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1.
Joyce S 《Cellular and molecular life sciences : CMLS》2001,58(3):442-469
Cellular and humoral immune mechanisms recruited to defend the host from infectious agents depend upon the early immune events
triggered by antigen. The cytokine milieu within which the immune response matures is the most important of many factors that
govern the nature of the immune response. Natural T cells, whose function is controlled by CD1d molecules, are an early source
of cytokines that can bestow type 1 or type 2 differentiative potential upon helper T lymphocytes. This review attempts to
illuminate the glycolipid antigen presentation properties of CD1d, how CD1d controls the function of natural T cells and how
CD1d and natural T cells interact to jump start the immune system. CD1d is postulated to function as a sensor, sensing alterations
in cellular lipid content by virtue of its affinity for such ligands. The presentation of a neo-self glycolipid, presumably
by infectious assault of antigen-presenting cells, activates natural T cells, which promptly release pro-inflammatory and
anti-inflammatory cytokines and jumpstart the immune system.
Received 10 July 2000; received after revision 16 October 2000, accepted 16 November 2000 相似文献
2.
D.B. Moody 《Cellular and molecular life sciences : CMLS》2001,58(10):1461-1474
T cells are well known to recognize peptide antigens presented by major histocompatibility (MHC) class I or class II molecules.
More recently, the CD1 family of antigen-presenting molecules has been shown to present both mammalian and microbial glycolipid
antigens for specific recognition by T cells. Human CD1c proteins mediate T cell recognition of polyisoprenyl glycolipids,
evolutionarily conserved phosphoglycolipids, which function in glycan synthesis pathways. This family of antigenic molecules
is particularly attractive for the study of the molecular features that control T cell recognition of self and foreign glycolipids
because natural polyisoprenols from mammals, fungi, protozoa, mycobacteria and eubacteria differ in structure. Moreover, these
naturally occurring structural differences can influence their recognition by CD1c-restricted T cells. This review of the
structural diversity and evolutionary relationships of polyisoprenoid glycolipids emphasizes those features of polyisoprenyl
glycolipid biosynthesis that are relevant to their functions as targets of CD1-mediated T cell responses.
Received 16 March 2001; received after revision 19 April 2001; accepted 23 April 2001 相似文献
3.
Kaifu T Escalière B Gastinel LN Vivier E Baratin M 《Cellular and molecular life sciences : CMLS》2011,68(21):3531-3539
Natural killer (NK) cells are lymphocytes of the innate immune system that sense target cells through a panel of activating
and inhibitory receptors. Together with NKG2D, the natural cytotoxicity receptors (NCRs) are major activating receptors involved
in tumor cell detection. Although numerous NKG2D ligands have been identified, characterization of the molecules interacting
with the NCRs is still incomplete. The identification of B7-H6 as a counter structure of the NCR NKp30 shed light on the molecular
basis of NK cell immunosurveillance. We review here the current knowledge on NKp30 and B7-H6, and we discuss their potential
role in anti-tumor immunity. 相似文献
4.
Del Val M Iborra S Ramos M Lázaro S 《Cellular and molecular life sciences : CMLS》2011,68(9):1543-1552
CD8+ T lymphocytes screen the surface of all cells in the body to detect pathogen infection or oncogenic transformation. They
recognize peptides derived from cellular proteins displayed at the plasma membrane by major histocompatibility complex (MHC)
class I molecules. Peptides are mostly by-products of cytosolic proteolytic enzymes. Peptidic ligands of MHC class I molecules
are also generated in the secretory and vesicular pathways. Features of protein substrates, of proteases and of available
MHC class I molecules for loading peptides in these compartments shape a singular collection of ligands that also contain
different, longer, and lower affinity peptides than ligands produced in the cytosol. Especially in individuals who lack the
transporters associated with antigen processing, TAP, and in infected and tumor cells where TAP is blocked, which thus have
no supply of peptides derived from the cytosol, MHC class I ligands generated in the secretory and vesicular pathways contribute
to shaping the CD8+ T lymphocyte response. 相似文献
5.
Whereas research on CD1d has emphasized a few glycosyl ceramides, the broader family of four human CD1 antigen-presenting molecules binds hundreds of distinct self-lipids. Individual lipid types bind within CD1 grooves in different ways, such that they partially fill the groove, match the groove volume, or protrude substantially from the groove. These differing modes of binding can now be connected to differing immunological functions, as individual lipids can act as stimulatory antigens, inhibitory ligands, or space-filling scaffolds. Because each type of CD1 protein folds to produce antigen-binding grooves with differing sizes and shapes, CD1a, CD1b, CD1c, CD1d, and CD1e have distinct mechanisms of capturing self-lipids and exchanging them for foreign lipids. The size discrepancy between endogeneous lipids and groove volume is most pronounced for CD1b. Recent studies show that the large CD1b cavity can simultaneously bind two self-lipids, the antigen, and its scaffold lipid, which can be exchanged for one large bacterial lipid. In this review, we will highlight recent studies showing how cells regulate lipid antigen loading and the roles CD1 groove structures have in control of the presentation of chemically diverse lipids to T cells. 相似文献
6.
Leukocyte integrins and inflammation 总被引:6,自引:0,他引:6
C. G. Gahmberg L. Valmu S. Fagerholm P. Kotovuori E. Ihanus L. Tian T. Pessa-Morikawa 《Cellular and molecular life sciences : CMLS》1998,54(6):549-555
Leukocyte adhesion is of pivotal functional importance. Without adequate adhesion, T lymphocytes and natural killer cells
are not cytotoxic, B cells cannot develop into antibody secreting plasma cells, leukocytes do not home into inflamed tissues
and myeloid cells are not able to phagocytize or exhibit chemotactic responses. During evolution several leukocyte adhesion
molecules have developed belonging to a few molecular families. Among these, the leukocyte-specific integrins (β
2 integrins, CD11/CD18 molecules) are among the most important. Much progress has taken place during the past few years, and
at present we have a considerable knowledge of their structure and function. Inflammation is critically dependent on integrin
activity, and its regulation forms the topic of this short review. 相似文献
7.
Triacylglycerols (TAGs), steryl esters (SEs) and wax esters (WEs) form the group of neutral lipids. Whereas TAGs are present
in all types of cell, the occurrence of SEs in prokaryotes is questionable, and the presence of WEs as storage molecules is
restricted to plants and a few bacteria. Here, we summarize recent knowledge on the formation, storage and degradation of
TAGs and SEs in various cell types. We describe the biochemical pathways involved in TAG and SE synthesis and discuss the
subcellular compartmentation of these processes. Recently, several novel enzymes governing the metabolism of storage lipids
have been identified and characterized. Regulatory aspects of neutral lipid storage are just beginning to be understood. Finally,
we describe consequences of defects in neutral lipid metabolism. Since severe diseases like atherosclerosis, obesity and type
2 diabetes are caused by lipid accumulation, mechanisms underlying neutral lipid synthesis, depot formation and mobilization
are of major interest for curing such diseases that are increasingly associated with modern civilization.
Received 18 January 2006; received after revision 7 March 2006; accepted 16 March 2006 相似文献
8.
Scavenger receptor family proteins: roles for atherosclerosis, host defence and disorders of the central nervous system 总被引:11,自引:1,他引:10
Y. Yamada T. Doi T. Hamakubo T. Kodama 《Cellular and molecular life sciences : CMLS》1998,54(7):628-640
In this review, we summarize the structure and function of the scavenger receptor family of proteins including class A (type
I and II macrophage scavenger receptors, MARCO), class B (CD36, scavenger receptor class BI), mucinlike (CD68/macrosialin,
dSR-CI) and endothelial (LOX-1) receptors. Two motifs have been identified as ligand-binding domains a charged collagen structure
of type I and II receptors, and an immunodominant domain of CD36. These structures can recognize a wide range of negatively
charged macromolecules, including oxidized low-density lipoproteins, damaged or apoptotic cells, and pathogenic microorganisms.
After binding, these ligands can be either internalized by endocytosis or phagocytosis, or remain at the cell surface and
mediate adhesion or lipid transfer through caveolae. Under physiological conditions, scavenger receptors serve to scavenge
or clean up cellular debris and other related materials, and they play a role in host defence. In pathological states, they
mediate the recruitment, activation and transformation of macrophages and other cells which may be related to the development
of atherosclerosis and to disorders caused by the accumulation of denatured materials, such as Alzheimer's disease.
Received 17 September 1997; received after revision 16 March 1998; accepted 17 March 1998 相似文献
9.
Antigen presentation by CD1 molecules and the generation of lipid-specific T cell immunity 总被引:2,自引:0,他引:2
It is now well demonstrated that the repertoire of T cells includes not only cells that recognize specific MHC-presented peptide antigens, but also cells that recognize specific self and foreign lipid antigens. This T cell recognition of lipid antigens is mediated by a family of conserved MHC class I-like cell surface glycoproteins known as CD1 molecules. These are specialized antigen-presenting molecules that directly bind a wide variety of lipids and present them for T cell recognition at the surface of antigen-presenting cells. Distinct populations of T cells exist that recognize CD1-presented lipids of microbial, environmental or self origin, and these T cells participate in immune responses associated with infectious, neoplastic, autoimmune and allergic diseases. Here we review the current knowledge of the biology of the CD1 system, including the structure, biosynthesis and trafficking of CD1 molecules, the structures of defined lipid antigens and the types of functional responses mediated by T cells specific for CD1-presented lipids. 相似文献
10.
M C Horzinek 《Experientia》1987,43(11-12):1193-1196
Although a very wide range of viral diseases exists in vertebrates, certain generalizations can be made regarding pathogenetic pathways on the molecular level. The presentation will focus on interactions of virions and their components with target cells. Using coronaviruses as examples the changes in virulence have been traced back to single mutational events; recombination, however, is likely to be an alternative mechanism by which virus-host interactions (e.g. the cell-, organ- or animal species-spectrum) can dramatically change. Receptor molecules are essential for the early interactions during infection and some of these have been identified. Events in the target cell and the host organism are discussed, and wherever possible, aspects of virus evolution and cooperation between infectious agents are highlighted. 相似文献
11.
Prion protein, a misfolded isoform of which is the essential component of the agent of prion diseases, still remains an enigmatic
protein whose physiological functions are at best hypothetical. To gain a better insight into its putative role, many studies
were undertaken to look for molecules that bind prion protein, and have notably identified divalent metal ions, several proteins,
and nucleic acids. At first sight, the diversity of prion protein’s ligands seems of little help to infer a plausible function.
However, the intrinsically disordered property of its N-terminal tail and the potential of the protein to adopt a transmembrane
topology, can both be taken into account to predict its different states during its cellular cycle and its possible functions,
of which the most promising correspond to a general scavenger, a sensor or adaptor in a signaling cascade, and an RNA chaperone.
Received 16 August 2006; received after revision 7 November 2006; accepted 13 December 2006 相似文献
12.
Wesch D Peters C Oberg HH Pietschmann K Kabelitz D 《Cellular and molecular life sciences : CMLS》2011,68(14):2357-2370
Toll-like receptors (TLR) are pattern-recognition receptors that recognize a broad variety of structurally conserved molecules
derived from microbes. The recognition of TLR ligands functions as a primary sensor of the innate immune system, leading to
subsequent indirect activation of the adaptive immunity as well as none-immune cells. However, TLR are also expressed by several
T cell subsets, and the respective ligands can directly modulate their effector functions. The present review summarizes the
recent findings of γδ T cell modulation by TLR ligands. TLR1/2/6, 3, and 5 ligands can act directly in combination with T
cell receptor (TCR) stimulation to enhance cytokine/chemokine production of freshly isolated human γδ T cells. In contrast
to human γδ T cells, murine and bovine γδ T cells can directly respond to TLR2 ligands with increased proliferation and cytokine
production in a TCR-independent manner. Indirect stimulatory effects on IFN-γ production of human and murine γδ T cells via
TLR-ligand activated dendritic cells have been described for TLR2, 3, 4, 7, and 9 ligands. In addition, TLR3 and 7 ligands
indirectly increase tumor cell lysis by human γδ T cells, whereas ligation of TLR8 abolishes the suppressive activity of human
tumor-infiltrating Vδ1 γδ T cells on αβ T cells and dendritic cells. Taken together, these data suggest that TLR-mediated
signals received by γδ T cells enhance the initiation of adaptive immune responses during bacterial and viral infection directly
or indirectly. Moreover, TLR ligands enhance cytotoxic tumor responses of γδ T cells and regulate the suppressive capacity
of γδ T cells. 相似文献
13.
Kingsbury MA Yung YC Peterson SE Westra JW Chun J 《Cellular and molecular life sciences : CMLS》2006,63(22):2626-2641
The brain is remarkable for its complex organization and functions, which have been historically assumed to arise from cells
with identical genomes. However, recent studies have shown that the brain is in fact a complex genetic mosaic of aneuploid
and euploid cells. The precise function of neural aneuploidy and mosaicism are currently being examined on multiple fronts
that include contributions to cellular diversity, cellular signaling and diseases of the central nervous system (CNS). Constitutive
aneuploidy in genetic diseases has proven roles in brain dysfunction, as observed in Down syndrome (trisomy 21) and mosaic
variegated aneuploidy. The existence of aneuploid cells within normal individuals raises the possibility that these cells
might have distinct functions in the normal and diseased brain, the latter contributing to sporadic CNS disorders including
cancer. Here we review what is known about neural aneuploidy, and offer speculations on its role in diseases of the brain.
Received 13 April 2006; received after revision 2 June 2006; accepted 13 July 2006 相似文献
14.
Insights into autotransplantation: the unexpected discovery of specific induction systems in bone marrow stromal cells 总被引:2,自引:0,他引:2
Dezawa M 《Cellular and molecular life sciences : CMLS》2006,63(23):2764-2772
Many kinds of cells, including embryonic stem cells and tissue stem cells, have been considered candidates for transplantation
therapy for neuro- and muscle-degenerative diseases. Bone marrow stromal cells (MSCs) also have great potential as therapeutic
agents since they are easily isolated and can be expanded from patients without serious ethical or technical problems. Recently,
new methods for the highly efficient and specific induction of functional neurons and skeletal muscle cells have been developed
for MSCs. These induced cells were transplanted into animal models of stroke, Parkinson’s disease and muscle degeneration,
resulting in the successful integration of transplanted cells and improvement in the behavior of the transplanted animals.
Here I describe the discovery of these induction systems and focus on the potential use of MSC-derived cells for ‘auto-cell
transplantation therapy’ in neuro- and muscle-degenerative diseases.
Received 27 April 2006; received after revision 5 June 2006; accepted 22 August 2006 相似文献
15.
Liao HF Yang YC Chen YY Hsu ML Shieh HR Chen YJ 《Cellular and molecular life sciences : CMLS》2007,64(1):104-111
Dendritic cells (DC) are specialized antigen-presenting cells. Bone marrow monocytes have been widely used to generate murine
myeloid DC. We found that mouse macrophages derived from bone marrow CD11b+ monocytes influenced the differentiation of these precursors into DC. Modulation of differentiation was demonstrated by the
down-regulation of CD11c, CD40, and CD86 expression and by IL-12 production. DC differentiated in the presence of conditioned
medium from bone marrow-derived macrophage culture (MCM) had impaired ability to stimulate proliferation of, and IFN- γ production
by, allogeneic CD4+ T cells. This inhibition of DC differentiation was mainly mediated by secretory products from macrophages but not by cell-cell
contact. MCM contained higher concentrations of macrophage-colony-stimulating factor (M-CSF), IL-10, and TGF- β1, whereas
IL-6 remained unchanged compared with conditioned medium from fresh monocytes. M-CSF may be the major mediator in MCM inhibiting
DC differentiation. This study demonstrates an important influence of bone marrow-derived macrophages on DC precursors during
DC differentiation.
Received 12 September 2006; received after revision 20 October 2006; accepted 13 November 2006 相似文献
16.
Until recently, the expression and primary function of the cell surface receptor CD40 and its ligand CD154 were considered
restricted to B and T lymphocytes, and their interactions required for the thymus-dependent humoral response. However, current
work from several groups challenges this view of the CD40/CD154 dyad as a mere mediator of lymphocyte communication. A variety
of non-lymphocytic cell types express both receptor and ligand, including hematopoetic and non-hematopoetic cells, such as
monocytes, basophils, eosinophils, dendritic cells, fibroblasts, smooth muscle, and endothelial cells. Accordingly, ligation
of CD40 mediates a broad variety of immune and inflammatory responses, such as the expression of adhesion molecules, cytokines,
matrix-degrading enzymes, prothrombotic activities, and apoptotic mediators. Consequently, CD40 signaling has been associated
with pathogenic processes of chronic inflammatory diseases, such as autoimmune diseases, neurodegenerative disorders, graft-versus-host
disease, cancer, and atherosclerosis. This review focuses on the synthesis and structure of CD40 and outlines CD154/CD40 signaling
pathways, and emphasizes the previously unexpected importance of the CD40/CD154 receptor/ligand dyad in a spectrum of immunoregulatory
processes and prevalent human diseases.
Received 10 January 2000; revised 16 June 2000; accepted 5 July 2000
RID="†"
ID="†" Review
RID="*"
ID="*" Corresponding author. 相似文献
17.
Zohra Dhouafli Karina Cuanalo-Contreras El Akrem Hayouni Charles E. Mays Claudio Soto Ines Moreno-Gonzalez 《Cellular and molecular life sciences : CMLS》2018,75(19):3521-3538
Protein misfolding and aggregation into fibrillar deposits is a common feature of a large group of degenerative diseases affecting the central nervous system or peripheral organs, termed protein misfolding disorders (PMDs). Despite their established toxic nature, clinical trials aiming to reduce misfolded aggregates have been unsuccessful in treating or curing PMDs. An interesting possibility for disease intervention is the regular intake of natural food or herbal extracts, which contain active molecules that inhibit aggregation or induce the disassembly of misfolded aggregates. Among natural compounds, phenolic molecules are of particular interest, since most have dual activity as amyloid aggregation inhibitors and antioxidants. In this article, we review many phenolic natural compounds which have been reported in diverse model systems to have the potential to delay or prevent the development of various PMDs, including Alzheimer’s and Parkinson’s diseases, prion diseases, amyotrophic lateral sclerosis, systemic amyloidosis, and type 2 diabetes. The lower toxicity of natural compounds compared to synthetic chemical molecules suggest that they could serve as a good starting point to discover protein misfolding inhibitors that might be useful for the treatment of various incurable diseases. 相似文献
18.
Born WK Zhang L Nakayama M Jin N Chain JL Huang Y Aydintug MK O'Brien RL 《Cellular and molecular life sciences : CMLS》2011,68(14):2335-2343
γδ T cells express adaptive antigen receptors encoded by rearranging genes. Their diversity is highest in the small region
of TCR V–J junctions, especially in the δ chain, which should enable the γδ TCRs to distinguish differences in small epitopes.
Indeed, recognition of small molecules, and of an epitope on a larger protein has been reported. Responses to small non-peptides
known as phospho-antigens are multi-clonal yet limited to a single γδ T cell subset in humans and non-human primates. Responses
to small peptides are multi-clonal or oligo-clonal, include more than one subset of γδ T cells, and occur in rodents and primates.
However, less effort has been devoted to investigate the peptide responses. To settle the questions of whether peptides can
be ligands for the γδ TCRs, and whether responses to small peptides might occur normally, peptide binding will have to be
demonstrated, and natural peptide ligands identified. 相似文献
19.
Temporins, anti-infective peptides with expanding properties 总被引:2,自引:1,他引:1
Mangoni ML 《Cellular and molecular life sciences : CMLS》2006,63(9):1060-1069
Antimicrobial peptides are effector molecules of the innate immune response of all pluricellular organisms, providing them
with first-line defence against pathogens. Amphibian skin secretions represent one of the richest natural sources for such
peptide antibiotics, and temporins, a large family of antimicrobial peptides from frog skin, are among the smallest ones found
in nature to date. Their functional role and modes of action have been described, along with their interesting and unique
properties. These properties make temporins good molecules for an in-depth understanding of host defence peptides in general.
Furthermore, they are attractive templates for the future design of new therapeutics against infectious diseases with new
modes of action, urgently needed due to the increasing resistance of microorganisms to the available drugs.
Received 8 November 2005; received after revision 19 December 2005; accepted 18 January 2006 相似文献
20.
Sieni E Cetica V Mastrodicasa E Pende D Moretta L Griffiths G Aricò M 《Cellular and molecular life sciences : CMLS》2012,69(1):29-40
Cytotoxic T lymphocytes, natural killer cells, and NKT cells are effector cells able to kill infected cells. In some inherited
human disorders, a defect in selected proteins involved in the cellular cytotoxicity mechanism results in specific clinical
syndromes, grouped under the name of familial hemophagocytic lymphohistiocytosis. Recent advances in genetic studies of these
patients has allowed the identification of different genetic subsets. Additional genetic immune deficiencies may also induce
a similar clinical picture. International cooperation and prospective trials resulted in refining the diagnostic and therapeutic
approach to these rare diseases with improved outcome but also with improved knowledge of the mechanisms underlying granule-mediated
cellular cytotoxicity in humans. 相似文献