Thesis (M.P.H.)--University of Michigan, 1944. / Cover title: Amebic dysentery and amebiasis.

Thesis (M.P.H.)--University of Michigan, 1944. / Cover title: Amebic dysentery and amebiasis.

Tesis--Universitas Indonesia. / Summary in English. "Dalil-dalil": [1] leaf inserted. Bibliography: p. 151-158.

This study investigated the immunological aspects of Entamoeba histolytica infection in Syrian hamsters. Immunization of hamsters by an intradermal injection with live axenic amoebae, conferred complete protection against amoebic liver abscess. Protection was achieved with homologous or heterologous strains of E. histolytica and was dose-dependent. Combination of thymectomy and anti T-cell serum treatment significantly increased the size of liver abscess and metastatic dissemination of the parasite. It was shown that a cell-mediated immune response controls the healing of skin ulcers in vaccinated animals and thus confers on them resistance to intrahepatic amoebic challenge infection. Resistance to hepatic infection with E. histolytica can be passively transferred to normal recipients with sensitized cells, but not with immune serum. Sensitized cells from vaccinated, protected or infected animal kill E. histolytica trophozoites in vitro. Splenectomy reduces the resistance of hamsters to amoebic infection. It is suggested that macrophages are required in the host defence against the establishment of amoebic abscess in the liver and dissemination of amoebae to other organs.

No description available.

No description available.

No description available.

Entamoeba histolytica is a protozoan parasite and the causative agent of amoebiasis. While infection is associated with suppression of cell-mediated, immunity, drug-cured patients are resistant to reinvasion by amoebae. Macrophages are the principal effector cells in host defence against E. histolytica via production of nitric oxide which is cytotoxic for the parasite. The objective of this study was to determine the T cell cytokine responses associated with host defence against E. histolytica . A mixed Th1/Th2 (Th0) response predominated at days 5--10 of amoebic liver abscess development in gerbils, as indicated by spleen and hepatic lymph node cell IL-2 (Th1 marker) and IL-4 (Th2 marker) production. However, T cell responses were profoundly suppressed at day 20 of infection. Serum collected at day 20, but not at other times, markedly suppressed T cell proliferative responses by inhibiting IL-2 production. A switch to a Th1 response occurred after day 20 of infection. Following drug-abbreviation of infection at day 20, animals were completely resistant to challenge infection in the liver and demonstrated a Th1 response. The Gal-lectin 170-kDa heavy subunit of E. histolytica is a protective antigen in gerbils and a potential subunit vaccine candidate. We determined which region of the Gal-lectin stimulates IL-12 production, as IL-12 is key to inducing Th1 cytokine responses. Native Gal-lectin plus interferon-gamma stimulated IL-12 p40 and p35 gene transcription and IL-12 p70 protein production in human macrophages. Using a panel of anti-170-kDa subunit monoclonal antibodies in inhibition studies, aa 596--998 was identified as the IL-12-inducing domain. These results suggest that this portion of the Gal-lectin has potential for use as a subunit vaccine to induce Th1-mediated immunity against E. histolytica .

Infections with Entamoeba histolytica are associated with impaired cell mediated immunity by an unknown mechanism. Macrophages are the most important cells in host defense against invasive amebiasis. The present study investigated the effect of E. histolytica on macrophage functions. Macrophages isolated from gerbils with amebic liver abscess and naive macrophages exposed to soluble amebic proteins induced profound alteration of eicosanoid formation both in cyclooxygenase and lipoxygenase pathways by enhanced PGE$ sb2$ and LTC$ sb4$ production. TNF-$ alpha$ production by macrophages was altered locally in amebic granulomas and at systemic sites during the infection and in response to amebic proteins stimulation in vitro. PGE$ sb2$ produced by macrophages in response to amebic proteins was involved in the down-regulation of TNF-$ alpha$ production. E. histolytica-induced dysfunction of macrophage cytotoxicity against amebae and tumor cells occurred by suppressing NO and by enhancing PGE$ sb2$ production. Amebic proteins suppressed the induction. of IFN-$ gamma$-induced bone marrow macrophage class II MHC Ia molecule synthesis and I-A$ beta$ mRNA expression by stimulating PGE$ sb2$ production. Taken together, these results demonstrate that E. histolytica induced PGE$ sb2$ production plays a central role in the suppression of macrophage effector and accessory cell functions.

A model for experimental cecal and hepatic amebiasis was developed and characterized in the gerbil (Meriones unguiculatus). Pathogenic and non-pathogenic Entamoeba histolytica strains were shown to cause damage in the cecum, proportional to their previous behavior in humans. Secretion of intestinal mucus, crypt hyperplasia and cytolysis of interglandular epithelium were prerequisites for amebic invasion. Ulcerative lesions with destruction of mucosal and submucosal tissues led to amebic dissemination to the liver. Formation of amebic liver abscesses followed subacute changes in the liver. Liver lesions resulted from the cytolytic effects of the enzymes of destroyed neutrophils. Growth of liver abscesses followed cytolysis of the fibrogranuloma walls. Immunodepression in amebiasis was confirmed by serologic findings and histologic alterations in the lymph nodes and spleen, and by a lowered antiamebic effect of lymphoid cells in vitro. A neutrophil stimulating and chemotactic factor from pathogenic amebic membranes was isolated and characterized. It was shown that both host and parasite factors are involved in the pathogenesis and pathology of amebiasis.