Negative Co-Receptors and Ligands [electronic resource] /
Ahmed, Rafi.editor.
Honjo, Tasuku.editor.
Adaptive immune responses serve as a key defense mechanism for the control of infections in vertebrates. Immune responses must be of sufficient strength to contain invading pathogens, antigen specific responses require regulatory mechanisms to ensure termination or downmodulation to avoid excessive damage to the host tissue. For both branches of the adaptive immune system, regulatory molecules i.e. coreceptors and ligands have been identified that control the signaling cascades initiated by engagement of the T cell and B cell antigen receptors. This book describes biological functions as well as molecular mechanisms of these molecules. Fc Receptor-Like molecules (FCRL) that have garnered increasing interest due to their differential patterns of lymphocyte expression and potential involvement in the pathogenesis of autoimmune disorders, immunodeficiency and lymphoid malignancies in humans. Programmed cell death-1 (PD-1) delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. The biological significance of PD-1 and its ligand suggest the therapeutic potential of manipulation of PD-1 pathway against various human diseases. TIM-3 acts as a negative regulator of Th1/Tc1 cell function by triggering cell death upon interaction with its ligand, galectin-9. This negative regulatory function of TIM-3 has now been expanded to include its involvement in establishing and/or maintaining a state of T cell dysfunction or 'exhaustion' observed in chronic viral diseases. The Ly49 receptors, which are expressed in a stochastic manner on subsets of murine Natural Killer (NK) cells, T cells, and other cells, are encoded by the Klra gene family and include receptors with either inhibitory or activating function. Most of the inhibitory Ly49 receptors recognize polymorphic epitopes on major histocompatibility complex (MHC) class I proteins as ligands. Fc-receptors for IgG (FcRs) are widely expressed on innate immune effector cells in mediating the protective function of IgG. This book discusses how the interaction of these different ligands to classical and novel Fc-receptors influences the immune response and which strategies microorganisms have developed to prevent them. The host derived cytokine IL-10 is a key player in the establishment and perpetuation of viral persistence.  This book covers the role of IL-10 in viral persistence and explores the exciting prospect of therapeutically blocking IL-10 to increase antiviral immunity and vaccine efficacy. TGF-ß inhibits the proliferation of T cells as well as cytokine production via Foxp3-dependent and independent mechanisms. Recent studies suggest that Smad2 as well as Smad3 play essential roles in Foxp3 induction and cytokine suppression, whereas Th17 differentiation is promoted via the Smad-independent pathway. Mutual suppression of signaling between TGF-ß and inflammatory cytokines has been shown to be necessary for the balance of immunity and tolerance.
Description based upon print version of record.
Negative Co-Receptors and Ligands; Contents; Contributors; TIM-3 and Its Regulatory Role in Immune Responses; 1 Introduction; 2 Protein Structure; 3 TIM-3 Ligands; 3.1 Identification of Galectin-9 as a TIM-3 Ligand; 3.2 Phosphatidylserine as a TIM-3 Ligand; 3.3 Carbohydrate Ligands for TIM-3; 4 Expression of TIM-3; 4.1 Transcriptional Control of TIM-3 Expression; 5 TIM-3 in Disease; 5.1 Genetic Basis for Role of TIM-3 in Disease; 6 TIM-3 in Autoimmune Diseases; 6.1 TIM-3 in Chronic Viral Infection; 6.2 TIM-3 in Other Diseases; 7 Conclusions; References
Role of PD-1 in Regulating T-Cell Immunity1 Identification of PD-1 and Its Ligands; 2 Structure of PD-1 and Its Ligands; 3 Regulation of PD-1 Expression; 4 PD-1 Signaling: Molecular Mechanisms of Inhibition; 5 Biological Significance of PD-1; 5.1 PD-1 in Autoimmunity; 5.2 PD-1 in Chronic Viral Infection; 5.3 PD-1 in Antitumor Immunity; 6 Conclusions; References; The Role of IL-10 in Regulating Immunity to Persistent Viral Infections; 1 Introduction; 1.1 Immune Dynamics During Acute and Persistent Virus Infection: The Failure of Antiviral Immunity
2 The Impact of Host-Based Regulatory Mechanisms in T Cell Exhaustion2.1 Discovery That Host-Based Suppressive Factors Inhibit Clearance of Persistent Viral Infection; 2.2 Multiple Regulatory Factors Suppress T Cell Responses During Viral Persistence; 2.3 Differential Impact of Reversing T Cell Exhaustion During Viral Persistence; 3 The Impact of IL-10 Toward Viral Persistence; 3.1 The Diverse Roles of IL-10 During Viral Infection; 3.2 Sources, Mechanisms, and Targets of IL-10 During Persistent Viral Infection
4 Targeting Immunosuppression: Potential Therapeutic Applications for Blocking IL-105 Past, Present, and Future; References; Inhibitory Ly49 Receptors on Mouse Natural Killer Cells; 1 Introduction; 2 Ly49 Haplotypes and Ligands; 3 Inhibitory Signaling Events; 4 Educational Impact of Ly49 Receptors on NK Cells; 5 Inhibitory Ly49 Receptors and Viral Infections; 6 Inhibitory Ly49 Receptors in Transplantation and Malignancy; 7 Concluding Remarks; References; Immunoregulatory Roles for Fc Receptor-Like Molecules; 1 Introduction
2 Identification of FCRL Molecules Reveals a New Level of B Cell Regulation3 FCRL Structural Properties; 4 FCRL Expression Patterns; 5 FCRL Functional Properties; 6 FCRL Involvement in Human Diseases; 7 Concluding Remarks; References; FcgammaRs in Health and Disease; 1 Introduction; 2 The Family of Canonical Fcgamma-Receptors; 3 Regulation of IgG Activity In Vivo; 4 Influence of Antibody Glycosylation and Novel Fcgamma-Receptors; 5 Role of FcgammaRs for Infection; 6 Microbial Immune Escape Mechanisms Targeting the IgG-FcgammaR Interaction; 7 Other Ligands for Fcgamma-Receptors; 8 Conclusions
References
Includes bibliographical references and index.
Adaptive immune responses serve as a key defense mechanism for the control of infections in vertebrates. Immune responses must be of sufficient strength to contain invading pathogens, antigen specific responses require regulatory mechanisms to ensure termination or downmodulation to avoid excessive damage to the host tissue. For both branches of the adaptive immune system, regulatory molecules i.e. coreceptors and ligands have been identified that control the signaling cascades initiated by engagement of the T cell and B cell antigen receptors. This book describes biological functions as well as molecular mechanisms of these molecules. Fc Receptor-Like molecules (FCRL) that have garnered increasing interest due to their differential patterns of lymphocyte expression and potential involvement in the pathogenesis of autoimmune disorders, immunodeficiency and lymphoid malignancies in humans. Programmed cell death-1 (PD-1) delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. The biological significance of PD-1 and its ligand suggest the therapeutic potential of manipulation of PD-1 pathway against various human diseases. TIM-3 acts as a negative regulator of Th1/Tc1 cell function by triggering cell death upon interaction with its ligand, galectin-9. This negative regulatory function of TIM-3 has now been expanded to include its involvement in establishing and/or maintaining a state of T cell dysfunction or 'exhaustion' observed in chronic viral diseases. The Ly49 receptors, which are expressed in a stochastic manner on subsets of murine Natural Killer (NK) cells, T cells, and other cells, are encoded by the Klra gene family and include receptors with either inhibitory or activating function. Most of the inhibitory Ly49 receptors recognize polymorphic epitopes on major histocompatibility complex (MHC) class I proteins as ligands. Fc-receptors for IgG (FcRs) are widely expressed on innate immune effector cells in mediating the protective function of IgG. This book discusses how the interaction of these different ligands to classical and novel Fc-receptors influences the immune response and which strategies microorganisms have developed to prevent them. The host derived cytokine IL-10 is a key player in the establishment and perpetuation of viral persistence.  This book covers the role of IL-10 in viral persistence and explores the exciting prospect of therapeutically blocking IL-10 to increase antiviral immunity and vaccine efficacy. TGF-ß inhibits the proliferation of T cells as well as cytokine production via Foxp3-dependent and independent mechanisms. Recent studies suggest that Smad2 as well as Smad3 play essential roles in Foxp3 induction and cytokine suppression, whereas Th17 differentiation is promoted via the Smad-independent pathway. Mutual suppression of signaling between TGF-ß and inflammatory cytokines has been shown to be necessary for the balance of immunity and tolerance.
Immunology.
Immunology.
Current topics in microbiology and immunology