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Critical Reviews in Immunology

Wei Li, Ramya Sivakumar, Anton A Titov, Seung-Chul Choi, Laurence Morel
Systemic lupus erythematosus (SLE) is an autoimmune disease in which organ damage is mediated by pathogenic autoantibodies directed against nucleic acids and protein complexes. Studies in SLE patients and in mouse models of lupus have implicated virtually every cell type in the immune system in the induction or amplification of the autoimmune response as well as the promotion of an inflammatory environment that aggravates tissue injury. Here, we review the contribution of CD4+ T cells, B cells, and myeloid cells to lupus pathogenesis and then discuss alterations in the metabolism of these cells that may contribute to disease, given the recent advances in the field of immunometabolism...
2016: Critical Reviews in Immunology
Derek B Danahy, Robert K Strother, Vladimir P Badovinac, Thomas S Griffith
Septic patients experience chronic immunosuppression resulting in enhanced susceptibility to infections normally controlled by T cells. Clinical research on septic patients has shown increased apoptosis and reduced total numbers of CD4 and CD8 T cells, suggesting contributing mechanism driving immunosuppression. Experimental models of sepsis, including cecal ligation and puncture, reverse translated this clinical observation to facilitate hypothesis-driven research and allow the use of an array of experimental tools to probe the impact of sepsis on T-cell immunity...
2016: Critical Reviews in Immunology
Hilmar Lemke
The clone-specific or idiotypic characters of B as well as T cell antigen receptors (BCRs/TCRs) are associated with (1) the third-complementarity-determining regions (CDR3s) that are created during V(D)J recombination (they scarcely occur in antibody light chains) and (2) BCR idiotopes created by somatic hypermutations (SHMs) during immune responses. Therefore, BCR/TCR idiotypic sites are antigen receptor-intrinsic Non-Self (AgR-iNS) portions that fulfill two tasks: serving as a crucial component of the epitope-binding paratope and serving as target sites for anti-idiotypic BCR/TCR paratopes of other anti-Non-Self clones that are contained in both normal repertoires...
2016: Critical Reviews in Immunology
Helton da Costa Santiago, Thomas B Nutman
Implied under the rubric of the hygiene hypothesis is that helminth infection can protect against allergic disease. It is well known that helminths induce processes associated with type 2 immune responses, but they also induce important regulatory responses that can modulate these type 2-associated responses-modulation that influences responses to bystander antigens including allergens. Indeed, most epidemiological studies demonstrate a beneficial effect of helminth infection on atopy, but there are also convincing data to demonstrate that helminth infection can precipitate or worsen allergic inflammation/disease...
2016: Critical Reviews in Immunology
Yudong Liu, Sara A Gibson, Etty N Benveniste, Hongwei Qin
Pathogenic CD4+ T cells and myeloid cells play critical roles in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. These immune cells secrete aberrantly high levels of pro-inflammatory cytokines that pathogenically bridge the innate and adaptive immune systems and damage neurons and oligodendrocytes. These cytokines include interleukin-2 (IL-2), IL-6, IL-12, IL-21, IL-23, granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon-γ (IFN-γ)...
2015: Critical Reviews in Immunology
Maura Rossetti, Roberto Spreafico
Current approaches to prevent or treat transplant rejection, graft-versus-host disease and severe autoimmunity rely on non-specific immunosuppressive drugs. Ongoing efforts aimed at harnessing regulatory T (Treg) cells hold promise for revolutionizing the current therapeutic options, reducing if not abandoning immune suppression in favor of immune tolerance. This paradigm shift carries the potential of dramatically enhancing efficacy, persistency, and specificity while reducing side effects. Here, we review the various strategies devised to manipulate Treg cells in vitro and in vivo, the clinical progress achieved to date, and critical issues that still need to be addressed...
2015: Critical Reviews in Immunology
Jacob D Galson, Dominic F Kelly, Johannes Truck
Advances in next-generation sequencing now allow characterization of the global B-cell receptor (BCR) heavy-chain repertoire at a level that reflects its huge diversity. This technology has provided great insight into the structure of the BCR repertoire and how it responds to specific antigen stimuli. There are numerous potential clinical and research applications of BCR repertoire sequencing, but a major hurdle in the realization of these applications is the identification of the antigen-specific sequences of interest from within the total repertoire...
2015: Critical Reviews in Immunology
Jing Zhao, Yutong Zhao
Interleukin-33 (IL-33) is a member of the IL-1 cytokine family. It modulates immune responses and biological functions through binding to its membrane receptor, ST2L. ST2L is a member of the Toll-like/IL-1 (TIR)-receptor superfamily, and its isoform, soluble ST2 (sST2), functions as an inhibitor of the IL-33/ST2L pathway. Levels of IL-33 and sST2 in serum and bronchoalveolar lavage fluid (BAL) are known biomarkers for a variety of disorders such as heart failure, non-small-cell lung cancer, and pulmonary inflammatory diseases...
2015: Critical Reviews in Immunology
Jerome Thiery, Thouraya Ben Safta, Linda Ziani, Salem Chouaib
Cytotoxic T lymphocytes and natural killer cells are key effector cells in the immune response against intracellular infection and transformed cells. These killer cells induce multiple programs of cell death to achieve their function of eliminating their targets. In this review, we summarize our current understanding of the signaling pathways involved in target cells apoptosis triggered by the cytotoxic effector cells. We also discuss the role of an important player in the field of apoptosis, the well-known p53 tumor suppressor, in the modulation of cytotoxic lymphocyte-mediated cell death...
2015: Critical Reviews in Immunology
Simone Burgler
CD38 is widely accepted as a marker for unfavorable prognosis in chronic lymphocytic leukemia (CLL). Nevertheless, its direct contribution to the disease pathogenesis is not very well understood. Recent data indicate that CD38 may promote CLL pathogenesis by enhancing proliferation in synergy with B-cell receptor (BCR) signaling and by supporting migration and homing of CLL cells to secondary lymphoid organs, where the malignant cells receive support from the tumor microenvironment. CD38 may also contribute to a suppressed anticancer immune response through the production of tolerogenic compounds...
2015: Critical Reviews in Immunology
Macarena S Aloi, Wei Su, Gwenn A Garden
The tumor-suppressor protein p53 belongs to a family of proteins that play pivotal roles in multiple cellular functions including cell proliferation, cell death, genome stability, and regulation of inflammation. Neuroinflammation is a common feature of central nervous system (CNS) pathology, and microglia are the specialized resident population of CNS myeloid cells that initiate innate immune responses. Microglia maintain CNS homeostasis through pathogen containment, phagocytosis of debris, and initiation of tissue-repair cascades...
2015: Critical Reviews in Immunology
Shawn P Fahl, Minshi Wang, Yong Zhang, Anne-Cecile E Duc, David L Wiest
Ribosomal proteins have long been known to serve critical roles in facilitating the biogenesis of the ribosome and its ability to synthesize proteins. However, evidence is emerging that suggests ribosomal proteins are also capable of performing tissue-restricted, regulatory functions that impact normal development and pathological conditions, including cancer. The challenge in studying such regulatory functions is that elimination of many ribosomal proteins also disrupts ribosome biogenesis and/or function...
2015: Critical Reviews in Immunology
Ikuma Nakagawa, Daisuke Kamimura, Toru Atsumi, Yasunobu Arima, Masaaki Murakami
Inflammation is a fundamental response induced by the immune system to protect the body against pathogens, tissue damage, and stress. At the same time, recent studies have suggested that chronically induced inflammation is involved in various human diseases and disorders. Thus, understanding the molecular mechanisms of chronic inflammation could provide therapeutic value. Many mediators such as cytokines or chemokines regulate inflammatory responses. Among them, interleukin(IL)-6 is a prominent cytokine that induces and maintains inflammatory reactions...
2015: Critical Reviews in Immunology
Irene Bonaccorsi, Stefania Campana, Barbara Morandi, Guido Ferlazzo
Dendritic cells (DCs) are master regulators of the immune response and, because of their peculiar features in antigen acquisition, processing, and presentation, they play a critical role in activating an efficient antigenspecific T-lymphocyte response against tumors. However, the DC family is composed of different cell subsets, which may differently contribute to tumor-specific T-cell activation. In addition to the DC subset involved, the induction of a tumor-specific adaptive immune response is also dependent on DC interactions with other innate cell effectors, such as natural killer cells...
2015: Critical Reviews in Immunology
Conor J Kearney, Amelia J Brennan, Phillip K Darcy, Jane Oliaro
A synapse is a specialized structure that forms when the plasma membrane of two cells come into close contact to facilitate communication and signaling. Cells of the immune system form 'immunological' synapses that have an ordered structure and are essential for immune cell activation, function and homeostasis. Optimal synapse formation is not only critical for the generation of effective immunity against pathogens but is also essential for immune surveillance against cancer and for the prevention of immune disorders...
2015: Critical Reviews in Immunology
Patricia E Collins, Ruaidhri J Carmody
Endotoxin tolerance in macrophages is a key regulatory mechanism to limit the innate immune response to infection or injury. Long considered a state of unresponsiveness to Toll-like receptor activation, tolerance is now recognized as a state of altered responsiveness to infection or injury. Endotoxin tolerance leads to a shift away from a pro-inflammatory response toward a response with key anti-inflammatory and pro-resolution features. Advances in our understanding of Toll-like receptor function have identified a number of molecular mechanisms that promote tolerance, but how these are integrated to achieve gene-specific regulation is an important outstanding question...
2015: Critical Reviews in Immunology
Jan Rossaint, Alexander Zarbock
Sepsis is a severe critical illness syndrome that arises from infectious insults. While the host immune system is generally beneficial, an overshooting and unregulated immune response can cause serious organ tissue injury. During sepsis, systemic hypotension, disturbed perfusion of the microcirculation, and direct tissue-toxicity caused by inflammatory immune reaction can occur and contribute to organ failure. The failure of two or more vital organ systems is termed multi-organ dysfunction syndrome (MODS) and resembles a very critical condition associated with high morbidity and mortality...
2015: Critical Reviews in Immunology
Takako Kizaki, Shogo Sato, Ken Shirato, Takuya Sakurai, Junetsu Ogasawara, Tetsuya Izawa, Yoshinobu Ohira, Kenji Suzuki, Hideki Ohno
Circadian rhythms have long been known to regulate numerous physiological processes that vary across the diurnal cycle. The circadian clock system also controls various parameters of the immune system and its biological defense functions, allowing an organism to anticipate daily changes in activity and feeding and the associated risk of infection. Inflammation is an immune response triggered in living organisms in response to external stimuli. The risk of sepsis, an excessive inflammatory response, has been shown to have a diurnal variation...
2015: Critical Reviews in Immunology
Huda Makhluf, Sujan Shresta
Dengue virus (DENV), the most prevalent mosquito-borne viral diseases in humans worldwide, causes dengue fever, a mild form of the disease, as well as dengue hemorrhagic fever/dengue shock syndrome, a more severe form which can be life-threatening. The four serotypes of DENV (DENV1-4) are positive-sense, single stranded RNA virus belonging to the Flaviviridae family and are transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Together, they are estimated to cause almost 100 million symptomatic cases, 2...
2015: Critical Reviews in Immunology
Philip Deitiker, M Zouhair Atassi
Autoimmune diseases (ADs), or autoinflammatoiy diseases, are growing in complexity as diagnoses improve and many factors escalate disease risk. Considerable genetic similarity is found among ADs, and they are frequently associated with major histocompatibility complex (MHC) genes. However, a given disease may be associated with more than one human leukocyte antigen (HLA) allotype, and a given HLA may be associated with more than one AD. The associations of non-MHC genes with AD present an additional problem, and the situation is further complicated by the role that other factors, such as age, diet, therapeutic drugs, and regional influences, play in disease...
2015: Critical Reviews in Immunology
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