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Activation of the innate immune system by CpG oligodeoxynucleotides: immunoprotective activity and safetyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleDOI 10.1007/s002810050027Authors Dennis M. Klinman, Food and Drug Administration Section of Retroviral Research, Center for Biologies Evaluation and Research Bldg 29A Rm 3 D 10 20892 Bethesda MDSoren Kamstrup, Food and Drug Administration Section of Retroviral Research, Center for Biologies Evaluation and Research Bldg 29A Rm 3 D 10 20892 Bethesda MDDaniela Verthelyi, Food and Drug Administration Section of Retroviral Research, Center for Biologies Evaluation and Research Bldg 29A Rm 3 D 10 20892 Bethesda MDIhsan Gursel, Food and Drug Administration Section of Retroviral Research, Center for...
Source: Springer Seminars in Immunopathology - April 8, 2009 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Signal transduction induced by immunostimulatory CpG DNAEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The immune recognition of unmethylated CpG motifs appears to be an example of the ability of the immune system to detect molecular patterns which are characteristic of microbes, but are not present in vertebrates. This detection is accomplished by the means of pattern recognition receptors (PRR). Unlike some other examples of PRR, immune recognition of CpG DNA appears to require cell uptake and to be accomplished through an intracellular PRR system. This then results in the activation of mitogen-activated protein kinases, culminating in the phosphorylation of transcription factors and the activation...
Source: Springer Seminars in Immunopathology - April 8, 2009 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Modulation of asthmatic response by immunostimulatory DNA sequencesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion A variety of DNA-based methods of modulating the immune and/or inflammatory response in animal models of asthma have shown significant promise. Antisense strategies seek to inhibit expression of specific host genes, whereas DNA vaccines aim to modulate the immune response to specific encoded allergens. In contrast, ISS DNA therapy seeks to redirect the host immune response from a Th2 to a Th1 response. Current human studies will help to determine which, if any, of these DNA based therapies is a safe and effective therapy for human asthma. Content Type Journal ArticleDOI 10.1007/s002810050021Aut...
Source: Springer Seminars in Immunopathology - April 8, 2009 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Interactions of fibroblasts with the extracellular matrix: implications for the understanding of fibrosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The cellular organization and the compartmentalization in multicellular organisms is mediated by the extracellular matrix (ECM). This structure is composed by a wide variety of different macromolecules which carry distinct domains with defined structural and/or biological activities. Cells are known to interact with these molecules via specific receptors. Following activation, these receptors transduce signals either directly to the intracellular cytoskeleton or via different signalling cascades. Cell-matrix interactions, therefore, not only control the shape and orientation of cells but can also di...
Source: Springer Seminars in Immunopathology - April 8, 2009 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Introductory note to: Fibrosis year 2000Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleDOI 10.1007/s002810000031Authors Carlo Chizzolini, Geneva University Hospital Division of Immunology and Allergy 1211 Geneva 14 Switzerland Journal Springer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325 Journal Volume Volume 21 Journal Issue Volume 21, Number 4 / June, 2000
Source: Springer Seminars in Immunopathology - April 8, 2009 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Fibroblast heterogeneity in physiological conditions and fibrotic diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleDOI 10.1007/s002810000032Authors Ante Jelaska, Boston University School of Medicine The Arthritis Center 715 Albany St. 02118 Boston MA USADavid Strehlow, Boston University School of Medicine The Arthritis Center 715 Albany St. 02118 Boston MA USAJoseph H. Korn, Boston University School of Medicine The Arthritis Center 715 Albany St. 02118 Boston MA USA Journal Springer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325 Journal Volume Volume 21 Journal Issue Volume 21, Number 4 / June, 2000
Source: Springer Seminars in Immunopathology - April 8, 2009 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Lung fibrosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleDOI 10.1007/s002810000036Authors Carmen Fonseca, University College London, (Royal Free Campus) Centre for Rheumatology, Department of Medicine, Royal Free and University College Medical School Rowland Hill Street NW3 2PF London UKDavid Abraham, University College London, (Royal Free Campus) Centre for Rheumatology, Department of Medicine, Royal Free and University College Medical School Rowland Hill Street NW3 2PF London UKCarol M. Black, University College London, (Royal Free Campus) Centre for Rheumatology, Department of Medicine, Royal Free and University College Medical School Rowland H...
Source: Springer Seminars in Immunopathology - April 8, 2009 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

T lymphocyte and fibroblast interactions: the case of skin involvement in systemic sclerosis and other examplesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleDOI 10.1007/s002810000035Authors Carlo Chizzolini, University Hospital Division of Immunology and Allergy 1211 Geneva 14 Switzerland Journal Springer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325 Journal Volume Volume 21 Journal Issue Volume 21, Number 4 / June, 2000
Source: Springer Seminars in Immunopathology - April 8, 2009 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Liver fibrosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Knowledge on the development and progression of liver fibrosis has grown exponentially in the past decade. At present, liver fibrogenesis is referred to as a dynamic process involving complex cellular and molecular mechanisms, resulting from the chronic activation of the tissue repair mechanisms that follows reiterated liver tissue injury. The identification and characterization of the cell types and of the different mediators involved in this process has allowed a “re-visitation” of several issues related to liver cirrhosis and its immediate consequences. Among these, evaluation of the relation...
Source: Springer Seminars in Immunopathology - April 8, 2009 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

γδ T cells, their T cell receptor usage and role in human diseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleDOI 10.1007/s002810050052Authors Dieter Kabelitz, Department of Immunology, Paul-Ehrlich-Institute, Paul-Ehrlich-Str. 51–59, D-63225 Langen, Germany DEDaniela Wesch, Department of Immunology, Paul-Ehrlich-Institute, Paul-Ehrlich-Str. 51–59, D-63225 Langen, Germany DEThomas Hinz, Department of Immunology, Paul-Ehrlich-Institute, Paul-Ehrlich-Str. 51–59, D-63225 Langen, Germany DE Journal Springer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325 Journal Volume Volume 21 Journal Issue Volume 21, Number 1 / March, 1999
Source: Springer Seminars in Immunopathology - October 22, 2008 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Photoimmunology—illuminating the immune system through photobiologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract??We review the field of photoimmunology with emphasis on immunosuppression induced by ultraviolet B radiation. Recent studies have focused on UVB-induced alterations in epidermal Langerhans cell function, resulting in a shift from Th1 to Th2 phenotype and the activation of regulatory T cells as the source of IL-10 that is central to this form of immunosuppression. Content TypeJournal Article JournalSpringer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325
Source: Springer Seminars in Immunopathology - March 5, 2007 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Topical vaccination: the skin as a unique portal to adaptive immune responsesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract??Skin is an ideal tissue for vaccine administration, as it is comprised of immunocompetent cells such as keratinocytes and Langerhans cells and elicits both innate and adaptive immune responses. In this paper, we summarize the immune responses induced by topical vaccination of the skin and review the effects of adjuvants on skin vaccination. We also summarize the existing techniques for skin vaccination. New techniques such as the use of lasers to enhance skin permeability are also discussed, as well as the role of the stratum corneum in skin vaccination. A recent study demonstrating enhanced skin vaccination by u...
Source: Springer Seminars in Immunopathology - March 5, 2007 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Toll-like receptors in the skinEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract??Toll-like receptors (TLRs) are important pattern-recognition receptors involved in host defense against a variety of pathogenic microorganisms. Activation of TLRs leads to the production of cytokines, chemokines, antimicrobial peptides, and upregulation costimulatory and adhesion molecules involved in innate and adaptive immune responses. TLRs are expressed on a variety of cell types found in the skin, including keratinocytes and Langerhans cells in the epidermis, resident and trafficking immune-system cells such as macrophages, dendritic cells, T and B cells, and mast cells in the dermis, endothelial cells of th...
Source: Springer Seminars in Immunopathology - February 23, 2007 Category: Pathology Tags: Springer Seminars in Immunopathology Source Type: journals

Activating and inhibitory FcγRs in autoimmune disordersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Autoimmune disorders are characterized by the destruction of self-tissues by the immune system. Multiple checkpoints are in place to prevent autoreactivity under normal circumstances. Coexpression of activating and inhibitory Fc receptors (FcR) represents such a checkpoint by establishing a threshold for immune cell activation. In many human autoimmune diseases, however, balanced FcR expression is disturbed. Analysis of murine model systems provides strong evidence that aberrant FcR expression can result in uncontrolled immune responses and the initiation of autoimmune disease. This review will summarize this data...
Source: Springer Seminars in Immunopathology - November 18, 2006 Category: Pathology Source Type: journals

Injecting drugs of abuse and immunity: implications for HIV vaccine testing and efficacyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The recreational use of legal and illegal drugs has significant effects on immune responses and can potentially modulate susceptibility to infection by a number of pathogens. A number of agents including cannabinoids (marijuana), cocaine opiates, amphetamines, nicotine and alcohol were demonstrated to have potentially adverse effects on the susceptibility to infections, mediated most likely, by adverse effects on immunity. As such, these drugs of abuse could have significant and potentially adverse effects on the vaccination efficacy of a number of vaccines currently on the market and on potential experimental vac...
Source: Springer Seminars in Immunopathology - November 17, 2006 Category: Pathology Source Type: journals

Fcε- and Fcγ-receptor signaling in diseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract It has become increasingly clear that receptors for the immunoglobulin Fc region play pivotal roles in immune homeostasis and disease. This review describes the fine regulation of the high-affinity IgE-receptor (FcεRI) signaling, especially focusing on the early events that are coordinately regulated by Src family protein tyrosine kinases (PTKs), FcεRI β-subunit, and membrane lipid rafts. Because allergen-mediated FcεRI cross-linking leads to the synthesis and release of a variety of proinflammatory mediators and cytokines, the duration and amplitude of the signal need to be strictly controlled...
Source: Springer Seminars in Immunopathology - November 16, 2006 Category: Pathology Source Type: journals

Fc gamma receptors and cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract FcγRs are a family of heterogeneous molecules that play opposite roles in immune response and control the effector functions of IgG antibodies. In many cancers, IgG antibodies are produced that recognize cancer cells, form immune complexes and therefore, activate FcγR. The therapeutic efficacy of monoclonal IgG antibodies against hematopoietic and epithelial tumors also argue for an important role of IgG antibodies in anti-tumor defenses. Since the 1980s, a series of lines of evidence in experimental models and in humans strongly suggest that FcγR are involved in the therapeutic activity of monoclon...
Source: Springer Seminars in Immunopathology - November 10, 2006 Category: Pathology Source Type: journals

Fcγ receptor-dependent effector mechanisms regulate CD19 and CD20 antibody immunotherapies for B lymphocyte malignancies and autoimmunityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Immunotherapy using Rituximab, an unconjugated CD20 monoclonal antibody, has proven effective for treating non-Hodgkin’s lymphoma and autoimmune disease. CD19 antibody immunotherapy is also effective in mouse models of lymphoma and autoimmunity. In both cases, mouse models have demonstrated that effector cell networks effectively deplete the vast majority of circulating and tissue B lymphocytes through Fcγ receptor-dependent pathways. In mice, B cell depletion is predominantly, if not exclusively, mediated by monocytes. CD20 mAbs rapidly deplete circulating and tissue B cells in an antibody isotype-rest...
Source: Springer Seminars in Immunopathology - November 8, 2006 Category: Pathology Source Type: journals

FcγRII and multi-system autoimmune diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The FcR are a crucial link in the immune response between humoral and cellular immunity and cell-based effector systems, mediating a wide variety of physiological and biochemical responses. The FcR for IgG (FcγR) and in particular the most widely expressed of these, FcγRII, are important in regulating adaptive immunity. Disruption of their function is a key factor in the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by chronic, multi-organ inflammation. Studies of the FcγRII include structure/function relationship...
Source: Springer Seminars in Immunopathology - November 8, 2006 Category: Pathology Source Type: journals

Fc receptors: their diverse functions in immunity and immune disordersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content TypeJournal Article JournalSpringer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325
Source: Springer Seminars in Immunopathology - October 24, 2006 Category: Pathology Source Type: journals

Molecular and functional characteristics of the Fcα/μR, a novel Fc receptor for IgM and IgAEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract IgM is the first antibody to be produced in a humoral immune response and is a major isotope of natural antibodies and may play an important role in innate immunity. On the other hand, IgA is a secreted antibody at the mucosal membrane such as the gastrointestinal and respiratory tracts and protects from initial invasion of microbes. However, how these antibodies are involved in immunity has been poorly elucidated. We previously identified a novel Fc receptor for IgA and IgM, designated Fcα/μ receptor (Fcα/μR), whose gene is closely located at the polymeric immunoglobulin receptor (poly-IgR), also a recepto...
Source: Springer Seminars in Immunopathology - October 24, 2006 Category: Pathology Source Type: journals

Cytokine-adjuvanted HIV-DNA vaccination strategiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract This review highlights some of the most common cytokines currently being tested as adjuvants in HIV-1-DNA vaccine regimens. We discuss their use in both the prophylactic and therapeutic setting. Finally, we describe a novel dendritic cell-targeted vaccine candidate for HIV-1 treatment and prevention called DermaVir and explore the combination of the DermaVir technology with the cytokine adjuvants interleukin-7 and interleukin-15. Content TypeJournal Article JournalSpringer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325
Source: Springer Seminars in Immunopathology - October 20, 2006 Category: Pathology Source Type: journals

IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4+ T cells in regional organized lymphoid structures. FcRn, through its ability to secrete and absorb IgG, thus integrates luminal antigen encounters with syste...
Source: Springer Seminars in Immunopathology - October 19, 2006 Category: Pathology Source Type: journals

The complex role of Fcγ receptors in the pathology of arthritisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Autoantibodies of the IgG class and the immune complexes they form are central players in the pathology of rheumatoid arthritis (RA). Receptors for the Fc part of IgG, FcγR constitute one of the main effector mechanisms through which IgG immune complexes exert their action. The different members of the FcγR family exhibit extensive structural homology leading to redundancy in ligand specificity and signal transduction. Moreover, the initiation of effector mechanisms by IgG immune complexes can also be mediated by the complement system. This strong redundancy and high degree of complexity hampers a direct in v...
Source: Springer Seminars in Immunopathology - October 17, 2006 Category: Pathology Source Type: journals

IgA and IgA-specific receptors in human disease: structural and functional insights into pathogenesis and therapeutic potentialEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract IgA antibodies play an important role in humoral immunity. IgA is the predominant antibody in mucosal secretions and the second most prevalent in the serum. It occupies a unique position among human antibodies in that it can both trigger and suppress inflammatory responses, depending on the situation. Recent structural and functional studies have revealed details of the structure of IgA and its interaction with key cell-surface receptors. We look at the role IgA and IgA receptors (particularly FcαRI) play in the pathogenesis of diseases such as IgA nephropathy and other autoimmune conditions. Finally, we addre...
Source: Springer Seminars in Immunopathology - October 17, 2006 Category: Pathology Source Type: journals

Progress in development and testing of novel recombinant vaccine platforms for HIVEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content TypeJournal Article JournalSpringer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325
Source: Springer Seminars in Immunopathology - October 17, 2006 Category: Pathology Source Type: journals

DNA vaccines for HIV: challenges and opportunitiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract In December 2005, the UNAIDS and WHO reported that the global epidemic known as acquired immunodeficiency syndrome (AIDS) has claimed the lives of more than 25 million adults and children over the past 26 years. These figures included an estimated 3.1 million AIDS-related deaths in 2005. Despite enormous efforts to control the spread of human immunodeficiency virus (HIV) new infection rates are on the rise. An estimated 40.3 million people are now living with HIV, including 4.9 million new infections this past year. Nearly half of new HIV infections are in young people between the ages of 15 and 24. While drug...
Source: Springer Seminars in Immunopathology - October 11, 2006 Category: Pathology Source Type: journals

Therapeutic immunization for HIVEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Vaccines have entered into human clinical trials against infectious diseases and as therapies against cancer. The HIV virus establishes a latent infection at a very early stage and the T cell memory of the infected patient is rapidly destroyed. However, results of immunotherapy after DNA and protein immunization show that vaccine-induced immune responses might be present for a long period of time. Patients subjected to therapeutic immunization appear to do well, and to have a small immunological advantage, which, however, will have to be improved. The vaccine therapy should start early, while adequate reservoir...
Source: Springer Seminars in Immunopathology - October 11, 2006 Category: Pathology Source Type: journals

Unraveling the genetics of systemic lupus erythematosusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The capacity to locate polymorphisms on a virtually complete map of the human genome coupled with the ability to accurately evaluate large numbers (by historical standards) of genetic markers has led to gene identification in complex diseases, such as systemic lupus erythematosus (SLE or lupus). While this is a phenotype with enormous clinical variation, the twin studies and the observed familial aggregation, along with the genetic effects now known, suggest a strong genetic component. Unlike type 1 diabetes, lupus genetics is not dominated by the powerful effect of a single locus. Instead, there are at least s...
Source: Springer Seminars in Immunopathology - September 22, 2006 Category: Pathology Source Type: journals

Combination DNA plus protein HIV vaccinesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract A major challenge in developing an HIV vaccine is to identify immunogens and delivery methods that will elicit balanced humoral and cell mediate immunities against primary isolates of HIV with diverse sequence variations. Since the discovery of using protein coding nucleic acids (mainly DNA but also possible RNA) as a means of immunization in the early 1990s, there has been rapid progress in the creative use of this novel approach for the development of HIV vaccines. Although the initial impetus of using DNA immunization was for the induction of strong cell-mediated immunity, recent studies have greatly expande...
Source: Springer Seminars in Immunopathology - September 21, 2006 Category: Pathology Source Type: journals

The role of toll-like receptors in systemic lupus erythematosusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Systemic lupus erythematosus is an autoimmune disease characterized by the production of autoantibodies against a relatively limited range of nuclear antigens. These autoantibodies result in the formation of immune complexes that deposit in tissues and induce inflammation, thereby contributing to disease pathology. Growing evidence suggests that recognition of nucleic acid motifs by Toll-like receptors may play a role in both the activation of antinuclear B cells and in the subsequent disease progression after immune complex formation. The endosomal localization of the nucleic acid-sensing Toll-like receptors (...
Source: Springer Seminars in Immunopathology - September 21, 2006 Category: Pathology Source Type: journals

Building collaborative networks for HIV/AIDS vaccine development: the AVIP experienceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The need for an effective HIV/AIDS vaccine is imperative to halt a pandemic that involves more than 40 million individuals worldwide as of 2005 and is causing enormous socio-economic losses, especially in developing countries (DC). The overall failure of more than two decades of HIV vaccine research justifies the demands for a concerted effort for the rapid development of new and efficacious vaccines against HIV/AIDS. In this context, building international collaborative networks is a must for speeding up scientific research and optimizing the use of funding in a synergistic fashion, as resources for HIV/AIDS a...
Source: Springer Seminars in Immunopathology - September 19, 2006 Category: Pathology Source Type: journals

Recombinant vesicular stomatitis virus as an HIV-1 vaccine vectorEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Recombinant vesicular stomatitis virus (rVSV) is currently under evaluation as a human immunodeficiency virus (HIV)-1 vaccine vector. The most compelling reasons to develop rVSV as a vaccine vector include a very low seroprevalence in humans, the ability to infect and robustly express foreign antigens in a broad range of cells, and vigorous growth in continuous cell lines used for vaccine manufacture. Numerous preclinical studies with rVSV vectors expressing antigens from a variety of human pathogens have demonstrated the versatility, flexibility, and potential efficacy of the rVSV vaccine platform. When admini...
Source: Springer Seminars in Immunopathology - September 15, 2006 Category: Pathology Source Type: journals

Significance of MHC class II haplotypes and IgG Fc receptors in SLEEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Systemic lupus erythematosus (SLE) is a systemic antibody-mediated autoimmune disease that develops under the control of multiple susceptibility genes. Genetic studies in murine and human SLE have identified several chromosomal intervals that contain candidate susceptibility genes. However, the ultimate identification of the genes and their roles in disease process need much further investigation. Spontaneous murine SLE models provide useful tools in this respect. In this chapter, we show this line of investigation, particularly focusing on the roles of major histocompatibility complex (MHC) class II and immuno...
Source: Springer Seminars in Immunopathology - September 14, 2006 Category: Pathology Source Type: journals

Genetics of SLE in miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Genetic studies in spontaneous, induced, and gene-manipulated mouse models of SLE have provided significant insights into the potential number and diversity of genes that can promote, resist, and modify lupus susceptibility. Novel genes and mechanisms of disease pathogenesis have also been identified. Importantly, mouse models have provided an initial view of the genomic landscape of lupus-affecting genes, and have documented the complexities of verifying and determining the role of specific candidate loci and genes. Mouse models of lupus should continue to serve as a vital approach to defining the genetics of ...
Source: Springer Seminars in Immunopathology - September 14, 2006 Category: Pathology Source Type: journals

Generation and maintenance of human memory cells during viral infectionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Long-term maintenance of memory T cell response is the hallmark of immune protection and hence the holy grail of most vaccine development studies. Persistent memory cells, developed after either viral infection or vaccination, ensure the generation of an antiviral response upon reexposure to the pathogen. During acute viral infections, as in the case of measles and influenza viruses, strong T cell effector functions, which eradicate the virus and protect patients against reexposure, are achieved by the generation of persistent protective memory cells. However, in chronic infections, T cells drastically lose eff...
Source: Springer Seminars in Immunopathology - September 12, 2006 Category: Pathology Source Type: journals

The genetics of systemic lupus erythematosus: understanding how SNPs confer disease susceptibilityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The identification of genes for autoimmune diseases is just the first step towards our understanding of disease pathogenesis. In investigating how mutations, deletions or other types of polymorphic defects occur, it is important to determine the pathways and the mechanisms through which susceptibility leads to disease. In this review I touch on three examples of studies that have attempted to understand the mechanisms of genetic susceptibility in three genes identified recently for systemic lupus erythematosus: PDCD1, PTPN22 and IRF5. We are just beginning to comprehend and much needs to be done. Content TypeJ...
Source: Springer Seminars in Immunopathology - September 9, 2006 Category: Pathology Source Type: journals

TCRζ mRNA splice variant forms observed in the peripheral blood T cells from systemic lupus erythematosus patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology. Tyrosine phosphorylation and protein expression of the T-cell receptor ζ chain (ζ) have been reported to be significantly decreased in SLE T cells. In addition, ζ mRNA with alternatively spliced 3′ untranslated region (ζmRNA/as-3′UTR) is detected predominantly in SLE T cells, and aberrant ζ mRNA accompanied by the mutations in the open reading frame including ζ mRNA lacking exon7 (ζmRNA/exon7-) is observed in SLE T cells. These ζ mRNA splice variant forms exhibit a reduction in the expression of TCR/CD3 complex ...
Source: Springer Seminars in Immunopathology - September 5, 2006 Category: Pathology Source Type: journals

Molecular and cellular basis for pathogenicity of autoantibodies: lessons from murine monoclonal autoantibodiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The pathogenesis of autoantibody-mediated cellular and tissue lesions in autoimmune diseases is most straightforwardly attributable to the combined action of self-antigen binding properties and effector functions associated with the Fc regions of the different immunoglobulin (Ig) isotypes. The analysis of two different sets of monoclonal autoantibodies derived from lupus-prone mice revealed remarkable differences in the pathogenic potentials of different IgG subclasses: (1) the IgG2a and IgG2b subclasses of anti-red blood cell (RBC) autoantibodies are the most pathogenic and efficiently activate two classes of ...
Source: Springer Seminars in Immunopathology - September 5, 2006 Category: Pathology Source Type: journals

Costimulatory molecules as immunotherapeutic targets in systemic lupus erythematosusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract T cells undergo full and productive activation when they traffic to lymph nodes where they encounter dendritic cells displaying foreign antigen in the context of MHC molecules on their surface. Recognition of these antigen–MHC complexes by the T cell’s receptor for antigen, or T cell receptor, provides the first of two obligate signals needed to drive cell proliferation. The second antigen-independent signal is provided by the costimulatory receptor, CD28, as it engages its ligand on the antigen-presenting cells. Failure of the T cell to receive this second signal after antigen recognition leaves the T cell...
Source: Springer Seminars in Immunopathology - September 2, 2006 Category: Pathology Source Type: journals

Apoptotic cell death and lupusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Programmed cell death and the disposal of cell corpses by phagocytic cells are highly regulated ongoing processes essential for the survival and well-being of higher organisms. Abnormalities in the susceptibility of certain cells to receptor-induced death are known to lead to certain human diseases (e.g., autoimmune lymphoproliferative syndrome) and may contribute to the pathogenesis of systemic lupus erythematosus. Impaired clearance of apoptotic cells is also likely to be an important factor in lupus pathogenesis, though the biological basis of such a defect remains elusive. Finally, the process of apoptosis ...
Source: Springer Seminars in Immunopathology - August 29, 2006 Category: Pathology Source Type: journals

Molecular pathogenesis of SLEEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content TypeJournal Article JournalSpringer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325
Source: Springer Seminars in Immunopathology - August 29, 2006 Category: Pathology Source Type: journals

Current topics in human SLE geneticsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Susceptibility to systemic lupus erythematosus (SLE) depends on genetic and environmental factors. Genome scan studies have identified eight chromosomal regions with significant linkage to SLE that are confirmed by individual cohorts, suggesting that susceptibility genes may be identified within each of these loci. Linkage studies and single nucleotide polymorphisms (SNPs) have led to the identification of positional candidate genes, and their functional allelic variants have demonstrated molecular pathogenesis of the disease. The discovery of positional candidate genes that are associated with various autoimmu...
Source: Springer Seminars in Immunopathology - August 29, 2006 Category: Pathology Source Type: journals

Polyfunctional analysis of human t cell responses: importance in vaccine immunogenicity and natural infectionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content TypeJournal Article JournalSpringer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325
Source: Springer Seminars in Immunopathology - August 25, 2006 Category: Pathology Source Type: journals

Regulatory T cells in human autoimmune diseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract In the most simplistic terms, immune tolerance can be envisioned as a balance with autoreactive cells that arise naturally in all individuals on one side and regulatory mechanisms designed to counter those autoreactive processes on the other. A tilt of the balance toward the autoreactive side, either by increasing the number or function of autoreactive cells or by diminishing regulatory mechanisms, is manifested as autoimmunity. In contrast, tilting of the balance toward increased regulation could conceivably cause immunodeficiency. Regulatory T cells (TREG), and particularly the naturally arising CD4+CD25+ sub...
Source: Springer Seminars in Immunopathology - August 22, 2006 Category: Pathology Source Type: journals

Regulatory T cells and innate immune regulation in tumor immunityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content TypeJournal Article JournalSpringer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325 Journal VolumeVolume 28 Journal IssueVolume 28, Number 1 / September, 2006
Source: Springer Seminars in Immunopathology - August 22, 2006 Category: Pathology Source Type: journals

Regulatory T cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content TypeJournal Article JournalSpringer Seminars in ImmunopathologyOnline ISSN 1432-2196Print ISSN 0344-4325 Journal VolumeVolume 28 Journal IssueVolume 28, Number 1 / September, 2006
Source: Springer Seminars in Immunopathology - August 22, 2006 Category: Pathology Source Type: journals

Regulatory T cells in pregnancyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Tolerance mechanisms are responsible for the survival of the fetus within the maternal uterus without being attacked by the cells of the maternal immune system despite their direct contact. Regulatory T cells (Treg) were claimed to be important players in the tolerance towards the fetus bearing alloantigens. Recent evidence confirmed an augmentation in the number of Treg during pregnancy and, most importantly, diminished numbers of Treg were associated with immunological rejection of the fetus. This could be prevented by adoptively transferring CD4+/CD25+ Treg cells from normal pregnant mice into abortion-prone...
Source: Springer Seminars in Immunopathology - August 22, 2006 Category: Pathology Source Type: journals

The role of virus-induced regulatory T cells in immunopathologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract In recent years, regulatory T cells have received increased attention for their role in immune responses to microbial infections. The list of microbial pathogens associated with regulatory T cell responses is growing rapidly and includes bacteria, viruses, parasites, and fungi. As the biology of regulatory T cells is revealed, we are discovering that their induction during infection is a normal aspect of immunity, necessary to limit collateral damage from inflammatory responses and aggressive immunological effectors. Thus, these cells play a critical role in maintaining the delicate balance between preventing i...
Source: Springer Seminars in Immunopathology - August 22, 2006 Category: Pathology Source Type: journals

Regulatory T cells and innate immune regulation in tumor immunityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Innate and adaptive immunity play important roles in immunosurveillance and tumor destruction. However, increasing evidence suggests that tumor-infiltrating immune cells may have a dual function: inhibiting or promoting tumor growth and progression. Although regulatory T (Treg) cells induce immune tolerance by suppressing host immune responses against self- or nonself-antigens, thus playing critical roles in preventing autoimmune diseases, they might inhibit antitumor immunity and promote tumor growth. Recent studies demonstrate that elevated proportions of Treg cells are present in various types of cancers and...
Source: Springer Seminars in Immunopathology - August 22, 2006 Category: Pathology Source Type: journals