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Critical Reviews in Immunology

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https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#1
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910766/natural-igm-and-the-development-of-b-cell-mediated-autoimmune-diseases
#2
Trang T T Nguyen, Nicole Baumgarth
Most serum immunoglobulin M (IgM) is "natural IgM", which is produced apparently spontaneously by a distinct subset of B cells requiring no exogenous antigenic or microbial stimuli. Natural IgM is an evolutionarily conserved molecule and reacts with a variety of epitopes expressed on both self- and non-self antigens. It has long been understood that secreted (s) IgM contributes to the removal of altered self-antigens, such as apoptotic and dying cells. As we outline in this review, it is thought that this sIgM housekeeping function removes potential triggers of autoresponse induction...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910765/gene-therapy-for-rheumatoid-arthritis
#3
Shuang Liu, Kazutaka Maeyama
With the aim of controlling disease relapse and bone deformation of individual joints, the application of gene therapy in rheumatoid arthritis (RA) has slowly progressed on a trial-and-error basis. Several new therapeutic targets have been identified in preclinical studies in animal models, although a limited number of gene-based clinical trials have been conducted. In this article, we summarize the status of gene therapy for RA by addressing issues related to innovating drug development. More disease- and target-specific preclinical tests are required to overcome the insufficient information regarding pharmacokinetics and toxicokinetics, which are related to safety issues in the field of RA gene therapy...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910764/metabolic-regulation-of-natural-killer-cell-ifn-%C3%AE-production
#4
Annelise Y Mah, Megan A Cooper
Metabolism is critical for a host of cellular functions and provides a source of intracellular energy. It has been recognized recently that metabolism also regulates differentiation and effector functions of immune cells. Although initial work in this field has focused largely on T lymphocytes, recent studies have demonstrated metabolic control of innate immune cells, including natural killer (NK) cells. Here, we review what is known regarding the metabolic requirements for NK cell activation, focusing on NK cell production of interferon-gamma (IFN-γ)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910763/il10-a-tale-of-an-evolutionarily-conserved-cytokine-across-vertebrates
#5
M Carla Piazzon, George Lutfalla, Maria Forlenza
IL10 was discovered in 1989, and since then it has been the subject of intense investigation, which has revealed its potent anti-inflammatory and regulatory activities in most immune processes during infection and disease. In 2003, the first non-mammalian IL10 sequence was identified in teleost fish, followed in 2004 by the chicken IL10 sequence. In this review, we summarize the work performed in non-mammalian vertebrates in which the IL10, IL10 receptors (IL10Rs), and their signaling components have been identified...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27480903/metabolic-factors-that-contribute-to-lupus-pathogenesis
#6
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
https://www.readbyqxmd.com/read/27480902/clinical-and-experimental-sepsis-impairs-cd8-t-cell-mediated-immunity
#7
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
https://www.readbyqxmd.com/read/27480901/antigen-receptor-intrinsic-non-self-the-key-to-understanding-regulatory-lymphocyte-mediated-idiotypic-control-of-adaptive-immune-responses
#8
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
https://www.readbyqxmd.com/read/27480900/role-in-allergic-diseases-of-immunological-cross-reactivity-between-allergens-and-homologues-of-parasite-proteins
#9
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
https://www.readbyqxmd.com/read/27279046/opportunities-for-translation-from-the-bench-therapeutic-intervention-of-the-jak-stat-pathway-in-neuroinflammatory-diseases
#10
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
https://www.readbyqxmd.com/read/27279045/regulatory-t-cell-therapy-in-transplantation-and-severe-autoimmunity
#11
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
https://www.readbyqxmd.com/read/27279044/identification-of-antigen-specific-b-cell-receptor-sequences-from-the-total-b-cell-repertoire
#12
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
https://www.readbyqxmd.com/read/27279043/interleukin-33-and-its-receptor-in-pulmonary-inflammatory-diseases
#13
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
https://www.readbyqxmd.com/read/27279042/mechanisms-of-cytotoxic-lymphocyte-mediated-apoptosis-and-relationship-with-the-tumor-suppressor-p53
#14
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
https://www.readbyqxmd.com/read/26853852/role-of-cd38-expression-in-diagnosis-and-pathogenesis-of-chronic-lymphocytic-leukemia-and-its-potential-as-therapeutic-target
#15
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
https://www.readbyqxmd.com/read/26853851/the-p53-transcriptional-network-influences-microglia-behavior-and-neuroinflammation
#16
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
https://www.readbyqxmd.com/read/26853850/regulatory-roles-of-rpl22-in-hematopoiesis-an-old-dog-with-new-tricks
#17
REVIEW
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
https://www.readbyqxmd.com/read/26853849/role-of-inflammation-amplifier-induced-growth-factor-expression-in-the-development-of-inflammatory-diseases
#18
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
https://www.readbyqxmd.com/read/26853848/acquisition-and-presentation-of-tumor-antigens-by-dendritic-cells
#19
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
https://www.readbyqxmd.com/read/26757394/the-role-of-the-immunological-synapse-formed-by-cytotoxic-lymphocytes-in-immunodeficiency-and-anti-tumor-immunity
#20
REVIEW
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
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