Beschreibung
Toll Receptors and the Renaissance of Innate Immunity Elizabeth H. Bassett and Tina Rich Overview n the last few pages of Immunology: The Science of Self-Nonself Discrimination Jan Klein ponders on what he would study if he were to start over in the lab. ^ Dismissing the I antibody, MHC, the T-cell and parasitology, he considers instead the phylogeny of immune reactions, particularly in ancient phyla. As for a favored cell he chooses the macrophage. Describ ing it as a ^^MddchenfUr alles," (all purpose kitchen maid) Klein believed that this immunocyte still had secrets to reveal. Toll-Like Receptor (TLR) biology would prove to be one of these secrets. Analyses of the evolution of these receptors (Tolls and TLRs) have also helped us to rethink immune system phylogeny. In the first part of this chapter the history of the discovery of Toll and TLR biology is described. The evolution of the TLR genes and theories of immune function are covered in later sections. The remainder of this book presents work from nine groups active in the field. In the first chapter, "The Function of Toll-Like Receptors", Zlatko Dembic sets the stage by introducing us to many of the components of the immune system and their relationships vis a vis Toll receptors. Zlatko finishes his chapter with a discussion about current immune system models and contributes his own 'integrity model'. Work from the laboratory of Nicholas Gay follows this in "Structures and Motifs Involved in Toll Signaling".
Inhaltsverzeichnis
Introduction Toll Receptors and the Renaissance of Innate Immunity ....................... 1 Beginnings ............................................................................................ 2 The Innate and Adaptive Immune Systems ........................................... 2 Saturation Screening of the Drosophila Genome .................................... 3 The Toll Receptor in Development ....................................................... 4 The Implication of Toll in Fly Immunity .............................................. 5 A Problem with Vaccination.................................................................. 6 The Question of Escape Mutants .......................................................... 7 The Evolution of Toll Receptors ........................................................... 8 To the Clinic ....................................................................................... 14 1. The Function of Toll-Like Receptors ................................................... 18 Developmental Functions .................................................................... 19 The Role in Defense ............................................................................ 22 Divisions of Immunity ........................................................................ 27 Expression and Function of TLRs in Cells of Autonomous Immunity ............................................................... 30 Expression and Function of TLRs in Cells of Central Immunity ......... 33 The Roles of TLRs in APCa¿'T Cell Interactions ................................ 39 TLRs and Theories about the Function of the Immune System ........... 44 TLRs in Health and Disease ................................................................ 51 2. Structures and Motifs Involved in Toll Signaling ................................. 56 Components of the Extracellular Pathway: The Extracellular Leucine-Rich Repeat Domain of TLRs ................ 56 Structural Diversity of TLR Ligands .................................................... 61 Mechanism of Ligand Binding and Signal Transduction ..................... 70 Pathogen Recognition by TLRs ........................................................... 70 Mechanism of Signal Transduction ..................................................... 74 Components of the Intracellular Pathway ............................................ 75 3. "Supramolecular" Activation Custers in Innate Immunity ................... 94 Lipopolysaccharide Recognition .......................................................... 95 Structure of LPS .................................................................................. 95 The Search for the LPS "Signal Transducer" ....................................... 96 Microdomains ................................................................................... 101 4. Interleukin-1 Receptor/Toll-Like Receptor Signaling ......................... 110 The "Hardware" of IL-1R/TLR Signaling ......................................... 110 The NF-eB Family of Transcription Factors ..................................... 115 IL-1R Signaling ................................................................................. 115 Mechanisms of TLR Signaling .......................................................... 118 Termination of IL-1R/TLR Signaling ............................................... 120 The Toll Pathway in Drosophila Melanogaster .................................... 122 TLR-Mediated Apoptosis .................................................................. 124 5. Virus Induced Signaling to Initiate the Interferon ...
