged on sleeping Sickness and Leprosy campaigns in the southern Sudan, and have come into close touch with the native population and learned much of their habits and customs, and got a working knowledge of some of their dialects. This experience has been invaluable in the necessarily rather interrupted researches into onchocerciasis, and has allowed one to pass fairer and more critical judgment on the often highly imaginative statements of natives. Microfilariae were often found in gland juice and blood smears during routine Trypanosomiasis inspections, and elephantiasis and hydroceles formed the basis of ones surgical practice, but the former were always imagined to be Microfilariae Wuchereria Bancrofii and the latter their sequelae. Some three years ago it was noticed that in certain arears an appreciable proportion of the young adult population were blind or had serious eye symptoms or complained of »night blindness». In 1932 Dr. Bryant, a colleague of mine working in Rumbek district described the disease as a retino-choroiditis and sometimes associated with signs of keratitis, iritis, iridocyclitis and synechiae. He pointed out that although "Simulium Damnosum", the vector, had not been found, the possibility of Onchocerca Volvulus as the cause must be borne in mind. Later, in 1933, he identified microfilariae of Onchocerca Volvulus in a case of hydrocele in the Heridi district. Since then a careful study of cases of elephantiasis, hydroceles, skin diseases, tumour formations, and of eye conditions has been made, the incidence and distribution of Onchocerca Volvulus roughly mapped out, and also the incidence of the insect vector. Other possible causal factors have been investigated, and a certain amount of experimental work done. Pathological specimens have been collected and examined by experts in London. The results of these investigations will be given and my arguments for considering Onchocerca Volvulus capable of causing those serious pathological changes set forth. A digest and historical review of the more important literature and a description of the parasite precedes the main Thesis.

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