On the adjuvant effect of aluminum hydroxide for mice

Linear relationships were found between the dose of A1(OH)3 adjuvant and the titer of anti-OVA antibodies formed by BDF1 mice. Mice immunized with OVA, DNP-KLH and then boosted with DNP-OVA formed anti-DNP antibodies only when A1(OH)3 was added to the injection of DNP-KLH; addition of A1(OH)3 to the priming injection of OVA decreased, rather than increased antibody formation.

Development of cell mediated immunity to flagellar antigens and acquired resistance to infection by Trypanosoma cruzi in mice

Modulation by BCG and/or cyclophosphamide of sensitization of mice with flagellar fraction (a tubulin-enriched fraction) prevented death of mice challenged with T. cruzi CL strain trypomastigotes recovered from Vero cells. A methodology was ceveloped to assay specific antigens and to determine optimal doses for sensitization and elicitation of DTH in mice. CL strain is predominantly myotropic strain which does not produce important parasitism of mononuclear phagocyte cells; these cells appear to control infection when activated in vivo. Maximum protection was seen in this study when BCG and cyclophosphamide were associated, but protection was observed also when cyclophosphamide, that prevents supressor T cells, was applied 2 days before flagellar fraction sensitization in normal mice. These experiments suggested that the macrophage may have an important role in the early phases of infection particularly when nonspecific stimulation is associated with specific sensitization. A correlation betwen delayed hypersensitivity to parasite antigens and protection was observed.

Atypical epidermal alterations in chronic Leishmania mexicana mexicana lesions fo C3H mice

C3H mice chronically infected with Leishmania m. mexicana, and in some groups treated with BCG or levamisole, presented atypical epidermal alterations, including pseudoepitheliomatous hyperplasia, hyperkeratosis and dysplasia. These alterations increased in frequency and intensity during the course of infection, but were not related to lesion size or tissue parasite load. Age matched normal, BCG and levamisole treated control mice, examined simultaneously, did not show epidermal modifications. In infected mice the dermis and hypodermis presented an inflammatory infiltrate of histiocytes, lymphocytes and plasma cells, accompanied at times by neutrophils and eosinophils, which did not vary with duration of infection.

Host factors influencing outcome of Leishmania mexicana infection in mice

Studies were undertaken to determine the influence of several host-related parameters on the course of Leishmania mexicana mexicana infection in inbred C57B1/10 (C57) and outbred albino (OA) mice. An important influence of the following variables was demonstrated: Host strain: lesions in C57s were significantly less variable in size and outcome than those of OAs under the conditions studied and even when persistent developed at a slower rate. Host age: Subcutanous injection of 2 x 10 [raised to the power of 4] to 2 x 10 [raised to the power of 6] amastigotes into the dorsum of the rear paw produced significantly larger lesions which healed more slowly in 2 mo. old C57s than in 4 mo. old mice. Reduced healing ability was observed in older (8 mo. old) female C57s, and low mortality occurred after 15 months of age in infected mice of both sexes. Lesion site: Following amastigote infection, lesions in paws of most C57s regress within 15 - 25 wks. In contrast, perinasal legions produced with the same number of parasites tend to persist for the life of the animal as slowly spreading irregular nodules. In animals infected in both locations, each lesion site behaves similarly to that in singly infected animals of the same age, i.e. regression in the two sites is independent. Our results indicate that while host strain may strongly influence infection outcoem, such variables as lesion site and host age play important roles and may explain, in part, reported inter- and intraexperimental variability in responses of murine hosts to a given leishmanial parasite.

Acquired resistance of mice against S. mansoni and lung granulomatous reaction induced by BCG

Studies carried out in Sw outbred mice showed that there is no correlation between the degree of lung granulomatous reaction and the level of acquired resistance against S. mansoni infection induced by BCG.

Evolution of sarcoma 180 in mice treated with hyperchlorinated water

Mice treated with hyperchlorinated water (50 ppm of chlorine) and control mice, drinking tap water (1-3 ppm of chlorine) were inoculated with 2.5 x 10 [raised to the power of 6] sarcoma 180 cells, by intraperitoneal route. Tumor evolution was measured by enumeration of tumor cells in peritoneal cavity and by evaluation of weight gain at different time intervals after tumor implantation. In mice treated with excessive amounts of chlorine there was enhancement of tumor growth demonstrated by: (a) shorter incubation period and increased weight gain (ascites formation) after tumor implantation; (b) increased number of tumor cells in the peritoneal cavity 2, 3 and 4 days after tumor challenge. The number of peritoneal cells exsudated after tumor implantation was lower in mice treated with hyperchlorinated water than in controls. The tumor enhancement observed after excessive chlorine ingestion would be due to: (a) reduction of the number of peritoneal macrophages that migrate to the peritoneal cavity and (b) reduction of the tumoricidal capacity of peritonela macrophages induced by the direct effect of chlorine or by the reduction of the amount of endogenous endotoxins due to the bactericidal effect of chlorine.

Evolution of sarcoma 180 in mice infected with Trypanosoma cruzi

Mice infected with Trypanosoma cruzi were challenged with 2x10[raised to the power of 6] cells of sarcoma 180 (ascite tumor) by i.p. route, on day seven post infection. Tumor development was followed by evaluation of weight gain, by measurement of ascitic fluid produced and enumeration of tumor cells in ascitic fluid. Infected mice were more resitant to tumor development as demonstrated by reduction in ascites formation and by reduction in the number of tumor cells in ascitic fluid, at different time intervals after tumor challenge. The number of peritoneal cells exsudated after tumor inoculation was greater in infected mice than in controls. This increased resitance of mice infected with T. cruzi to tumor development could be due to the action of macrophages activated by the infection and by the action of endotoxins absorbed from the gut or produced by the own parasite.

Some characteristics of hyperreactivity to bacterial lipopolysaccharide induced in mice by Trypanosoma cruzi infection

Mice infected with T. cruzi strain, acquire a high level of susceptibility to the effects of bacterial gram-negative LPS. The LD50 of adult female SW mice to LPS from S. typhosa, decreases from 450 to 2,5 mcg 10-12 days after T. cruzi infection. This hyperreactivity to LPS induced by T. cruzi presents all the characteristics of that found in infection caused by many other agents. During the acaute phase of experimental infection with T. cruzi Y strain, mice generally die with a hypovolemic shock very similar to that induced in uninfected animals injected with an adequate dose of bacterial endotoxin. There is evidence for and against the hypothesis that LPS absorbed from the instestinal tract may be involved in the mechanism of death of mice during the acute phase of T. cruzi infection.

Lymph node cell responsiveness in BALB/C mice infected with Leishmania mexicana

In the present study we measured the blastogenic response of lymph node cells from BALB/c mice infected with Leishmania mexicana throughout the course of infection. Results showed that infected mice displayed normal blastogenic responses in the lymph nodes until twenty weeks of infection. Thereafter, there was a gradual suppression. Comparison of the immunoresponsiveness in the spleen and lymph nodes, revealed normal responses in the lymph nodes several weeks after suppression in the spleen had occurred. Suppression of blastogenic responses in the lymph nodes was related to an adherent macrophage-like cell which actively suppressed normal proliferative responses to mitogens.

The conduction system of the heart in mice chronically infected with Trypanosoma cruzi: histopathological lesions and electrocardiographic correlations

Chronic focal and diffuse myiocarditis with interstitial fibrosis developed in Swiss outbred mice and in the inbred AKR and A/J strains of mice which were chronically infected with several Trypanosoma cruzi strains belonging to three biological types (Type I, II and III). High incidence of electrocardiographic changes with predominance of intraventricular conduction disturbances, 1st. and 2nd. degree AV block, arrhythmias, comparable with those found in human Chagas' disease, were also present. Morphological study of the conduction tissue of the heart revealed inflammatory and fibrotic changes. The presence of inflammation in the inter-atrial septum almost always coincided with the inflammatory involvement of the ventricular conduction system. Focal inflammation was associated with vacuolization and focal necrosis of the specific fibers. Most of the lesions were seen affecting the His bundel (76.3% of the cases), the right bundle branch (73.3%), AV node (43.9%) and left bundle branch (37.5%). Correlation between morphological changes in the conduction tissue and electrocardiographic alteration occured in 53.0 to 62.5% of the cases, according to the experimental groups.

Extra-tissular Schistosoma mansoni egg granulomata in the peritoneal cavity of mice

The presence of Schistosoma mansoni eggs surrounded by inflammatory cells were detected within the peritoneal cavity of experimentally infected mice. The histological and ultrastructural analysis revealed the predominantly macrophagic composition of these structures. The presence of epithelioid cells, macrophages in different stages of activation and the architectural pattern of the cells, characterize these structures as extra-tissular true granulomas. Granulomas much similar to those observed in the peritoneal cavity of infected mice were also detected after the intraperitoneal injection of viable eggs in non-infected mice. Collagen fibers were observed in between the inflammatory cells of granulomas obtained 10 weeks after infection and 48 hours after the injection of viable eggs into the peritoneal cavity. In later times of infection or injection the amount of collagen fibers increases resulting in a typical pattern of healed schistosoma egg granulomas. The possible influence of the immune response on the genesis of the granulomatous reaction as well as the influence of the vascularized connective tissue on this process is discussed.

Congenital and nursing effects on the evolution of Schistosoma mansoni infection in mice

Modification of the immune response to schistosomal infection in children or offspring born to mother R infected with Schistosoma mansoni has been demonstrated in human and in experimental schistosomiasis. One of the hypothesis to explain this fact could be the transfer of circulating antigens and antibodies from mother to foetus through the placenta or from mother to child by milk. The results of this spontaneous transference are controversial in the literature. In an attempt to investigate these questions, we studied one hundred and twenty offspring (Swiss mice), sixty born to infected-mothers (group A) and sixty born to non-infected mothers (group B). These were percutaneously infected with 50 cercariae/mouse, and divided in six sub-groups (20 mice/sub-group), according to the following schedule: after birth (sub-groups A.I and B.I), 10 days old (sub-groups A.II and B.II) and 21 days old (sub-groups A.III and B.III). After the exposure period, the young mice returned to their own mothers for nursing. Six weeks later, the mice were killed. We obtained the following results: 1) There is transference of antibody to cercariae (CAP), adult worms (SWAP) and egg antigens (SEA) from the infected mothers to the offspring, probably through placenta and milk; 2) Offspring born to infected mothers exhibit much less coagulative hepatic necrosis and show a lower number of eggs in the small intestine and a less intense and predominant exsudative stage of the hepatic granulomas when compared with the exsudative-productive stage of the control groups. The findings suggest that congenital and nursing factors can interfere on the development of the schistosomiasis infection, causing an hyporesponse to the eggs.