Abstract:
:In humans and experimental animals the presence of bacterial lipopolysaccharide (endotoxin, LPS) signals the presence of gram-negative bacteria. Recognition of LPS triggers gene induction by myeloid and nonmyeloid lineage cells. These inducible genes encode proteins that include cytokines, adhesive proteins, and enzymes that produce low molecular weight proinflammatory mediators. Together the products of these inducible genes upregulate host defense systems that participate in eliminating the bacterial infection. Unfortunately, these same mediators contribute to a serious human disease known as septic shock. Considerable progress has been made during the past decade in determining the sources, identities, and sequence of release of these mediators. In contrast, until recently, marked gaps in our knowledge existed regarding the identity of the LPS receptor and intracellular signaling pathways responsible for LPS-induced cell activation. The discovery in 1986 of a plasma protein termed LPS binding protein (LBP) led to the discovery of unanticipated mechanisms of LPS-induced cell activation. CD14 was found as a soluble serum protein or as a glycosylphosphatidylinositol (GPI)-anchored protein of myeloid lineage cells; it now occupies a key role in LPS-induced cell activation as we understand it today. Here we discuss how LBP enables LPS binding to CD14 and how complexes of LPS and soluble or GPI-anchored CD14 participate in cell activation. We also review the evidence supporting a model for a functional LPS receptor of myeloid cells, which is multimeric, comprised of GPI-anchored CD14 and a presently unidentified transmembrane protein that together bind LPS and initiate cell activation via kinase cascades.
journal_name
Annu Rev Immunoljournal_title
Annual review of immunologyauthors
Ulevitch RJ,Tobias PSdoi
10.1146/annurev.iy.13.040195.002253subject
Has Abstractpub_date
1995-01-01 00:00:00pages
437-57eissn
0732-0582issn
1545-3278journal_volume
13pub_type
杂志文章,评审abstract::The signaling lymphocyte activation molecule (SLAM)-associated protein, SAP, was first identified as the protein affected in most cases of X-linked lymphoproliferative (XLP) syndrome, a rare genetic disorder characterized by abnormal responses to Epstein-Barr virus infection, lymphoproliferative syndromes, and dysgamm...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-030409-101302
更新日期:2011-01-01 00:00:00
abstract::CD4+ T lymphocytes initiate and regulate both the specific and nonspecific effector mechanisms of allergic immune responses. The definition of immunogenic components within allergens has allowed the specificity of the T-cell repertoire to be examined, and the refinement of their molecular structure is now facilitating...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.09.040191.000435
更新日期:1991-01-01 00:00:00
abstract::CD45 is one of the most abundant leukocyte cell surface glycoproteins and is expressed exclusively upon cells of the hematopoietic system. Different isoforms of CD45 are generated by alternative splicing and are expressed in cell type-specific patterns on functional subpopulations of lymphocytes. In a major advance, C...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.12.040194.000505
更新日期:1994-01-01 00:00:00
abstract::The genes encoding the alpha and beta chain of the T-cell receptor and the gamma gene have been cloned, and their structure, organization, ontogeny of expression, pattern of rearrangement, and diversification are now generally understood. In most cases, the immunoglobulin paradigm applied very well to the correspondin...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.04.040186.002525
更新日期:1986-01-01 00:00:00
abstract::Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNF alpha, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cy...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.14.1.397
更新日期:1996-01-01 00:00:00
abstract::Only a handful of the more than 100,000 fungal species on our planet cause disease in humans, yet the number of life-threatening fungal infections in patients has recently skyrocketed as a result of advances in medical care that often suppress immunity intensely. This emerging crisis has created pressing needs to clar...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-020711-074958
更新日期:2012-01-01 00:00:00
abstract::Only 5 to 10% of immunocompetent humans are susceptible to tuberculosis, and over 85% of them develop the disease exclusively in the lungs. Human immunodeficiency virus (HIV)-infected humans, in contrast, can develop systemic disease that is more quickly lethal. This is in keeping with other evidence showing that susc...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.22.012703.104635
更新日期:2004-01-01 00:00:00
abstract::To combat infection, the fruit fly Drosophila melanogaster relies on multiple innate defense reactions, many of which are shared with higher organisms. These reactions include the use of physical barriers together with local and systemic immune responses. First, epithelia, such as those beneath the cuticle, in the ali...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.25.022106.141615
更新日期:2007-01-01 00:00:00
abstract::Chemokines are chemotactic cytokines that control the migratory patterns and positioning of all immune cells. Although chemokines were initially appreciated as important mediators of acute inflammation, we now know that this complex system of approximately 50 endogenous chemokine ligands and 20 G protein-coupled seven...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032713-120145
更新日期:2014-01-01 00:00:00
abstract::Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate Styela plicata, they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator...
journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev-immunol-071719-094903
更新日期:2020-04-26 00:00:00
abstract::The innate immune system relies on its capacity to rapidly detect invading pathogenic microbes as foreign and to eliminate them. The discovery of Toll-like receptors (TLRs) provided a class of membrane receptors that sense extracellular microbes and trigger antipathogen signaling cascades. More recently, intracellular...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.021908.132715
更新日期:2009-01-01 00:00:00
abstract::HTLV-I infection is causally associated with a variety of human diseases including leukemia/lymphoma, myelopathy, uveitis, and arthropathy. Tax protein of HTLV-I, which is considered oncogenic, binds to transcription factors or other cytoplasmic cellular molecules involved in the fundamental cell function and thereby ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.15.1.15
更新日期:1997-01-01 00:00:00
abstract::MHC class I molecules are peptide receptors of stringent specificity which however still allow millions of different ligands. This is achieved by the following specificity characteristics summarized as allele specific peptide motifs: Peptides are of defined length, depending on the class I allele (either 8 or 9 residu...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.11.040193.001241
更新日期:1993-01-01 00:00:00
abstract::T helper cell differentiation occurs in the context of the extracellular cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multi...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-020711-075058
更新日期:2012-01-01 00:00:00
abstract::T cell activation leads to dramatic shifts in cell metabolism to protect against pathogens and to orchestrate the action of other immune cells. Quiescent T cells require predominantly ATP-generating processes, whereas proliferating effector T cells require high metabolic flux through growth-promoting pathways. Further...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032712-095956
更新日期:2013-01-01 00:00:00
abstract::T helper lymphocytes can be divided into two distinct subsets of effector cells based on their functional capabilities and the profile of cytokines they produce. The Th1 subset of CD4+ T cells secretes cytokines usually associated with inflammation, such as IFN-gamma and TNF and induces cell-mediated immune responses....
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.15.1.297
更新日期:1997-01-01 00:00:00
abstract::Rejection of transplanted tissue allografts results from T-cell recognition of histocompatibility antigens expressed by cells of the donor graft. This review focuses on the phenotype, specificity, and function of the T cells mediating rejection responses against skin allografts, and on the immune mechanisms by which h...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.10.040192.002001
更新日期:1992-01-01 00:00:00
abstract::The diverse microbial populations constituting the intestinal microbiota promote immune development and differentiation, but because of their complex metabolic requirements and the consequent difficulty culturing them, they remained, until recently, largely uncharacterized and mysterious. In the last decade, deep nucl...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032713-120238
更新日期:2015-01-01 00:00:00
abstract::A host has two methods to defend against pathogens: It can clear the pathogens or reduce their impact on health in other ways. The first, resistance, is well studied. Study of the second, which ecologists call tolerance, is in its infancy. Tolerance measures the dose response curve of a host's health in reaction to a ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-020711-075030
更新日期:2012-01-01 00:00:00
abstract::Over the past decade, key protein interactions contributing to T cell antigen recognition have been characterized in molecular detail. These have included interactions involving the T cell antigen receptor (TCR) itself, its coreceptors CD4 and CD8, the accessory molecule CD2, and the costimulatory receptors CD28 and C...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.21.120601.141036
更新日期:2003-01-01 00:00:00
abstract::Recent elucidation of the role of central tolerance in preventing organ-specific autoimmunity has changed our concepts of self/nonself discrimination. This paradigmatic shift is largely attributable to the discovery of promiscuous expression of tissue-restricted self-antigens (TRAs) by medullary thymic epithelial cell...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.23.021704.115601
更新日期:2006-01-01 00:00:00
abstract::During the last several years, the mechanism of IFN gamma-dependent signal transduction has been the focus of intense investigation. This research has recently culminated in the elucidation of a comprehensive molecular understanding of the events that underlie IFN gamma-induced cellular responses. The structure and fu...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.15.1.563
更新日期:1997-01-01 00:00:00
abstract::The immune system is composed of single cells, and its function is entirely dependent on the capacity of these cells to traffic, localize within tissues, and interact with each other in a precisely coordinated fashion. There is growing evidence that the large families of chemokines and chemokine receptors provide a fl...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.18.1.593
更新日期:2000-01-01 00:00:00
abstract::The nonobese diabetic (NOD) mouse is a model of human autoimmune insulin-dependent diabetes mellitus. The NOD mouse also serves as a model for studying complex polygenic diseases because at least fourteen different loci are linked to disease development. The first Idd locus recognized, Idd1, is linked to the major his...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.13.040195.001143
更新日期:1995-01-01 00:00:00
abstract::Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimeric antigen receptor (CAR) T cells were recently approved by the US Food and Drug Administration and are poised to enter the practice of medicine for leukemia and lymphoma, demonstrating that e...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-042718-041407
更新日期:2019-04-26 00:00:00
abstract::Recent years have witnessed an emergence of interest in understanding metabolic changes associated with immune responses, termed immunometabolism. As oxygen is central to all aerobic metabolism, hypoxia is now recognized to contribute fundamentally to inflammatory and immune responses. Studies from a number of groups ...
journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev-immunol-100819-121537
更新日期:2020-04-26 00:00:00
abstract::Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflamma...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032713-120252
更新日期:2015-01-01 00:00:00
abstract::The complement system is an evolutionarily ancient key component of innate immunity required for the detection and removal of invading pathogens. It was discovered more than 100 years ago and was originally defined as a liver-derived, blood-circulating sentinel system that classically mediates the opsonization and lyt...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-042617-053245
更新日期:2018-04-26 00:00:00
abstract::Major histocompatibility complex (MHC) class II molecules are heterodimeric cell surface proteins that are critically important for the development and function of cells in the immune system. In particular, the maturation of CD4+ T cells is dependent on the expression of MHC class II molecules on thymic epithelium, wh...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.13.040195.002221
更新日期:1995-01-01 00:00:00
abstract::The gastrointestinal tract harbors numerous commensal bacteria, referred to as the microbiota, that benefit host health by digesting dietary components and eliminating pathogens. The intestinal microbiota maintains epithelial barrier integrity and shapes the mucosal immune system, balancing host defense and oral toler...
journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev-immunol-070119-115104
更新日期:2020-04-26 00:00:00