In vitro antibody-mediated macrophage activity on Breinlia macropi microfilariae. II. Ultrastructural and video recording investigations of adherence and cytotoxicity.

Video recordings and ultrastructural studies have revealed an intricate sequence of antibody-mediated cytotoxic activity by quokka peritoneal macrophages on Breinlia macropi microfilariae. The microfilaricidal activity was effected by at least two types of macrophages measuring 17 micrometers and 8 micrometers in diameter respectively. The relatively large macrophages were responsible for trapping, encircling and eventually degrading the highly motile microfilariae in a sequence of events in which the participating macrophages may interdigitate. The smaller macrophages adhered transiently to a number of adjacent sites on the surface of a trapped microfilaria, resulting in a series of damaged spots. This activity of the small macrophages was interpreted as responsible for killing the microfilaria. Thus the microfilaricidal activity was interpreted to be accomplished by the co-operative functions of the relatively large and small macrophages.

In vitro antibody-mediated macrophage activity on Breinlia macropi microfilariae. I. Adherence and cytotoxicity.

Intense adherence accompanied by cytotoxicity, which initially occurred at 4 h of interaction was observed when the microfilariae of Breinlia macropi were introduced to cultures of quokka peritoneal macrophages previously sensitized in 20% immune serum. No significant difference in the adherence or cytotoxic effects was observed among macrophages from normal, microfilaraemic and amicrofilaraemic quokkas. However, the serum component mediating these effects was found only in microfilaraemic and seropositive amicrofilaraemic quokkas. This mediator was heat-labile and its mediation of the adherence and cytotoxic effects was independent of complement. Because of its apparent dissociation from IgG and its heat lability, the possibility that the mediator resides in the previously-described reaginic antibody of the quokkas was discussed.

Isolation of Murray Valley encephalitis virus and other arboviruses in the Ord River Valley 1972-1976.

This paper summarizes the isolation of arboviruses from mosquitoes collected in the Ord Valley between 1972 and 1976. A total of one hundred and ninety five strains of at least fifteen antigenically distinct viruses have been isolated. Seven of these isolates appear to be "new' antigenic types, and several are undergoing further testing. These are three new rhabdoviruses (Kununurra [OR194], a virus provisionally named Kimberley [OR250] and OR189 [provisionally named Parry's Creek]), three ungrouped, non-haemagglutinating viruses (OR379, OR512, OR869) and a virus (OR540) which reacts to Poly Anopheles A world grouping fluid. The remaining viruses have been previously identified in Australia. These include Murray Valley encephalitis (MVE), Kunjin, Kokobera, Sindbis, Koongol, Wongal, Wongorr and a virus in the Corriparta serological group. The most important finding of these studies is that MVE displays as annually recurrent pattern of activity with a peak seasonal transmission rate at the end of the wet monsoon. This is the first definition of a probable endemic focus of MVE activity in Australia. The major vector for the majority of the viruses isolated was, by inference, Culex annulirostris. However, Aedeomyia catasticta was implicated as a major vector of the Corriparta group virus.

A preliminary investigation of the ecology of arboviruses in the Derby area of the Kimberley region, Western Australia.

A survey of mosquito populations in the Derby area of the Kimberley region, Western Australia, in March/April of 1977 yielded a total of 3,318 adult female mosquitoes. Fifteen taxa were represented, seven being new locality records for this area. Culex annulirostris was the dominant species, comprising 85.41% of the total catch. All mosquitoes collected were processed for virus isolation and thirteen strains of four (and possibly five) distinct arboviruses were obtained, all from pools of Culex annulirostris. These viruses include Murray Valley encephalitis, Ross River, Wongal, an untyped non-haemagglutinating member of the Koongol group and a virus which reacts to polyvalent antisera against the Anopheles A and B groups. With the exception of Ross River, all these viruses had been previously isolated from the Ord River Valley, some 500 km to the north-east. Comparison of virus isolations in the Ord Valley and Derby supports the suggestion that both sites share a common viral flora. Both also display an exceedingly high overall isolation rate (approximately 20% for Cx. annulirostris pools). Such comparisons suggest that a number of arboviruses transmitted by Cx. annulirostris are active throughout the Kimberley region and have peak isolation rates at the end of the wet season. Further studies are needed to fully define these viral cycles.

Influence of H-2 and non-H-2 genes on resistance to murine cytomegalovirus infection.

The resistance of adult mice to acute lethal infection with murine cytomegalovirus is controlled by genes linked to the H-2 complex. The k haplotype is approximately 10 times more resistant than the b or d haplotypes. Susceptibility is inherited as a completely dominant trait. At least two genes within the H-2 complex are involved, one mapping to the K/IA subregion and the other to the D subregion. The data suggest that interactions may occur between these K- and D-end genes which further affect resistance to the virus. The precise mechanism of H-2 gene control of resistance to murine cytomegalovirus remains to be elucidated. Non-H-2 linked genes also affect resistance to the virus, particularly in the C57BL genetic background, which is associated with an increased resistance to murine cytomegalovirus. Newborn mice of all strains are equally susceptible: both the H-2- and the non-H-2-associated resistances develop in the first few weeks of life and are retained up to at least 18 months of age.

Biologic and immunologic studies on a murine model of regional lymph node metastasis.

Some biologic, hematologic, and immunologic aspects of the growth and metastasis of the MC-2 fibrosarcoma indicated its suitability as a model for the study of lymphogenous metastasis. The tumor was maintained in syngeneic female BALB/c mice by the serial sc passage of 10(5) viable tumor cells. It metastasized macroscopically in all mice to regional lymph nodes (RLN) and to the lungs. Both forward and retrograde node-to-node metastases were found. Tumor growth and metastasis were associated with splenomegaly, thymus atrophy, cachexia, neutrophilia, lymphopenia, and anemia. Tumor excision at various times after inoculation showed that all mice whose tumors were excised when there was histologic evidence of metastasis in all RLN (day 13; mean of tumor wt, 122 mg) died subsequently from metastases, whereas no animals died whose tumors were excised on or before day 8 (mean of tumor wt, 15 mg). The onset of metastasis was seen in some RLN on day 8. All survivors were immune to challenge with 10(5) viable tumor cells, which demonstrated the immunogenicity of the tumor. Concomitant tumor immunity could be demonstrated prior to the onset of metastasis (days 6 and 7) but not early (days 0--2) or late (days 15, 19, and 20) in primary-site tumor growth. The early immune response to the tumor demonstrable as concomitant tumor immunity appeared to be abrogated by the progressive growth and metastasis of the neoplasm. Tumor cells passaged in adult thymectomized, X-irradiated, syngeneic recipients produced larger RLN metastases and smaller primary tumors than those passaged in control mice.

Induction of long-term tolerance in the quokka (Setonix brachyurus) by thymus and skin allografts into early pouch young.

Intact quokkas (Setonix brachyurus) were grafted with thymus and skin as neonates. Fifty seven percent of primary thymus grafts persisted when donors were less than 32 days of age, compared with only 20% when the dornors were juveniles. This suggested that neonatal tissue was more readily accepted than tissue from adult animals. When the recipients had left the pouch, induced tolerance was tested by grafting thymus and skin from the original donors. Second thymus grafts were generally unsuccessful; however, second skin grafts were accepted and remained intact over the three-year period of observation, provided that the hosts were less than about 40 days of age at the time the first graft were placed.

Resistance to murine cytomegalovirus linked to the major histocompatibility complex of the mouse.

Studies of the resistance patterns to infection with a murine cytomegalovirus in inbred strains of mice revealed the existence of resistant and susceptible strains. Resistance was found to be associated with possession of the H-2k allele at the major histocompatibility locus of the mouse. The F1 hybrid between a resistant strain (C3H/HeJ) and a susceptible strain (BALB/c) was found to have a resistance intermediate between that of both parents, indicating that the gene(s) controlling resistance is partly dominant. Susceptible BALB/c mice could be made resistant to lethal infection by pre-treatment with thioglycollate broth but not by pre-treatment with endotoxin or BCG. Resistant C3H/HeJ mice could be made susceptible to lethal infection by pre-treatment with cyclophosphamide.

Ord River arboviruses--the study site and mosquitoes.

The Ord Valey of tropical Western Australia has been studied for arbovirus activity following the development of a man-made lake of considerable size, a diversion dam and an irrigation scheme. Kununurra, the largest town in the valley, is the focus for very large populations of birds and mosquitoes. The irrigation areas have not been important as mosquito breeding areas because of the excessive use of insecticides. Lake Argyle does not support high mosquito a bird population at present. However, this may change as the ecosystem stabilizes. The mosquito fauna of the Ord Valley is dominated by Culex annulirostris.

Ord River arboviruses--isolations from mosquitoes.

One hundred and thirty presumptive viruses have been isolated from 485 pools made from 23,872 mosquitoes collected in the Ord River area of North-West Australia. One hundred and eleven of the virus isolates isolates came from pools of Culex annulirostis, the dominant mosquito species caught in the vicinity of Kununurra. Forty-five of the viruses pathogenic for newborn mice have been further characterized-19 as Flaviviruses, 1 Alphavirus, 9 Koongol, 1 Mapputta and 15 non-haemagglutinating viruses of which 6 are Corripata. Thirty-seven isolates were from Culex annulirostis, 7 from Aedomyia catasticta and 1 from aedes tremulus. All Corriparta isolates were from Aedomyia catasticta. The Flaviviruses comprised 13 Kunjin and 6 MVE isolates.

Ord River arboviruses--serological epidemiology.

This paper presents the results of haemagglutination-inhibition tests carried out on sera from 441 persons, 1,080 cattle and 335 birds in the Kimberley area. Two Alphaviruses (group A) (Ross River and Sindbis) and one Flavivirus (Murray Valley Encephalitis) were used for the preparation of haemagglutinins in the haemagglutination-inhibition tests. The tests showed a high percentage of antibody of Murray Valley Encephalitis in humans, birds and cattle, with an obvious focus of infection in the study site when cattle sera from different geographic areas were compared. These results are discussed in relation to the evolution and ecology of arboviruses in the Ord River area.

The placement of viruses in the aetiology of cancer.

The role of viruses as causative agents of cancer in man has been examined for more than 50 years. These studies have recently been intensified by employing newly developed, more sensitive techniques in virology and immunology. In spite of proof that viruses cause cancer in animals and that about one-quarter of the known 600 viruses possess oncogenic potential, definite proof of their aetiology in human cancer remains elusive even though cancer research is a highly respectable and costly pursuit. Nevertheless, the probabilities are high that human cancer viruses have been and will be identified and that their induced diseases can be prevented or controlled. It is accepted that some benign tumours of man (such as warts) are induced by a virus infection. This article examines the current situation and highlights the difficulties, hopes and usefulness of research in this field.

Levamisole augmentation of lymphocyte hyporesponsiveness to phytohaemagglutinin in patients with pulmonary tuberculosis.

Levamisole has been shown to augment the in vitro responsiveness of lymphocytes to PHA stimulation. The response of lymphocytes of 14 (42%) of 33 patients with pulmonary tuberculosis was augmented by levamisole. Augmentation was observed in 9 (64%) of 14 PHA hyporesponsives lymphocytes and in 5 (26%) of 19 normo-responsive lymphocytes.