Immunological Reviews
0105-2896
1600-065X
Anh Quốc
Cơ quản chủ quản: Wiley-Blackwell Publishing Ltd , WILEY
Lĩnh vực:
Immunology and AllergyImmunology
Các bài báo tiêu biểu
Fibroblast‐like synoviocytes: key effector cells in rheumatoid arthritis Summary: Rheumatoid arthritis (RA) remains a significant unmet medical need despite significant therapeutic advances. The pathogenesis of RA is complex and includes many cell types, including T cells, B cells, and macrophages. Fibroblast‐like synoviocytes (FLS) in the synovial intimal lining also play a key role by producing cytokines that perpetuate inflammation and proteases that contribute to cartilage destruction. Rheumatoid FLS develop a unique aggressive phenotype that increases invasiveness into the extracellular matrix and further exacerbates joint damage. Recent advances in understanding the biology of FLS, including their regulation regulate innate immune responses and activation of intracellular signaling mechanisms that control their behavior, provide novel insights into disease mechanisms. New agents that target FLS could potentially complement the current therapies without major deleterious effect on adaptive immune responses.
Tập 233 Số 1 - Trang 233-255 - 2010
The prophenoloxidase‐activating system in invertebrates Summary: A major innate defense system in invertebrates is the melanization of pathogens and damaged tissues. This important process is controlled by the enzyme phenoloxidase (PO) that in turn is regulated in a highly elaborate manner for avoiding unnecessary production of highly toxic and reactive compounds. Recent progress, especially in arthropods, in the elucidation of mechanisms controlling the activation of zymogenic proPO into active PO by a cascade of serine proteinases and other factors is reviewed. The proPO‐activating system (proPO system) is triggered by the presence of minute amounts of compounds of microbial origins, such as β‐1,3‐glucans, lipopolysaccharides, and peptidoglycans, which ensures that the system will become active in the presence of potential pathogens. The presence of specific proteinase inhibitors prevents superfluous activation. Concomitant with proPO activation, many other immune reactions will be produced, such as the generation of factors with anti‐microbial, cytotoxic, opsonic, or encapsulation‐promoting activities.
Tập 198 Số 1 - Trang 116-126 - 2004
Foxp3<sup>+</sup>CD25<sup>+</sup>CD4<sup>+</sup> natural regulatory T cells in dominant self‐tolerance and autoimmune disease Summary: Naturally arising CD25+ CD4+ regulatory T (Treg) cells, most of which are produced by the normal thymus as a functionally mature T‐cell subpopulation, play key roles in the maintenance of immunologic self‐tolerance and negative control of a variety of physiological and pathological immune responses. Natural Tregs specifically express Foxp3, a transcription factor that plays a critical role in their development and function. Complete depletion of Foxp3‐expressing natural Tregs, whether they are CD25+ or CD25– , activates even weak or rare self‐reactive T‐cell clones, inducing severe and widespread autoimmune/inflammatory diseases. Natural Tregs are highly dependent on exogenously provided interleukin (IL)‐2 for their survival in the periphery. In addition to Foxp3 and IL‐2/IL‐2 receptor, deficiency or functional alteration of other molecules, expressed by T cells or non‐T cells, may affect the development/function of Tregs or self‐reactive T cells, or both, and consequently tip the peripheral balance between the two populations toward autoimmunity. Elucidation of the molecular and cellular basis of this Treg‐mediated active maintenance of self‐tolerance will facilitate both our understanding of the pathogenetic mechanism of autoimmune disease and the development of novel methods of autoimmune disease prevention and treatment via enhancing and re‐establishing Treg‐mediated dominant control over self‐reactive T cells.
Tập 212 Số 1 - Trang 8-27 - 2006
Immunologic tolerance maintained by CD25<sup>+</sup> CD4<sup>+</sup> regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance Summary: There is accumulating evidence that T‐cell‐mediated dominant control of self‐reactive T‐cells contributes to the maintenance of immunologic self‐tolerance and its alteration can cause autoimmune disease. Efforts to delineate such a regulatory T‐cell population have revealed that CD25+ cells in the CD4+ population in normal naive animals bear the ability to prevent autoimmune disease in vivo and, upon antigenic stimulation, suppress the activation/proliferation of other T cells in vitro . The CD25+ CD4+ regulatory T cells, which are naturally anergic and suppressive, appear to be produced by the normal thymus as a functionally distinct subpopulation of T cells. They play critical roles not only in preventing autoimmunity but also in controlling tumor immunity and transplantation tolerance.
Tập 182 Số 1 - Trang 18-32 - 2001
NF‐κB and the link between inflammation and cancer Summary: The nuclear factor‐κB (NF‐κB) transcription factor family has been considered the central mediator of the inflammatory process and a key participant in innate and adaptive immune responses. Coincident with the molecular cloning of NF‐κB/RelA and identification of its kinship to the v‐Rel oncogene, it was anticipated that NF‐κB itself would be involved in cancer development. Oncogenic activating mutations in NF‐κB genes are rare and have been identified only in some lymphoid malignancies, while most NF‐κB activating mutations in lymphoid malignancies occur in upstream signaling components that feed into NF‐κB. NF‐κB activation is also prevalent in carcinomas, in which NF‐κB activation is mainly driven by inflammatory cytokines within the tumor microenvironment. Importantly, however, in all malignancies, NF‐κB acts in a cell type‐specific manner: activating survival genes within cancer cells and inflammation‐promoting genes in components of the tumor microenvironment. Yet, the complex biological functions of NF‐κB have made its therapeutic targeting a challenge.
Tập 246 Số 1 - Trang 379-400 - 2012
Molecular mechanism and function of CD40/CD40L engagement in the immune system Summary: During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen‐presenting cells, as well as non‐immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non‐immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti‐tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.
Tập 229 Số 1 - Trang 152-172 - 2009
Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases Summary Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyroptosis is a form of inflammatory programmed cell death pathway activated by human and mouse caspase‐1, human caspase‐4 and caspase‐5, or mouse caspase‐11. These inflammatory caspases are used by the host to control bacterial, viral, fungal, or protozoan pathogens. Pyroptosis requires cleavage and activation of the pore‐forming effector protein gasdermin D by inflammatory caspases. Physical rupture of the cell causes release of the pro‐inflammatory cytokines IL ‐1β and IL ‐18, alarmins and endogenous danger‐associated molecular patterns, signifying the inflammatory potential of pyroptosis. Here, we describe the central role of inflammatory caspases and pyroptosis in mediating immunity to infection and clearance of pathogens.
Tập 277 Số 1 - Trang 61-75 - 2017
Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease Summary The intestinal tract of mammals is colonized by a large number of microorganisms including trillions of bacteria that are referred to collectively as the gut microbiota. These indigenous microorganisms have co‐evolved with the host in a symbiotic relationship. In addition to metabolic benefits, symbiotic bacteria provide the host with several functions that promote immune homeostasis, immune responses, and protection against pathogen colonization. The ability of symbiotic bacteria to inhibit pathogen colonization is mediated via several mechanisms including direct killing, competition for limited nutrients, and enhancement of immune responses. Pathogens have evolved strategies to promote their replication in the presence of the gut microbiota. Perturbation of the gut microbiota structure by environmental and genetic factors increases the risk of pathogen infection, promotes the overgrowth of harmful pathobionts, and the development of inflammatory disease. Understanding the interaction of the microbiota with pathogens and the immune system will provide critical insight into the pathogenesis of disease and the development of strategies to prevent and treat inflammatory disease.
Tập 279 Số 1 - Trang 70-89 - 2017
Innate immunity to virus infection Summary: The innate immune system is essential for the initial detection of invading viruses and subsequent activation of adaptive immunity. Three classes of receptors, designated retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs), Toll‐like receptors (TLRs), and nucleotide oligomerization domain (NOD)‐like receptors (NLRs), sense viral components, such as double‐stranded RNA (dsRNA), single‐stranded RNA, and DNA. RLRs and TLRs play essential roles in the production of type I interferons (IFNs) and proinflammatory cytokines in cell type‐specific manners. While the RLRs play essential roles in the recognition of RNA viruses in various cells, plasmacytoid dendritic cells utilize TLRs for detecting virus invasion. NLRs play a role in the production of mature interleukin‐1β to dsRNA stimulation. Activation of innate immune cells is critical for mounting adaptive immune responses. In this review, we discuss recent advances in our understanding of the mechanisms of viral RNA recognition by these different types of receptors and its relation to acquired immune responses.
Tập 227 Số 1 - Trang 75-86 - 2009
Anti‐microbial peptides: from invertebrates to vertebrates Summary: Gene‐encoded anti‐microbial peptides (AMPs) are widespread in nature, as they are synthesized by microorganisms as well as by multicellular organisms from both the vegetal and the animal kingdoms. These naturally occurring AMPs form a first line of host defense against pathogens and are involved in innate immunity. Depending on their tissue distribution, AMPs ensure either a systemic or a local protection of the organism against environmental pathogens. They are classified into three major groups: (i) peptides with an α‐helical conformation (insect cecropins, magainins, etc.), (ii) cyclic and open‐ended cyclic peptides with pairs of cysteine residues (defensins, protegrin, etc.), and (iii) peptides with an over‐representation of some amino acids (proline rich, histidine rich, etc.). Most AMPs display hydrophobic and cationic properties, have a molecular mass below 25–30 kDa, and adopt an amphipathic structure (α‐helix, β‐hairpin‐like β‐sheet, β‐sheet, or α‐helix/β‐sheet mixed structures) that is believed to be essential to their anti‐microbial action. Interestingly, in recent years, a series of novel AMPs have been discovered as processed forms of large proteins. Despite the extreme diversity in their primary and secondary structures, all natural AMPs have the in vitro particularity to affect a large number of microorganisms (bacteria, fungi, yeast, virus, etc.) with identical or complementary activity spectra. This review focuses on AMPs forming α‐helices, β‐hairpin‐like β‐sheets, β‐sheets, or α‐helix/β‐sheet mixed structures from invertebrate and vertebrate origins. These molecules show some promise for therapeutic use.
Tập 198 Số 1 - Trang 169-184 - 2004