MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Immunological Reviews' source. Wed, 08 Feb 2012 06:42:52 +0100 http://www.medworm.com/index.php?rid=5514706&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01086.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514706 Sun, 18 Dec 2011 15:54:33 +0100 5514706 http://www.medworm.com/index.php?rid=5514705&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01077.x Summary:  Mammals are subject to colonization by an astronomical number of mutualistic and commensal microorganisms on their environmental exposed surfaces. These mutualistic species build up a complex community, called the indigenous microbiota, which aid their hosts in several physiological activities. In this review, we show that the transition between a non‐colonized and a colonized state is associated with modification on the pattern of host inflammatory and behavioral responsiveness. There is a shift from innate anti‐inflammatory cytokine production to efficient release of proinflammatory mediators and rapid mobilization of leukocytes upon infection or other stimuli. In addition, host responses to hypernociceptive and stressful stimuli are modulated by indigenous microbiota, pa... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514705 Sun, 18 Dec 2011 15:54:31 +0100 5514705 http://www.medworm.com/index.php?rid=5514704&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01084.x Summary:  The last several years have seen breakthroughs in techniques to track the symbiont communities that normally colonize mammals (the microbiota) and in cataloguing the universe of the genes they carry (the microbiome). Applying these methods to human patients and corresponding murine models should allow us to decipher just how the microbiota impacts type‐1 diabetes, i.e. which particular microbes are responsible and the cellular and molecular processes that are involved. Here, at its threshold, we set the stage for what promises to be an exciting rejuvenated area of investigation. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514704 Sun, 18 Dec 2011 15:54:29 +0100 5514704 http://www.medworm.com/index.php?rid=5514703&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01076.x Summary:  Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects about 0.1% of the worldwide population. This deleterious disease is marked by infiltration of myelin‐specific T cells that attack the protective myelin sheath that surrounds CNS nerve axons. Upon demyelination, saltatory nerve conduction is disrupted, and patients experience neurologic deficiencies. The exact cause for MS remains unknown, although most evidence supports the hypothesis that both genetic and environmental factors contribute to disease development. Epidemiologic evidence supports a role for environmental pathogens, such as viruses, as potentially key contributors to MS induction. Pathogens can induce autoimmunity via several well‐studied mechanisms with the most p... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514703 Sun, 18 Dec 2011 15:54:28 +0100 5514703 http://www.medworm.com/index.php?rid=5514702&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01073.x Summary:  Human skin and mucosal surfaces are in constant contact with resident and invasive microbes. Recognition of microbial products by receptors of the innate immune system triggers rapid innate defense and transduces signals necessary for initiating and maintaining the adaptive immune responses. Microbial sensing by innate pattern‐recognition receptors is not restricted to pathogens. Rather, proper development, function, and maintenance of innate and adaptive immunity rely on continuous recognition of products derived from the microorganisms indigenous to the internal and external surfaces of mammalian host. Tonic immune activation by the resident microbiota governs host susceptibility to intestinal and extra‐intestinal infections, including those caused by viruses. This review... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514702 Sun, 18 Dec 2011 15:54:26 +0100 5514702 http://www.medworm.com/index.php?rid=5514701&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01074.x Summary:  Nearly all human beings, by the time they reach adolescence, are infected with multiple herpesviruses. At any given time, this family of viruses accounts for 35–40 billion human infections worldwide, making herpesviruses among the most prevalent pathogens known to exist. Compared to most other viruses, herpesviruses are also unique in that infection lasts the life of the host. Remarkably, despite their prevalence and persistence, little is known about how these viruses interact with their hosts, especially during the clinically asymptomatic phase of infection referred to as latency. This review explores data in human and animal systems that reveal the ability of latent herpesviruses to modulate the immune response to self and environmental antigens. From the perspective of th... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514701 Sun, 18 Dec 2011 15:54:24 +0100 5514701 http://www.medworm.com/index.php?rid=5514700&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01071.x Summary:  The nuclear hormone receptor retinoid‐related orphan receptor γt (RORγt) induces a pro‐inflammatory program in lymphoid cells, culminating in the expression of interleukin‐6 (IL‐6), IL‐17, IL‐22, granulocyte‐macrophage colony‐stimulating factor, and tumor necrosis factor. During ontogeny, the first type of cells expressing RORγt are lymphoid tissue inducer cells, a type of innate lymphoid cell (ILC) generated in mammalian fetuses to induce the development of lymph nodes and Peyer’s patches. After birth, RORγt+ ILCs and RORγt+ T cells are involved in the defense of epithelial surfaces against extracellular microbes and play an important role in the intestinal homeostasis with symbiotic microbiota. The development and evolution of RORγt+ cells is intimatel... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514700 Sun, 18 Dec 2011 15:54:23 +0100 5514700 http://www.medworm.com/index.php?rid=5514699&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01080.x Summary:  Certain autoimmune diseases as well as asthma have increased in recent decades, particularly in developed countries. The hygiene hypothesis has been the prevailing model to account for this increase; however, epidemiology studies also support the contribution of diet and obesity to inflammatory diseases. Diet affects the composition of the gut microbiota, and recent studies have identified various molecules and mechanisms that connect diet, the gut microbiota, and immune responses. Herein, we discuss the effects of microbial metabolites, such as short chain fatty acids, on epithelial integrity as well as immune cell function. We propose that dysbiosis contributes to compromised epithelial integrity and disrupted immune tolerance. In addition, dietary molecules affect the functi... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514699 Sun, 18 Dec 2011 15:54:21 +0100 5514699 http://www.medworm.com/index.php?rid=5514698&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01078.x Summary:  Large numbers of environmental antigens, including commensal bacteria and food‐derived antigens, constitutively interact with the epithelial layer of the gastrointestinal (GI) tract. Commensal bacteria peacefully cohabit with the host GI tract and exert multiple beneficial or destructive effects on their host. Intestinal epithelial cells (IECs) constitute the first physical and immunological protective wall against invasive pathogens and a cohabitation niche for commensal bacteria. As the physiological homeostasis of IECs is maintained by multiple biological processes such as apoptosis, autophagy, and the handling of endoplasmic reticulum stress, the aberrant kinetics of these biological events, which have genetic and environmental causes, leads to the development of host int... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514698 Sun, 18 Dec 2011 15:54:19 +0100 5514698 http://www.medworm.com/index.php?rid=5514697&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01072.x Summary:  Immunoglobulin A (IgA) is the main secretory immunoglobulin of mucous membranes and is powerfully induced by the presence of commensal microbes in the intestine. B cells undergo class switch recombination to IgA in the mucosa‐associated lymphoid tissues, particularly mesenteric lymph nodes (MLNs) and Peyer’s patches, through both T‐dependent and T‐independent pathways. IgA B cells primed in the mucosa traffic from the intestinal lymphoid structures, initially through the lymphatics and then join the bloodstream, to home back to the intestinal mucosa as IgA‐secreting plasma cells. Once induced, anti‐bacterial IgA can be extremely long‐lived but is replaced if there is induction of additional IgA specificities by other microbes. The mucosal immune system is anatomic... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514697 Sun, 18 Dec 2011 15:54:18 +0100 5514697 http://www.medworm.com/index.php?rid=5514696&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01081.x Summary:  The gastrointestinal system is a common entry point for pathogenic microbes to access the inner environment of the body. Anti‐microbial factors produced by the intestinal mucosa limit the translocation of both commensal and pathogenic microbes across the intestinal epithelial cell barrier. The regulation of these host defense mechanisms largely depends on the activation of innate immune receptors by microbial molecules. Under steady‐state conditions, the microbiota provides constitutive signals to the innate immune system, which helps to maintain a healthy inflammatory tone within the intestinal mucosa and, thus, enhances resistance to infection with enteric pathogens. During an acute infection, the intestinal epithelial cell barrier is breached, and the detection of microb... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514696 Sun, 18 Dec 2011 15:54:16 +0100 5514696 http://www.medworm.com/index.php?rid=5514695&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01082.x Summary:  Defensins are small, multifunctional cationic peptides. They typically contain six conserved cysteines whose three intramolecular disulfides stabilize a largely β‐sheet structure. This review of human α‐defensins begins by describing their evolution, including their likely relationship to the Big Defensins of invertebrates, and their kinship to the β‐defensin peptides of many if not all vertebrates, and the θ‐defensins found in certain non‐human primates. We provide a short history of the search for leukocyte‐derived microbicidal molecules, emphasizing the roles played by luck (good), preconceived notions (mostly bad), and proper timing (essential). The antimicrobial, antiviral, antitoxic, and binding properties of human α‐defensins are summarized. The struct... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514695 Sun, 18 Dec 2011 15:54:15 +0100 5514695 http://www.medworm.com/index.php?rid=5514694&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01070.x Summary:  The mammalian intestine is colonized by a dense microbial community, the microbiota. Homeostatic and symbiotic interactions facilitate the peaceful co‐existence between the microbiota and the host, and inhibit colonization by most incoming pathogens (‘colonization resistance’). However, if pathogenic intruders overcome colonization resistance, a fierce, innate inflammatory defense can be mounted within hours, the adaptive arm of the immune system is initiated, and the pathogen is fought back. The molecular nature of the homeostatic interactions, the pathogen’s ability to overcome colonization resistance, and the triggering of native and adaptive mucosal immune responses are still poorly understood. To study these mechanisms, the streptomycin mouse model for Salmonella d... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514694 Sun, 18 Dec 2011 15:54:13 +0100 5514694 http://www.medworm.com/index.php?rid=5514693&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01083.x Summary:  Billions of years of coevolution shaped the mutually beneficial relationships between metazoans and symbiotic commensal microorganisms. Commensal microorganisms profoundly affect the physiology of the host and provide the host with survival advantages in several ways, while they could also trigger pathogenic immune responses and threaten the well‐being of the host. Recent advances in DNA sequencing technology enabled the analysis of commensal microbiota, and improvements in the techniques of culturing gut‐resident microorganisms and of rearing gnotobiotic rodents have made it possible to assess the effect of individual component of microbial communities on host physiology. In this review, we discuss the current understanding of the interactions of commensal microbiota with ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514693 Sun, 18 Dec 2011 15:54:11 +0100 5514693 http://www.medworm.com/index.php?rid=5514692&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01079.x Summary:  The healthy gut tolerates very large numbers of diverse bacterial species belonging mainly to the Bacteroidetes and Firmicutes phyla. These bacteria normally coexist peacefully with the gut and help maintain immune homeostasis and tolerance. The mechanisms promoting tolerance affect various cell populations, including the epithelial cells lining the gut, resident dendritic cells (DCs), and gut‐homing T cells. Gut bacteria also influence multiple signaling pathways from Toll‐like receptors to nuclear factor κB and regulate the functionality of DCs and T cells. Several bacterial species have been identified that promote T‐cell differentiation, in particular T‐helper 17 and T‐regulatory cells. Insight into the molecular mechanisms by which bacteria mediate these effects... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514692 Sun, 18 Dec 2011 15:54:10 +0100 5514692 http://www.medworm.com/index.php?rid=5514691&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01075.x Summary:  Over the past several years, there have been remarkable advances in our understanding of how commensal organisms shape host immunity. Although the full cast of immunogenic bacteria and their immunomodulatory molecules remains to be elucidated, lessons learned from the interactions between bacterial zwitterionic polysaccharides (ZPSs) and the host immune system represent an integral step toward better understanding how the intestinal microbiota effect immunologic changes. Somewhat paradoxically, ZPSs, which are found in numerous commensal organisms, are able to elicit both proinflammatory and immunoregulatory responses; both these outcomes involve fine‐tuning the balance between T‐helper 17 cells and interleukin‐10‐producing regulatory T cells. In this review, we discuss... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514691 Sun, 18 Dec 2011 15:54:08 +0100 5514691 http://www.medworm.com/index.php?rid=5514690&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01085.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514690 Sun, 18 Dec 2011 15:54:06 +0100 5514690 http://www.medworm.com/index.php?rid=5514689&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01087.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5514689 Sun, 18 Dec 2011 15:54:04 +0100 5514689 http://www.medworm.com/index.php?rid=5346337&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01069.x Summary:  OX40 (CD134) is a tumor necrosis factor (TNF) receptor expressed primarily on activated CD4+ and CD8+ T cells and transmits a potent costimulatory signal when engaged. OX40 is transiently expressed after T‐cell receptor engagement and is upregulated on the most recently antigen‐activated T cells within inflammatory lesions (e.g. sites of autoimmune destruction and on tumor‐infiltrating lymphocytes). Hence, it is an attractive target to modulate immune responses: OX40 blocking agents to inhibit undesirable inflammation or OX40 agonists to enhance immune responses. In regards to this review, OX40 agonists enhance anti‐tumor immunity, which leads to therapeutic effects in mouse tumor models. A team of laboratory and clinical scientists at the Providence Cancer Center has c... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346337 Tue, 25 Oct 2011 16:10:26 +0100 5346337 http://www.medworm.com/index.php?rid=5346336&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01063.x Summary:  GITR [glucocorticoid inducible tumor necrosis factor receptor (TNFR)‐related protein] and 4‐1BB are costimulatory TNFR family members that are expressed on regulatory and effector T cells as well as on other cells of the immune system. Here we discuss the role of GITR and 4‐1BB on T cells during viral infections and in cancer immunotherapy. Systemic treatment with agonistic anti‐4‐1BB antibody leads to a number of immune system abnormalities, and clinical trials of anti‐4‐1BB have been terminated. However, other modes of 4‐1BB ligation may be less toxic. To date, similar toxicities have not been reported for anti‐GITR treatment of mice, although anti‐GITR antibodies can exacerbate mouse autoimmune models. Intrinsic effects of GITR and 4‐1BB on effector T c... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346336 Tue, 25 Oct 2011 16:10:24 +0100 5346336 http://www.medworm.com/index.php?rid=5346335&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01068.x Summary:  DR3 (TNFRSF25) is a member of the tumor necrosis factor receptor (TNFR) superfamily expressed primarily on lymphocytes and is a receptor for the TNF family cytokine TL1A (TNFSF15). DR3 costimulates T‐cell activation, but it is unique among these receptors in that it signals through an intracytoplasmic death domain and the adapter protein TRADD (TNFR‐associated death domain). TL1A costimulates T cells to produce a wide variety of cytokines and can promote expansion of activated and regulatory T cells in vivo. Studies in mice deficient in DR3 or TL1A or in animals treated with antibodies that block the activity of TL1A have revealed a specific role for DR3 in enhancing effector T‐cell proliferation at the site of tissue inflammation in autoimmune disease models. DR3 appears... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346335 Tue, 25 Oct 2011 16:10:23 +0100 5346335 http://www.medworm.com/index.php?rid=5346334&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01064.x Summary:  The tumor necrosis factor (TNF) receptor superfamily member herpesvirus entry mediator (HVEM) (TNFRSF14) regulates T‐cell immune responses by activating both inflammatory and inhibitory signaling pathways. HVEM acts as both a receptor for the canonical TNF‐related ligands, LIGHT [lymphotoxin‐like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed on T lymphocytes] and lymphotoxin‐α, and as a ligand for the immunoglobulin superfamily proteins BTLA (B and T lymphocyte attenuator) and CD160, a feature distinguishing HVEM from other immune regulatory molecules. The ability of HVEM to interact with multiple ligands in distinct configurations creates a functionally diverse set of intrinsic and bidirectional si... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346334 Tue, 25 Oct 2011 16:10:21 +0100 5346334 http://www.medworm.com/index.php?rid=5346333&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01062.x Summary:  The human respiratory tract is an entry point for over 200 known viruses that collectively contribute to millions of annual deaths worldwide. Consequently, the World Health Organization has designated respiratory viral infections as a priority for vaccine development. Despite enormous advances in understanding the attributes of a protective mucosal antiviral immune response, current vaccines continue to fail in effectively generating long‐lived protective CD8+ T‐cell immunity. To date, the majority of licensed human vaccines afford protection against infectious pathogens through the generation of specific immunoglobulin responses. In recent years, the selective manipulation of specific costimulatory pathways, which are critical in regulating T cell‐mediated immune respons... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346333 Tue, 25 Oct 2011 16:10:20 +0100 5346333 http://www.medworm.com/index.php?rid=5346332&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01057.x Summary:  CD4+ effector and memory T cells play a pivotal role in the development of both normal and pathogenic immune responses. This review focuses on the molecular and cellular mechanisms that regulate their development, with particular focus on the tumor necrosis factor superfamily members OX40 (TNFRSF4) and CD30 (TNFRSF8). We discuss the evidence that in mice, these molecular signaling pathways act synergistically to regulate the development of both effector and memory CD4+ T cells but that the cells that regulate memory versus effector function are distinct, effectively allowing the independent regulation of the memory and effector CD4+ T‐cell pools. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346332 Tue, 25 Oct 2011 16:10:18 +0100 5346332 http://www.medworm.com/index.php?rid=5346331&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01067.x Summary:  Members of the tumor necrosis factor receptor superfamily (TNFRSF) participate prominently in B‐cell maturation and function. In particular, B‐cell activating factor belonging to the TNF family receptor (BAFF‐R), B‐cell maturation antigen (BCMA), and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) play critical roles in promoting B‐cell survival at distinct stages of development by engaging a proliferation‐inducing ligand (APRIL) and/or BAFF. CD40 is also essential for directing the humoral response to T‐cell‐dependent antigens. Signaling by the TNFRSF is mediated primarily, albeit not exclusively, via the TNFR‐associated factor (TRAF) proteins and activation of the canonical and/or non‐canonical nuclear factor‐κB (N... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346331 Tue, 25 Oct 2011 16:10:17 +0100 5346331 http://www.medworm.com/index.php?rid=5346330&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01054.x Summary:  Our immune system performs the vital function of recognizing and eliminating invading pathogens and malignancies. There is an increasing appreciation that the immune system also actively mediates tissue responses under both physiological and pathological conditions, significantly impacting the inflammatory, fibrogenic, and regenerative components. Likewise, there is a growing understanding of how epithelial, endothelial, and other non‐hematopoietic tissue cell types actively contribute to the interplay that shapes tissue responses. While much of the molecular basis underlying the immune regulation of tissue responses remains to be delineated, the tumor necrosis factor (TNF) superfamily ligand/receptor pair of TNF‐like weak inducer of apoptosis (TWEAK) and fibroblast growth ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346330 Tue, 25 Oct 2011 16:10:15 +0100 5346330 http://www.medworm.com/index.php?rid=5346329&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01056.x Summary:  Generating an immune response tailored to destroy an infecting organism while limiting bystander damage involves guiding T‐cell activation using a variety of cues taken from the immunogen (antigen type, dose, and persistence, accompanying danger signals) as well as the host (tissue environment, T‐cell frequency, and affinity for antigen). Dendritic cells (DCs) serve as translators of much of this information and are critically required for effective pathogen and tumor clearance. Moreover, dysregulation of DC activation can lead to autoimmunity. Inhibition of the lymphotoxin (LT) and CD40 pathways has been shown to be effective at quieting inflammation in settings where DC–T‐cell interactions are key instigators of disease progression. In this review, we compare and cont... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346329 Tue, 25 Oct 2011 16:10:14 +0100 5346329 http://www.medworm.com/index.php?rid=5346328&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01061.x Summary:  Lymph nodes (LNs) maintain active homeostasis at steady state. However, in response to changes in the local environment, such as local infection, cancer, vaccination, and autoimmune disease, dramatic remodeling of LN occurs. This remodeling includes changes in size, lymph and blood flow, immune cell trafficking and cellularity, lymphatic and blood vessel growth and activation, as well as microarchitecture. Therefore, inflammatory conditions often lead to enlarged nodes; after local inflammation resolves, LNs actively regress in size and return to steady state. Remodeling of lymphatic vessels (LVs) and blood vessels (BVs) during both the expansion and regression phases are key steps in controlling LN size as well as function. The cells, membrane‐associated molecules, and solub... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346328 Tue, 25 Oct 2011 16:10:12 +0100 5346328 http://www.medworm.com/index.php?rid=5346327&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01055.x Summary:  A large and diverse group of receptors utilizes the family of cytoplasmic signaling proteins known as tumor necrosis factor receptor (TNFR)‐associated factors (TRAFs). In recent years, there has been a resurgence of interest and exploration of the roles played by TRAF3 and TRAF5 in cellular regulation, particularly in cells of the immune system, the cell types of focus in this review. This work has revealed that TRAF3 and TRAF5 can play diverse roles for different receptors even in the same cell type, as well as distinct roles in different cell types. Evidence indicates that TRAF3 and TRAF5 play important roles beyond the TNFR‐superfamily (SF) and viral mimics of its members, mediating certain innate immune receptor and cytokine receptor signals, and most recently, signals ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346327 Tue, 25 Oct 2011 16:10:10 +0100 5346327 http://www.medworm.com/index.php?rid=5346326&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01059.x Summary:  Nuclear‐factor κB (NF‐κB) transcription factors are activated by a wide variety of stimuli in diverse cell types and control key aspects of immune function and development. Receptor‐mediated activation of NF‐κB appears to occur through two distinct signaling pathways termed as the canonical and non‐canonical NF‐κB pathways. Although much work has demonstrated the physiological importance of non‐canonical NF‐κB signaling to immunity and its involvement in diverse pathologies, such as cancers and autoimmune disease, the architecture and regulation of the pathway is only beginning to be understood. The non‐canonical pathway appears to be activated by a select set of receptors within the tumor necrosis factor superfamily, and we discuss the molecular mechanis... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346326 Tue, 25 Oct 2011 16:10:09 +0100 5346326 http://www.medworm.com/index.php?rid=5346325&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01060.x Summary:  Tumor necrosis factor receptor (TNFR) superfamily members mediate the cellular response to a wide variety of biological inputs. The responses range from cell death, survival, differentiation, proliferation, to the regulation of immunity. All these physiological responses are regulated by a limited number of highly pleiotropic kinases. The fact that the same signaling molecules are involved in transducing signals from TNFR superfamily members that regulate different and even opposing processes raises the question of how their specificity is determined. Regulatory strategies that can contribute to signaling specificity include scaffolding to control kinase specificity, combinatorial use of several signal transducers, and temporal control of signaling. In this review, we discuss t... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346325 Tue, 25 Oct 2011 16:10:07 +0100 5346325 http://www.medworm.com/index.php?rid=5346324&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01066.x Summary:  Tumor necrosis factor (TNF) is crucial for innate immunity, but deregulated TNF signaling also plays an eminent role in the pathogenesis of many chronic inflammatory diseases and cancer‐related inflammation. The signals that mediate both the beneficial and the harmful effects of TNF are initiated when TNF binds to its receptors on the surface of target cells. TNF receptor 1 (TNFR1) is ubiquitously expressed, whereas TNFR2 is mainly expressed on lymphocytes and endothelial cells. This review focuses on the molecular and physiological consequences of the interaction of TNF with TNFR1. The different outcomes of TNF signaling originate at the apical signaling complex that forms when TNF binds to TNFR1, the TNFR1 signaling complex (TNF‐RSC). By integrating recently gained insigh... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346324 Tue, 25 Oct 2011 16:10:06 +0100 5346324 http://www.medworm.com/index.php?rid=5346323&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01065.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5346323 Tue, 25 Oct 2011 16:10:04 +0100 5346323 http://www.medworm.com/index.php?rid=5179212&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01045.x Summary:  One of the fundamental aspects of the innate immune system is its capacity to discriminate between self and non‐self or altered self, and to quickly respond by eliciting effector mechanisms that act in concert to restore normalcy. This capacity is determined by a set of evolutionarily conserved pattern recognition receptors (PRRs) that sense the presence of microbial motifs or endogenous danger signals, including tissue damage, cellular transformation or metabolic perturbation, and orchestrate the nature, duration and intensity of the innate immune response. Nod‐like receptors (NLRs), a group of intracellular PRRs, are particularly essential as evident by the high incidence of genetic variations in their genes in various diseases of homeostasis. Here, I overview the signali... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179212 Wed, 31 Aug 2011 03:16:22 +0100 5179212 http://www.medworm.com/index.php?rid=5179211&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01038.x Summary:  Evidence is accumulating that the mitochondria form an integral platform from which innate signaling takes place. Recent studies revealed that the mitochondria are shaping the innate response to intracellular pathogens, and mitochondrial function is modulating and being modulated by innate immune signaling. Further, cell biologic analyses have uncovered the dynamic relocalization of key components involved in cytosolic viral recognition and signaling to the mitochondria, as well as the mobilization of mitochondria to the sites of viral replication. In this review, we provide an integrated view of how cellular stress and signals following cytosolic viral recognition are intimately linked and coordinated at the mitochondria. We incorporate recent findings into our current underst... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179211 Wed, 31 Aug 2011 03:16:20 +0100 5179211 http://www.medworm.com/index.php?rid=5179210&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01044.x Summary:  Programmed cell death is a necessary part of development and tissue homeostasis enabling the removal of unwanted cells. In the setting of infectious disease, cells that have been commandeered by microbial pathogens become detrimental to the host. When macrophages and dendritic cells are compromised in this way, they can be lysed by pyroptosis, a cell death mechanism that is distinct from apoptosis and oncosis/necrosis. Pyroptosis is triggered by Caspase‐1 after its activation by various inflammasomes and results in lysis of the affected cell. Both pyroptosis and apoptosis are programmed cell death mechanisms but are dependent on different caspases, unlike oncosis. Similar to oncosis and unlike apoptosis, pyroptosis results in cellular lysis and release of the cytosolic conten... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179210 Wed, 31 Aug 2011 03:16:19 +0100 5179210 http://www.medworm.com/index.php?rid=5179209&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01040.x Summary:  The immune system plays an essential role in protecting the host against infections and to accomplish this task has evolved mechanisms to recognize microbes and destroy them. In addition, it monitors the health of cells and responds to ones that have been injured and killed, even if this occurs under sterile conditions. This process is initiated when dying cells expose intracellular molecules that can be recognized by cells of the innate immune system. As a consequence of this recognition, dendritic cells are activated in ways that help to promote T‐cell responses to antigens associated with the dying cells. In addition, macrophages are stimulated to produce the cytokine interleukin‐1 that then acts on radioresistant parenchymal cells in the host in ways that drive a robust... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179209 Wed, 31 Aug 2011 03:16:18 +0100 5179209 http://www.medworm.com/index.php?rid=5179208&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01041.x Summary:  The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ‐line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so‐called pathogen‐associated molecular patterns (PAMPs). A subset of PRRs, belonging to the NOD‐like receptor (NLR) and the PYHIN protein families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi‐protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the mammalian cysteine protease caspase‐1, a central mediator of innate immunity. Active caspase‐1 promotes the maturation and release of interleukin‐1β (IL‐1β) and IL�... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179208 Wed, 31 Aug 2011 03:16:17 +0100 5179208 http://www.medworm.com/index.php?rid=5179207&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01042.x Summary:  Inflammasomes are multi‐protein complexes that sense microbial molecules and endogenous danger signals in intracellular compartments. Inflammasome assembly results in caspase‐1 activation, which in turn drives maturation and secretion of the pro‐inflammatory cytokines interleukin 1β (IL‐1β) and IL‐18, and induces pyroptosis to eliminate the infectious agent. The importance of inflammasomes in regulating immune responses was recognized with the discovery of polymorphisms in genes encoding inflammasome components and their linkage to aberrant production of IL‐1β and IL‐18 in autoimmune and hereditary periodic fevers syndromes. We review the current knowledge on the role of inflammasomes in regulating innate and adaptive immune responses with an emphasis on the ro... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179207 Wed, 31 Aug 2011 03:16:16 +0100 5179207 http://www.medworm.com/index.php?rid=5179206&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01043.x Summary:  The NLRP3 inflammasome is activated in response to a variety of signals that are indicative of damage to the host including tissue damage, metabolic stress, and infection. Upon activation, the NLRP3 inflammasome serves as a platform for activation of the cysteine protease caspase‐1, which leads to the processing and secretion of the proinflammatory cytokines interleukin‐1β (IL‐1β) and IL‐18. Dysregulated NLRP3 inflammasome activation is associated with both heritable and acquired inflammatory diseases. Here, we review new insights into the mechanism of NLRP3 inflammasome activation and its role in disease pathogenesis. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179206 Wed, 31 Aug 2011 03:16:15 +0100 5179206 http://www.medworm.com/index.php?rid=5179205&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01046.x Summary:  An inflammasome is a multiprotein complex that serves as a platform for caspase‐1 activation and caspase‐1‐dependent proteolytic maturation and secretion of interleukin‐1β (IL‐1β). Though a number of inflammasomes have been described, the NLRP3 inflammasome is the most extensively studied but also the most elusive. It is unique in that it responds to numerous physically and chemically diverse stimuli. The potent proinflammatory and pyrogenic activities of IL‐1β necessitate that inflammasome activity is tightly controlled. To this end, a priming step is first required to induce the expression of both NLRP3 and proIL‐1β. This event renders the cell competent for NLRP3 inflammasome activation and IL‐1β secretion, and it is highly regulated by negative feedback... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179205 Wed, 31 Aug 2011 03:16:14 +0100 5179205 http://www.medworm.com/index.php?rid=5179204&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01050.x Summary:  The cells of the innate immune system mobilize a coordinated immune response towards invading microbes and after disturbances in tissue homeostasis. These immune responses typically lead to infection control and tissue repair. Exaggerated or uncontrolled immune responses, however, can also induce acute of chronic inflammatory pathologies that are characteristic for many common diseases such as sepsis, arthritis, atherosclerosis, or Alzheimer’s disease. In recent years, the concerted efforts of many scientists have uncovered numerous mechanisms by which immune cells detect foreign or changed self‐substances that appear in infections or during tissue damage. These substances stimulate signaling receptors, which leads to cellular activation and the induction of effector mechan... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179204 Wed, 31 Aug 2011 03:16:13 +0100 5179204 http://www.medworm.com/index.php?rid=5179203&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01053.x Summary:  The innate immune response is the first line of defense against infection and relies on the ability of immune cells to detect the presence of infection through germline‐encoded pattern recognition receptors. These include the Toll‐like receptors, the retinoic acid inducible gene‐like receptors, the nucleotide oligomerization domain‐like receptors, and a number of DNA‐sensing molecules. Members of the PYHIN protein family have recently emerged as sensors of microbial DNA. PYHIN proteins bind microbial DNA and form caspase‐1‐activating inflammasomes (AIM2) or drive type I IFN gene transcription (IFI16). Here, we review these discoveries and highlight the emerging role of the PYHIN protein family in mammalian host defenses. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179203 Wed, 31 Aug 2011 03:16:12 +0100 5179203 http://www.medworm.com/index.php?rid=5179202&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01051.x Summary:  The innate immune system is responsible for detecting microbial invasion of the cell and for stimulating host defense countermeasures. These anti‐pathogen procedures include the transcriptional activation of powerful antiviral genes such as the type I interferons (IFNs) or the triggering of inflammatory responses through interleukin‐1 (IL‐1) production. Over the past decade, key cellular sensors responsible for triggering innate immune signaling pathways and host defense have started to be resolved and include the Toll‐like receptor (TLR), RIG‐I‐like helicase, and the cytoplasmic nucleotide‐binding oligermerization domain‐like receptor families. These sensors recognize non‐self pathogen‐associated molecular patterns such as microbial lipopolysaccharides and ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179202 Wed, 31 Aug 2011 03:16:11 +0100 5179202 http://www.medworm.com/index.php?rid=5179201&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01052.x Summary:  Viral infection results in the generation of non‐self RNA species in the cells, which is recognized by retinoic acid inducible gene‐I‐like receptors (RLRs), and initiates innate antiviral responses, including the production of proinflammatory cytokines and type I interferon. In this review, we summarize reports on virus‐specificity of RLRs, structures of non‐self RNA patterns, structural biology of RLRs, and the signaling adapter molecules involved in antiviral innate immunity. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179201 Wed, 31 Aug 2011 03:16:10 +0100 5179201 http://www.medworm.com/index.php?rid=5179200&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01049.x Summary:  The innate immune system detects viruses through molecular sensors that trigger the production of type I interferons (IFN‐I) and inflammatory cytokines. As viruses vary tremendously in size, structure, genomic composition, and tissue tropism, multiple sensors are required to detect their presence in various cell types and tissues. In this review, we summarize current knowledge of the diversity, specificity, and signaling pathways downstream of viral sensors and ask whether two distinct sensors that recognize the same viral component are complementary, compensatory, or simply redundant. We also discuss why viral sensors are differentially distributed in distinct cell types and whether a particular cell type dominates the IFN‐I response during viral infection. Finally, we rev... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179200 Wed, 31 Aug 2011 03:16:09 +0100 5179200 http://www.medworm.com/index.php?rid=5179199&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01048.x Summary:  Host cells trigger signals for innate immune responses upon recognition of conserved structures in microbial pathogens. Nucleic acids, which are critical components for inheriting genetic information in all species including pathogens, are key structures sensed by the innate immune system. The corresponding receptors for foreign nucleic acids include members of Toll‐like receptors, RIG‐I‐like receptors, and intracellular DNA sensors. While nucleic acid recognition by these receptors is required for host defense against the pathogen, there is a potential risk to the host of self‐nucleic acids recognition, thus precipitating autoimmune and autoinflammatory diseases. In this review, we discuss the roles of nucleic acid‐sensing receptors in guarding against pathogen invas... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179199 Wed, 31 Aug 2011 03:16:08 +0100 5179199 http://www.medworm.com/index.php?rid=5179198&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01047.x Summary:  Peptidoglycan is a conserved structural component of the bacterial cell wall with molecular motifs unique to bacteria. The mammalian immune system takes advantage of these properties and has evolved to recognize this microbial associated molecular pattern. Mammals have four secreted peptidoglycan recognition proteins, PGLYRP‐1‐4, as well as two intracellular sensors of peptidoglycan, Nod1 and Nod2. Recognition of peptidoglycan is important in initiating and shaping the immune response under both homeostatic and infection conditions. During infection, peptidoglycan recognition drives both cell‐autonomous and whole‐organism defense responses. Here, we examine recent advances in the understanding of how peptidoglycan recognition shapes mammalian immune responses in these d... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179198 Wed, 31 Aug 2011 03:16:07 +0100 5179198 http://www.medworm.com/index.php?rid=5179197&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01037.x Summary:  Two‐signal models have a rich history in immunology. In the classic two‐signal model of T‐cell activation, signal one consists of engagement of the T‐cell receptor by antigen/major histocompatibility complex, whereas signal two arises from costimulatory ligands on antigen‐presenting cells. A requirement for two independent signals helps to ensure that T‐cell responses are initiated only in response to bona fide infectious threats. Our studies have led us to conclude that initiation of innate immune responses to pathogens also often requires two signals: signal one is initiated by a microbe‐derived ligand, such as lipopolysaccharide (LPS) or flagellin, whereas signal two conveys additional contextual information that often accompanies infectious microbes. Although ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179197 Wed, 31 Aug 2011 03:16:06 +0100 5179197 http://www.medworm.com/index.php?rid=5179196&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01039.x Summary:  Initial recognition of bacteria by the innate immune system is thought to occur primarily by germline‐encoded pattern recognition receptors (PRRs). These receptors are present in multiple compartments of host cells and are thus capable of surveying both the intracellular and extracellular milieu for bacteria. It has generally been presumed that the cellular location of these receptors dictates what type of bacteria they respond to: extracellular bacteria being recognized by cell surface receptors, such as certain Toll‐like receptors, and bacteria that are capable of breaching the plasma membrane and entering the cytoplasm, being sensed by cytoplasmic receptors, including the Nod‐like receptors (NLRs). Increasingly, it is becoming apparent that this is a false dichotomy an... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179196 Wed, 31 Aug 2011 03:16:05 +0100 5179196 http://www.medworm.com/index.php?rid=5179195&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01058.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=5179195 Wed, 31 Aug 2011 03:16:04 +0100 5179195 http://www.medworm.com/index.php?rid=4965589&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01034.x Summary:Immune modulation for treatment of allergic diseases aims to decrease the pathologic immune response rather than to cause a return to an immunologically naive or unresponsive state. Our expanding knowledge of innate and adaptive immune responses at the molecular level has led to development of immunomodulators for several allergic diseases, particularly asthma, allergic rhinitis, and eosinophilic esophagitis. Although successful immune modulation in mouse models of allergic disease have often failed to translate into significant results in human clinical trials, much has been learned about the pleotropic nature of cytokines and their effector mechanisms and of the varied phenotypes of allergic disease. We examine strategies of immune modulation in allergic diseases that have underg... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965589 Sat, 25 Jun 2011 17:30:16 +0100 4965589 http://www.medworm.com/index.php?rid=4965588&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01028.x Summary:In the century since Paul Portier and Charles Richet described their landmark findings of severe fatal reactions in dogs re‐exposed to venom after vaccination with sea anemone venom, treatment for anaphylaxis continues to evolve. The incidence of anaphylaxis continues to be difficult to measure. Underreporting due to patients not seeking medical care as well as failure to identify anaphylaxis affects our understanding of the magnitude of the disease. Treatment with intramuscular epinephrine continues to be the recommended first‐line therapy, although studies indicate that education of both the patients and the medical community is needed. Adverse food reactions continue to be the leading cause of anaphylaxis presenting for emergency care. Current therapy for food‐induced anap... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965588 Sat, 25 Jun 2011 17:30:15 +0100 4965588 http://www.medworm.com/index.php?rid=4965587&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01027.x Summary:Atopic dermatitis (AD) is an important chronic or relapsing inflammatory skin disease that often precedes asthma and allergic disorders. New insights into the genetics and pathophysiology of AD point to an important role of structural abnormalities in the epidermis as well as immune dysregulation not only for this skin disease but also for the development of asthma and allergies. Patients with AD have a unique predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus. Measures directed at healing and protecting the skin barrier and addressing the immune dysregulation are essential in the treatment of patients with AD, and early intervention may improve outcomes for both the skin disease as well as other target or... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965587 Sat, 25 Jun 2011 17:30:14 +0100 4965587 http://www.medworm.com/index.php?rid=4965586&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01032.x Summary:A large body of experimental evidence supports the hypothesis that T‐helper 2 (Th2) cytokines orchestrate allergic airway inflammation in animal models. However, human asthma is heterogeneous with respect to clinical features, cellular sources of inflammation, and response to common therapies. This disease heterogeneity has been investigated using sputum cytology as well as unbiased clustering approaches using cellular and clinical data. Important differences in cytokine‐driven inflammation may underlie this heterogeneity, and studies in human subjects with asthma have begun to elucidate these molecular differences. This molecular heterogeneity may be assessed by existing biomarkers (induced sputum evaluation or exhaled nitric oxide testing) or may require novel biomarkers. Eff... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965586 Sat, 25 Jun 2011 17:30:14 +0100 4965586 http://www.medworm.com/index.php?rid=4965585&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01030.x Summary:  The adoption of the concept that asthma is primarily a disease most frequently associated with elaboration of T‐helper 2 (Th2)‐type inflammation has led to the widely held concept that its origins, exacerbation, and persistence are allergen driven. Taking aside the asthma that is expressed in non‐allergic individuals leaves the great proportion of asthma that is associated with allergy (or atopy) and that often has its onset in early childhood. Evidence is presented that asthma is primarily an epithelial disorder and that its origin as well as its clinical manifestations have more to do with altered epithelial physical and functional barrier properties than being purely linked to allergic pathways. In genetically susceptible individuals, impaired epithelial barrier functi... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965585 Sat, 25 Jun 2011 17:30:13 +0100 4965585 http://www.medworm.com/index.php?rid=4965584&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01033.x This article reviews our current knowledge regarding the roles of the epithelial cell in airway inflammation and host defense. The interactions of inhaled environmental factors and pathogens with epithelial cells are also discussed, with an emphasis on epithelial innate immune responses and contributions of epithelial cells to immune regulation. Recent evidence suggesting that epithelial cells play an active role in inducing several of the structural changes, collectively referred to airway remodeling, seen in the airways of asthmatic subjects is reviewed. Finally, the concept that the epithelium is a major target for the actions of a number of classes of inhaled medications is discussed, as are the potential mechanisms by which selected drugs may alter epithelial function. (Source: Immuno... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965584 Sat, 25 Jun 2011 17:30:13 +0100 4965584 http://www.medworm.com/index.php?rid=4965583&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01022.x Summary:  Airway smooth muscle (ASM) manifests a hyperresponsive phenotype in airway disorders such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Current evidence also suggests that ASM modulates immune responses by secreting mediators and expressing cell surface molecules. Such processes amplify or dampen inflammation by inflammatory cells in the airways or by altering cellular responses to viruses, bacteria, or pathogens known to exacerbate airways diseases. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965583 Sat, 25 Jun 2011 17:30:12 +0100 4965583 http://www.medworm.com/index.php?rid=4965582&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01026.x Summary:  Eosinophils are leukocytes resident in mucosal tissues. During T‐helper 2 (Th2)‐type inflammation, eosinophils are recruited from bone marrow and blood to the sites of immune response. While eosinophils have been considered end‐stage cells involved in host protection against parasite infection and immunopathology in hypersensitivity disease, recent studies changed this perspective. Eosinophils are now considered multifunctional leukocytes involved in tissue homeostasis, modulation of adaptive immune responses, and innate immunity to certain microbes. Eosinophils are capable of producing immunoregulatory cytokines and are actively involved in regulation of Th2‐type immune responses. However, such new information does not preclude earlier observations showing that eosinop... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965582 Sat, 25 Jun 2011 17:30:11 +0100 4965582 http://www.medworm.com/index.php?rid=4965581&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01023.x Summary:  After approximately 130 years since their discovery as rare granulocytes that circulate in blood, basophils are just now gaining respect as significant contributors in the pathogenesis underlying allergic inflammation and disease. While long known for secreting preformed and newly synthesized mediators and for selectively infiltrating tissue during immunoglobulin E (IgE)‐mediated inflammation, their role has largely been viewed as redundant to that of tissue mast cells in functioning as effector cells. This line of thought has persisted even though it has been known in humans for approximately 20 years that basophils additionally produce relatively large quantities of cytokines, e.g. interleukin‐4 (IL‐4)/IL‐13, that are central for the manifestations of allergic dis... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965581 Sat, 25 Jun 2011 17:30:11 +0100 4965581 http://www.medworm.com/index.php?rid=4965580&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01024.x Summary:  Immunoglobulin E (IgE) antibodies have long been recognized as the antigen‐specific triggers of allergic reactions. This review briefly introduces the established functions of IgE in immediate hypersensitivity and then focuses on emerging evidence from our own investigations as well as those of others that IgE plays important roles in protective immunity against parasites and exerts regulatory influences in the expression of its own receptors, FcεRI and CD23, as well as controlling mast cell homeostasis. We provide an overview of the multifaceted ways in which IgE antibodies contribute to the pathology of food allergy and speculate regarding potential mechanisms of action of IgE blockade. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965580 Sat, 25 Jun 2011 17:30:10 +0100 4965580 http://www.medworm.com/index.php?rid=4965579&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01025.x Summary:  The innate immune system consists of multiple cell types that express germline‐encoded pattern recognition receptors that recognize pathogen‐associated molecular patterns (PAMPs) or danger‐associated molecular patterns (DAMPs). Allergens are frequently found in forms and mixtures that contain PAMPs and DAMPs. The innate immune system is interposed between the external environment and the internal acquired immune system. It is also an integral part of the airways, gut, and skin. These tissues face continuous exposure to allergens, PAMPs, and DAMPs. Interaction of allergens with the innate immune system normally results in immune tolerance but, in the case of allergic disease, this interaction induces recurring and/or chronic inflammation as well as the loss of immunologic ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965579 Sat, 25 Jun 2011 17:30:09 +0100 4965579 http://www.medworm.com/index.php?rid=4965578&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01035.x Summary:  Ozone (O3) and endotoxin are common environmental contaminants that cause asthma exacerbation. These pollutants have similar phenotype response characteristics, including induction of neutrophilic inflammation, changes in airway macrophage immunophenotypes, and ability to enhance response to inhaled allergen. Evoked phenotyping studies of volunteers exposed to O3 and endotoxin were used to identify the response characteristics of volunteers to these pollutants. New studies support the hypotheses that similar innate immune and oxidant processes modulate response to these agents. These include TLR4 and inflammasome‐mediated signaling and cytokine production. Innate immune responses are also impacted by oxidative stress. It is likely that continued discovery of common molecular ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965578 Sat, 25 Jun 2011 17:30:09 +0100 4965578 http://www.medworm.com/index.php?rid=4965577&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01031.x Summary:  Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen‐specific immunoglobulin E (allergic sensitization) and those who wheeze with human rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infant... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965577 Sat, 25 Jun 2011 17:30:08 +0100 4965577 http://www.medworm.com/index.php?rid=4965576&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01021.x Summary:  Allergens are recognized as the proteins that induce immunoglobulin E (IgE) responses in humans. The proteins come from a range of sources and, not surprisingly, have many different biological functions. However, the delivery of allergens to the nose is exclusively on particles, which carry a range of molecules in addition to the protein allergens. These molecules include pathogen‐associated molecular patterns (PAMPs) that can alter the response. Although the response to allergens is characterized by IgE antibodies, it also includes other isotypes (IgG, IgA, and IgG4), as well as T cells. The challenge is to identify the characteristics of these exposures that favor the production of this form of response. The primary features of the exposure appear to be the delivery in part... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965576 Sat, 25 Jun 2011 17:30:07 +0100 4965576 http://www.medworm.com/index.php?rid=4965575&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01020.x Summary:  Allergic inflammation is due to a complex interplay between several inflammatory cells, including mast cells, basophils, lymphocytes, dendritic cells, eosinophils, and sometimes neutrophils. These cells produce multiple inflammatory mediators, including lipids, purines, cytokines, chemokines, and reactive oxygen species. Allergic inflammation affects target cells, such as epithelial cells, fibroblasts, vascular cells, and airway smooth muscle cells, which become an important source of inflammatory mediators. Sensory nerves are sensitized and activated during allergic inflammation and produce symptoms. Allergic inflammatory responses are orchestrated by several transcription factors, particularly NF‐κB and GATA3. Inflammatory genes are also regulated by epigenetic mechanisms,... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965575 Sat, 25 Jun 2011 17:30:06 +0100 4965575 http://www.medworm.com/index.php?rid=4965574&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01029.x Summary:  Asthma and allergy are common conditions with complex etiologies involving both genetic and environmental contributions. Recent genome‐wide association studies (GWAS) and meta‐analyses of GWAS have begun to shed light on both common and distinct pathways that contribute to asthma and allergic diseases. Associations with variation in genes encoding the epithelial cell‐derived cytokines, interleukin‐33 (IL‐33) and thymic stromal lymphopoietin (TSLP), and the IL1RL1 gene encoding the IL‐33 receptor, ST2, highlight the central roles for innate immune response pathways that promote the activation and differentiation of T‐helper 2 cells in the pathogenesis of both asthma and allergic diseases. In contrast, variation at the 17q21 asthma locus, encoding the ORMDL3 and GSD... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965574 Sat, 25 Jun 2011 17:30:05 +0100 4965574 http://www.medworm.com/index.php?rid=4965573&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01036.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4965573 Sat, 25 Jun 2011 17:30:04 +0100 4965573 http://www.medworm.com/index.php?rid=4712842&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01018.x Summary:  Regulatory T (Treg) cells play central role in regulation of immune responses to self‐antigens, allergens, and commensal microbiota as well as immune responses to infectious agents and tumors. Transcriptional factor Foxp3 serves as a lineage specification factor of Treg cells. Paucity of Treg cells due to loss‐of‐function mutations of the Foxp3 gene is responsible for highly aggressive, fatal, systemic immune‐mediated inflammatory lesions in mice and humans. Recent studies of Foxp3 expression and function provided critical novel insights into biology of Treg cells and into cellular mechanisms of the immune homeostasis. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712842 Fri, 15 Apr 2011 01:00:25 +0100 4712842 http://www.medworm.com/index.php?rid=4712841&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01017.x Summary:  The gut‐associated lymphoid tissue is the largest immune organ in the body and is the primary route by which we are exposed to antigens. Tolerance induction is the default immune pathway in the gut, and the type of tolerance induced relates to the dose of antigen fed: anergy/deletion (high dose) or regulatory T‐cell (Treg) induction (low dose). Conditioning of gut dendritic cells (DCs) by gut epithelial cells and the gut flora, which itself has a major influence on gut immunity, induces CD103+ retinoic acid‐dependent DC that induces Tregs. A number of Tregs are induced at mucosal surfaces. Th3 type Tregs are transforming growth factor‐β dependent and express latency‐associated peptide (LAP) on their surface and were discovered in the context of oral tolerance. Tr1 ty... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712841 Fri, 15 Apr 2011 01:00:23 +0100 4712841 http://www.medworm.com/index.php?rid=4712840&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01016.x Summary:  Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously activated by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T‐cell tolerance to myelin antigens and to understand how some myelin‐specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin‐specific T cells, as most myelin‐specific T cells are eliminated by clonal deletion in the thymu... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712840 Fri, 15 Apr 2011 01:00:22 +0100 4712840 http://www.medworm.com/index.php?rid=4712839&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01015.x Summary:  One of the most fundamental problems in immunology is the seemingly schizophrenic ability of the immune system to launch robust immunity against pathogens, while acquiring and maintaining a state of tolerance to the body’s own tissues and the trillions of commensal microorganisms and food antigens that confront it every day. A fundamental role for the innate immune system, particularly dendritic cells (DCs), in orchestrating immunological tolerance has been appreciated, but emerging studies have highlighted the nature of the innate receptors and the signaling pathways that program DCs to a tolerogenic state. Furthermore, several studies have emphasized the major role played by cellular interactions and the microenvironment in programming tolerogenic DCs. Here, we review these... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712839 Fri, 15 Apr 2011 01:00:21 +0100 4712839 http://www.medworm.com/index.php?rid=4712838&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01011.x Summary:  Positive and negative costimulation by members of the CD28 family is critical for the development of productive immune responses against foreign pathogens and their proper termination to prevent inflammation‐induced tissue damage. In addition, costimulatory signals are critical for the establishment and maintenance of peripheral tolerance. This paradigm has been established in many animal models and has led to the development of immunotherapies targeting costimulation pathways for the treatment of cancer, autoimmune disease, and allograft rejection. During the last decade, the complexity of the biology of costimulatory pathways has greatly increased due to the realization that costimulation does not affect only effector T cells but also influences regulatory T cells and antig... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712838 Fri, 15 Apr 2011 01:00:19 +0100 4712838 http://www.medworm.com/index.php?rid=4712837&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01014.x Summary:  Self‐reactive T cells in the body are controlled by mechanisms of peripheral tolerance that limit their activation and induction of immune pathology. Our understanding of these mechanisms has been advanced by the use of tissue‐specific promoters to express neo‐self‐antigens. Here, we present findings using the RIP‐gp (rat insulin promoter‐glycoprotein) transgenic mouse, which expresses the lymphocytic choriomeningitis virus glycoprotein (LCMV‐gp) specifically in the pancreatic β islet cells. T cells responsive to this antigen remain ignorant of the LCMV‐gp expressed by the islets, and breaking tolerance is dependent upon the maturation status of antigen‐presenting cells, the avidity of the T‐cell receptor ligation, and the level of major histocompatibility ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712837 Fri, 15 Apr 2011 01:00:17 +0100 4712837 http://www.medworm.com/index.php?rid=4712836&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01010.x Summary:  Allogeneic hematopoietic stem cell transplantation (HSCT) has been a curative therapeutic option for a wide range of immune hematologic malignant and non‐malignant disorders including genetic diseases and inborn errors. Once in the host, allogeneic transplanted cells have not only to ensure myeloid repopulation and immunological reconstitution but also to acquire tolerance to host human leukocyte antigens via central or peripheral mechanisms. Peripheral tolerance after allogeneic HSCT depends on several regulatory mechanisms aimed at blocking alloimmune reactivity while preserving immune responses to pathogens and tumor antigens. Patients transplanted with HSCT represent an ideal model system in humans to identify and characterize the key cellular and molecular players underl... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712836 Fri, 15 Apr 2011 01:00:16 +0100 4712836 http://www.medworm.com/index.php?rid=4712835&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01012.x Summary:  CD4+ T cells are the master regulators of adaptive immune responses, and many autoimmune diseases arise due to a breakdown of self‐tolerance in CD4+ T cells. Activation of CD4+ T cells is regulated by not only the binding of peptide‐major histocompatibility complexes to T‐cell receptor but also costimulatory signals from antigen‐presenting cells. Recently, there has been progress in understanding the extracellular and intracellular mechanisms that are required for implementation and maintenance of T‐cell tolerance. Understanding of the molecular mechanisms underlying T‐cell tolerance will lead to development of pharmacological approaches either to promote the tolerance state in terms of autoimmunity or to break tolerance in cancer. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712835 Fri, 15 Apr 2011 01:00:14 +0100 4712835 http://www.medworm.com/index.php?rid=4712834&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01013.x Summary:  Exposure to alloantigen in vivo or in vitro induces alloantigen reactive regulatory T cells that can control transplant rejection. The mechanisms that underpin the activity of alloantigen reactive regulatory T cells in vivo are common with those of regulatory T cells that prevent autoimmunity. The identification and characterization of regulatory T cells that control rejection and contribute to the induction of immunologic unresponsiveness to alloantigens in vivo has opened up exciting opportunities for new therapies in transplantation. Findings from laboratory studies are informing the design of clinical protocols using regulatory T cells as a cellular therapy. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712834 Fri, 15 Apr 2011 01:00:13 +0100 4712834 http://www.medworm.com/index.php?rid=4712833&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01007.x Summary:  The continual interaction of the immune system with a developing tumor is thought to result in the establishment of a dynamic state of equilibrium. This equilibrium depends on the balance between effector and regulatory T‐cell compartments. Whereas regulatory T cells can infiltrate and accumulate within tumors, effector T cells fail to efficiently do so. Furthermore, effector T cells that do infiltrate the tumor become tightly controlled by different regulatory cellular subsets and inhibitory molecules. The outcome of this balance is critical to survival, and whereas in some cases the equilibrium can rapidly result in the elimination of the transformed cells by the immune system, in many other cases the tumor manages to escape immune control. In this review, we discuss releva... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712833 Fri, 15 Apr 2011 01:00:11 +0100 4712833 http://www.medworm.com/index.php?rid=4712832&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01008.x Summary:  The negative selection of self‐reactive thymocytes depends on the expression of tissue‐specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire‐induced tissue‐specific antigen in the thymus can lead to autoimmunity in the antigen‐expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue‐specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire‐expressing cells (eTACs) can med... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712832 Fri, 15 Apr 2011 01:00:10 +0100 4712832 http://www.medworm.com/index.php?rid=4712831&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01006.x Summary:  Immune responses during infection, injury, and cancer proceed in the presence of tissue injury and cell death. Consequently, the system must deal with its own dead cells while it determines the appropriate response to the invader. As apoptotic cells are known to induce immune tolerance and necrotic cells can be potent stimulators of immunity, this decision becomes more complex. The key to understanding the immunologic choices made during cell death is to examine the mechanisms of tolerance induction by dying cells and then relate them to the mechanisms of immunity. Ideally, immunogenic cell death should be directed toward tumor cells and infected cells, whereas tolerogenic cell death should be associated with preventing unwanted immune responses to self. In this review, we disc... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712831 Fri, 15 Apr 2011 01:00:09 +0100 4712831 http://www.medworm.com/index.php?rid=4712830&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01004.x Summary:  Signaling through the interleukin‐2 receptor (IL‐2R) contributes to T‐cell tolerance by controlling three important aspects of regulatory T‐cell (Treg) biology. IL‐2 is essential for thymic Treg development and regulates Treg homeostasis and suppressive function. Analogous to activated conventional T lymphocytes, IL‐2R signaling also plays an important part in Treg cell growth, survival, and effector differentiation. However, Treg cells somewhat distinctively assimilate IL‐2R signaling. In particular, Treg cells require essentially only IL‐2‐dependent receptor proximal signal transducer and activator of transcription 5 (Stat5) activation, as they contain inhibitory pathways to minimize IL‐2R‐dependent activation of the phosphatidyinositol 3‐kinase/Akt pa... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712830 Fri, 15 Apr 2011 01:00:08 +0100 4712830 http://www.medworm.com/index.php?rid=4712829&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01003.x Summary:  Strategies for inducing immune tolerance are fundamentally similar across a spectrum of immune‐mediated disorders, including allergic disease, autoimmunity, and rejection of allografts. In each case, the objective of establishing an immunoregulatory balance is challenged by variable upswings in effector cell populations and proinflammatory mediators of immunity, requiring careful, and innovative therapeutic intervention to restore stability. The Immune Tolerance Network, an international consortium sponsored by the National Institutes of Health, seeks to advance both the scientific understanding and the clinical success of immune therapies for these disorders, through an innovative and collaborative effort involving clinical trials and mechanistic studies. Over the last decad... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712829 Fri, 15 Apr 2011 01:00:06 +0100 4712829 http://www.medworm.com/index.php?rid=4712828&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01009.x Summary:  Historically, research on transplant rejection and tolerance has focused on cells of the adaptive immune system, especially T cells. Anti‐graft effector T cells are necessary and sufficient for the rejection of most allografts, while regulatory T cells, either arising naturally or as a result of a specific treatment regimen, are crucial to long‐term graft tolerance. Although the role of T cells in transplant rejection and tolerance is well‐established, the role that the innate immune system plays in these processes is only recently being appreciated. Cells of the innate immune system, such as dendritic cells (DCs) and natural killer cells, can become activated by microbial products or endogenous pro‐inflammatory ligands released during the mechanical and ischemia‐repe... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712828 Fri, 15 Apr 2011 01:00:05 +0100 4712828 http://www.medworm.com/index.php?rid=4712827&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01002.x Summary:  Antigen‐presenting molecules vary between individuals of the same species, making it more difficult for pathogens to evade immune recognition and spread through the whole population. As a result of this genetic diversity, transplants between individuals are recognized as foreign and are rejected. This alloreactivity turns placental viviparity into a major immunological challenge. The maternal immune system has to balance the opposing needs of maintaining robust immune reactivity to protect both mother and fetus from invading pathogens, while at the same time tolerating highly immunogenic paternal alloantigens in order to sustain fetal integrity. Regulatory T cells are responsible for the establishment of tolerance by modulating the immune response, and uterine natural killer ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712827 Fri, 15 Apr 2011 01:00:04 +0100 4712827 http://www.medworm.com/index.php?rid=4712826&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01019.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4712826 Fri, 15 Apr 2011 01:00:04 +0100 4712826 http://www.medworm.com/index.php?rid=4535497&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2011.01005.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535497 Tue, 01 Mar 2011 00:00:00 +0100 4535497 http://www.medworm.com/index.php?rid=4535496&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00988.x Summary:  Malaria is a vector‐borne infectious disease caused by unicellular parasites of the genus Plasmodium. These obligate intracellular parasites have the unique capacity to infect and replicate within erythrocytes, which are terminally differentiated host cells that lack antigen presentation pathways. Prior to the cyclic erythrocytic infections that cause the characteristic clinical symptoms of malaria, the parasite undergoes an essential and clinically silent expansion phase in the liver. By infecting privileged host cells, employing programs of complex life stage conversions and expressing varying immunodominant antigens, Plasmodium parasites have evolved mechanisms to downmodulate protective immune responses against ongoing and even future infections. Consequently, anti‐mala... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535496 Tue, 01 Mar 2011 00:00:00 +0100 4535496 http://www.medworm.com/index.php?rid=4535495&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00983.x Summary:  More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T‐helper 1 (Th1)‐ and Th2‐dominated immune responses, respectively. This infectious disease model was later used to identify and assess the role of key factors, such as interleukin‐12 (IL‐12) and IL‐4, in Th1 and Th2 maturation. While infection by Leishmania remains a popular model for immunologists who wish to assess the role of their favorite molecule in T‐cell differentiation, other investigators have tried to better understand how Leishmania interact with its insect and mammalian hosts. In this review, we discuss some of these new data with an emphasis on the ear... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535495 Tue, 01 Mar 2011 00:00:00 +0100 4535495 http://www.medworm.com/index.php?rid=4535494&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00992.x Summary: Toxoplasma gondii is an obligate intracellular parasite. Following oral infection the parasite crosses the intestinal epithelial barrier to disseminate throughout the body and establish latent infection in central nervous tissues. The clinical presentation ranges from asymptomatic to severe neurological disorders in immunocompromised individuals. Since the clinical presentation is diverse and depends, among other factors, on the immune status of the host, in the present review, we introduce parasitological, epidemiological, clinical, and molecular biological aspects of infection with T. gondii to set the stage for an in‐depth discussion of host immune responses. Since immune responses in humans have not been investigated in detail the present review is exclusively referring to... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535494 Tue, 01 Mar 2011 00:00:00 +0100 4535494 http://www.medworm.com/index.php?rid=4535493&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00984.x Summary: Mycobacterium tuberculosis is an extremely successful pathogen that demonstrates the capacity to modulate its host both at the cellular and tissue levels. At the cellular level, the bacterium enters its host macrophage and arrests phagosome maturation, thus avoiding many of the microbicidal responses associated with this phagocyte. Nonetheless, the intracellular environment places certain demands on the pathogen, which, in response, senses the environmental shifts and upregulates specific metabolic programs to allow access to nutrients, minimize the consequences of stress, and sustain infection. Despite its intracellular niche, Mycobacterium tuberculosis demonstrates a marked capacity to modulate the tissues surrounding infected cells through the release of potent, bioactive cel... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535493 Tue, 01 Mar 2011 00:00:00 +0100 4535493 http://www.medworm.com/index.php?rid=4535492&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00994.x Summary:  Tuberculosis (TB) is a complex disease, and the success of the bacterium as an intracellular pathogen is the outcome of its close and longstanding coevolution with the mammalian host. The dialogue between Mycobacterium tuberculosis and the host is becoming understandable at the molecular, cellular, and tissue level. This has led to the elucidation of the (i) interaction between pattern recognition receptors and pathogen‐associated molecular patterns, (ii) cross‐talk between immune cells, and (iii) mechanisms underlying granuloma development. Disease as an eventual but not a necessary consequence of infection results from a sensitive balance between protective immunity and destructive pathology. Early events, governed largely by conserved mechanisms of host recognition, impa... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535492 Tue, 01 Mar 2011 00:00:00 +0100 4535492 http://www.medworm.com/index.php?rid=4535491&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00982.x Summary: Brucella is an intracellular bacterial pathogen that causes abortion and infertility in mammals and leads to a debilitating febrile illness that can progress into a long lasting disease with severe complications in humans. Its virulence depends on survival and replication properties in host cells. In this review, we describe the stealthy strategy used by Brucella to escape recognition of the innate immunity and the means by which this bacterium evades intracellular destruction. We also discuss the development of adaptive immunity and its modulation during brucellosis that in course leads to chronic infections. Brucella has developed specific strategies to influence antigen presentation mediated by cells. There is increasing evidence that Brucella also modulates signaling events ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535491 Tue, 01 Mar 2011 00:00:00 +0100 4535491 http://www.medworm.com/index.php?rid=4535490&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00999.x Summary: Salmonella enterica is a genetically broad species harboring isolates that display considerable antigenic heterogeneity and significant differences in virulence potential. Salmonella generally exhibit an invasive potential and they can survive for extended periods within cells of the immune system. They cause acute or chronic infections that can be local (e.g. gastroenteritis) or systemic (e.g. typhoid). In vivo Salmonella infections are complex with multiple arms of the immune system being engaged. Both humoral and cellular responses can be detected and characterized, but full protective immunity is not always induced, even following natural infection. The murine model has proven to be a fertile ground for exploring immune mechanisms and observations in the mouse have often, al... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535490 Tue, 01 Mar 2011 00:00:00 +0100 4535490 http://www.medworm.com/index.php?rid=4535489&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00981.x Summary: Salmonella enterica is a frequent gastrointestinal pathogen with ability to cause diseases ranging from local gastrointestinal inflammation and diarrhea to life‐threatening typhoid fever. Salmonella is an invasive, facultative intracellular pathogen that infects various cell types of the host and can survive and proliferate in different populations of immune cells. During pathogenesis, Salmonella is confronted with various lines of immune defense. To successfully colonize host organisms, the pathogen deploys a set of sophisticated mechanisms of immune evasion and direct manipulation of immune cell functions. In addition to resistance against innate immune mechanisms, including the ability to avoid killing by macrophages and dendritic cells (DCs), Salmonella interferes with ant... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535489 Tue, 01 Mar 2011 00:00:00 +0100 4535489 http://www.medworm.com/index.php?rid=4535488&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00993.x Summary: Listeria monocytogenes is an intracellular bacterium responsible for a disease characterized by several clinical features, such as septicemia, brain infection, abortion, and perinatal infection. These clinical features are attributed to its amazing capacity to cross several barriers in susceptible hosts. Intracellular infection is a consequence of the bacterium’s capacity to enter a wide variety of mammalian cells, to not only survive but also replicate therein, and to its faculty to spread from one cell to the next, thereby escaping the humoral immune response. Here, we review both the well‐established and the newly discovered strategies used by this bacterium to achieve this intracellular lifestyle while escaping from the host innate immune response. More than ever, Lister... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535488 Tue, 01 Mar 2011 00:00:00 +0100 4535488 http://www.medworm.com/index.php?rid=4535487&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00987.x Summary:  As man has moved rapidly from the hunter–gatherer environment to the living conditions of the industrialized countries, the incidences of some cancers have increased alarmingly. Recent increases are usually attributed to dietary changes or to altered exposures to putative carcinogens associated with the modern lifestyle. However, the changes in cancer incidence parallel similar increases in non‐neoplastic chronic inflammatory disorders (inflammatory bowel disease, allergies, and autoimmunity), and the epidemiology is often strikingly similar. This parallel is worth exploring, because the increases in chronic inflammatory disorders are at least partly explained by immunoregulatory defects resulting from diminished exposure to microorganisms that co‐evolved with mammals and... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535487 Tue, 01 Mar 2011 00:00:00 +0100 4535487 http://www.medworm.com/index.php?rid=4535486&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00985.x Summary:  Vector‐borne diseases, transmitted by bloodsucking arthropods, pose worldwide socio‐medical and economical problems. Some of the major human infectious diseases, such as malaria, Dengue fever, and yellow fever, are transmitted by mosquitoes. While the majority of pathogens enjoy extracellular life styles in insects, viruses and some endosymbionts are strictly intracellular. Here, we summarize our knowledge on defense reactions against intracellular microorganisms in dipteran insects and discuss the potential of insects as models to study human pathogens. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535486 Tue, 01 Mar 2011 00:00:00 +0100 4535486 http://www.medworm.com/index.php?rid=4535485&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00998.x Summary:  As biomedical research becomes increasingly data‐intensive, it is increasingly essential to integrate genomic‐scale datasets, so as to generate a more holistic picture of complex biological processes. The systems biology paradigm may differ in strategy from traditional reductionist scientific methods, but the goal remains the same: to generate tenable hypotheses driving the experimental elucidation of biological mechanisms. Intracellular pathogens provide an excellent opportunity for systems analysis, as many of these organisms are amenable to genetic manipulation, allowing their biology to be played off against that of the host. Moreover, many of the most fundamental biological properties of these microbes (host cell invasion, immune evasion, intracellular replication, lon... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535485 Tue, 01 Mar 2011 00:00:00 +0100 4535485 http://www.medworm.com/index.php?rid=4535484&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00996.x Summary:  Intracellular pathogens contribute to a significant proportion of infectious disease morbidity and mortality worldwide. Increasing evidence points to a major role for host genetics in explaining inter‐individual variation in susceptibility to infectious diseases. A number of monogenic disorders predisposing to infectious disease have been reported, including susceptibility to intracellular pathogens in association with mutations in genes of the interleukin‐12/interleukin‐23/interferon‐γ axis. Common genetic variants have also been demonstrated to regulate susceptibility to intracellular infection, for example the CCR5Δ32 polymorphism that modulates human immunodeficiency virus‐1 (HIV‐1) disease progression. Genome‐wide association study approaches are being incr... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535484 Tue, 01 Mar 2011 00:00:00 +0100 4535484 http://www.medworm.com/index.php?rid=4535483&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00995.x Summary:  Autophagy was viewed until very recently primarily as a metabolic and intracellular biomass and organelle quality and quantity control pathway. It has now been recognized that autophagy represents a bona fide immunologic process with a wide array of roles in immunity. The immunologic functions of autophagy, as we understand them now, span both innate and adaptive immunity. They range from unique and sometimes highly specialized immunologic effectors and regulatory functions (referred to here as type I immunophagy) to generic homeostatic influence on immune cells (type II immunophagy), akin to the effects on survival and homeostasis of other cell types in the body. As a concept‐building tool for understanding why and how autophagy is intertwined with immunity, it is useful to ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535483 Tue, 01 Mar 2011 00:00:00 +0100 4535483 http://www.medworm.com/index.php?rid=4535482&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00990.x Summary:  Intracellular parasitism has arisen only a few times during the long ancestry of protozoan parasites including in diverse groups such as microsporidians, kinetoplastids, and apicomplexans. Strategies used to gain entry differ widely from injection (e.g. microsporidians), active penetration of the host cell (e.g. Toxoplasma), recruitment of lysosomes to a plasma membrane wound (e.g. Trypanosoma cruzi), to host cell‐mediated phagocytosis (e.g. Leishmania). The resulting range of intracellular niches is equally diverse ranging from cytosolic (e.g. T. cruzi) to residing within a non‐fusigenic vacuole (e.g. Toxoplasma, Encephalitozoon) or a modified phagolysosome (e.g. Leishmania). These lifestyle choices influence access to nutrients, interaction with host cell signaling pathwa... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535482 Tue, 01 Mar 2011 00:00:00 +0100 4535482 http://www.medworm.com/index.php?rid=4535481&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00991.x This article reviews the protective and deleterious roles of B cells during intracellular bacterial infections and discusses how manipulating their antibody‐independent functions may be a powerful means to therapeutically improve host resistance against these diseases. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535481 Tue, 01 Mar 2011 00:00:00 +0100 4535481 http://www.medworm.com/index.php?rid=4535480&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.01000.x Summary:  Studies on immunologic memory in animal models and especially in the human system are instrumental to identify mechanisms and correlates of protection necessary for vaccine development. In this article, we provide an overview of the cellular basis of immunologic memory. We also describe experimental approaches based on high throughput cell cultures, which we have developed to interrogate human memory T cells, B cells, and plasma cells. We discuss how these approaches can provide new tools and information for vaccine design, in a process that we define as ‘analytic vaccinology’. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535480 Tue, 01 Mar 2011 00:00:00 +0100 4535480 http://www.medworm.com/index.php?rid=4535479&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00997.x Summary:  For many intracellular bacteria, both adaptively acquired and innately encoded effector T cells play a central role in the control, and in some cases, clearance of these pathogens. Through the rapid identification of those cells harboring intracellular bacteria, effector T cells have the capacity to both directly control the infection and shape the immune response to the pathogen. Here, we review the mechanisms by which effector T cells control intracellular infection and emphasize the means by which they recognize their targets. As will become evident, the diversity of both redundant and non‐redundant effector mechanisms in conjunction with broad recognition of both protein and non‐protein antigens allows for the identification of a broad array of bacterial pathogens and l... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535479 Tue, 01 Mar 2011 00:00:00 +0100 4535479 http://www.medworm.com/index.php?rid=4535478&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00989.x Summary:  Innate immunity to intracellular pathogens encompasses a range of interactions of cellular and humoral activities of the host with the invading microorganism, determining the outcome of infection. Here, we review the particular role of macrophage recognition receptors and effector responses in the uptake of microbes and their products. We place this in context and raise issues for discussion and further experimentation. (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535478 Tue, 01 Mar 2011 00:00:00 +0100 4535478 http://www.medworm.com/index.php?rid=4535477&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.01001.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4535477 Tue, 01 Mar 2011 00:00:00 +0100 4535477 http://www.medworm.com/index.php?rid=4352230&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00976.x Summary:  The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low‐ and middle‐income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world’s poorest people living below the World Bank poverty... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352230 Sat, 01 Jan 2011 00:00:00 +0100 4352230 http://www.medworm.com/index.php?rid=4352229&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00969.x Summary:  The lethal anthrax disease is caused by spores of the Gram‐positive Bacillus anthracis, a member of the cereus group of bacilli. Although the disease is very rare in the Western world, development of anthrax countermeasures gains increasing attention due to the potential use of B. anthracis spores as a bio‐terror weapon. Protective antigen (PA), the non‐toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into the host target cells. PA elicits a protective immune response and represents the basis for all current anthrax vaccines. Anti‐PA neutralizing antibodies are useful correlates for protection and for vaccine efficacy evaluation. Post exposure anti‐toxemic and anti‐bacteremic ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352229 Sat, 01 Jan 2011 00:00:00 +0100 4352229 http://www.medworm.com/index.php?rid=4352228&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00973.x Summary:  No antiviral vaccine is perfect. For some important pathogens, there are no effective vaccines. Many current vaccines are based on the working principles of Jenner and Pasteur, that is, empiric administration of attenuated or inactivated forms of the pathogen. Tapping the full potential of vaccination requires a thorough understanding of the mechanism of immune activation by pathogens and their individual components. Though the rate of discovery continues to accelerate, the complexity of the immune system is daunting, particularly when integrated into the overall physiology of the host. Here, we review the application of multiphoton microscopy to examine host‐pathogen interactions, focusing on our recent efforts to understand mouse CD8+ T‐cell responses to viruses at the le... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352228 Sat, 01 Jan 2011 00:00:00 +0100 4352228 http://www.medworm.com/index.php?rid=4352227&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00971.x Summary:  Vaccines represent a potent tool to prevent or contain infectious diseases with high morbidity or mortality. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the effective elicitation of protective immune responses by vaccines. Recent research suggests that this represents the cooperative action of the innate and adaptive immune systems. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules, whose list is constantly updated to fill the several empty spaces of this puzzle. The recent development of new technologies and computational tools permits the comprehensive and quantitative analysis of the interactions between all of the components of immunity over t... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352227 Sat, 01 Jan 2011 00:00:00 +0100 4352227 http://www.medworm.com/index.php?rid=4352226&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00978.x Summary:  Our improved understanding of how innate immune responses can be initiated and how they can shape adaptive B‐ and T‐cell responses is having a significant impact on vaccine development by directing the development of defined adjuvants. Experience with first generation vaccines, as well as rapid advances in developing defined vaccines containing Toll‐like receptor ligands (TLRLs), indicate that an expanded number of safe and effective vaccines containing such molecules will be available in the future. In this review, we outline current knowledge regarding TLRs, detailing the different cell types that express TLRs, the various signaling pathways TLRs utilize, and the currently known TLRLs. We then discuss the current status of TLRLs within vaccine development programs, incl... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352226 Sat, 01 Jan 2011 00:00:00 +0100 4352226 http://www.medworm.com/index.php?rid=4352225&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00974.x Summary:  Studying the spread of influenza in human populations and protection by influenza vaccines provides important insights into immunity against influenza. The 2009 H1N1 pandemic has taught the most recent lessons. Neutralizing and receptor‐blocking antibodies against hemagglutinin are the primary means of protection from the spread of pandemic and seasonal strains. Anti‐neuraminidase antibodies seem to play a secondary role. More broadly cross‐reactive forms of immunity may lessen disease severity but are insufficient to prevent epidemic spread. Priming by prior exposure to related influenza strains through infection or immunization permits rapid, potent antibody responses to immunization. Priming is of greater importance to the design of immunization strategies than the imm... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352225 Sat, 01 Jan 2011 00:00:00 +0100 4352225 http://www.medworm.com/index.php?rid=4352224&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00972.x Summary:  Respiratory syncytial virus (RSV) is an important cause of respiratory disease causing high rates of hospitalizations in infants, significant morbidity in children and adults, and excess mortality in the elderly. Major barriers to vaccine development include early age of RSV infection, capacity of RSV to evade innate immunity, failure of RSV‐induced adaptive immunity to prevent reinfection, history of RSV vaccine‐enhanced disease, and lack of an animal model fully permissive to human RSV infection. These biological challenges, safety concerns, and practical issues have significantly prolonged the RSV vaccine development process. One great advantage compared to other difficult viral vaccine targets is that passively administered neutralizing monoclonal antibody is known to p... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352224 Sat, 01 Jan 2011 00:00:00 +0100 4352224 http://www.medworm.com/index.php?rid=4352223&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00970.x Summary:  Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross‐talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352223 Sat, 01 Jan 2011 00:00:00 +0100 4352223 http://www.medworm.com/index.php?rid=4352222&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00968.x Summary:  The Merck STEP and the Thai RV144 human immunodeficiency virus (HIV) vaccine trials confirmed that we still have a long way to go before developing a prophylactic HIV vaccine. The main issue at hand is that we have yet to identify an immunological correlate of protection against HIV. While many question the T‐cell‐based approach towards vaccine development, it is likely that T cells will be a necessary part of any vaccine strategy. CD8+ T cells remain an attractive option because of their ability to specifically recognize and eliminate virally infected host cells. In this review, we recapitulate the evidence for CD8+ T cells as an immunological correlate against HIV, but more importantly, we assess the means by which we evaluate their antiviral capacity. To achieve a breakt... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352222 Sat, 01 Jan 2011 00:00:00 +0100 4352222 http://www.medworm.com/index.php?rid=4352221&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00977.x Summary:  Encouraging efficacy data have been obtained in the hepatitis C virus (HCV) chimpanzee model using prophylactic vaccines comprising adjuvanted recombinant envelope gpE1/gpE2 glycoproteins or prime/boost immunization regimens using defective adenoviruses and plasmid DNA expressing non‐structural genes. While usually not resulting in sterilizing immunity after experimental challenge, the progression to chronic, persistent infection (which is responsible for HCV‐associated pathogenicity in human) is inhibited. These and other vaccine candidates are in clinical development for both prophylactic as well as possible therapeutic applications. Given that other vaccines tested in the chimpanzee model may be possibly increasing the rate of chronicity, it is very important that this m... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352221 Sat, 01 Jan 2011 00:00:00 +0100 4352221 http://www.medworm.com/index.php?rid=4352220&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00966.x Summary:  The recent development of vaccines prophylactic against human papillomavirus (HPV) infection has the potential to reduce the incidence of cervical cancer globally by up to 70% over the next 40 years, if universal immunization is adopted. As these prophylactic vaccines do not alter the natural history of established HPV infection, immunotherapies to treat persistent HPV infection and associated precancers would be of benefit to assist with cervical cancer control. Efforts to develop immuno‐therapeutic vaccines have been hampered by the relative non‐immunogenicity of HPV infection, by immunoregulatory processes in skin, and by subversion of immune response induction and immune effector functions by papillomavirus proteins. This review describes HPV‐specific immune respons... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352220 Sat, 01 Jan 2011 00:00:00 +0100 4352220 http://www.medworm.com/index.php?rid=4352219&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00980.x Summary:  This review provides a detailed look at the attributes and immunologic mechanisms of plasmid DNA vaccines and their utility as laboratory tools as well as potential human vaccines. The immunogenicity and efficacy of DNA vaccines in a variety of preclinical models is used to illustrate how they differ from traditional vaccines in novel ways due to the in situ antigen production and the ease with which they are constructed. The ability to make new DNA vaccines without needing to handle a virulent pathogen or to adapt the pathogen for manufacturing purposes demonstrates the potential value of this vaccine technology for use against emerging and epidemic pathogens. Similarly, personalized anti‐tumor DNA vaccines can also readily be made from a biopsy. Because DNA vaccines bias th... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352219 Sat, 01 Jan 2011 00:00:00 +0100 4352219 http://www.medworm.com/index.php?rid=4352218&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00967.x Summary:  The increasing level of understanding of the lentivirus biology has been instrumental in shaping the design strategy of creating therapeutic lentiviral delivery vectors. As a result, lentiviral vectors have become one of the most powerful gene transfer vehicles. They are widely used for therapeutic purposes as well as in studies of basic biology, due to their unique characteristics. Lentiviral vectors have been successfully employed to mediate durable and efficient antigen expression and presentation in dendritic cells both in vitro and in vivo, leading to the activation of cellular immunity and humoral responses. This capability makes the lentiviral vector an ideal choice for immunizations that target a wide range of cancers and infectious diseases. Further advances into optim... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352218 Sat, 01 Jan 2011 00:00:00 +0100 4352218 http://www.medworm.com/index.php?rid=4352217&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00979.x Summary:  Enthusiasm for therapeutic cancer vaccines has been rejuvenated with the recent completion of several large, randomized phase III clinical trials that in some cases have reported an improvement in progression free or overall survival. However, an honest appraisal of their efficacy reveals modest clinical benefit and a frequent requirement for patients with relatively indolent cancers and minimal or no measurable disease. Experience with adoptive cell transfer‐based immunotherapies unequivocally establishes that T cells can mediate durable complete responses, even in the setting of advanced metastatic disease. Further, these findings reveal that the successful vaccines of the future must confront: (i) a corrupted tumor microenvironment containing regulatory T cells and aberran... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352217 Sat, 01 Jan 2011 00:00:00 +0100 4352217 http://www.medworm.com/index.php?rid=4352216&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00975.x Summary:  The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new‐generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and ... Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352216 Sat, 01 Jan 2011 00:00:00 +0100 4352216 http://www.medworm.com/index.php?rid=4352215&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00986.x (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4352215 Sat, 01 Jan 2011 00:00:00 +0100 4352215 http://www.medworm.com/index.php?rid=4108642&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00951.x Summary:  (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4108642 Fri, 29 Oct 2010 01:10:23 +0100 4108642 http://www.medworm.com/index.php?rid=4108641&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00952.x Summary:  (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4108641 Fri, 29 Oct 2010 01:10:22 +0100 4108641 http://www.medworm.com/index.php?rid=4108640&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00961.x Summary:  (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4108640 Fri, 29 Oct 2010 01:10:21 +0100 4108640 http://www.medworm.com/index.php?rid=4108639&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00962.x Summary:  (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4108639 Fri, 29 Oct 2010 01:10:21 +0100 4108639 http://www.medworm.com/index.php?rid=4108638&cid=s_33160_3_f&fid=33160&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-065X.2010.00958.x Summary:  (Source: Immunological Reviews) Immunological Reviews journals http://www.medworm.com/rss/comments.php?id=4108638 Fri, 29 Oct 2010 01:10:20 +0100 4108638 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