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In order to investigate activation of the innate immune system in routine toxoplasmosis, T- and B-cell-deficient SCID mice and their co-isogenic immunocompetent C.B-17 counterparts were orally infected with a low-virulent strain of Toxoplasma gondii (DX strain). SCID mice developed a fatal necrotizing toxoplasmosis, whereas CD4+ and CD8 + T cells contributing to inflammatory infiltrates conferred resistance to immunocompetent mice. Significant amounts of interferon-γ (IFN-γ) were detectable in SCID mice. The most likely source for this cytokine is activated natural killer (N K )cells. In comparison to immunocompetent mice I FN-γ levels were reduced in cerebrospinal fluid (CSF) and serum of SCID mice at days 7 and 14 of disease. Similar amounts of turnour necrosis factor (TNF) were detected in both strains of mice. In addition, immunohistochemistry showed major histocompatibility complex (MHC) class II antigen expression on SCID and C.B-17 microglial cells and macrophages demonstrating activation of these cells in both strains. However, the up-regulation of MHC class II antigen on microglia was less pronounced in SC1D mice, presumably due to reduced levels of IFN-γ. Interleukin-6 (IL-6) levels in CSF and serum were elevated in both strains and correlated with systemic and intracerebral disease activity. In conclusion, our results demonstrate activation of macrophages and NK cells as the predominant defence mechanisms of the comprised SCID immune system during toxoplasma infection. This implies a major role for the innate immune system during early stages of toxoplasmosis although T cells are necessary to control the infection efficiently. [ABSTRACT FROM AUTHOR]

Rabbits were immunised repeatedly with bovine brain galactocerebroside. Almost all animals developed overt polyradiculoneuropathy. Circulating IgG antibodies to galactocerebroside in the serum and deposits of IgG in the spinal roots were detectable weeks before definite clinical, morphological, and electrophysiological alterations occurred. The levels of IgG antibody titres to galactocerebroside did not correlate with the severity of the clinical disease and of nerve conduction slowing. Remyelination and a virtually complete recovery of nerve dysfunction occurred although circulating antibodies to galactocerebroside were still present. [ABSTRACT FROM AUTHOR]

Anti-Leu 7 monoclonal antibody (MAB), a marker of natural killer cells, and a human MAB to myelin-associated glycoprotein (MAG) from a patient with a demyelinating neuropathy specifically stained Schmidt-Lanterman incisures, paranodal and periaxonal regions in peripheral nerve myelin by immunocytochemistry on thin plastic sections, while compact myelin was labelled in paraffin-embedded material. Preabsorption studies indicated that the antigen recognised was a MAG epitope shared by MAG and Leu 7. In spinal cord both MABS bound to oligodendrocytes and a subclass of anterior horn cells. Our findings support the hypothesis that shared antigens between the nervous and the immune systems do exist in situ, which may be important in the pathogenesis of demyelinating neuropathies with monoclonal gammopathies. [ABSTRACT FROM AUTHOR]

In order to investigate activation of the innate immune system in murine toxoplasmosis, T- and B-cell-deficient SCID mice and their co-isogenic immunocompetent C.B-17 counterparts were orally infected with a low-virulent strain of Toxoplasma gondii (DX strain). SCID mice developed a fatal necrotizing toxoplasmosis, whereas CD4+ and CD8+ T cells contributing to inflammatory infiltrates conferred resistance to immunocompetent mice. Significant amounts of interferon-gamma (IFN-gamma) were detectable in SCID mice. The most likely source for this cytokine is activated natural killer (NK) cells. In comparison to immunocompetent mice IFN-gamma levels were reduced in cerebrospinal fluid (CSF) and serum of SCID mice at days 7 and 14 of disease. Similar amounts of tumour necrosis factor (TNF) were detected in both strains of mice. In addition, immunohistochemistry showed major histocompatibility complex (MHC) class II antigen expression on SCID and C.B-17 microglial cells and macrophages demonstrating activation of these cells in both strains. However, the up-regulation of MHC class II antigen on microglia was less pronounced in SCID mice, presumably due to reduced levels of IFN-gamma. Interleukin-6 (IL-6) levels in CSF and serum were elevated in both strains and correlated with systemic and intracerebral disease activity. In conclusion, our results demonstrate activation of macrophages and NK cells as the predominant defence mechanisms of the comprised SCID immune system during toxoplasma infection. This implies a major role for the innate immune system during early stages of toxoplasmosis although T cells are necessary to control the infection efficiently.