Latest Articles Include:
- From the editors
- Nature Reviews Immunology 10(5):285 (2010)
In this issue, we present a series of comprehensive Review, Perspective and Comment articles on the field of therapeutic antibodies, highlighting the recent advances and future challenges for their development and use in the treatment of cancer, autoimmunity and infectious diseases.Georges Köhler and César Milstein first described the hybridoma technique for the production of monoclonal antibodies in 1975, a discovery that revolutionized science and medicine. - Innate immunity: Ready, AIM, fire!
- Nature Reviews Immunology 10(5):287 (2010)
Reporting in Nature Immunology, two independent groups of researchers provide the first genetic evidence that the DNA sensor AIM2 (absent in melanoma 2) is crucial for immunity against certain bacterial infections and DNA viruses.AIM2 was recently identified as a cytoplasmic receptor that recognizes double-stranded DNA and assembles with the caspase 1-activating adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) to form the AIM2 inflammasome. - Viral immunity: How CMV bypasses immune memory
- Nature Reviews Immunology 10(5):288 (2010)
Persistent infection with cytomegalovirus (CMV) induces high-frequency CMV-specific T cell responses and high titres of neutralizing antibodies, but this immune response cannot prevent superinfection with another strain of CMV. A study published in Science now explains the mechanism behind this ability of secondary CMV infections to evade immune memory. - Immune regulation: Tidy TIM
- Nature Reviews Immunology 10(5):288 (2010)
The T cell immunoglobulin domain and mucin domain family member TIM4 (also known as TIMD4) is expressed by macrophages and dendritic cells (DCs) and binds to both phosphatidylserine on apoptotic cells and to TIM1 (also known as TIMD1) on activated T cells. TIM4 has been attributed with both activating and inhibitory immune functions but its predominant role in vivo has remained unclear. - T cell responses: IL-2 overrules tolerogenic liver responses
- Nature Reviews Immunology 10(5):289 (2010)
Antigen-presenting cells (APCs) in the liver generally induce T cell tolerance rather than T cell immunity. Of the APCs in the liver, liver sinusoidal endothelial cells (LSECs) are highly adept at taking up soluble antigens from the blood and cross-presenting these antigens on MHC class I molecules to passing naive CD8+ T cells. - Immune tolerance: New peacekeepers identified
- Nature Reviews Immunology 10(5):290 (2010)
Lymph node stromal cells (LNSCs) have been shown to be mediators of antigen-specific peripheral T cell tolerance through the expression of peripheral tissue antigens (PTAs). However, the specific cell subsets involved were not known. - Scientific basis for 'man flu'
- Nature Reviews Immunology 10(5):290 (2010)
Men may have weaker immune systems than women and suffer disease more seriously and for longer, say scientists at the University of Cambridge, UK. The study, published in the Proceedings of the Royal Society B: Biological Sciences (24 Mar 2010), gives scientific credence to the phenomenon colloquially referred to as 'man flu' and suggests that "Maybe men aren't just playing sick, but really are more susceptible" (The Times, 24 Mar 2010). - Innate immunity: Toll tremors
- Nature Reviews Immunology 10(5):291 (2010)
Epilepsy is a chronic neurological disorder in which affected individuals suffer from recurring, unprovoked seizures. There is evidence to suggest that inflammatory processes can promote seizures, and damage to the brain following neurotrauma, stroke or infection is associated with a high risk of developing epilepsy. - In brief: Therapeutic antibodies, Therapeutic antibodies, Therapeutic antibodies
- Nature Reviews Immunology 10(5):291 (2010)
Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce β-chemokines Moody , M. A.et al. J. Exp. Med. 207, 763–776 (2010) - Tumour immunology: Promoting tolerance
- Nature Reviews Immunology 10(5):292 (2010)
Tumour cells can promote their survival by shifting the host immune response from immunogenic to tolerogenic. Swartz and colleagues have shown that tumours can do this by exploiting a pathway that is normally involved in maintaining tolerance in the lymph node stroma. - In brief: Autoimmunity, Regulatory T cells, Innate immunity
- Nature Reviews Immunology 10(5):292 (2010)
T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis Axtell , R. C.et al. Nature Med. 16, 406–412 (2010) - Mucosal immunology: Inflammasome activation in the gut
- Nature Reviews Immunology 10(5):293 (2010)
Innate immune signalling pathways triggered by commensal bacteria have an important role in maintaining homeostasis in the gut. However, excessive inflammation is known to contribute to the development of colitis and colitis-associated colorectal cancer. - Therapeutic antibodies: past, present and future
- Nature Reviews Immunology 10(5):297 (2010)
Over the past 10 years, the market for monoclonal antibodies has grown exponentially. This focus issue brings together articles on the basic biology of antibodies and their therapeutic use, providing an overview of the latest prospects and continued challenges for the development of safe, efficient and affordable therapeutic antibodies. - Comment: Can primary immunodeficiencies help to provide insights into infectious risks of therapeutic antibodies?
- Nature Reviews Immunology 10(5):299 (2010)
Patients treated with monoclonal antibodies directed against immunological molecules may be viewed as being similar to patients with primary immunodeficiency (PID) of the corresponding antibody target, with regards to infectious risk. László Maródi and Jean-Laurent Casanova propose that the natural history of PIDs might indicate which infectious diseases should be monitored in patients receiving therapeutic antibodies. - Therapeutic antibodies for autoimmunity and inflammation
Chan AC Carter PJ - Nature Reviews Immunology 10(5):301 (2010)
The development of therapeutic antibodies has evolved over the past decade into a mainstay of therapeutic options for patients with autoimmune and inflammatory diseases. Substantial advances in understanding the biology of human diseases have been made and tremendous benefit to patients has been gained with the first generation of therapeutic antibodies. The lessons learnt from these antibodies have provided the foundation for the discovery and development of future therapeutic antibodies. Here we review how key insights obtained from the development of therapeutic antibodies complemented by newer antibody engineering technologies are delivering a second generation of therapeutic antibodies with promise for greater clinical efficacy and safety. - Monoclonal antibodies: versatile platforms for cancer immunotherapy
Weiner LM Surana R Wang S - Nature Reviews Immunology 10(5):317 (2010)
Antibodies are important therapeutic agents for cancer. Recently, it has become clear that antibodies possess several clinically relevant mechanisms of action. Many clinically useful antibodies can manipulate tumour-related signalling. In addition, antibodies exhibit various immunomodulatory properties and, by directly activating or inhibiting molecules of the immune system, antibodies can promote the induction of antitumour immune responses. These immunomodulatory properties can form the basis for new cancer treatment strategies. - FcγRIIB in autoimmunity and infection: evolutionary and therapeutic implications
Smith KG Clatworthy MR - Nature Reviews Immunology 10(5):328 (2010)
FcγRIIB is the only inhibitory Fc receptor. It controls many aspects of immune and inflammatory responses, and variation in the gene encoding this protein has long been associated with susceptibility to autoimmune disease, particularly systemic lupus erythematosus (SLE). FcγRIIB is also involved in the complex regulation of defence against infection. A loss-of-function polymorphism in FcγRIIB protects against severe malaria, the investigation of which is beginning to clarify the evolutionary pressures that drive ethnic variation in autoimmunity. Our increased understanding of the function of FcγRIIB also has potentially far-reaching therapeutic implications, being involved in the mechanism of action of intravenous immunoglobulin, controlling the efficacy of monoclonal antibody therapy and providing a direct therapeutic target. - Strategies and challenges for the next generation of therapeutic antibodies
Beck A Wurch T Bailly C Corvaia N - Nature Reviews Immunology 10(5):345 (2010)
Antibodies and related products are the fastest growing class of therapeutic agents. By analysing the regulatory approvals of IgG-based biotherapeutic agents in the past 10 years, we can gain insights into the successful strategies used by pharmaceutical companies so far to bring innovative drugs to the market. Many challenges will have to be faced in the next decade to bring more efficient and affordable antibody-based drugs to the clinic. Here, we discuss strategies to select the best therapeutic antigen targets, to optimize the structure of IgG antibodies and to design related or new structures with additional functions. - Dynamic imaging of host–pathogen interactions in vivo
Coombes JL Robey EA - Nature Reviews Immunology 10(5):353 (2010)
In the past decade, advances in microscopic imaging methods, together with the development of genetically encoded fluorescent reporters, have made it possible to directly visualize the behaviour of cells in living tissues. At the same time, immunologists have been turning their attention from the traditional focus on responses to model antigens to a new focus on in vivo infection models. Recently, these two trends have intersected with exciting results. Here we discuss how dynamic imaging of in vivo infection has revealed fascinating and unexpected details of host–pathogen interactions at a new level of spatial and temporal resolution. - Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells
Glass CK Saijo K - Nature Reviews Immunology 10(5):365 (2010)
Members of the nuclear receptor superfamily of ligand-dependent transcription factors regulate diverse aspects of immunity and inflammation by both positively and negatively regulating gene expression. Here, we review recent studies providing insights into the distinct mechanisms that enable nuclear receptors to antagonize pro-inflammatory programmes of gene expression in macrophages and T cells by altering the turnover or recruitment of co-repressors and co-activators in a gene-specific manner. These nuclear receptor-dependent transrepression pathways are proposed to have roles in controlling the initiation, magnitude and duration of pro-inflammatory gene expression and are amenable to pharmacological manipulation.
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