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Critical Reviews in Immunology

Daniela Frasca, Bonnie B Blomberg
This review highlights recent findings on the effects of aging on influenza vaccine responses, with major emphasis on T and B cells, which are significantly impaired by aging. We discuss changes in T cell production and thymic output; T cell subsets; and TCR repertoire, function, and response to latent persistent infection. We also discuss changes in B cell subsets, repertoire, and function, and how function is impaired by increased intrinsic B cell inflammation and reduced signal transduction. This review presents age-related effects on antigen-presenting cells, summarizes recent studies, including our own, aimed at the identification of biomarkers of protective vaccine responses, and provides examples of recent technical advances and insights into human vaccine responses that are helping to define the features associated with successful vaccination and that may enable a more predictive vaccinology in the future...
2016: Critical Reviews in Immunology
Tessa Dhaeze, Niels Hellings
Follicular regulatory T cells (TFRs) are a subset of regulatory T cells that reside in the secondary lymphoid organs and participate in controlling the germinal center (GC) response. The GC response forms the basis of adaptive immunity to foreign protein antigens. In autoimmune diseases, hyperreactivity to self-antigens occurs that may result from an aberrant control of the GC response. TFR dysfunctionality may be one of the factors contributing to this breakdown of self-tolerance. In this review, we discuss how the investigation of circulating TFRs can help us understand their relative contribution to autoimmune-mediated disease processes...
2016: Critical Reviews in Immunology
Lee Ann Garrett-Sinha, Alyssa Kearly, Anne B Satterthwaite
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by excess B- and T-cell activation, the development of autoantibodies against self-antigens including nuclear antigens, and immune complex deposition in target organs, which triggers an inflammatory response and tissue damage. The genetic and environmental factors that contribute to the development of SLE have been studied extensively in both humans and mouse models of the disease. One of the important genetic contributions to SLE development is an alteration in the expression of the transcription factor Ets1, which regulates the functional differentiation of lymphocytes...
2016: Critical Reviews in Immunology
Juan A Flores, Santiago Balseiro-Gómez, Eva Ales
Secretory granules (SGs) of mast cells (MCs) release their contents to mediate many biological events and a variety of inflammatory diseases and have important protective roles in innate host defense and pathological functions in allergic reactions and anaphylaxis. There are two modes of MC degranulation during the release of granule contents to the extracellular environment. Anaphylactic degranulation (AND) after IgE-mediated activation is characterized by a rapid swelling and fusion of MC granules as well as abrupt mediators release...
2016: Critical Reviews in Immunology
Alessandra Zingoni, Elisabetta Vulpis, Ilaria Nardone, Alessandra Soriani, Cinzia Fionda, Marco Cippitelli, Angela Santoni
Natural killer (NK) cells are critical immune effector cells capable of mediating antitumor responses. These cytotoxic lymphocytes recognize transformed cells through a mechanism mainly dependent on the engagement of several activating receptors. However, many tumors have developed strategies to evade immunosurveillance and detection by NK cells. A relevant immune escape mechanism is the down regulation of NK cell activating ligands on the surface of tumor cells by proteolytic shedding mediated by different members of metalloproteinase families...
2016: Critical Reviews in Immunology
Stephane Esnault, Elizabeth A Kelly
Compelling evidence has demonstrated that the eosinophils bring negative biological outcomes in several diseases, including eosinophilic asthma and hypereosinophilic syndromes. Eosinophils produce and store a broad range of toxic proteins and other mediators that enhance the inflammatory response and lead to tissue damage. For instance, in asthma, a close relationship has been demonstrated between increased lung eosinophilia, asthma exacerbation, and loss of lung function. The use of an anti-IL-5 therapy in severe eosinophilic asthmatic patients is efficient to reduce exacerbations...
2016: Critical Reviews in Immunology
Gianfranco Lauletta, Sabino Russi, Fabio Pavone, Andrea Marzullo, Marilina Tampoia, Domenico Sansonno, Franco Dammacco
Autoimmune hepatitis is an acute or mostly chronic liver disease that can affect both adults and children and has a clear prevalence for the female sex. A definite etiology has not been established, but it is known that genetic predisposing profiles and exogenous trigger factors are involved. The main diagnostic criteria include typical histological features, the occurrence of serum auto-antibodies, and increased levels of transaminases and gamma-globulins. Instances of autoimmune hepatitis sharing features with other autoimmune liver diseases have also been observed...
2016: Critical Reviews in Immunology
Sarang Tartey, Osamu Takeuchi
Extensive studies in last decade have demonstrated that dynamic control of gene transcription is key in the regulation of inflammatory responses. Although signaling pathways and transcription factors have a central role, growing evidence for the involvement of chromatin in the regulation of gene expression in immune cells has uncovered an evolutionarily conserved role of pathogen recognition and epigenetic regulation. The substantial potential of these responses to drive pathological inflammation and tissue damage highlights the need for rigorous control of these responses...
2016: Critical Reviews in Immunology
Lucas T Jennelle, Aditya P Dandekar, Tshifhiwa Magoro, Young S Hahn
Understanding of antigen-presenting cell (APC) participation in tissue inflammation and metabolism has advanced through numerous studies using systems biology approaches. Previously unrecognized connections between these research areas have been elucidated in the context of inflammatory disease involving innate and adaptive immune responses. A new conceptual framework bridges APC biology, metabolism, and cytokines in the generation of effective T-cell responses. Exploring these connections is paramount to addressing the rising tide of multi-organ system diseases, particularly chronic diseases associated with metabolic syndrome, infection, and cancer...
2016: Critical Reviews in Immunology
Felix Radford, Sanjay Tyagi, Maria Laura Gennaro, Richard Pine, Yuri Bushkin
Fluorescence in situ hybridization coupled with flow cytometry (FISH-Flow) is a highly quantitative, high-throughput platform allowing precise quantification of total mRNA transcripts in single cells. In undiagnosed infections posing a significant health burden worldwide, such as latent tuberculosis or asymptomatic recurrent malaria, an important challenge is to develop accurate diagnostic tools. Antigen-specific T cells create a persistent memory to pathogens, making them useful for diagnosis of infection...
2016: Critical Reviews in Immunology
Taizo Wada, Tadayuki Akagi
Neutrophil-specific granule deficiency (SGD) is a rare autosomal recessive primary immunodeficiency characterized by bilobed neutrophil nuclei and lack of neutrophil-specific granule proteins such as lactoferrin. A deficiency of a myeloid-specific transcription factor, CCAAT/enhancer binding protein-epsilon (C/EBPε), has been identified as a cause of SGD. C/EBPε binds to DNA though its basic leucine zipper (bZIP) domain, and regulates terminal differentiation of neutrophils and expression of specific granule genes...
2016: Critical Reviews in Immunology
Susanne Michen, Achim Temme
Natural killer (NK) cells are lymphoid cells of the innate immune system; they stand at the first defense line against viruses and transformed cells. NK cells use an array of germline-encoded activating and inhibitory receptors that sense virus-infected cells or malignant cells displaying altered surface expression of activating and inhibitory NK cell ligands. They exert potent cytotoxic responses to cellular targets and thus are candidate effector cells for immunotherapy of cancer. In particular, the genetic engineering of NK cells with chimeric antigen receptors (CARs) against surface-expressed tumor-associated antigens (TAAs) seems promising...
2016: Critical Reviews in Immunology
Petros Christopoulos, Paul Fisch
Acquired T-cell immunodeficiency can occur in thymoma patients with or without hypogammaglobulinemia (Good's syndrome), but it has received little attention to date. It appears predominantly associated with lymphocyte-rich (i.e., cortical or mixed) thymomas and frequently coexists with autoimmune manifestations. The main abnormalities are an increase in circulating naive T cells, cutaneous T-cell anergy, TCR hyporesponsiveness in vitro as well as a numerical and functional impairment of regulatory T cells. All of these probably result from an abnormal T-cell maturation in the neoplastic thymic microenvironment...
2016: Critical Reviews in Immunology
Veronica M Ringel-Scaia, Dylan K McDaniel, Irving C Allen
Recent advances have revealed significant insight into inflammatory bowel disease (IBD) pathobiology. Ulcerative colitis and Crohn's disease, the chronic relapsing clinical manifestations of IBD, are complex disorders with genetic and environmental influences. These diseases are associated with the dysregulation of immune tolerance, excessive inflammation, and damage to the epithelial cell barrier. Increasing evidence indicates that pattern recognition receptors, including Toll-like receptors (TLRs) and nucleotide-binding domain and leucine-rich repeat-containing proteins (NLRs), function to maintain immune system homeostasis, modulate the gastrointestinal microbiome, and promote proper intestinal epithelial cell regeneration and repair...
2016: Critical Reviews in Immunology
Simon Kollnberger
HLA-class I molecules form trimeric complexes (pMHC) of peptides, class I heavy chains, and β2microglobulins (β2m) that regulate immune responses by binding to T cells and other immune receptors. B2m-free class I heavy chains (FHCs) form on cells either as a consequence of the natural turnover of pMHC or, in the case of HLA-F, are expressed without β2m. Distinct characteristics of certain HLA-class I members, such as HLA-B27 and HLA-F, stabilize these forms facilitating interactions with immune receptors...
2016: Critical Reviews in Immunology
Kei Ohnuma, Ryo Hatano, Takumi Itoh, Noriaki Iwao, Nam H Dang, Chikao Morimoto
Obliterative bronchiolitis is the primary noninfectious pulmonary complication after allogeneic hematopoietic cell transplantation and the only pathognomonic manifestation of pulmonary chronic graft-versus-host disease (cGVHD). In our recent study, we identified a novel effect of IL-26, which is absent in rodents, on transplant related-obliterative bronchiolitis. Sublethally irradiated NOD/Shi-scidIL2rγnull mice transplanted with human umbilical cord blood gradually exhibited obliterative bronchiolitis with increased collagen deposition and predominant infiltration with human IL-26+CD26+CD4 T cells...
2016: Critical Reviews in Immunology
Julia Strandmark, Sebastian Rausch, Susanne Hartmann
Eosinophil numbers are highly elevated during helminth infections and a range of allergic and inflammatory disorders, but eosinophils are also present in several tissues in the absence of infection. Indeed, new findings demonstrate that eosinophils may be involved in events as diverse as glucose metabolism, mammary gland development, intestinal health, tissue remodeling, thymic selection, and B-cell survival. Although eosinophils often correlate with pathological parameters during conditions such as inflammatory bowel disease and asthma, the evidence for their contribution to tissue pathology remains controversial...
2016: Critical Reviews in Immunology
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
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
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
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