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Cytokine circuits in brain
127 involves virus entry. This region includes the V3 loop but does not contain regions of gpl20 most important for CD4 binding. Virus strains that efficiently infect mononuclear phagocytes are resistant to neutralization by soluble CD4 (sCD4). This sCD4 resistance is conferred by the same
region of gpl20 important for cell tropism. These studies suggest that target cell interactions with gpl20, in addition to or in conjunction with CD4 binding, are necessary for efficient virus entry.
The immune system The anatomy of viral persistence Michael B.A. Oldstone Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA Key words: Viral persistence; Lymphocytes; Macrophages; Immunosuppression Viral persistence consists of two essential components: a failure of the immune system to recognize and clear virus and a successful replicate strategy of the virus. One maimer for viruses to initiate and maintain persistence is by direct infection of lymphocytes and/or macrophages. Activated lymphocytes ordinarily detect and eliminate the foreign agent and the cells it infects. Macrophages present antigen to lymphocytes thereby activating them so lymphocytes can function specifically. Thus, viruses can infect cells that compromise the immune system resulting in immunosuppression against the infecting agent thereby providing the virus a selective advantage for survival in a hostile immunologic environment. Virus specific MHC restricted cytotoxic T lymphocytes (CTL) play a cardinal role in clearance of several viruses. Using genetic and biochemical approaches, epitopes on viral protein(s) recognized by C-'TLhave been mapped. These epitopes, in experimental model, can be
utilized in vaccines that offer protection from both acute and persistent infections. Further, a "common" epitope can be mapped that when placed in a vaccine protects against several distinct MHC haplotypes thereby making vaccination via CTL protection in man a viable option. Additionally, virus can evade immune surveillance, based Oll its tropism in certain specialized differentiated cells like neurons. Such cells show a defect in the transcription of the MHC heavy chain and/or transcription of HAM1 and HAM-2 leading to an inability to present virus (viral peptide) to their surfaces. HAM-1 and HAM-2 are multiple drug resistant proteins that are believed to translocate peptides from the cytosol to the ER. This selective advantage preserves neurons from destruction by the immune system, but also likely accounts for why neurons are able to harbor a wide variety of DNA and RNA viruses throughout an infected host's life.
Cytokine circuits in brain Etty Benveniste University of Alabama, Birmingham, AL, USA Key words: Glial cells; Cytokines; Central nervous system; Immune system In recent years, there has been increasing evidence that soluble mediators such as cytokines from activated T-lymphocytes and macrophages are able to modulate the growth and function of cells found within the central nervous system (CNS), specifically macroglia and microglia cells. Furthermore, glial cells, upon activation, can secrete immunoregulatory factors that influence lymphoid/monouuclear cells, as well as the glial cells themselves. Thus, the potential exists for bidirectional communication between lymphoid cells and glial cells within the CNS, which in part is mediated via cytokines. This presentation oll cytokines in the CNS will highlight the action of a select group of cytokines, namely those
implicated in contributing to inflammatory and immune responses. These include intedeukin-i (IL-1), interleukin-6 (IL-6), interferon-gamma (IFN-y), tumor necrosis factoralpha (TNF-c0, and transforming growth factor-beta (TGF[5). The main focus of this presentation will be on how glial cells both respond to, and synthesize, cytokines, and how these changes in gene expression and function contribute to various neurologic disease states, including AIDS dementia complex. Where applicable, information concerning the intracellular signaling pathways and molecular mechanisms by which various genes (cytokines, class II MHC) are modulated in the CNS will be discussed.
region of gpl20 important for cell tropism. These studies suggest that target cell interactions with gpl20, in addition to or in conjunction with CD4 binding, are necessary for efficient virus entry.
The immune system The anatomy of viral persistence Michael B.A. Oldstone Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA Key words: Viral persistence; Lymphocytes; Macrophages; Immunosuppression Viral persistence consists of two essential components: a failure of the immune system to recognize and clear virus and a successful replicate strategy of the virus. One maimer for viruses to initiate and maintain persistence is by direct infection of lymphocytes and/or macrophages. Activated lymphocytes ordinarily detect and eliminate the foreign agent and the cells it infects. Macrophages present antigen to lymphocytes thereby activating them so lymphocytes can function specifically. Thus, viruses can infect cells that compromise the immune system resulting in immunosuppression against the infecting agent thereby providing the virus a selective advantage for survival in a hostile immunologic environment. Virus specific MHC restricted cytotoxic T lymphocytes (CTL) play a cardinal role in clearance of several viruses. Using genetic and biochemical approaches, epitopes on viral protein(s) recognized by C-'TLhave been mapped. These epitopes, in experimental model, can be
utilized in vaccines that offer protection from both acute and persistent infections. Further, a "common" epitope can be mapped that when placed in a vaccine protects against several distinct MHC haplotypes thereby making vaccination via CTL protection in man a viable option. Additionally, virus can evade immune surveillance, based Oll its tropism in certain specialized differentiated cells like neurons. Such cells show a defect in the transcription of the MHC heavy chain and/or transcription of HAM1 and HAM-2 leading to an inability to present virus (viral peptide) to their surfaces. HAM-1 and HAM-2 are multiple drug resistant proteins that are believed to translocate peptides from the cytosol to the ER. This selective advantage preserves neurons from destruction by the immune system, but also likely accounts for why neurons are able to harbor a wide variety of DNA and RNA viruses throughout an infected host's life.
Cytokine circuits in brain Etty Benveniste University of Alabama, Birmingham, AL, USA Key words: Glial cells; Cytokines; Central nervous system; Immune system In recent years, there has been increasing evidence that soluble mediators such as cytokines from activated T-lymphocytes and macrophages are able to modulate the growth and function of cells found within the central nervous system (CNS), specifically macroglia and microglia cells. Furthermore, glial cells, upon activation, can secrete immunoregulatory factors that influence lymphoid/monouuclear cells, as well as the glial cells themselves. Thus, the potential exists for bidirectional communication between lymphoid cells and glial cells within the CNS, which in part is mediated via cytokines. This presentation oll cytokines in the CNS will highlight the action of a select group of cytokines, namely those
implicated in contributing to inflammatory and immune responses. These include intedeukin-i (IL-1), interleukin-6 (IL-6), interferon-gamma (IFN-y), tumor necrosis factoralpha (TNF-c0, and transforming growth factor-beta (TGF[5). The main focus of this presentation will be on how glial cells both respond to, and synthesize, cytokines, and how these changes in gene expression and function contribute to various neurologic disease states, including AIDS dementia complex. Where applicable, information concerning the intracellular signaling pathways and molecular mechanisms by which various genes (cytokines, class II MHC) are modulated in the CNS will be discussed.