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.

During the last decade, rapid progress has been made in the area of microbial immu- nity. New conceptual frameworks have emerged with regard to the processing and presen- tation of peptides and nonpeptide antigens from microbes, especially bacteria, to T cells in the context of classical MHC class I and nonconventional MHC I molecules. Experimen- tal models have been instrumental in defining some of these pathways for generating pro- tective immune responses against microbes, which form the basis for the design of new vaccines. New evidence has stressed the importance of innate immunity in microbial in- fections. The concept of dichotomy within T helper cells has revealed the role of these cell types in resistance and susceptibility to microbial-mediated pathology. These latest devel- opments in microbial immunity are discussed in this volume. Natural killer cell development is known to be regulated by the presence of MHC class I antigens. Receptors for MHC class I molecules on NK cells have been discovered. Interaction of these receptors with their specific ligands leads to inhibition of cytotoxicity. Vinay Kumar and colleagues review NK cell differentiation and ontogeny, and functions of NK cells in experimental animals. Lewis Lanier discusses the role of a newly discov- ered molecule, DAP 12, in KIR and other receptor-mediated signal transduction in NK cells. Eric Long describes the regulation of immune response by inhibitory receptors.

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

The ability to remember an antigenic encounter for several decades, even for a life time, is one of the fundamental properties of the immune system. This phenomenon known as "immunological memory," is the foundation upon which the concept if vaccination rests. Therefore, understanding the mechanisms by which immunological memory is regulated is of paramount importance. Recent advances in immunology, particularly in the field of innate immunity, suggest that the innate immune system plays fundamental roles in influencing immunological memory. Indeed, emerging evidence suggests that events that occur early, within hours if not minutes of pathogen or vaccine entry profoundly shape the quantity, quality and duration of immunological memory. The present volume assembles a collection of essays from leading experts that span the entire spectrum research from understanding the molecular mechanisms of innate immune recognition, to dendritic cell function, to the generation and maintenance of antigen-specific B and T-cell responses.