Cerebrospinal fluid immune complexes in multiple sclerosis.

Using a C1q binding test, immune complexes have been detected in one half of cerebrospinal fluid samples from patients with multiple sclerosis. These results provide additional evidence for the participation of an immune reaction in the disease process.     

Immunogenicity of agarose-immobilized immune complexes

Summary A novel method is described for production of heterologous antisera to a specific tumor-associated murine antigen by immunization with agarose-trapped immune complexes.     

Cross-presentation of IgG-containing immune complexes

IgG is a molecule that functionally combines facets of both innate and adaptive immunity and therefore bridges both arms of the immune system. On the one hand, IgG is created by adaptive immune cells, but can be generated by B cells independently of T cell help. On the other hand, once secreted, IgG can rapidly deliver antigens into intracellular processing pathways, which enable efficient priming of T cell responses towards epitopes from the cognate antigen initially bound by the IgG. While this process has long been known to participate in CD4⁺ T cell activation, IgG-mediated delivery of exogenous antigens into a major histocompatibility complex (MHC) class I processing pathway has received less attention. The coordinated engagement of IgG with IgG receptors expressed on the cell-surface (FcγR) and within the endolysosomal system (FcRn) is a highly potent means to deliver antigen into processing pathways that promote cross-presentation of MHC class I and presentation of MHC class II-restricted epitopes within the same dendritic cell. This review focuses on the mechanisms by which IgG-containing immune complexes mediate such cross-presentation and the implications that this understanding has for manipulation of immune-mediated diseases that depend upon or are due to the activities of CD8⁺ T cells.     

Cerebrospinal fluid production during temperature stress and feeding in the conscious monkey

Zusammenfassung Das Flüssigkeitsvolumen des Ventrikelliquors wurde in Affen (im 3. Ventrikel kanuliert) gemessen. Die Produktion von Ventrikelliquor verringerte sich stark während 40–50 min, und zwar bei Nahrungsaufnahme, bei Erwärmung oder Abkühlung. Hernach Rückkehr des normalen Liquorvolumens.

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Supported in part by U.S. Office of Naval Research Contract No. NO 00014-67-A-0003 and Grant No. GB 7906 from the National Science Foundation. The authors are indebted to P.Curzon for valuable technical assistance.     

Transgenic mouse models of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system (CNS) and a frequent cause of neurological disability in young adults. Multifocal inflammatory lesions in the CNS white matter, demyelination, oligodendrocyte loss, axonal damage, as well as astrogliosis represent the histological hallmarks of the disease. These pathological features of MS can be mimicked, at least in part, using animal models. This review discusses the current concepts of the immune effector mechanisms driving CNS demyelination in murine models. It highlights the fundamental contribution of transgenesis in identifying the mediators and mechanisms involved in the pathophysiology of MS models.     

Astrocytes in multiple sclerosis: A product of their environment

It has long been thought that astrocytes, like other glial cells, simply provide a support mechanism for neuronal function in the healthy and inflamed central nervous system (CNS). However, recent evidence suggests that astrocytes play an active and dual role in CNS inflammatory diseases such as multiple sclerosis (MS). Astrocytes not only have the ability to enhance immune responses and inhibit myelin repair, but they can also be protective and limit CNS inflammation while supporting oligodendrocyte and axonal regeneration. The particular impact of these cells on the pathogenesis and repair of an inflammatory demyelinating process is dependent upon a number of factors, including the stage of the disease, the type and microenvironment of the lesion, and the interactions with other cell types and factors that influence their activation. In this review, we summarize recent data supporting the idea that astrocytes play a complex role in the regulation of CNS autoimmunity.     

Quantitative enzyme profiles of plaques of multiple sclerosis

Zusammenfassung Quantitative histochemische Methoden für Milchsäuredehydrogenase und DPN-Diaphorase wurden zum Studium von Plaques von multipler Sklerose in menschlichempost-mortem-Material angewendet. Im Vergleich mit myelinisierter weisser Substanz zeigten die Plaques eine um 28% vermehrte Fermentaktivität in der Randzone und eine Abnahme von 64% innerhalb des demyelinisierten Gewebes, was mit Veränderungen der intrazellulären Fermentverteilung in Beziehung gebracht werden kann.

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This research was supported by U.S. Public Health Grant B-3250.     

Metallothionein expression in the central nervous system of multiple sclerosis patients

Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS by tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show here that, as in EAE, MT-I+II proteins were expressed in brain lesions of MS patients. Cells expressing MT-I+II were mainly astrocytes and activated monocytes/macrophages. Interestingly, the levels of MT-I+II were slightly increased in the inactive MS lesions in comparison with the active lesions, suggesting that MTs may be important in disease remission.     

Inhibition of sensitized leukocyte's in vitro reactivity by circulating immune complexes in prostate cancer

Summary Circulating immune complexes in the sera of patients with confirmed histological diagnosis of carcinoma of the prostate, were found to interfere in the sensitized leukocyte's in vitro reactivity to prostate cancer associated antigen as evaluated by tube leukocyte adherence inhibition assay, thereby suggesting an inhibitory role of such serum factors in host's anti tumor cell mediated immune responses.4 November 1986     

Inhibition of sensitized leukocyte's in vitro reactivity by circulating immune complexes in prostate cancer

Circulating immune complexes in the sera of patients with confirmed histological diagnosis of carcinoma of the prostate, were found to interfere in the sensitized leukocyte's in vitro reactivity to prostate cancer associated antigen as evaluated by tube leukocyte adherence inhibition assay, thereby suggesting an inhibitory role of such serum factors in host's anti tumor cell mediated immune responses.