Showing papers in "International Reviews of Immunology in 2011"
TL;DR: In this review, a comprehensively review the recent progress in the field of PAMP recognition by PRRs and the signaling pathways activated byPRRs.
Abstract: Microbial infection initiates complex interactions between the pathogen and the host. Pathogens express several signature molecules, known as pathogen-associated molecular patterns (PAMPs), which are essential for survival and pathogenicity. PAMPs are sensed by evolutionarily conserved, germline-encoded host sensors known as pathogen recognition receptors (PRRs). Recognition of PAMPs by PRRs rapidly triggers an array of anti-microbial immune responses through the induction of various inflammatory cytokines, chemokines and type I interferons. These responses also initiate the development of pathogen-specific, long-lasting adaptive immunity through B and T lymphocytes. Several families of PRRs, including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and DNA receptors (cytosolic sensors for DNA), are known to play a crucial role in host defense. In this review, we comprehensively review the recent progress in the field of PAMP recognition by PRRs and the signaling pathways activated by PRRs.
1,896 citations
TL;DR: Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals, showing features of both an innate and an adaptive response to gluten prolamins.
Abstract: Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. It is one of the most common lifelong disorders on a worldwide basis. Celiac enteropathy is the final consequence of an abnormal immune reaction, showing features of both an innate and an adaptive response to gluten prolamins. The clinical spectrum is wide, including cases with either typical intestinal or atypical extraintestinal features, and silent forms. The only available treatment consists in dietary exclusion of grains containing gluten. New pharmacological treatment are currently under scrutiny.
203 citations
TL;DR: This review summarizes current knowledge of the associations between the intestinal microbiota and celiac disease and its possible modes of action in pathogenesis and suggests deeper understanding of these interactions can help redefine how this disorder is investigated.
Abstract: Celiac disease is a multifactorial disorder that involves interactions between genetic and environmental factors. Gluten proteins are responsible for the symptoms of celiac disease, but other environmental factors that influence the intestinal ecosystem, including the milk-feeding type and gastrointestinal infections, may also play a role. Moreover, intestinal dysbiosis, characterized by increased Gram-negative bacteria and reduced bifidobacteria, has been detected in celiac disease patients. This review summarizes current knowledge of the associations between the intestinal microbiota and celiac disease and its possible modes of action in pathogenesis. Deeper understanding of these interactions can help redefine how this disorder is investigated.
130 citations
TL;DR: Clinically approved adjuvants, including Montanide™ ISA-51 and 720, and keyhole-limpet proteins can be used to enhance tumor cell immunogenicity by stimulating both humoral and cellular anti-tumor responses.
Abstract: Whole tumor cell lysates can serve as excellent multivalent vaccines for priming tumor-specific CD8+ and CD4+ T cells. Whole cell vaccines can be prepared with hypochlorous acid oxidation, UVB-irradiation and repeat cycles of freeze and thaw. One major obstacle to successful immunotherapy is breaking self-tolerance to tumor antigens. Clinically approved adjuvants, including Montanide™ ISA-51 and 720, and keyhole-limpet proteins can be used to enhance tumor cell immunogenicity by stimulating both humoral and cellular anti-tumor responses. Other potential adjuvants, such as Toll-like receptor agonists (e.g., CpG, MPLA and PolyI:C), and cytokines (e.g., granulocyte-macrophage colony stimulating factor), have also been investigated.
105 citations
TL;DR: Current knowledge on potential mechanisms underlying the biphasic, bidirectional regulation of NF-κB by the UPR is summarized and possible roles for ER stress in the regulation of inflammation are considered.
Abstract: Under inflammatory situations, endoplasmic reticulum (ER) stress occurs at local sites and modulates inflammatory processes. NF-κB is a key regulator for immune and inflammatory responses, and its activity is influenced by ER stress positively or negatively. Recent investigation suggested that ER stress induces activation of NF-κB in the early phase, whereas in the later phase, consequent unfolded protein response (UPR) inhibits NF-κB. This review summarizes current knowledge on potential mechanisms underlying the biphasic, bidirectional regulation of NF-κB by the UPR and possible roles for ER stress in the regulation of inflammation.
100 citations
TL;DR: This review aims to underline the most reliable cancer testis antigens under investigation at this moment, which were demonstrated to be very promising for the early diagnosis and development of vaccines for ovarian cancer.
Abstract: Ovarian cancer is the fifth leading cause of cancer death in women and the leading cause from gynecological malignancies. Despite the recently improved outcomes of new chemotherapeutical agents in the therapy of ovarian cancer and the increased 5-year survival rate, the mortality of this malignancy disease remains unchanged. Ovarian cancer therapy is often correlated to the stage of the tumor, but the first step is usually surgical treatment. Afterward, various courses of chemotherapy and radiation are suggested. Obviously, the higher the developmental stage of the tumor, the less the probability is in eradicating it surgically, especially in relation to metastasis. It is clear that an early diagnosis of ovarian cancer is important for the survival of these patients. In order to identify ovarian cancer patients in the early stages, a number of studies are focusing on a particular class of antigens called cancer testis antigens. These antigens display high expression in tumors of different histology, but are normally restricted to the testis and have low or no expression in normal tissues. The testes are an immunologically-privileged site due to the presence of tight junctions between adjacent Sertoli cells that constitute the blood-testis barrier, which prevents auto-immune reactions. In the past few years, some of these antigens were demonstrated to be very promising for the early diagnosis and development of vaccines for ovarian cancer. This review aims to underline the most reliable cancer testis antigens under investigation at this moment.
67 citations
TL;DR: In celiac disease, highly sensitive and specific serum endomysial and transglutaminase 2 antibody tests are widely used in identifying patients for diagnostic endoscopy and small-bowel biopsy, and other diagnostic approaches beyond conventional histology have been introduced.
Abstract: In celiac disease, highly sensitive and specific serum endomysial and transglutaminase 2 antibody tests are widely used in identifying patients for diagnostic endoscopy and small-bowel biopsy. In addition, the recently developed deamidated gliadin peptide antibody tests show promise in celiac disease diagnostics. In view of these apparent problems attending the diagnostic gold standard, gluten-induced small-bowel mucosal villous atrophy with crypt hyperplasia, other diagnostic approaches beyond conventional histology have been introduced. Furthermore, the diagnostic criteria for celiac disease are currently under revision with an eye also to noninvasive diagnostic strategies.
38 citations
TL;DR: This review illustrates the significance of CCL5-dependent pathways in HCV-related immunopathogenesis by elaborating on biological mechanisms interconnecting peripheral and tissue immunology, liver pathology, HSC activation, and interferon-α immunotherapy.
Abstract: C-C motif ligand 5 (CCL5) facilitates induction of chemotaxis in immune cells and activation of hepatic stellate cells (HSC) at sites of liver inflammation during chronic hepatitis C virus (HCV) infection. Importantly, CCL5 participates in the establishment of T-helper 1 responses crucial in controlling liver disease and HCV infection outcome and demonstrates distinct gene expression patterns between the blood and the liver, stressing the importance of immunoregulatory networks differentially functioning between these compartments. This review illustrates the significance of CCL5-dependent pathways in HCV-related immunopathogenesis by elaborating on biological mechanisms interconnecting peripheral and tissue immunology, liver pathology, HSC activation, and interferon-α immunotherapy.
32 citations
TL;DR: The nature, cellular interactions, and prognostic significance of the main APC populations in ovarian cancer are summarized, and the relevance of manipulating APC subsets for patient treatment is discussed.
Abstract: The major human antigen-presenting cells (APCs) include monocytes/macrophages, myeloid dendritic cells (mDC), plasmacytoid dendritic cells (pDC), and B cells. These APC subsets have been observed in ovarian tumor environments. Their phenotypes and functionalities are subjected to alteration by multiple factors in the tumor environment. In this review, we summarize the nature, cellular interactions, and prognostic significance of the main APC populations in ovarian cancer, and discuss the relevance of manipulating APC subsets for patient treatment.
32 citations
TL;DR: Mouse strains and protocols have been developed that are now just beginning to address the complex interactions among the innate and adaptive immune responses to gluten, as well as gluten-dependent autoimmunity in celiac disease.
Abstract: Several animal models have been recently developed to recapitulate various components of the complex process that is celiac disease. In addition to the increasing diversity of murine models there are now monkey models of celiac disease. Mouse strains and protocols have been developed that are now just beginning to address the complex interactions among the innate and adaptive immune responses to gluten, as well as gluten-dependent autoimmunity in celiac disease. The most important conclusion that these models have provided us with so far is that while all three components (innate gluten sensitivity, adaptive gluten sensitivity, and autoimmunity) are independent phenomena, all are necessary for celiac disease to develop.
30 citations
TL;DR: The fundaments of chimeric antigen receptors in terms of structure, function, possible targets and pre-clinical and clinical applications are described, paving the road to a wider application of this exciting new technology.
Abstract: The concept of chimeric antigen receptors (CARs) as molecules able to redirect T lymphocytes toward tumor cells is currently being exploited in the field of cancer immunotherapy. Despite promising preliminary results, some clinical trials evidenced limitations for this technology that must be overcome for more extensive application of CARs in tumor immunotherapy. We describe here the fundaments of these molecules in terms of structure, function, possible targets and preclinical and clinical applications. We also discuss strategies that can potentially overcome the limitations seen so far, paving the road to a wider application of this exciting new technology.
TL;DR: The authors comprehensively describe the methods used to identify disease-specific peptide/MHC class I epitopes and generate antibodies to these markers and offer several examples that illustrate the promise of using these antibodies as anti-cancer agents.
Abstract: The human leukocyte antigen (HLA; also called major histocompatibility, or MHC) class I system presents peptides that distinguish healthy from diseased cells. Therefore, the discovery of peptide/MHC class I markers can provide highly specific targets for immunotherapy. Over the course of almost two decades, various strategies have been used, with mixed success, to produce antibodies that have recognition specificity for unique peptide/MHC class I complexes that mark infected and cancerous cells. Using these antibody reagents, novel peptide/MHC class I targets have been directly validated on diseased cells and new insight has been gained into the mechanisms of antigen presentation. More recently, these antibodies have shown promise for clinical applications such as therapeutic targeting of cancerous and infected cells and diagnosis and imaging of diseased cells. In this review, the authors comprehensively describe the methods used to identify disease-specific peptide/MHC class I epitopes and generate antibodies to these markers. Finally, they offer several examples that illustrate the promise of using these antibodies as anti-cancer agents.
TL;DR: This review covers immune and anatomic considerations specific for ovarian cancer immune therapy and potential means for future investigations and means to integrate immune with other approaches.
Abstract: This review covers immune and anatomic considerations specific for ovarian cancer immune therapy. Prior approaches and potential reasons for lack of better efficacy are discussed, along with newer approaches in pre-clinical and early clinical development. Potential means for future investigations and means to integrate immune with other approaches are discussed.
TL;DR: Sperm protein 17 is expressed by tumors, including ovarian cancer, indicating that it is an ideal target for cancer immunotherapy, and plays a role in tumorigenesis and drug resistance.
Abstract: Sperm protein 17 belongs to the cancer/testis antigen family and was found to play a key role in the cell fusion process between the mammalian spermatozoa and egg. Sperm protein 17-specific autoantibodies in vasectomized males suggest its high expression in the testis. Sperm protein 17 expression levels are low or absent in normal tissues, other than the testis. Sperm protein 17 is expressed by tumors, including ovarian cancer, indicating that it is an ideal target for cancer immunotherapy, and plays a role in tumorigenesis and drug resistance. This review recapitulates the milestones of sperm protein 17 research and highlights its potential use in translational medicine.
TL;DR: This review focuses on selected cell populations in the peritoneal cavity immune system and their potential role in epithelial ovarian cancer immunopathogenesis, with most attention to dendritic cells because they are considered to be superior in their antigen-presenting ability.
Abstract: The development of epithelial ovarian cancer is associated with changes in the peritoneal cavity microenvironment. Tumor cells produce different factors, which impairs differentiation, maturation, and function of antigen-presenting cells. In this review, we focus on selected cell populations in the peritoneal cavity immune system and their potential role in epithelial ovarian cancer immunopathogenesis. We devote most attention to dendritic cells because they are considered to be superior in their antigen-presenting ability, compared with both macrophages and B lymphocytes. We also present a brief characterization of tumor-infiltraiting cells in epithelial ovarian cancer patients.
TL;DR: The basic mechanisms of tumor immune surveillance are reviewed with a particular focus on ovarian cancer, and cutting-edge strategies to promote immune system eradication of ovarian tumors are discussed.
Abstract: Despite decades of research, ovarian cancer remains a lethal disease. Recent studies have reported the critical role played by the immune system in controlling growth and spread of ovarian tumors. Accordingly, immunotherapy has been indicated as the most likely successful new approach in the treatment of the disease. Unfortunately, ovarian cancer triggers immune inhibitory mechanisms that hamper anti-tumor responses. Therefore, future immunotherapies should be able to overcome these obstacles. Here we review the basic mechanisms of tumor immune surveillance with a particular focus on ovarian cancer, and we discuss cutting-edge strategies to promote immune system eradication of ovarian tumors.
TL;DR: This review focuses on the interaction of different chronic viruses with dendritic cells and the viruses’ ability to exploit this critical cell type to their advantage so as to establish persistence within the host.
Abstract: The human immune system is under constant challenge from many viruses, some of which the body is successfully able to clear. Other viruses have evolved to escape the host immune responses and thus persist, leading to the development of chronic diseases. Dendritic cells are professional antigen-presenting cells that play a major role in both innate and adaptive immunity against different pathogens. This review focuses on the interaction of different chronic viruses with dendritic cells and the viruses’ ability to exploit this critical cell type to their advantage so as to establish persistence within the host.
TL;DR: The initial use in the treatment of bacterial infections in children with HIV/AIDS has been replaced by the treatment, in combination with antiretroviral therapy, of these autoimmune/inflammatory conditions.
Abstract: Intravenous immunoglobulins (IVIGs) are generally used as replacement therapy for humoral immunodeficiencies. In consideration of their immune-modulating properties, they are also employed as "immune-modulating/anti-inflammatory" treatment in different clinical conditions. In HIV-1 infection, an increased incidence of autoimmune and auto-inflammatory manifestations has been described, probably as a consequence of the chronic immune activation associated with the disease. The initial use in the treatment of bacterial infections in children with HIV/AIDS has been replaced by the treatment, in combination with antiretroviral therapy, of these autoimmune/inflammatory conditions. We review the results obtained with IVIGs therapy in these HIV-1-associated clinical manifestations.
TL;DR: In depth understanding of the pathogenesis of CD creates the premises of developing novel, more accurate animal models that should support a rationale development of new prophylactic and therapeutic interventions.
Abstract: The current issue of the International Reviews of Immunology is dedicated entirely to Celiac Disease (CD). Recent development of additional biomarkers and diagnostics resulted in a sharp revision of the prevalence of this condition, with a previously unrecognized subclinical occurrence in the adult population. This was paralleled by groundbreaking progress in understanding its molecular pathogenesis: while gluten-derived peptides activate the innate immunity, post-translationally modified gluten elicits an adaptive immunity. These arms amplify each other, resulting in a self- perpetuating autoimmune condition, influenced by disturbances of the gut flora and mucus chemistry. The process evolves dramatically in a subset of patients with vulnerable immune homeostasis (eg. Treg cells) explaining the progressive, aggravating syndrome in the clinically overt version of CD. In depth understanding of the pathogenesis of CD thus creates the premises of developing novel, more accurate animal models that should support a rationale development of new prophylactic and therapeutic interventions.
TL;DR: A novel, integrated approach to immunotherapy that combines novel technologies to discover and target disease-specific peptide/HLA class I complexes, which makes the entire proteome accessible to antibody reagents and offers unsurpassed specificity for targeting cancerous and infected cells.
Abstract: The development of immunotherapies offers significant promise for clinical applications in cancer and infectious diseases. Here the authors describe a novel, integrated approach to immunotherapy that combines novel technologies to discover and target disease-specific peptide/HLA class I complexes. This unique class of markers makes the entire proteome accessible to antibody reagents and offers unsurpassed specificity for targeting cancerous and infected cells. Arm one of the three-armed approach uses an innovative technology for the efficient, direct discovery of new peptide/HLA class I markers. Arm two applies a powerful and inventive strategy to generate T-cell receptor mimics (TCRms), which are antibodies with exquisite binding specificity for peptide/HLA class I markers, and uses TCRms to validate the specific expression of markers on cancerous and infected cells. The third arm uses TCRms to target and kill diseased cells with high sensitivity and specificity. In summary, the combination of two pionee...
TL;DR: The authors critically review the different immunotherapeutic approaches in melanoma and suggest several new approaches that should be considered for further investigation.
Abstract: Due to its immunogenecity and evidence of immune responses resulting in tumor regression, metastatic melanoma has been the target for numerous immunotherapeutic approaches. Unfortunately, based on the clinical outcomes, even the successful induction of tumor-specific responses does not correlate with efficacy. Immunotherapies can be divided into antigen-specific approaches, which seek to induce T cells specific to one or several known tumor associated antigens (TAA), or with antigen-nonspecific approaches, which generally activate T cells to become nonspecifically lytic effectors. Here the authors critically review the different immunotherapeutic approaches in melanoma.
TL;DR: This issue, Dr. Masanori Kitamura outlines major evidence to date, that links the UPR to immunity through the pivotal node, NF-kB, that regulates production of a large array of proinflammatory molecules.
Abstract: In this issue, we are hosting several reviews focusing on: (1) the interface between the immune system and endogenous or exogenous immune danger sensed through the unfolded protein response (UPR) a...
TL;DR: An overview is provided of the recent progress made in the sMHC I and sMIC fields, with emphasis on their structure, formation, and function, and the key-questions that still await answers are addressed.
Abstract: It has become clear that soluble MHC I (sMHC I) and soluble MIC (sMIC), which are highly elevated in sera of cancer patients, can be viewed to be tolerogenic, and that metalloproteinases are involved in their generation process. In this review, an overview is provided of the recent progress made in the sMHC I and sMIC fields, with emphasis on their structure, formation, and function, and the key-questions that still await answers are addressed. Understanding better their formation mechanism, it will become more feasible to modulate the immune responses in cancer patients by targeting molecules involved in their generation process.
TL;DR: This issue of International Reviews of Immunology focuses on the immunology of ovarian cancer, with a particular emphasis on the role of antigen-presenting cells in shaping immunological stasis within the tumor microenvironment.
Abstract: Although there has been a marked resurgence of optimism that tumor vaccination or active immunotherapy may hold the prospect of clinical benefit for ovarian cancer patients, this optimism has been tempered by an appreciation that ovarian cancer represents a paradigm for the art of immunological defense. The pathogenesis of ovarian cancer is characterized by the evolution of multiple immunosuppressive mechanisms in the tumor microenvironment, several of which correlate with increased morbidity and mortality in ovarian cancer patients. This issue of International Reviews of Immunology focuses on the immunology of ovarian cancer, with a particular emphasis on the role of antigen-presenting cells in shaping immunological stasis within the tumor microenvironment. An understanding of these mechanisms will likely guide the development of novel adjuvants to alleviate local immune suppression in support of clinically effective ovarian tumor vaccination.
TL;DR: This issue of the journal is hosting in this issue, two reviews discussing the complex matter and dynamic balance between immunity and viral infections, as the concept of fine modulation of that balance still carries the promise of yielding novel therapies.
Abstract: As the immune system essentially evolved to fight off or keep at bay life-threatening infectious agents rather than cancer, the question remains as to how to best redeploy it for the treatment of a broader range of diseases. This is reflected by an unprecedented diversification of platform technologies in development, facilitated by rapid progress in biotechnology. In this issue, we host several contributions outlining major efforts in developing novel immune interventions spanning antigen-specific vaccination, non-antigen-targeted immune intervention, genetically engineered lymphocytes, and ultraspecific antigen-targeted ligands. In addition, the journal is hosting in this issue, two reviews discussing the complex matter and dynamic balance between immunity and viral infections, as the concept of fine modulation of that balance still carries the promise of yielding novel therapies.