Download Advances in the Immunopathogenesis of Multiple Sclerosis by P. A. Muraro, A. Lugaresi, D. Gambi (auth.), D. Gambi, P. A. PDF

By P. A. Muraro, A. Lugaresi, D. Gambi (auth.), D. Gambi, P. A. Muraro, A. Lugaresi, U. Ecari (eds.)

P.A. MURARO, A. LUGARESI, D. GAMBI a number of the pathological facets of a number of sclerosis (MS) lesions were recognized for over a century. it's only lately, although, that diversified styles of demyelination were associated with targeted pathways of immune-mediated tissue destruction. particularly, the inter-individual heterogeneity of MS lesions has urged that assorted mechanisms may well act in numerous sufferers, accounting for the variety saw in scientific path, immunological findings in peripheral blood and cere­ brospinal fluid (CSF), and reaction to immunomodulatory remedies. to supply an summary of the fundamental mechanisms very likely excited by MS lesion initiation and improvement, a global assembly was once geared up within the context of the once a year Congress of the Italian Neuroimmunology organization (AINI), held on the collage of Chieti, in Chieti Italy on 29 October 1998. The excessive typical of displays triggered us to file them in prolonged shape, to spotlight contemporary seasoned­ gress within the knowing of simple mechanisms maintaining MS immuno­ pathogenesis. A significant function within the attainable mechanisms resulting in myelin destruc­ tion has been attributed to T lymphocytes reactive to myelin antigens. experiences at the myelin antigen-specific T mobilephone repertoire have contributed major advances to our wisdom of autoimmunity (Chapters 1,2).

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Theoretically, each peptide mixture is made up of approximately 3 x lOll (19 9 ) individual sequences for a library composed of approximately 6 x 10 12 decapeptides. XXXXx,'{x,'{ Position 6 defined, all others randomized ...... Position 7 defined, all others randomized wXXXXXXXXXX Position 8 defined, all others randomized YXXXXXXXXXX Position 9 defined, all others randomized Testing importance of Alanine in position 1 Cysteine in position 1 Aspartic acid in position 1 Glutmnic acid in positron 1 Phenylalanine in position 1 Tryptophan in position 1 Tyrosine in position 1 XXXXXXXXXO: Position 10 defined, all others randomized Fig.

13. B. Hemmer et aI. Specific T cell recognition of minimally homologous peptides: evidence for endogenous ligands. Immunity 2:655-663 Wucherpfennig KW, Strominger JL (1995) Molecular mimicry in T cellmediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80:695-705 Houghten RA (1985) General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids.

These explants preserve their organotypic structure and model the in vivo interplay of neural cell types in vitro. Analysis of this cultured brain tissue demonstrated that intact neurons prevent induction of MHC class II molecules on astrocytes [8]. MHC class II expression was not induced on astrocytes neighboring neurons in untreated explants. However, blockade of neuronal activity with tetrodotoxin (TTX) restored MHC class II inducibility on astrocytes. The release of neurotransmitters, such as glutamate, is directly linked to neuronal electrical activity, and neurotransmitters can act on neighboring astrocytes by inducing Ca2+ oscillations via specific ligand-gated receptors [9].

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