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F von Lichtenberg

Publications and source records attributed to F von Lichtenberg.

At least 19 recordsLinked to original sources
PubMed2000

IL-12 gene-deficient C57BL/6 mice are susceptible to Leishmania donovani but have diminished hepatic immunopathology.

To determine the in vivo role of IL-12 in the development of protective immunity in visceral leishmaniasis caused by Leishmania donovani, we examined the course of L. donovani infection in IL-12-deficient C57BL/6 (IL-12-/-) mice. IL-12-/- mice displayed significantly higher parasite burdens in their livers and spleens than wild-type C57BL/6 mice throughout the course of infection. Despite high parasite burdens, the onset of hepatosplenomegaly was significantly delayed in L. donovani-infected IL-12-/-. Moreover, livers and spleens from IL-12-/- mice displayed significantly less inflammation and poorly formed granulomatous lesions than those from IL-12+/+ mice throughout the course of infection. Antigen-stimulated splenocytes from IL-12-/- mice produced significantly less IFN-gamma but more IL-4 than IL-12+/+ mice. These findings indicate that although endogenous IL-12 is critical for the development of protective immunity to L. donovani, it is also responsible for inducing the significant immunopathology associated with visceral leishmaniasis.

Animals↗
PubMed1989

Pathology resulting from the administration of a live attenuated anti-Schistosoma haematobium vaccine in baboons.

Baboons (Papio anubis) were injected in the leg muscle with 18,000 20 Krad irradiated schistosomula of Schistosoma haematobium. Four protocols were followed: single, primary injection; single injection into animals primed by patent S. haematobium infection; secondary vaccine injection following an earlier injection; and single injection following praziquantel treatment of infected animals. Injection of the putative vaccine elicited localized mixed inflammatory infiltration at the site of injection which was both intense and prolonged. Three grades of tissue reaction were seen: the relatively mild primary response; the response in infected animals which had enhanced tissue eosinophilia; and the response in animals primed by prior injection and drug-treated prior infection. The latter 2 showed intensification of eosinophilia, stellate abscesses in the lesion centers, and perischistosomular Hoeppli precipitates. Intramuscular lesions peaked at 14 days for the primary response and at 7 days for all secondary responses. Traces of the milder lesions persisted beyond 4 weeks; more severe reactions healed more rapidly. Some schistosomula survived for 14 days in the milder reactions. A few larvae were deposited in the skin by backflushing of the injectate which produced local inflammation. Compared to mice, live schistosome vaccines injected into baboons elicited greater local inflammation; however, while evidence suggested that sporadic vaccine schistosomula did reach the lymphatic nodes draining the injection sites, no systemic lesions were found and the injection sites healed in approximately 5-6 weeks without permanent damage.

Animals↗
PubMed1987

The Wellcome Trust lecture. Inflammatory responses to filarial connective tissue parasites.

The inflammatory responses to lymphatic filariae and to Onchocerca volvulus are reviewed with particular attention to evolutionary biology; inflammatory host spectrum; non-specific components; immunoregulation; immune evasion versus immunomodulation; chronic tissue damage and scarring and disease models. Basic principles of pathogenesis are emphasized, comparisons drawn with schistosome infection, and critical items of missing information are highlighted.

Animals↗
PubMed1986

Effects of protective immune serum on the yields of parasites and pulmonary cell reactions in schistosome-infected rats.

Yields of parasites during the period of worm migration from the lungs to the portal circulation were measured in S. mansoni-infected Fischer rats passively immunized with protective serum from twice-infected donor rats. Two effects of protective serum were observed in recipient rats relative to normal serum recipients: yields of schistosomula from lungs were higher and yields of (immature) worms from the portal circulation were lower throughout the period analyzed. Histopathological analysis of lung tissue confirmed the presence of greater numbers of schistosomula in lungs of passively immunized rats. In addition, the percent of lung schistosomula involved in all categories of inflammatory reactions was greater in recipients of protective rat serum. The kinetics of accumulation of worms perfused from the portal circulation of normal and passively immunized rats indicate that in the latter group a smaller fraction of worms successfully migrates to the portal circulation. These findings support the hypothesis that protective activity of the serum prevents a portion of worms from successfully completing migration from the lung to the portal circulation.

Animals↗
PubMed1985

Immunopathology of Schistosoma japonicum infection in athymic mice.

Athymic (nu/nu) mice and heterozygous littermate controls (nu/+) were examined 7 and 10 weeks after infection with 10 cercariae of Schistosoma japonicum. Schistosome infection developed normally in both groups of mice and eggs were produced in normal numbers. Nu/nu mice developed small circumoval granulomas with minimal fibrosis while nu/+ mice developed large fibrotic granulomas. Unlike the mononuclear responses to S. mansoni eggs at 7 weeks, those to S. japonicum often were abscess like with narrow rims of liver cell necrosis or microvesicular fatty change. However, evolving granulomas in nu/+ mice were enriched with eosinophils, epithelioid macrophages, immature granulocytes and plasma cells, all scarce in the corresponding nu/nu lesions as were fibroblasts and collagen fibres, thus accounting for their smaller mean size and better healing. Our aggregate evidence shows that normal granuloma formation and cellularity in S. japonicum infection is controlled by T-cells as is the case for S. mansoni, and not by antibodies or immune complexes.

Animals↗
PubMed1985

Immunopathology of Schistosoma japonicum and S. mansoni infection in B cell depleted mice.

To investigate the role of antibody in the pathogenesis of hepatic granulomas around schistosome eggs, mice were depleted of B cells by treatment from birth with anti-IgM serum and were subsequently infected with Schistosoma japonicum or S. mansoni. Anti-IgM treatment did not affect the development or fecundity of the worms or the larvae within the egg shells. Normal circumoval granulomas were present in the livers of B cell depleted mice 7 or 8 weeks after infection clearly indicating that antibody and immune complexes have no necessary role in the formation of granulomas. Hepatic fibrosis was also similar in B cell depleted and untreated mice at these times. Ten weeks after infection the size of S. japonicum egg granulomas in untreated mice had decreased but no change in the size of granulomas had occurred in B cell depleted mice, and hepatic fibrosis was more marked in treated than in untreated mice. Similar changes were noted in S. mansoni infected mice, assayed at 8 and at 12-13.5 weeks after infection. The effects of B cell depletion in the more chronic infections may be related to the absence of antibody but could also be caused by an influence on B cell-dependent suppressor T cells.

Age Factors↗
PubMed1983

Pathology of a live attenuated anti-schistosome vaccine in mice.

Tissue responses of mice to intramuscular injection of 50 kR 60Co-attenuated schistosomula of Schistosoma mansoni were studied. Controls included injection of unattenuated schistosomula, medium alone, antigen-coated beads, and alum-adsorbed tetanus/diphtheria toxoids. Primary reactions to tissue-confined deposits of injected schistosomula, whether attenuated or not, were relatively intense and prolonged. Parasite attrition proceeded steadily, with most destroyed by the 7th day; however, a few intact organisms persisted up to 4 weeks. Cryopreservation did not alter the course of parasite attrition nor host reaction. Irradiated larvae were not found in lymph nodes, lungs, or liver. Neutrophils dominated the early reactions and were gradually replaced by mononuclear phagocytes, lymphoid cells, and eosinophils. Fibroblast proliferation and muscle regeneration began by day 3; reaction size and intensity peaked by day 7. From weeks 1-4, inflammatory infiltrates and regenerative proliferation underwent gradual involution, and injection sites were healed with no scarring by the end of 4-5 weeks. Mice primed by infection or by prior injection showed an accelerated course of inflammation, enhanced tissue eosinophilia, and more rapid healing. An unwanted, but prominent, feature of schistosomular vaccine reactions in mice was tracking of the inflammatory infiltrate along connective tissue septal and nerve sheaths, the latter raising the question of the pain potential of the vaccine. To conclude, in mice, attenuated schistosomular vaccines cause relatively marked local inflammatory responses but no systemic lesions at all, and their injection sites heal without permanent damage.

Animals↗
PubMed1982

Lawn-mower arm.

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Forearm Injuries↗
PubMed1980

Pulmonary cell reactions in natural and acquired host resistance to Schistosoma mansoni.

In order to examine the relationship between host leukocytic reactions to schistosomula and innate or acquired resistance to Schistosoma mansoni, in vivo pulmonary cell responses in CD/F rats, LVG hamsters, C57BL/6 and CBA mice, following either cercarial skin exposure or intravenous injection of schistosomula (the "lung model"), were quantified and analyzed. Major leukocytic reactions to schistosomula injected into the lungs varied according to host strain, with increasing responses occurring in the order CBA < LVG < C57 < CDF. Adult worm recoveries, by portal perfusion of these hosts, ranked in a strain order reciprocal to that of lung cell responses. All hosts developed anamnestic, eosinophil-enriched responses on secondary intravenous schistosomula challenge. In mice, this in vivo eosinophilic, augmented response could be elicited by glutaraldehyde-fixed as well as by intact challenge schistosomula. After primary percutaneous cercarial exposure, lung responses at 5 days were significant in rats, and after secondary challenge, in both rats and hamsters, but were virtaully nil in mice, whether previously exposed to S. mansoni or not. Thus, schistosomulum attrition was partly dependent on parasite encounters of various kinds with host mono- and granulocytes, but was of major consequence only in hosts with native (rat) or acquired resistance (all hosts), while playing a minor role in naive permissive hosts (mouse, hamster). The failure of previously-infected mice to develop early lung residual killing foci in response to skin-penetrated schistosomula is unique among the known laboratory hosts of S. mansoni.

Animals↗
PubMed1979

Schistosoma mansoni infections in T-cell deprived mice, and the ameliorating effect of administering homologous chronic infection serum. II. Pathology.

Liver changes occurring in mice deprived of their T-cells by a combination of thymectomy and anti-mouse thymocyte serum, and in immunologically intact control mice, were followed during the early stages of heavy Schistosoma mansoni infections. Lesions in both groups began developing by day 38 and were maximal by day 48. Hepatic changes in control mice culminated in large hypersensitivity granulomas, tissue eosinophilia, portal periphlebitis, fibrosis, vascular obstruction, and infarction leading to arterialization and preferential sinusoidal channeling. Deprived mice showed greatly reduced egg reactions composed principally of macrophages, monocytes, and occasional neutrophils, and only minimal alteration of liver architecture; however, focal and disseminated hepatocellular lesions became prominent as the infections progressed, and by day 48 virtually every hepatocyte was affected. Typically, hepatocytes showed microvesicular cytoplasmic damage (steatosis) or ballooning degeneration with accompanying nuclear pyknosis or karyorrhexis. This cellular pathology may be attributed to the direct or indirect effect of eggs or egg products on liver cells. The administration of chronic infection serum obtained from immunocompetent mice to T-cell deprived mice dramatically eliminated the hepatocellular lesions. It also increased eosinophil participation and fibrosis in the egg reactions but did not restore the size and other cellular features typical of egg hypersensitivity granulomas. Serum from uninfected normal mice was found to lack these effects.

Animals↗
PubMed1979

Potentiation of schistosome granuloma formation. By lentinan--a T-cell adjuvant.

Lentinan is a fungal polysaccharide which acts as a T-cell adjuvant. When this glucan was administered to thymus-intact mice by intraperitoneal injection, conspicuously enlarged lung granulomas formed in response to either Schistosoma mansoni or S japonicum eggs or to antigen-coated polyacrylamide beads. Liver granulomas in cercaria-induced S mansoni infection were augmented up to eight-fold in volume. By contrast, nude mice showed a complete absence of hypersensitivity granulomas, regardless of whether they received lentinan. Lentinan-potentiated granulomas show a distinctive histopathologic picture characterized by abundant, large, pale-staining macrophages; reduced and redistributed eosinophil populations; and frequent, extensive central necrosis, uncommon in unpotentiated schistosome foci. They also differ in their distributions of egg antigen and of host immunoglobulins. Optimal lentinan effects followed a single 1-mg dose when given to sensitized mice on the day of intravenous challenge with S mansoni eggs rather than at the time of intraperitoneal sensitization or following challenge. This adjuvant appears to act on effector T cells or on macrophages interacting with T cells; its effect on macrophages in a latex bead foreign body granuloma was minimal. A number of other lentinan-associated systemic effects on parasite and host were noted and described, including reduced female schistosome egg output.

Adjuvants, Immunologic↗
PubMed1979

Quantitative changes in astrocytes after portacaval shunting in chimpanzees and in man with normal liver parenchyma.

Chimpanzees without liver cell damage, but subjected to portacaval anastomosis, showed behavioral changes that were accompanied by "Alzheimer II" astrocyte hyperplasia and nuclear enlargement. These findings were similar to those in a human patient with encephalopathy, secondary to a portacaval shunt, whose liver was normal. Controlled quantitative study of astrocytic hyperplasia in different anatomic regions showed the hyperplasia to involve the gray matter with only moderate topographic variation. Individual degrees of hyperplasia somewhat paralleled the severity of clinical symptoms and ammonia levels; no clear-cut relationship with time after shunting could be established. Portacaval shunt encephalopathy in chimpanzees greatly resembles that in man and, thus, lends itself to more detailed experimental analysis.

Aged↗
PubMed1978

Early developmental changes of the schistosomula of Schistosoma mansoni in vitro and in mouse lung.

Fresh (3 h) schistosomula of Schistosoma mansoni were obtained by the skin penetration method and injected intravenously into groups of mice either immediately or after 48 h incubation in tissue culture. Schistosomula were then recovered from the lungs 1 to 2 days after injection. The recovery results showed that the ability of uncultured schistosomula to emerge from lung tissue increased with time, became maximal on the 3rd day and diminished thereafter. In contrast, cultured schistosomula were able to emerge from chopped lung at a much earlier time after injection. Fresh schistosomula, as well as those recovered from mouse lungs, were assayed by indirect immunofluorescence for the presence of parasite and host antigens. Similarly, fresh schistosomula which had been incubated in foetal calf serum, with or without mouse red blood cells, were assayed for parasite and host antigens after 3-24 h of culture. Fresh schistosomula expressed parasite antigen with greater intensity than those recovered from mouse lungs and showed no trace of host antigen. Lung schistosomula, on the other hand, expressed less parasite antigen but more red blood cell antigen with increasing time in the host. Schistosomula cultured in the absence of mouse red blood cells expressed only parasite antigen throughout the period in culture, while those cultured in the presence of mouse red blood cells also expressed parasite antigen during the entire period in culture but, in addition, by 24 h host antigen could also be detected. These developmental and adaptational changes may play a role in determining the survival of parasites in the normal or immune host.

Animals↗
PubMed1978

Tissue eosinophil proliferation and maturation in schistosome-infected mice and hamsters.

Extramedullary eosinophilopoiesis is described as a regular pathological feature of murine and cricetine schistosome infections. Using the Dominici staining technique, colonies of developing eosinophils were commonly found in certain tissue sites of dense oviposition, particularly in the liver, and in associated lymphoreticular tissues. The relationship of these observations to the role of eosinophilic leukocytes in schistosomiasis is discussed.

Animals↗