Self/nonself最新文献

{"title":"Visual analytics for immunologists: Data compression and fractal distributions.","authors":"Elena N Naumova","doi":"10.4161/self.1.3.12876","DOIUrl":"10.4161/self.1.3.12876","url":null,"abstract":"<p><p>Visual analytics is the science of analytical reasoning that facilitates research through the use of interactive visual interfaces. New techniques of visual analytics are designed to aid the understanding of complex systems versus traditional blind-context rules to explore massive volumes of interrelated data. Nowhere else is visualization more important in analysis than in the emerging fields of life sciences, where amounts of collected data grow increasingly in exponential rates.The complexity of the immune system in immunology makes visual analytics especially important for understanding how this system works. In this context, our effort should be focused on avoiding accurate but potentially misleading use of visual interfaces. The proposed approach of data compression and visualization that reveal structural and functional features of immune responses enhances systemic and comprehensive description and provides the platform for hypothesis generation. Further, this approach can evolve into a powerful visual-analytical tool for prospective and real-time monitoring and can provide an intuitive and interpretable illustration of vital dynamics that govern immune responses in an individual and populations.The undertaken explorations demonstrate the critical role of novel techniques of visual analytics in stimulating research in immunology and other life sciences and in leading us to understanding of complex biological systems and processes.</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 3","pages":"241-249"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047786/pdf/self0103_0241.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29810371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self/nonself perception, reproduction and the extended MHC.","authors":"Andreas Ziegler,&nbsp;Pablo Sandro Carvalho Santos,&nbsp;Thomas Kellermann,&nbsp;Barbara Uchanska-Ziegler","doi":"10.4161/self.1.3.12736","DOIUrl":"https://doi.org/10.4161/self.1.3.12736","url":null,"abstract":"<p><p>Self/nonself perception governs mate selection in most eukaryotic species. It relies on a number of natural barriers that act before, during and after copulation. These hurdles prevent a costly investment into an embryo with potentially suboptimal genetic and immunological properties and aim at discouraging fertilization when male and female gametes exhibit extensive sharing of alleles. Due to the fact that several genes belonging to the extended major histocompatibility complex (xMHC) carry out crucial immune functions and are the most polymorphic within vertebrate genomes, it is likely that securing heterozygosity and the selection of rare alleles within this gene complex contributes to endowing the offspring with an advantage in fighting infections. Apart from MHC class I and II antigens, the products of several other genes within the xMHC are candidates for participating in mate choice, especially since the respective loci are subject to long-range linkage disequilibrium which may aid to preserve functionally connected alleles within a given haplotype. Among these loci are polymorphic odorant receptor genes that are expressed not only in the olfactory epithelium, but also within male reproductive tissues. They may thus not only be of importance in olfaction-influenced mate choice, by recognizing MHC-dependent individual-specific olfactory signals, but could also guide spermatozoa along chemical gradients to their target, the oocyte. By focusing on the human HLA complex and genes within its vicinity, we show here that the products of several xMHC-specified molecules might be involved in self/nonself perception during reproduction. Although the molecular details are often unknown, the existence of highly diverse, yet intertwined pre- and post-copulatory barriers suggests that xMHC-encoded proteins may be important for various stages of mate choice, germ cell development, as well as embryonic and foetal life in mammals and other vertebrates. Many of these genes should thus be regarded as crucial not only within the immune system, but also in reproduction.</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 3","pages":"176-191"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.3.12736","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29810369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycosylation: An intrinsic sign of \"danger\"","authors":"Jacob Rachmilewitz","doi":"10.4161/self.1.3.12330","DOIUrl":"https://doi.org/10.4161/self.1.3.12330","url":null,"abstract":"<p><p>The \"danger\" model of immunity posits that the immune system is triggered by endogenous danger signals, rather than exogenous non-self signals per se. It has been proposed that danger signals may consist of both intracellular \"pre-packed\" molecules released from damaged cells and stress-induced proteins. Here we focus on glycosylation aberrancies as a unifying concept for danger signaling. According to this proposition glycosylation patterns reliably reflect cellular phenotypic state and appearance of altered carbohydrate structures may constitute a pivotal phenotypic alteration that alarms the immune system to danger and initiates immunity. Viewed from this vantage point, healthy cells avert immune recognition by virtue of their normal terminal glycosylation patterns. By contrast, abnormal cells display and release glycoproteins and glycolipids with aberrant terminal glycosylation trees, which in turn immunologically flag these cells. Diverse carbohydrate-binding receptors are expressed on immune cells and are used to detect these phenotypic changes. Thus, in addition to the \"pre-packed\" and stress-induced signals this glycosylation-based signal represents an endogenous signal reliably reflecting the cell phenotypic status, enabling the immune system to monitor the tissue/cell's physical condition and to respond accordingly.</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 3","pages":"250-254"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.3.12330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29810373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The SCHOOL of nature: III. From mechanistic understanding to novel therapies.","authors":"Alexander B Sigalov","doi":"10.4161/self.1.3.12794","DOIUrl":"10.4161/self.1.3.12794","url":null,"abstract":"<p><p>Protein-protein interactions play a central role in biological processes and thus represent an appealing target for innovative drug design and development. They can be targeted by small molecule inhibitors, modulatory peptides and peptidomimetics, which represent a superior alternative to protein therapeutics that carry many disadvantages. Considering that transmembrane signal transduction is an attractive process to therapeutically control multiple diseases, it is fundamentally and clinically important to mechanistically understand how signal transduction occurs. Uncovering specific protein-protein interactions critical for signal transduction, a general platform for receptor-mediated signaling, the signaling chain homooligomerization (SCHOOL) platform, suggests these interactions as universal therapeutic targets. Within the platform, the general principles of signaling are similar for a variety of functionally unrelated receptors. This suggests that global therapeutic strategies targeting key protein-protein interactions involved in receptor triggering and transmembrane signal transduction may be used to treat a diverse set of diseases. This also assumes that clinical knowledge and therapeutic strategies can be transferred between seemingly disparate disorders, such as T cell-mediated skin diseases and platelet disorders or combined to develop novel pharmacological approaches. Intriguingly, human viruses use the SCHOOL-like strategies to modulate and/or escape the host immune response. These viral mechanisms are highly optimized over the millennia, and the lessons learned from viral pathogenesis can be used practically for rational drug design. Proof of the SCHOOL concept in the development of novel therapies for atopic dermatitis, rheumatoid arthritis, cancer, platelet disorders and other multiple indications with unmet needs opens new horizons in therapeutics.</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 3","pages":"192-224"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047783/pdf/self0103_0192.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29810375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD28 co-signaling in the adaptive immune response.","authors":"Pavel Riha,&nbsp;Christopher E Rudd","doi":"10.4161/self.1.3.12968","DOIUrl":"https://doi.org/10.4161/self.1.3.12968","url":null,"abstract":"<p><p>T-cell proliferation and function depends on signals from the antigen-receptor complex (TCR/CD3) and by various co-receptors such as CD28 and CTLA-4. The balance of positive and negative signals determines the outcome of the T-cell response to foreign and self-antigen. CD28 is a prominent co-receptor in naïve and memory T-cell responses. Its blockade has been exploited clinically to dampen T-cell responses to self-antigen. Current evidence shows that CD28 both potentiates TCR signaling and engages a unique array of mediators (PI3K, Grb2, FLNa) in the regulation of aspects of T-cell signaling including the transcription factor NFkB. In this mini-review, we provide an up-to-date overview of our understanding of the signaling mechanisms that underlie CD28 function and its potential application to the modulation of reactivity to autoimmunity.</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 3","pages":"231-240"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.3.12968","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29810372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognate interactions between mast cells and helper T lymphocytes.","authors":"Salvatore Valitutti,&nbsp;Eric Espinosa","doi":"10.4161/self.1.2.11795","DOIUrl":"https://doi.org/10.4161/self.1.2.11795","url":null,"abstract":"<p><p>Mast cells are key effectors in allergy and inflammation. Endowed with a large panel of surface receptors and a huge arsenal of bioactive mediators, they readily communicate with various cellular partners during innate and adaptive immune responses. Recent lines of evidence show that mast cells are also able to establish cognate interactions with helper T lymphocytes for antigen presentation and bidirectional cell-cell cooperation. In this short review we focus on the role of mast cells as unconventional antigen presenting cells for helper T lymphocytes. We discuss how looking at mast cell biology from this new angle can help to better understand their pleiotropic role in health and disease.</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 2","pages":"114-122"},"PeriodicalIF":0.0,"publicationDate":"2010-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.2.11795","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29698789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The SCHOOL of nature: II. Protein order, disorder and oligomericity in transmembrane signaling.","authors":"Alexander B Sigalov","doi":"10.4161/self.1.2.11590","DOIUrl":"10.4161/self.1.2.11590","url":null,"abstract":"<p><p>Recent reports have revealed that many proteins that do not adopt globular structures under native conditions, thus termed intrinsically disordered proteins (IDPs), are involved in cell signaling. Intriguingly, physiologically relevant oligomerization of IDPs has been recently observed and shown to exhibit unique biophysical characteristics, including the lack of significant changes in chemical shift and peak intensity upon binding. In this work, I summarize several distinct features of protein disorder that are especially important as related to receptor-mediated transmembrane signal transduction. I also hypothesize that interactions of IDPs with their protein or lipid partners represent a general biphasic process with the \"no disorder-to-order\" fast interaction which, depending on the interacting partner, may or may not be accompanied by the slow formation of a secondary structure. Further, I suggest signaling-related functional connections between protein order, disorder, and oligomericity and hypothesize that receptor oligomerization induced or tuned upon ligand binding outside the cell is translated across the membrane into protein oligomerization inside the cell, thus providing a general platform, the Signaling Chain HOmoOLigomerization (SCHOOL) platform, for receptor-mediated signaling. This structures our current multidisciplinary knowledge and views of the mechanisms governing the coupling of recognition to signal transduction and cell response. Importantly, this approach not only reveals previously unrecognized striking similarities in the basic mechanistic principles of function of numerous functionally diverse and unrelated surface membrane receptors, but also suggests the similarity between therapeutic targets, thus opening new horizons for both fundamental and clinically relevant studies.</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 2","pages":"89-102"},"PeriodicalIF":0.0,"publicationDate":"2010-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065667/pdf/self0102_0089.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29698787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The development of mature B lymphocytes requires the combined function of CD19 and the p110δ subunit of PI3K.","authors":"Dorottya Kövesdi,&nbsp;Sarah E Bell,&nbsp;Martin Turner","doi":"10.4161/self.1.2.11796","DOIUrl":"https://doi.org/10.4161/self.1.2.11796","url":null,"abstract":"<p><p>Mice lacking either CD19 or p110δ have reduced numbers of marginal zone and B1 B cells but normal numbers of naïve B2 cells which occupy the follicles of the lymphoid organs. We show here that mice lacking both CD19 and p110δ have normal B cell development in the bone marrow but have a significant reduction in the number of naïve B2 cells in the bone marrow, spleen and lymph nodes. These p110δ/CD19 double mutant B cells show a survival defect and reduced responsiveness to the pro-survival cytokine BAFF despite normal NFκB2/p100 processing and elevated expression of Bcl-2. Although the combined loss of p110δ and CD19 did not increase switching to Ig-lambda in immature B cells, mature B lymphocytes from the lymph nodes of p110δ/CD19 double mutant mice express highly elevated levels of mRNA encoding RAG-1 and RAG-2, which confirms the existing synergy between CD19 and p110δ-mediated signaling.</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 2","pages":"144-153"},"PeriodicalIF":0.0,"publicationDate":"2010-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.2.11796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29749428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clustering of rare peptide segments in the HCV immunome.","authors":"Angela Stufano, Giovanni Capone, Barbara Pesetti, Lorenzo Polimeno, Darja Kanduc","doi":"10.4161/self.1.2.11391","DOIUrl":"10.4161/self.1.2.11391","url":null,"abstract":"<p><p>Our previous research and a comprehensive meta-analysis of data from the literature on epitope mapping has revealed that the B cell epitope repertoire is allocated to rare peptide motifs, i.e., antigenic peptide sequences endowed with a low level of similarity to the host proteome. From a clinical point of view, low-similarity peptides able to evoke an immune response appear to be of special interest for the rational design of vaccines for poorly treatable diseases such as hepatitis-C virus (HCV) infection. Indeed, low similarity peptides would guarantee the highest specificity and lowest cross-reactivity, i.e., effectiveness without adverse side-effects. In this study, aimed at gaining further information for the development of effective anti-HCV peptide-based vaccines, the HCV epitopes recognized by human antibodies and currently catalogued in the Immune Epitope Data Base (IEDB) were examined for pentamer sequence similarities to the human proteome. We report that the analyzed HCV determinants are characterized by the presence of fragment absent from (or scarcely represented in) human proteins. These data confirm the low-similarity hypothesis, according to which a low-similarity to the host proteome defines the nonself character of microbial antigens and modulates peptide immunogenicity. Moreover, this study indicates a concrete and safe immunotherapeutic approach which might be used in a universal anti-HCV vaccine.</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 2","pages":"154-162"},"PeriodicalIF":0.0,"publicationDate":"2010-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065674/pdf/self0102_0154.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29749429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-inhibitory molecules: Controlling the effectors or controlling the controllers?","authors":"Govindarajan Thangavelu,&nbsp;Christa Smolarchuk,&nbsp;Colin C Anderson","doi":"10.4161/self.1.2.11548","DOIUrl":"https://doi.org/10.4161/self.1.2.11548","url":null,"abstract":"<p><p>Nearly forty years ago the concept was proposed that lymphocytes are negatively regulated by what are now called co-inhibitory signals. Nevertheless, it is only the more recent identification of numerous co-inhibitors and their critical functions that has brought co-inhibition to the forefront of immunologic research. Although co-inhibitory signals have been considered to directly regulate conventional T cells, more recent data has indicated a convergence between co-inhibitory signals and the other major negative control mechanism in the periphery that is mediated by regulatory T cells. Furthermore, it is now clear that lymphocytes are not the sole domain of co-inhibitory signals, as cells of the innate immune system, themselves controllers of immunity, are regulated by co-inhibitors they express. Thus, in order to better understand negative regulation in the periphery and apply this knowledge to the treatment of disease, a major focus for the future should be the definition of the conditions where co-inhibition controls effector cells intrinsically versus extrinsically (via regulatory or innate cells).</p>","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 2","pages":"77-88"},"PeriodicalIF":0.0,"publicationDate":"2010-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.2.11548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29698788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}