WorldWideScience

Sample records for adaptive immune systems

  1. Adaptation in the innate immune system and heterologous innate immunity.

    Science.gov (United States)

    Martin, Stefan F

    2014-11-01

    The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

  2. Intercellular Communication in the Adaptive Immune System

    Science.gov (United States)

    Chakraborty, Arup

    2004-03-01

    Higher organisms, like humans, have an adaptive immune system that can respond to pathogens that have not been encountered before. T lymphocytes (T cells) are the orchestrators of the adaptive immune response. They interact with cells, called antigen presenting cells (APC), that display molecular signatures of pathogens. Recently, video microscopy experiments have revealed that when T cells detect antigen on APC surfaces, a spatially patterned supramolecular assembly of different types of molecules forms in the junction between cell membranes. This recognition motif is implicated in information transfer between APC and T cells, and so, is labeled the immunological synapse. The observation of synapse formation sparked two broad questions: How does the synapse form? Why does the synapse form? I will describe progress made in answering these fundamental questions in biology by synergistic use of statistical mechanical theory/computation, chemical engineering principles, and genetic and biochemical experiments. The talk will also touch upon mechanisms that may underlie the extreme sensitivity with which T cells discriminate between self and non-self.

  3. The immune system, adaptation, and machine learning

    Science.gov (United States)

    Farmer, J. Doyne; Packard, Norman H.; Perelson, Alan S.

    1986-10-01

    The immune system is capable of learning, memory, and pattern recognition. By employing genetic operators on a time scale fast enough to observe experimentally, the immune system is able to recognize novel shapes without preprogramming. Here we describe a dynamical model for the immune system that is based on the network hypothesis of Jerne, and is simple enough to simulate on a computer. This model has a strong similarity to an approach to learning and artificial intelligence introduced by Holland, called the classifier system. We demonstrate that simple versions of the classifier system can be cast as a nonlinear dynamical system, and explore the analogy between the immune and classifier systems in detail. Through this comparison we hope to gain insight into the way they perform specific tasks, and to suggest new approaches that might be of value in learning systems.

  4. Scale-free dynamics of somatic adaptability in immune system

    CERN Document Server

    Saito, Shiro

    2009-01-01

    The long-time dynamics of somatic adaptability in immune system is simulated by a simple physical model. The immune system described by the model exhibits a scale free behavior as is observed in living systems. The balance between the positive and negative feedbacks of the model leads to a robust immune system where the positive one corresponds to the formation of memory cells and the negative one to immunosuppression. Also the immunosenescence of the system is discussed based on the time-dependence of the epigenetic landscape of the adaptive immune cells in the shape space.

  5. Evolution of innate and adaptive immune systems in jawless vertebrates.

    Science.gov (United States)

    Kasamatsu, Jun

    2013-01-01

    Because jawless vertebrates are the most primitive vertebrates, they have been studied to gain understanding of the evolutionary processes that gave rise to the innate and adaptive immune systems in vertebrates. Jawless vertebrates have developed lymphocyte-like cells that morphologically resemble the T and B cells of jawed vertebrates, but they express variable lymphocyte receptors (VLRs) instead of the T and B cell receptors that specifically recognize antigens in jawed vertebrates. These VLRs act as antigen receptors, diversity being generated in their antigen-binding sites by assembly of highly diverse leucine-rich repeat modules. Therefore, jawless vertebrates have developed adaptive immune systems based on the VLRs. Although pattern recognition receptors, including Toll-like receptors (TLRs) and Rig-like receptors (RLRs), and their adaptor genes are conserved in jawless vertebrates, some transcription factor and inflammatory cytokine genes in the TLR and RLR pathways are not present. However, like jawed vertebrates, the initiation of adaptive immune responses in jawless vertebrates appears to require prior activation of the innate immune system. These observations imply that the innate immune systems of jawless vertebrates have a unique molecular basis that is distinct from that of jawed vertebrates. Altogether, although the molecular details of the innate and adaptive immune systems differ between jawless and jawed vertebrates, jawless vertebrates have developed versions of these immune systems that are similar to those of jawed vertebrates.

  6. The Adaptive Immune System of Haloferax volcanii

    Directory of Open Access Journals (Sweden)

    Lisa-Katharina Maier

    2015-02-01

    Full Text Available To fight off invading genetic elements, prokaryotes have developed an elaborate defence system that is both adaptable and heritable—the CRISPR-Cas system (CRISPR is short for: clustered regularly interspaced short palindromic repeats and Cas: CRISPR associated. Comprised of proteins and multiple small RNAs, this prokaryotic defence system is present in 90% of archaeal and 40% of bacterial species, and enables foreign intruders to be eliminated in a sequence-specific manner. There are three major types (I–III and at least 14 subtypes of this system, with only some of the subtypes having been analysed in detail, and many aspects of the defence reaction remaining to be elucidated. Few archaeal examples have so far been analysed. Here we summarize the characteristics of the CRISPR-Cas system of Haloferax volcanii, an extremely halophilic archaeon originally isolated from the Dead Sea. It carries a single CRISPR-Cas system of type I-B, with a Cascade like complex composed of Cas proteins Cas5, Cas6b and Cas7. Cas6b is essential for CRISPR RNA (crRNA maturation but is otherwise not required for the defence reaction. A systematic search revealed that six protospacer adjacent motif (PAM sequences are recognised by the Haloferax defence system. For successful invader recognition, a non-contiguous seed sequence of 10 base-pairs between the crRNA and the invader is required.

  7. Evolution and age characteristics of the innate and adaptive immune system

    OpenAIRE

    ABATUROV A.E.; Agafonova, E. A.; Abaturova, N.I.; Babich, V. L.

    2016-01-01

    The article describes the basic principles of the immune systems' function. Its given notions of organs and cells of the immune system, especially native and adaptive immunity. The article presents the evolution of age-related features of the immune response.Key words: immunity, native immunity, adaptive immunity.

  8. CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.

    Science.gov (United States)

    Barrangou, Rodolphe; Marraffini, Luciano A

    2014-04-24

    Clustered regularly interspaced short palindromic repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing and can be repurposed for numerous DNA targeting applications including transcriptional control.

  9. Quantifying adaptive evolution in the Drosophila immune system.

    Directory of Open Access Journals (Sweden)

    Darren J Obbard

    2009-10-01

    Full Text Available It is estimated that a large proportion of amino acid substitutions in Drosophila have been fixed by natural selection, and as organisms are faced with an ever-changing array of pathogens and parasites to which they must adapt, we have investigated the role of parasite-mediated selection as a likely cause. To quantify the effect, and to identify which genes and pathways are most likely to be involved in the host-parasite arms race, we have re-sequenced population samples of 136 immunity and 287 position-matched non-immunity genes in two species of Drosophila. Using these data, and a new extension of the McDonald-Kreitman approach, we estimate that natural selection fixes advantageous amino acid changes in immunity genes at nearly double the rate of other genes. We find the rate of adaptive evolution in immunity genes is also more variable than other genes, with a small subset of immune genes evolving under intense selection. These genes, which are likely to represent hotspots of host-parasite coevolution, tend to share similar functions or belong to the same pathways, such as the antiviral RNAi pathway and the IMD signalling pathway. These patterns appear to be general features of immune system evolution in both species, as rates of adaptive evolution are correlated between the D. melanogaster and D. simulans lineages. In summary, our data provide quantitative estimates of the elevated rate of adaptive evolution in immune system genes relative to the rest of the genome, and they suggest that adaptation to parasites is an important force driving molecular evolution.

  10. Quantifying adaptive evolution in the Drosophila immune system.

    Science.gov (United States)

    Obbard, Darren J; Welch, John J; Kim, Kang-Wook; Jiggins, Francis M

    2009-10-01

    It is estimated that a large proportion of amino acid substitutions in Drosophila have been fixed by natural selection, and as organisms are faced with an ever-changing array of pathogens and parasites to which they must adapt, we have investigated the role of parasite-mediated selection as a likely cause. To quantify the effect, and to identify which genes and pathways are most likely to be involved in the host-parasite arms race, we have re-sequenced population samples of 136 immunity and 287 position-matched non-immunity genes in two species of Drosophila. Using these data, and a new extension of the McDonald-Kreitman approach, we estimate that natural selection fixes advantageous amino acid changes in immunity genes at nearly double the rate of other genes. We find the rate of adaptive evolution in immunity genes is also more variable than other genes, with a small subset of immune genes evolving under intense selection. These genes, which are likely to represent hotspots of host-parasite coevolution, tend to share similar functions or belong to the same pathways, such as the antiviral RNAi pathway and the IMD signalling pathway. These patterns appear to be general features of immune system evolution in both species, as rates of adaptive evolution are correlated between the D. melanogaster and D. simulans lineages. In summary, our data provide quantitative estimates of the elevated rate of adaptive evolution in immune system genes relative to the rest of the genome, and they suggest that adaptation to parasites is an important force driving molecular evolution.

  11. Cancer immunoediting by the innate immune system in the absence of adaptive immunity.

    Science.gov (United States)

    O'Sullivan, Timothy; Saddawi-Konefka, Robert; Vermi, William; Koebel, Catherine M; Arthur, Cora; White, J Michael; Uppaluri, Ravi; Andrews, Daniel M; Ngiow, Shin Foong; Teng, Michele W L; Smyth, Mark J; Schreiber, Robert D; Bui, Jack D

    2012-09-24

    Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3'methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2(-/-), and RAG2(-/-)x γc(-/-) mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2(-/-)x γc(-/-) mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting.

  12. The role of the adaptive immune system in regulation of gut microbiota.

    Science.gov (United States)

    Kato, Lucia M; Kawamoto, Shimpei; Maruya, Mikako; Fagarasan, Sidonia

    2014-07-01

    The gut nourishes rich bacterial communities that affect profoundly the functions of the immune system. The relationship between gut microbiota and the immune system is one of reciprocity. The microbiota contributes to nutrient processing and the development, maturation, and function of the immune system. Conversely, the immune system, particularly the adaptive immune system, plays a key role in shaping the repertoire of gut microbiota. The fitness of host immune system is reflected in the gut microbiota, and deficiencies in either innate or adaptive immunity impact on diversity and structures of bacterial communities in the gut. Here, we discuss the mechanisms that underlie this reciprocity and emphasize how the adaptive immune system via immunoglobulins (i.e. IgA) contributes to diversification and balance of gut microbiota required for immune homeostasis.

  13. Adaptive immunity to fungi.

    Science.gov (United States)

    Verma, Akash; Wüthrich, Marcel; Deepe, George; Klein, Bruce

    2014-11-06

    Life-threatening fungal infections have risen sharply in recent years, owing to the advances and intensity of medical care that may blunt immunity in patients. This emerging crisis has created the growing need to clarify immune defense mechanisms against fungi with the ultimate goal of therapeutic intervention. We describe recent insights in understanding the mammalian immune defenses that are deployed against pathogenic fungi. We focus on adaptive immunity to the major medically important fungi and emphasize three elements that coordinate the response: (1) dendritic cells and subsets that are mobilized against fungi in various anatomical compartments; (2) fungal molecular patterns and their corresponding receptors that signal responses and shape the differentiation of T-cell subsets and B cells; and, ultimately (3) the effector and regulatory mechanisms that eliminate these invaders while constraining collateral damage to vital tissue. These insights create a foundation for the development of new, immune-based strategies for prevention or enhanced clearance of systemic fungal diseases.

  14. Stochastic stage-structured modeling of the adaptive immune system

    Energy Technology Data Exchange (ETDEWEB)

    Chao, D. L. (Dennis L.); Davenport, M. P. (Miles P.); Forrest, S. (Stephanie); Perelson, Alan S.,

    2003-01-01

    We have constructed a computer model of the cytotoxic T lymphocyte (CTL) response to antigen and the maintenance of immunological memory. Because immune responses often begin with small numbers of cells and there is great variation among individual immune systems, we have chosen to implement a stochastic model that captures the life cycle of T cells more faithfully than deterministic models. Past models of the immune response have been differential equation based, which do not capture stochastic effects, or agent-based, which are computationally expensive. We use a stochastic stage-structured approach that has many of the advantages of agent-based modeling but is more efficient. Our model can provide insights into the effect infections have on the CTL repertoire and the response to subsequent infections.

  15. CRISPR-Cas adaptive immune systems of the sulfolobales

    DEFF Research Database (Denmark)

    Garrett, Roger Antony; Shah, Shiraz Ali; Erdmann, Susanne

    2015-01-01

    The Sulfolobales have provided good model organisms for studying CRISPR-Cas systems of the crenarchaeal kingdom of the archaea. These organisms are infected by a wide range of exceptional archaea-specific viruses and conjugative plasmids, and their CRISPR-Cas systems generally exhibit extensive...... structural and functional diversity. They carry large and multiple CRISPR loci and often multiple copies of diverse Type I and Type III interference modules as well as more homogeneous adaptation modules. These acidothermophilic organisms have recently provided seminal insights into both the adaptation...... process, the diverse modes of interference, and their modes of regulation. The functions of the adaptation and interference modules tend to be loosely coupled and the stringency of the crRNA-DNA sequence matching during DNA interference is relatively low, in contrast to some more streamlined CRISPR...

  16. Origins of adaptive immunity.

    Science.gov (United States)

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  17. Adaptation of the immune system as a response to pregnancy

    Directory of Open Access Journals (Sweden)

    Milašinović Ljubomir

    2002-01-01

    Full Text Available Introduction Pregnancy is an intriguing immunologic phenomenon. In spite of genetic differences, maternal and fetal cells are in close contact over the whole course of pregnancy with no evidence of either humoral and/or cellular immunologic response of mother to fetus as an allotransplant. The general opinion is that the fundamental protective mechanism must be located locally at the contact-plate, between the maternal and fetal tissues. Immunologic investigations proved the presence of specific systems which block the function of antipaternal maternal antibodies, as well as formation of cytotoxic maternal T-cells to paternal antigens. The system preventing rejection of graft during pregnancy is functioning at the level of maternal and fetal tissues. The protective mechanisms are coded by genes of MCH region, locus HLA-G. Protective mechanisms in the placenta The placenta protects itself against antibody-mediated damage. A high level of complement-regulatory proteins (CD46, CD55 and CD59, being the response to the synthesis of complement-fixing maternal antibodies to paternal antigens and regulation of the placental HLA expression as a preventive reaction of the feto-placental unit to the influence of maternal CTL, are the most important protective mechanisms of placenta. Protective mechanisms shared by the placenta and uterus Protective mechanisms common both for placenta and uterus are as follows: expressions of Fas ligand prevention of infiltration of activated immune cells, regulation of immunosuppression which prevents proliferation of immune cells and high natural immunity (Na cells and macrophages of the decidua.

  18. Coordinate actions of innate immune responses oppose those of the adaptive immune system during Salmonella infection of mice.

    Science.gov (United States)

    Hotson, Andrew N; Gopinath, Smita; Nicolau, Monica; Khasanova, Anna; Finck, Rachel; Monack, Denise; Nolan, Garry P

    2016-01-12

    The immune system enacts a coordinated response when faced with complex environmental and pathogenic perturbations. We used the heterogeneous responses of mice to persistent Salmonella infection to model system-wide coordination of the immune response to bacterial burden. We hypothesized that the variability in outcomes of bacterial growth and immune response across genetically identical mice could be used to identify immune elements that serve as integrators enabling co-regulation and interconnectedness of the innate and adaptive immune systems. Correlation analysis of immune response variation to Salmonella infection linked bacterial load with at least four discrete, interacting functional immune response "cassettes." One of these, the innate cassette, in the chronically infected mice included features of the innate immune system, systemic neutrophilia, and high serum concentrations of the proinflammatory cytokine interleukin-6. Compared with mice with a moderate bacterial load, mice with the highest bacterial burden exhibited high activity of this innate cassette, which was associated with a dampened activity of the adaptive T cell cassette-with fewer plasma cells and CD4(+) T helper 1 cells and increased numbers of regulatory T cells-and with a dampened activity of the cytokine signaling cassette. System-wide manipulation of neutrophil numbers revealed that neutrophils regulated signal transducer and activator of transcription (STAT) signaling in B cells during infection. Thus, a network-level approach demonstrated unappreciated interconnections that balanced innate and adaptive immune responses during the dynamic course of disease and identified signals associated with pathogen transmission status, as well as a regulatory role for neutrophils in cytokine signaling.

  19. The adaptive immune system as a fundamental regulator of adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Winer, Shawn; Winer, Daniel A

    2012-09-01

    Over the past decade, chronic inflammation in visceral adipose tissue (VAT) has gained acceptance as a lead promoter of insulin resistance in obesity. A great deal of evidence has pointed to the role of adipokines and innate immune cells, in particular, adipose tissue macrophages, in the regulation of fat inflammation and glucose homeostasis. However, more recently, cells of the adaptive immune system, specifically B and T lymphocytes, have emerged as unexpected promoters and controllers of insulin resistance. These adaptive immune cells infiltrate obesity expanded VAT and through cytokine secretion and macrophage modulation dictate the extent of the local inflammatory response, thereby directly impacting insulin resistance. The remarkable ability of our adaptive immune system to regulate insulin sensitivity and metabolism has unmasked a novel physiological function of this system, and promises new diagnostic and therapeutic strategies to manage the disease. This review highlights critical roles of adipose tissue lymphocytes in governing glucose homeostasis.

  20. Adaptive Immunity to Fungi

    Science.gov (United States)

    Verma, Akash; Wüthrich, Marcel; Deepe, George; Klein, Bruce

    2015-01-01

    Life-threatening fungal infections have risen sharply in recent years, owing to the advances and intensity of medical care that may blunt immunity in patients. This emerging crisis has created the growing need to clarify immune defense mechanisms against fungi with the ultimate goal of therapeutic intervention. We describe recent insights in understanding the mammalian immune defenses that are deployed against pathogenic fungi. We focus on adaptive immunity to the major medically important fungi and emphasize three elements that coordinate the response: (1) dendritic cells and subsets that are mobilized against fungi in various anatomical compartments; (2) fungal molecular patterns and their corresponding receptors that signal responses and shape the differentiation of T-cell subsets and B cells; and, ultimately (3) the effector and regulatory mechanisms that eliminate these invaders while constraining collateral damage to vital tissue. These insights create a foundation for the development of new, immune-based strategies for prevention or enhanced clearance of systemic fungal diseases. PMID:25377140

  1. Genes of the adaptive immune system are expressed early in zebrafish larval development following lipopolysaccharide stimulation

    Institute of Scientific and Technical Information of China (English)

    LI Fengling; ZHANG Shicui; WANG Zhiping; LI Hongyan

    2011-01-01

    Information regarding immunocompetence of the adaptive immune system (AIS) in zebrafish Danio rerio remains limited. Here, we stimulated an immune response in fish embryos,larvae and adults using lipopolysaccharide (LPS) and measured the upregulation of a number of AIS-related genes (Rag2, AID, TCRAC, IgLC-1, mIg, sIg, IgZ and DAB) 3 and 18 h later. We found that all of the genes evaluated were strongly induced following LPS stimulation, with most of them responding at 8 d post fertilization. This confirms that a functional adaptive immune response is present in D. rerio larvae, and provides a window for further functional analyses.

  2. Are the innate and adaptive immune systems setting hypertension on fire?

    Science.gov (United States)

    Bomfim, Gisele F; Rodrigues, Fernanda Luciano; Carneiro, Fernando S

    2017-03-01

    Hypertension is the most common chronic cardiovascular disease and is associated with several pathological states, being an important cause of morbidity and mortality around the world. Low-grade inflammation plays a key role in hypertension and the innate and adaptive immune systems seem to contribute to hypertension development and maintenance. Hypertension is associated with vascular inflammation, increased vascular cytokines levels and infiltration of immune cells in the vasculature, kidneys and heart. However, the mechanisms that trigger inflammation and immune system activation in hypertension are completely unknown. Cells from the innate immune system express pattern recognition receptors (PRR), which detect conserved pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) that induce innate effector mechanisms to produce endogenous signals, such as inflammatory cytokines and chemokines, to alert the host about danger. Additionally, antigen-presenting cells (APC) act as sentinels that are activated by PAMPs and DAMPs to sense the presence of the antigen/neoantigen, which ensues the adaptive immune system activation. In this context, different lymphocyte types are activated and contribute to inflammation and end-organ damage in hypertension. This review will focus on experimental and clinical evidence demonstrating the contribution of the innate and adaptive immune systems to the development of hypertension.

  3. Adapting to new threats: the generation of memory by CRISPR-Cas immune systems.

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    Heler, Robert; Marraffini, Luciano A; Bikard, David

    2014-07-01

    Clustered, regularly interspaced, short palindromic repeats (CRISPR) loci and their associated genes (cas) confer bacteria and archaea with adaptive immunity against phages and other invading genetic elements. A fundamental requirement of any immune system is the ability to build a memory of past infections in order to deal more efficiently with recurrent infections. The adaptive feature of CRISPR-Cas immune systems relies on their ability to memorize DNA sequences of invading molecules and integrate them in between the repetitive sequences of the CRISPR array in the form of 'spacers'. The transcription of a spacer generates a small antisense RNA that is used by RNA-guided Cas nucleases to cleave the invading nucleic acid in order to protect the cell from infection. The acquisition of new spacers allows the CRISPR-Cas immune system to rapidly adapt against new threats and is therefore termed 'adaptation'. Recent studies have begun to elucidate the genetic requirements for adaptation and have demonstrated that rather than being a stochastic process, the selection of new spacers is influenced by several factors. We review here our current knowledge of the CRISPR adaptation mechanism.

  4. Modulatory Effects of Antidepressant Classes on the Innate and Adaptive Immune System in Depression.

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    Eyre, H A; Lavretsky, H; Kartika, J; Qassim, A; Baune, B T

    2016-05-01

    Current reviews exploring for unique immune-modulatory profiles of antidepressant classes are limited by focusing mainly on cytokine modulation only and neglecting other aspects of the innate and adaptive immune system. These reviews also do not include recent comparative clinical trials, immune-genetic studies and therapeutics with unique neurotransmitter profiles (e. g., agomelatine). This systematic review extends the established literature by comprehensively reviewing the effects of antidepressants classes on both the innate and adaptive immune system. Antidepressants appear, in general, to reduce pro-inflammatory factor levels, particularly C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. We caution against conclusions as to which antidepressant possesses the greater anti-inflammatory effect, given the methodological heterogeneity among studies and the small number of comparative studies. The effects of antidepressant classes on adaptive immune factors are complex and poorly understood, and few studies have been conducted. Methodological heterogeneity is high among these studies (e. g., length of study, cohort characteristics, dosage used and immune marker analysis). We recommend larger, comparative studies - in clinical and pre-clinical populations.

  5. The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy.

    Science.gov (United States)

    Law, Andrew M K; Lim, Elgene; Ormandy, Christopher J; Gallego-Ortega, David

    2017-04-01

    A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy. Among these cell types, immune cells have emerged as a promising target for therapy. The adaptive and the innate immune system play an important role in normal mammary development and breast cancer. The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily, T lymphocytes, is lower in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression. A consideration of components of both the innate and the adaptive immune system is essential for the design and development of immunotherapies in breast cancer. In this review, we focus on the importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) as potential targets for breast cancer therapy.

  6. CRISPR-Cas adaptive immune systems of the sulfolobales

    DEFF Research Database (Denmark)

    Garrett, Roger Antony; Shah, Shiraz Ali; Erdmann, Susanne;

    2015-01-01

    The Sulfolobales have provided good model organisms for studying CRISPR-Cas systems of the crenarchaeal kingdom of the archaea. These organisms are infected by a wide range of exceptional archaea-specific viruses and conjugative plasmids, and their CRISPR-Cas systems generally exhibit extensive......, and this is consistent with these proteins tending to coevolve with core Cas proteins. Various novel aspects of CRISPR-Cas systems of the Sulfolobales are considered including an alternative spacer acquisition mechanism, reversible spacer acquisition, the formation and significance of antisense CRISPR RNAs, and a novel...... mechanism for avoidance of CRISPR-Cas defense. Finally, questions regarding the basis for the complexity, diversity, and apparent redundancy, of the intracellular CRISPR-Cas systems are discussed....

  7. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Science.gov (United States)

    Singh, Shailbala; Yang, Guojun; Schluns, Kimberly S; Anthony, Scott M; Sastry, K Jagannadha

    2014-01-01

    Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  8. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    Full Text Available Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer for harnessing the adjuvant potential of natural killer T (NKT cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  9. CRISPR-Cas: evolution of an RNA-based adaptive immunity system in prokaryotes.

    Science.gov (United States)

    Koonin, Eugene V; Makarova, Kira S

    2013-05-01

    The CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR-associated genes) is an adaptive immunity system in bacteria and archaea that functions via a distinct self-non-self recognition mechanism that is partially analogous to the mechanism of eukaryotic RNA interference (RNAi). The CRISPR-Cas system incorporates fragments of virus or plasmid DNA into the CRISPR repeat cassettes and employs the processed transcripts of these spacers as guide RNAs to cleave the cognate foreign DNA or RNA. The Cas proteins, however, are not homologous to the proteins involved in RNAi and comprise numerous, highly diverged families. The majority of the Cas proteins contain diverse variants of the RNA recognition motif (RRM), a widespread RNA-binding domain. Despite the fast evolution that is typical of the cas genes, the presence of diverse versions of the RRM in most Cas proteins provides for a simple scenario for the evolution of the three distinct types of CRISPR-cas systems. In addition to several proteins that are directly implicated in the immune response, the cas genes encode a variety of proteins that are homologous to prokaryotic toxins that typically possess nuclease activity. The predicted toxins associated with CRISPR-Cas systems include the essential Cas2 protein, proteins of COG1517 that, in addition to a ligand-binding domain and a helix-turn-helix domain, typically contain different nuclease domains and several other predicted nucleases. The tight association of the CRISPR-Cas immunity systems with predicted toxins that, upon activation, would induce dormancy or cell death suggests that adaptive immunity and dormancy/suicide response are functionally coupled. Such coupling could manifest in the persistence state being induced and potentially providing conditions for more effective action of the immune system or in cell death being triggered when immunity fails.

  10. Design of Immune-Algorithm-Based Adaptive Fuzzy Controllers for Active Suspension Systems

    Directory of Open Access Journals (Sweden)

    Ming-Yuan Shieh

    2014-04-01

    Full Text Available The aim of this paper is to integrate the artificial immune systems and adaptive fuzzy control for the automobile suspension system, which is regarded as a multiobjective optimization problem. Moreover, the fuzzy control rules and membership controls are then introduced for identification and memorization. It leads fast convergence in the search process. Afterwards, by using the diversity of the antibody group, trapping into local optimum can be avoided, and the system possesses a global search capacity and a faster local search for finding a global optimal solution. Experimental results show that the artificial immune system with the recognition and memory functions allows the system to rapidly converge and search for the global optimal approximate solutions.

  11. Physical model of the immune response of bacteria against bacteriophage through the adaptive CRISPR-Cas immune system

    Science.gov (United States)

    Han, Pu; Niestemski, Liang Ren; Barrick, Jeffrey E.; Deem, Michael W.

    2013-04-01

    Bacteria and archaea have evolved an adaptive, heritable immune system that recognizes and protects against viruses or plasmids. This system, known as the CRISPR-Cas system, allows the host to recognize and incorporate short foreign DNA or RNA sequences, called ‘spacers’ into its CRISPR system. Spacers in the CRISPR system provide a record of the history of bacteria and phage coevolution. We use a physical model to study the dynamics of this coevolution as it evolves stochastically over time. We focus on the impact of mutation and recombination on bacteria and phage evolution and evasion. We discuss the effect of different spacer deletion mechanisms on the coevolutionary dynamics. We make predictions about bacteria and phage population growth, spacer diversity within the CRISPR locus, and spacer protection against the phage population.

  12. Aircraft Abnormal Conditions Detection, Identification, and Evaluation Using Innate and Adaptive Immune Systems Interaction

    Science.gov (United States)

    Al Azzawi, Dia

    Abnormal flight conditions play a major role in aircraft accidents frequently causing loss of control. To ensure aircraft operation safety in all situations, intelligent system monitoring and adaptation must rely on accurately detecting the presence of abnormal conditions as soon as they take place, identifying their root cause(s), estimating their nature and severity, and predicting their impact on the flight envelope. Due to the complexity and multidimensionality of the aircraft system under abnormal conditions, these requirements are extremely difficult to satisfy using existing analytical and/or statistical approaches. Moreover, current methodologies have addressed only isolated classes of abnormal conditions and a reduced number of aircraft dynamic parameters within a limited region of the flight envelope. This research effort aims at developing an integrated and comprehensive framework for the aircraft abnormal conditions detection, identification, and evaluation based on the artificial immune systems paradigm, which has the capability to address the complexity and multidimensionality issues related to aircraft systems. Within the proposed framework, a novel algorithm was developed for the abnormal conditions detection problem and extended to the abnormal conditions identification and evaluation. The algorithm and its extensions were inspired from the functionality of the biological dendritic cells (an important part of the innate immune system) and their interaction with the different components of the adaptive immune system. Immunity-based methodologies for re-assessing the flight envelope at post-failure and predicting the impact of the abnormal conditions on the performance and handling qualities are also proposed and investigated in this study. The generality of the approach makes it applicable to any system. Data for artificial immune system development were collected from flight tests of a supersonic research aircraft within a motion-based flight

  13. Within-host co-evolution of chronic viruses and the adaptive immune system

    Science.gov (United States)

    Nourmohammad, Armita

    We normally think of evolution occurring in a population of organisms, in response to their external environment. Rapid evolution of cellular populations also occurs within our bodies, as the adaptive immune system works to eliminate infection. Some pathogens, such as HIV, are able to persist in a host for extended periods of time, during which they also evolve to evade the immune response. In this talk I will introduce an analytical framework for the rapid co-evolution of B-cell and viral populations, based on the molecular interactions between them. Since the co-evolution of antibodies and viruses is perpetually out of equilibrium, I will show how to quantify the amount of adaptation in each of the two populations by analysis of their co-evolutionary history. I will discuss the consequences of competition between lineages of antibodies, and characterize the fate of a given lineage dependent on the state of the antibody and viral populations. In particular, I will discuss the conditions for emergence of highly potent broadly neutralizing antibodies, which are now recognized as critical for designing an effective vaccine against HIV.

  14. CRISPR-Cas: From the Bacterial Adaptive Immune System to a Versatile Tool for Genome Engineering.

    Science.gov (United States)

    Kirchner, Marion; Schneider, Sabine

    2015-11-01

    The field of biology has been revolutionized by the recent advancement of an adaptive bacterial immune system as a universal genome engineering tool. Bacteria and archaea use repetitive genomic elements termed clustered regularly interspaced short palindromic repeats (CRISPR) in combination with an RNA-guided nuclease (CRISPR-associated nuclease: Cas) to target and destroy invading DNA. By choosing the appropriate sequence of the guide RNA, this two-component system can be used to efficiently modify, target, and edit genomic loci of interest in plants, insects, fungi, mammalian cells, and whole organisms. This has opened up new frontiers in genome engineering, including the potential to treat or cure human genetic disorders. Now the potential risks as well as the ethical, social, and legal implications of this powerful new technique move into the limelight.

  15. Immune System

    NARCIS (Netherlands)

    Kuper, C.F.; Ruehl-Fehlert, C.; Elmore, S.A.; Parker, G.A.

    2013-01-01

    Cells of the immune system are found in every organ, from the classic lymphoid organs to tissues such as liver, mucosae, and omental adipose tissue. Toxicity to the immune system may be from a direct or indirect injury to lymphoid organs. The morphological responses range from lymphocyte depletion t

  16. The role of idiotypic interactions in the adaptive immune system: a belief-propagation approach

    Science.gov (United States)

    Bartolucci, Silvia; Mozeika, Alexander; Annibale, Alessia

    2016-08-01

    In this work we use belief-propagation techniques to study the equilibrium behaviour of a minimal model for the immune system comprising interacting T and B clones. We investigate the effect of the so-called idiotypic interactions among complementary B clones on the system’s activation. Our results show that B-B interactions increase the system’s resilience to noise, making clonal activation more stable, while increasing the cross-talk between different clones. We derive analytically the noise level at which a B clone gets activated, in the absence of cross-talk, and find that this increases with the strength of idiotypic interactions and with the number of T cells sending signals to the B clones. We also derive, analytically and numerically, via population dynamics, the critical line where clonal cross-talk arises. Our approach allows us to derive the B clone size distribution, which can be experimentally measured and gives important information about the adaptive immune system response to antigens and vaccination.

  17. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  18. Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity.

    Directory of Open Access Journals (Sweden)

    Timothy J Nice

    2016-06-01

    Full Text Available In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV replicates in dendritic cells (DCs and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1-/- recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.

  19. Characterization of human antiviral adaptive immune responses during hepatotropic virus infection in HLA-transgenic human immune system mice.

    Science.gov (United States)

    Billerbeck, Eva; Horwitz, Joshua A; Labitt, Rachael N; Donovan, Bridget M; Vega, Kevin; Budell, William C; Koo, Gloria C; Rice, Charles M; Ploss, Alexander

    2013-08-15

    Humanized mice have emerged as a promising model to study human immunity in vivo. Although they are susceptible to many pathogens exhibiting an almost exclusive human tropism, human immune responses to infection remain functionally impaired. It has recently been demonstrated that the expression of HLA molecules improves human immunity to lymphotropic virus infections in humanized mice. However, little is known about the extent of functional human immune responses in nonlymphoid tissues, such as in the liver, and the role of HLA expression in this context. Therefore, we analyzed human antiviral immunity in humanized mice during a hepatotropic adenovirus infection. We compared immune responses of conventional humanized NOD SCID IL-2Rγ-deficient (NSG) mice to those of a novel NOD SCID IL-2Rγ-deficient strain transgenic for both HLA-A*0201 and a chimeric HLA-DR*0101 molecule. Using a firefly luciferase-expressing adenovirus and in vivo bioluminescence imaging, we demonstrate a human T cell-dependent partial clearance of adenovirus-infected cells from the liver of HLA-transgenic humanized mice. This correlated with liver infiltration and activation of T cells, as well as the detection of Ag-specific humoral and cellular immune responses. When infected with a hepatitis C virus NS3-expressing adenovirus, HLA-transgenic humanized mice mounted an HLA-A*0201-restricted hepatitis C virus NS3-specific CD8(+) T cell response. In conclusion, our study provides evidence for the generation of partial functional antiviral immune responses against a hepatotropic pathogen in humanized HLA-transgenic mice. The adenovirus reporter system used in our study may serve as simple in vivo method to evaluate future strategies for improving human intrahepatic immune responses in humanized mice.

  20. The Immune System Out of Shape? : Shaping of adaptive immunity by persistent viral infections in young children

    NARCIS (Netherlands)

    D. van den Heuvel (Diana)

    2015-01-01

    markdownabstractDuring pregnancy, a fetus is protected from a large part of the pathogens of the environment. As a result, a newborn’s immune system is immature and unexperienced, and mainly composed of innate leukocytes and naive lymphocytes. Immunological memory, and concomitant functional immunit

  1. Expansion of signaling genes for adaptive immune system evolution in early vertebrates

    Directory of Open Access Journals (Sweden)

    Okada Kinya

    2008-05-01

    Full Text Available Abstract Background The adaptive immune system (AIS of jawed vertebrates is a sophisticated system mediated by numerous genes in specialized cells. Phylogenetic analysis indicates that emergence of the AIS followed the occurrence of two rounds of whole-genome duplication (2R-WGD in early vertebrates, but little direct evidence linking these two events is available. Results We examined the relationship between 2R-WGD and the gain of AIS-related functions by numerous genes. To analyze the evolution of the many genes related to signal transduction in the AIS (defined as AIS genes, we identified groups of genes (defined as AIS subfamilies that included at least one human AIS gene, its paralogs (if any, and its Drosophila ortholog(s. Genomic mapping revealed that numerous pairs of AIS genes and their paralogs were part of paralogons – series of paralogous regions that derive from a common ancestor – throughout the human genome, indicating that the genes were retained as duplicates after 2R-WGD. Outgroup comparison analysis revealed that subfamilies in which human and fly genes shared a nervous system-related function were significantly enriched among AIS subfamilies, as compared with the overall incidence of shared nervous system-related functions among all subfamilies in bilaterians. This finding statistically supports the hypothesis that AIS-related signaling genes were ancestrally involved in the nervous system of urbilaterians. Conclusion The current results suggest that 2R-WGD played a major role in the duplication of many signaling genes, ancestrally used in nervous system development and function, that were later co-opted for new functions during evolution of the AIS.

  2. Research on Fuzzy Immune Self-Adaptive PID Algorithm Based on New Smith Predictor for Networked Control System

    Directory of Open Access Journals (Sweden)

    Haitao Zhang

    2015-01-01

    Full Text Available We first analyze the effect of network-induced delay on the stability of networked control systems (NCSs. Then, aiming at stochastic characteristics of the time delay, we introduce a new Smith predictor to remove the exponential function with the time delay in the closed-loop characteristic equation of the NCS. Furthermore, we combine the fuzzy PID algorithm with the fuzzy immune control algorithm and present a fuzzy immune self-adaptive PID algorithm to compensate the influence of the model deviation of the controlled object. At last, a kind of fuzzy immune self-adaptive PID algorithm based on new Smith predictor is presented to apply to the NCS. The simulation research on a DC motor is given to show the effectiveness of the proposed algorithm.

  3. Alternative adaptive immunity in invertebrates

    DEFF Research Database (Denmark)

    Kurtz, Joachim; Armitage, Sophie Alice Octavia

    2006-01-01

    Vertebrate adaptive immunity is characterized by challenge-specific long-term protection. This specific memory is achieved through the vast diversity of somatically rearranged immunological receptors such as antibodies. Whether or not invertebrates are capable of a comparable phenotypic plasticit...... and memory has long been a matter of debate. A recent study on Anopheles gambiae mosquitoes now establishes Down syndrome cell adhesion molecule (Dscam) as a key immune surveillance factor with characteristics analogous to antibodies....

  4. Genome complexity in the coelacanth is reflected in its adaptive immune system.

    Science.gov (United States)

    Saha, Nil Ratan; Ota, Tatsuya; Litman, Gary W; Hansen, John; Parra, Zuly; Hsu, Ellen; Buonocore, Francesco; Canapa, Adriana; Cheng, Jan-Fang; Amemiya, Chris T

    2014-09-01

    We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations.

  5. Genome complexity in the coelacanth is reflected in its adaptive immune system

    Science.gov (United States)

    Saha, Nil Ratan; Ota, Tatsuya; Litman, Gary W.; Hansen, John; Parra, Zuly; Hsu, Ellen; Buonocore, Francesco; Canapa, Adriana; Cheng, Jan-Fang; Amemiya, Chris T.

    2014-01-01

    We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations.

  6. Alternative adaptive immunity strategies: coelacanth, cod and shark immunity.

    Science.gov (United States)

    Buonocore, Francesco; Gerdol, Marco

    2016-01-01

    The advent of high throughput sequencing has permitted to investigate the genome and the transcriptome of novel non-model species with unprecedented depth. This technological advance provided a better understanding of the evolution of adaptive immune genes in gnathostomes, revealing several unexpected features in different fish species which are of particular interest. In the present paper, we review the current understanding of the adaptive immune system of the coelacanth, the elephant shark and the Atlantic cod. The study of coelacanth, the only living extant of the long thought to be extinct Sarcopterygian lineage, is fundamental to bring new insights on the evolution of the immune system in higher vertebrates. Surprisingly, coelacanths are the only known jawed vertebrates to lack IgM, whereas two IgD/W loci are present. Cartilaginous fish are of great interest due to their basal position in the vertebrate tree of life; the genome of the elephant shark revealed the lack of several important immune genes related to T cell functions, which suggest the existence of a primordial set of TH1-like cells. Finally, the Atlantic cod lacks a functional major histocompatibility II complex, but balances this evolutionary loss with the expansion of specific gene families, including MHC I, Toll-like receptors and antimicrobial peptides. Overall, these data point out that several fish species present an unconventional adaptive immune system, but the loss of important immune genes is balanced by adaptive evolutionary strategies which still guarantee the establishment of an efficient immune response against the pathogens they have to fight during their life.

  7. Natural innate and adaptive immunity to cancer.

    Science.gov (United States)

    Vesely, Matthew D; Kershaw, Michael H; Schreiber, Robert D; Smyth, Mark J

    2011-01-01

    The immune system can identify and destroy nascent tumor cells in a process termed cancer immunosurveillance, which functions as an important defense against cancer. Recently, data obtained from numerous investigations in mouse models of cancer and in humans with cancer offer compelling evidence that particular innate and adaptive immune cell types, effector molecules, and pathways can sometimes collectively function as extrinsic tumor-suppressor mechanisms. However, the immune system can also promote tumor progression. Together, the dual host-protective and tumor-promoting actions of immunity are referred to as cancer immunoediting. In this review, we discuss the current experimental and human clinical data supporting a cancer immunoediting process that provide the fundamental basis for further study of immunity to cancer and for the rational design of immunotherapies against cancer.

  8. Artificial Immune Systems Tutorial

    CERN Document Server

    Aickelin, Uwe

    2008-01-01

    The biological immune system is a robust, complex, adaptive system that defends the body from foreign pathogens. It is able to categorize all cells (or molecules) within the body as self-cells or non-self cells. It does this with the help of a distributed task force that has the intelligence to take action from a local and also a global perspective using its network of chemical messengers for communication. There are two major branches of the immune system. The innate immune system is an unchanging mechanism that detects and destroys certain invading organisms, whilst the adaptive immune system responds to previously unknown foreign cells and builds a response to them that can remain in the body over a long period of time. This remarkable information processing biological system has caught the attention of computer science in recent years. A novel computational intelligence technique, inspired by immunology, has emerged, called Artificial Immune Systems. Several concepts from the immune have been extracted an...

  9. Artificial Immune Systems

    CERN Document Server

    Aickelin, Uwe

    2009-01-01

    The biological immune system is a robust, complex, adaptive system that defends the body from foreign pathogens. It is able to categorize all cells (or molecules) within the body as self-cells or non-self cells. It does this with the help of a distributed task force that has the intelligence to take action from a local and also a global perspective using its network of chemical messengers for communication. There are two major branches of the immune system. The innate immune system is an unchanging mechanism that detects and destroys certain invading organisms, whilst the adaptive immune system responds to previously unknown foreign cells and builds a response to them that can remain in the body over a long period of time. This remarkable information processing biological system has caught the attention of computer science in recent years. A novel computational intelligence technique, inspired by immunology, has emerged, called Artificial Immune Systems. Several concepts from the immune have been extracted an...

  10. CRISPR/Cas and Cmr modules, mobility and evolution of adaptive immune systems

    DEFF Research Database (Denmark)

    Shah, Shiraz Ali; Garrett, Roger Antony

    2011-01-01

    CRISPR/Cas and CRISPR/Cmr immune machineries of archaea and bacteria provide an adaptive and effective defence mechanism directed specifically against viruses and plasmids. Present data suggest that both CRISPR/Cas and Cmr modules can behave like integral genetic elements. They tend to be located...... in the more variable regions of chromosomes and are displaced by genome shuffling mechanisms including transposition. CRISPR loci may be broken up and dispersed in chromosomes by transposons with the potential for creating genetic novelty. Both CRISPR/Cas and Cmr modules appear to exchange readily between...... the significant barriers imposed by their differing conjugative, transcriptional and translational mechanisms. There are parallels between the CRISPR crRNAs and eukaryal siRNAs, most notably to germ cell piRNAs which are directed, with the help of effector proteins, to silence or destroy transposons...

  11. Food-Nonfood Discrimination in Ancestral Vertebrates: Gamete Cannibalism and the Origin of the Adaptive Immune System.

    Science.gov (United States)

    Corcos, D

    2015-11-01

    Adaptive immunity is a complex system that appeared twice in vertebrates (in gnathostomes and in jawless fish) although it is not required for invertebrate defence. The adaptive immune system is tightly associated with self-non-self discrimination, and it is now clear that this interplay is not limited to the prevention of autoreactivity. Micro-organisms are usually considered for their pathogenicity or symbiotic ability, but, for most small metazoans, they mainly constitute food. Vertebrates are characterized by feeding by predation on larger preys, when compared to their ancestors who were filter feeders and ate micro-organisms. Predation gives a strong selective advantage, not only due to the availability of new food resources but also by the ability to eliminate competitors for environmental resources (intraguild predation (IGP)). Unlike size-structured IGP, intraspecific predation of juveniles, zygotes or gametes can be detrimental for species fitness in some circumstances. The ability of individuals to recognize highly polymorphic molecules on the surface of gametes present in the plankton and so distinguish self versus non-self gametes might have constituted a strong selective advantage in intraspecific competition. Here, I propose the theory that the capacity to rearrange receptors has been selected in ancestral vertebrates as a consequence of this strong need for discriminating between hetero-cannibalism versus filial cannibalism. This evolutionary origin sheds light on presently unexplained features of the immune system, including the existence of regulatory T cells and of non-pathogenic natural autoimmunity.

  12. Artificial immune system based on adaptive clonal selection for feature selection and parameters optimisation of support vector machines

    Science.gov (United States)

    Sadat Hashemipour, Maryam; Soleimani, Seyed Ali

    2016-01-01

    Artificial immune system (AIS) algorithm based on clonal selection method can be defined as a soft computing method inspired by theoretical immune system in order to solve science and engineering problems. Support vector machine (SVM) is a popular pattern classification method with many diverse applications. Kernel parameter setting in the SVM training procedure along with the feature selection significantly impacts on the classification accuracy rate. In this study, AIS based on Adaptive Clonal Selection (AISACS) algorithm has been used to optimise the SVM parameters and feature subset selection without degrading the SVM classification accuracy. Several public datasets of University of California Irvine machine learning (UCI) repository are employed to calculate the classification accuracy rate in order to evaluate the AISACS approach then it was compared with grid search algorithm and Genetic Algorithm (GA) approach. The experimental results show that the feature reduction rate and running time of the AISACS approach are better than the GA approach.

  13. [The effect of adaptation to the periodic action of hypoxia on the indices of the immunity system and on the course of allergic diseases].

    Science.gov (United States)

    Meerson, F Z; Frolov, B A; Volianik, M N; Boev, V M; Bannikov, V K; Smoliagin, A I; Tverdokhleb, V P; Afonina, S N; Livshits, N M; Frolova, M A

    1990-01-01

    The authors studied the effect of adaptation to periodical exposure to hypoxia on the organism's immune status and the values of neurohumoral regulation in children with bronchial asthma and adults suffering from allergic dermatoses and autoimmune thyroiditis. It was found that adaptation facilitated normalization of humoral values of immunity in allergic and autoimmune disorders (the content of serum immunoglobulins increased while the level of circulating immune complexes reduced) and was attended by a stable therapeutic effect. The revealed changes of the immune values occurred in increase of the reserve potency of the hypothalamo-hypophyseal-adrenal and sympathoadrenal systems and reduction of the blood histamine level.

  14. Ubiquitin in the immune system

    OpenAIRE

    Julia Zinngrebe; Antonella Montinaro; Nieves Peltzer; Henning Walczak

    2013-01-01

    Ubiquitination is a post-translational modification process that has been implicated in the regulation of innate and adaptive immune responses. There is increasing evidence that both ubiquitination and its reversal, deubiquitination, play crucial roles not only during the development of the immune system but also in the orchestration of an immune response by ensuring the proper functioning of the different cell types that constitute the immune system. Here, we provide an overview of the lates...

  15. Adaptive immune resistance: How cancer protects from immune attack

    Science.gov (United States)

    Ribas, Antoni

    2015-01-01

    Adaptive immune resistance is a process where the cancer changes its phenotype in response to a cytotoxic or pro-inflammatory immune response, thereby evading it. This adaptive process is triggered by the specific recognition of cancer cells by T cells, which leads to the production of immune-activating cytokines. Cancers then hijack mechanisms developed to limit inflammatory and immune responses and protect themselves from the T cell attack. Inhibiting adaptive immune resistance is the mechanistic basis of responses to PD-1 or PD-L1 blocking antibodies, and may be of relevance for the development of other cancer immunotherapy strategies. PMID:26272491

  16. Sildenafil Can Affect Innate and Adaptive Immune System in Both Experimental Animals and Patients

    Directory of Open Access Journals (Sweden)

    Monika Kniotek

    2017-01-01

    Full Text Available Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I, is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects. Sildenafil influences angiogenesis, platelet activation, proliferation of regulatory T cells, and production of proinflammatory cytokines and autoantibodies. Sildenafil action in humans and animals appears to be different. Surprisingly, it also acts differently in males and females organisms. Although the immunomodulatory effects of PDE5 inhibitors appear to be promising, none of them reached the point of being tested in clinical trials. Data on the influence of selective PDE5-Is on the human immune system are limited. The main objective of this review is to discuss the immunomodulatory effects of sildenafil in both patients and experimental animals. This is the first review of the current state of knowledge about the effects of sildenafil on the immune system.

  17. Sildenafil Can Affect Innate and Adaptive Immune System in Both Experimental Animals and Patients

    Science.gov (United States)

    Boguska, Agnieszka

    2017-01-01

    Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects. Sildenafil influences angiogenesis, platelet activation, proliferation of regulatory T cells, and production of proinflammatory cytokines and autoantibodies. Sildenafil action in humans and animals appears to be different. Surprisingly, it also acts differently in males and females organisms. Although the immunomodulatory effects of PDE5 inhibitors appear to be promising, none of them reached the point of being tested in clinical trials. Data on the influence of selective PDE5-Is on the human immune system are limited. The main objective of this review is to discuss the immunomodulatory effects of sildenafil in both patients and experimental animals. This is the first review of the current state of knowledge about the effects of sildenafil on the immune system.

  18. CRISPR-Cas Adaptive Immune Systems of the Sulfolobales: Unravelling Their Complexity and Diversity

    Directory of Open Access Journals (Sweden)

    Roger A. Garrett

    2015-03-01

    Full Text Available The Sulfolobales have provided good model organisms for studying CRISPR-Cas systems of the crenarchaeal kingdom of the archaea. These organisms are infected by a wide range of exceptional archaea-specific viruses and conjugative plasmids, and their CRISPR-Cas systems generally exhibit extensive structural and functional diversity. They carry large and multiple CRISPR loci and often multiple copies of diverse Type I and Type III interference modules as well as more homogeneous adaptation modules. These acidothermophilic organisms have recently provided seminal insights into both the adaptation process, the diverse modes of interference, and their modes of regulation. The functions of the adaptation and interference modules tend to be loosely coupled and the stringency of the crRNA-DNA sequence matching during DNA interference is relatively low, in contrast to some more streamlined CRISPR-Cas systems of bacteria. Despite this, there is evidence for a complex and differential regulation of expression of the diverse functional modules in response to viral infection. Recent work also supports critical roles for non-core Cas proteins, especially during Type III-directed interference, and this is consistent with these proteins tending to coevolve with core Cas proteins. Various novel aspects of CRISPR-Cas systems of the Sulfolobales are considered including an alternative spacer acquisition mechanism, reversible spacer acquisition, the formation and significance of antisense CRISPR RNAs, and a novel mechanism for avoidance of CRISPR-Cas defense. Finally, questions regarding the basis for the complexity, diversity, and apparent redundancy, of the intracellular CRISPR-Cas systems are discussed.

  19. Inflammatory bowel disease related innate immunity and adaptive immunity

    Science.gov (United States)

    Huang, Yuan; Chen, Zhonge

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn’s disease (CD). Its pathogenesis remains not yet clear. Current researchers believe that after environmental factors act on individuals with genetic susceptibility, an abnormal intestinal immune response is launched under stimulation of intestinal flora. However, previous studies only focused on adaptive immunity in the pathogenesis of IBD. Currently, roles of innate immune response in the pathogenesis of intestinal inflammation have also drawn much attention. In this study, IBD related innate immunity and adaptive immunity were explained, especially the immune mechanisms in the pathogenesis of IBD. PMID:27398134

  20. [Advances in molecular mechanisms of adaptive immunity mediated by type I-E CRISPR/Cas system--A review].

    Science.gov (United States)

    Sun, Dongchang; Qiu, Juanping

    2016-01-01

    To better adapt to the environment, prokaryocyte can take up exogenous genes (from bacteriophages, plasmids or genomes of other species) through horizontal gene transfer. Accompanied by the acquisition of exogenous genes, prokaryocyte is challenged by the invasion of 'selfish genes'. Therefore, to protect against the risk of gene transfer, prokaryocyte needs to establish mechanisms for selectively taking up or degrading exogenous DNA. In recent years, researchers discovered an adaptive immunity, which is mediated by the small RNA guided DNA degradation, prevents the invasion of exogenous genes in prokaryocyte. During the immune process, partial DNA fragments are firstly integrated.to the clustered regularly interspaced short palindromic repeats (CRISPR) located within the genome DNA, and then the mature CRISPR RNA transcript and the CRISPR associated proteins (Cas) form a complex CRISPR/Cas for degrading exogenous DNA. In this review, we will first briefly describe the CRISPR/Cas systems and then mainly focus on the recent advances of the function mechanism and the regulation mechanism of the type I-E CRISPR/Cas system in Escherichia coli.

  1. Role of Hp system in adaptation of specific immunity indices to the influence of moderate physical activity

    Directory of Open Access Journals (Sweden)

    V. L. Sokolenko

    2014-04-01

    Full Text Available The aim of this study is to determine the role of haptoglobin phenotype in realization of adaptive responses of cellular and humoral immunity indices to moderate exercise caused by physical training. The study was implemented in the group of second-year students aged 18–20 who lived in the same climatic and geographical conditions for a long period of time. The students didn’t have any acute or chronic diseases and attended the main group of physical training. 60 persons were investigated. Immune system indices analysis was carried out in September before and after physical training lessons. Leukocyte level was calculated using hemocytometer, lymphocyte level was determined on the base of blood smear (dyeing for Romanowsky–Giemsa. Expression of surface antigene by peripheral blood lymphocyte was determined by immuno-fluorescence method with the use of monoclonal antibodies. The level of immunoglobulin in plasma was determined by radial immunodiffusion or Mancini method. To assess the phenotype of haptoglobin (Hp we used the method of electrophoresis in starch gels. In the course of research we have detected the reduction of the relative and total number of lymphocytes regardless of haptoglobin phenotype in the group of students after physical training; this is a typical feature of the initial stages of stress response. We observed statistically reliable decrease in total number of analyzed subpopulations of T-lymphocyte in the group of students with phenotype Hp2-2 which was obviously the result of changes in the general level of lymphocytes in the peripheral blood. In the group of students with phenotype Hp1-1 absolute number of T-lymphocyte with phenotype CD3+ and CD4+ is reduced. In the group of students with phenotype Hp2-1 we have seen only the tendency to decrease in functional mature T-lymphocyte and their helper subpopulation. In the group of students with phenotype Hp2-2 the relative number of helper T-lymphocyte with the

  2. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  3. A myriad of functions and complex regulation of the CCR7/CCL19/CCL21 chemokine axis in the adaptive immune system.

    Science.gov (United States)

    Comerford, Iain; Harata-Lee, Yuka; Bunting, Mark D; Gregor, Carly; Kara, Ervin E; McColl, Shaun R

    2013-06-01

    The chemokine receptor CCR7 and its ligands CCL19 and CCL21 control a diverse array of migratory events in adaptive immune function. Most prominently, CCR7 promotes homing of T cells and DCs to T cell areas of lymphoid tissues where T cell priming occurs. However, CCR7 and its ligands also contribute to a multitude of adaptive immune functions including thymocyte development, secondary lymphoid organogenesis, high affinity antibody responses, regulatory and memory T cell function, and lymphocyte egress from tissues. In this survey, we summarise the role of CCR7 in adaptive immunity and describe recent progress in understanding how this axis is regulated. In particular we highlight CCX-CKR, which scavenges both CCR7 ligands, and discuss its emerging significance in the immune system.

  4. Genetic Adaptation and Neandertal Admixture Shaped the Immune System of Human Populations.

    Science.gov (United States)

    Quach, Hélène; Rotival, Maxime; Pothlichet, Julien; Loh, Yong-Hwee Eddie; Dannemann, Michael; Zidane, Nora; Laval, Guillaume; Patin, Etienne; Harmant, Christine; Lopez, Marie; Deschamps, Matthieu; Naffakh, Nadia; Duffy, Darragh; Coen, Anja; Leroux-Roels, Geert; Clément, Frederic; Boland, Anne; Deleuze, Jean-François; Kelso, Janet; Albert, Matthew L; Quintana-Murci, Lluis

    2016-10-20

    Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli-ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus-and mapped expression quantitative trait loci (eQTLs). We identify numerous cis-eQTLs that contribute to the marked differences in immune responses detected within and between populations and a strong trans-eQTL hotspot at TLR1 that decreases expression of pro-inflammatory genes in Europeans only. We find that immune-responsive regulatory variants are enriched in population-specific signals of natural selection and show that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges. Together, our study uncovers evolutionarily important determinants of differences in host immune responsiveness between human populations.

  5. [Adaptive immune response of people living near chemically hazardous object].

    Science.gov (United States)

    Petlenko, S V; Ivanov, M B; Goverdovskiĭ, Iu B; Bogdanova, E G; Golubkov, A V

    2011-10-01

    The article presents data dynamics of adaptive immune responses of people for a long time living in adverse environmental conditions caused by pollution of the environment by industrial toxic waste. It is shown that in the process of adaptation to adverse environmental factors, changes in the immune system are in the phase fluctuations of immunological parameters that are accompanied by changes in the structure of immunodependent pathology. Most sensitive to prolonged exposure to toxic compounds are the cellular mechanisms of immune protection. Violations of the structural and quantitative and functional parameters of the link of the immune system are leading to the formation of immunopathological processes.

  6. The effects of stress hormones on immune function may be vital for the adaptive reconfiguration of the immune system during fight-or-flight behavior.

    Science.gov (United States)

    Adamo, Shelley A

    2014-09-01

    Intense, short-term stress (i.e., robust activation of the fight-or-flight response) typically produces a transient decline in resistance to disease in animals across phyla. Chemical mediators of the stress response (e.g., stress hormones) help induce this decline, suggesting that this transient immunosuppression is an evolved response. However, determining the function of stress hormones on immune function is difficult because of their complexity. Nevertheless, evidence suggests that stress hormones help maintain maximal resistance to disease during the physiological changes needed to optimize the body for intense physical activity. Work on insects demonstrates that stress hormones both shunt resources away from the immune system during fight-or-flight responses as well as reconfigure the immune system. Reconfiguring the immune system minimizes the impact of the loss of these resources and reduces the increased costs of some immune functions due to the physiological changes demanded by the fight-or-flight response. For example, during the stress response of the cricket Gryllus texensis, some molecular resources are shunted away from the immune system and toward lipid transport, resulting in a reduction in resistance to disease. However, insects' immune cells (hemocytes) have receptors for octopamine (the insect stress neurohormone). Octopamine increases many hemocyte functions, such as phagocytosis, and these changes would tend to mitigate the decline in immunity due to the loss of molecular resources. Moreover, because the stress response generates oxidative stress, some immune responses are probably more costly when activated during a stress response (e.g., those that produce reactive molecules). Some of these immune responses are depressed during stress in crickets, while others, whose costs are probably not increased during a stress response, are enhanced. Some effects of stress hormones on immune systems may be better understood as examples of reconfiguration

  7. Evolution of adaptive immune recognition in jawless vertebrates.

    Science.gov (United States)

    Saha, Nil Ratan; Smith, Jeramiah; Amemiya, Chris T

    2010-02-01

    All extant vertebrates possess an adaptive immune system wherein diverse immune receptors are created and deployed in specialized blood cell lineages. Recent advances in DNA sequencing and developmental resources for basal vertebrates have facilitated numerous comparative analyses that have shed new light on the molecular and cellular bases of immune defense and the mechanisms of immune receptor diversification in the "jawless" vertebrates. With data from these key species in hand, it is becoming possible to infer some general aspects of the early evolution of vertebrate adaptive immunity. All jawed vertebrates assemble their antigen-receptor genes through combinatorial recombination of different "diversity" segments into immunoglobulin or T-cell receptor genes. However, the jawless vertebrates employ an analogous, but independently derived set of immune receptors in order to recognize and bind antigens: the variable lymphocyte receptors (VLRs). The means by which this locus generates receptor diversity and achieves antigen specificity is of considerable interest because these mechanisms represent a completely independent strategy for building a large immune repertoire. Therefore, studies of the VLR system are providing insight into the fundamental principles and evolutionary potential of adaptive immune recognition systems. Here we review and synthesize the wealth of data that have been generated towards understanding the evolution of the adaptive immune system in the jawless vertebrates.

  8. Immune System

    Science.gov (United States)

    ... and mature there to become B cells or leave for the thymus gland, where they mature to become T cells. B lymphocytes and T lymphocytes have separate jobs to do: B lymphocytes are like the body's military intelligence system, seeking out their targets and sending defenses to ...

  9. Innate and adaptive immunity in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Britta Siegmund; Martin Zeitz

    2011-01-01

    Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time. Functional studies from in vivo models of intestinal inflammation as well as results from genome-wide association studies strongly suggest a cross-regulation of both arms. The present review will illustrate this interaction by selecting examples from innate immunity and adaptive immunity, and their direct impact on each other. Broadening our view by focusing on the cross-regulated areas of the mucosal immune system will not only facilitate our understanding of disease, but furthermore will allow identification of future therapeutic targets.

  10. Innate and adaptive immunity in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    BrittaSiegmund; MartinZeitz

    2011-01-01

    Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time. Functional studies from in vivo models of intestinal inflammation as well as results from genome-wide association studies strongly suggest a crossregulation of both arms. The present review will illustrate this interaction by selecting examples from innate immunity and adaptive immunity, and their direct impact on each other. Broadening our view by focusing on the cross-regulated areas of the mucosal immune system will not only facilitate our understanding of disease, but furthermore will allow identification of future therapeutic targets.

  11. Immune regulation by pericytes: modulating innate and adaptive immunity

    DEFF Research Database (Denmark)

    Navarro, Rocio; Compte, Marta; Álvarez-Vallina, Luis;

    2016-01-01

    respond to a series of proinflammatory stimuli and are able to sense different types of danger through expression of functional pattern recognition receptors, contributing to the onset of innate immune responses. In this context, PC not only secrete a variety of chemokines, but they also overexpress...... adhesion molecules such as ICAM-1 and VCAM-1 involved in the control of immune cell trafficking across vessel walls. In addition to their role in innate immunity, pericytes are involved in adaptive immunity. It has been reported that interaction with PC anergizes T cells, attributed, at least in part...

  12. Dynamics of immune system vulnerabilities

    Science.gov (United States)

    Stromberg, Sean P.

    The adaptive immune system can be viewed as a complex system, which adapts, over time, to reflect the history of infections experienced by the organism. Understanding its operation requires viewing it in terms of tradeoffs under constraints and evolutionary history. It typically displays "robust, yet fragile" behavior, meaning common tasks are robust to small changes but novel threats or changes in environment can have dire consequences. In this dissertation we use mechanistic models to study several biological processes: the immune response, the homeostasis of cells in the lymphatic system, and the process that normally prevents autoreactive cells from entering the lymphatic system. Using these models we then study the effects of these processes interacting. We show that the mechanisms that regulate the numbers of cells in the immune system, in conjunction with the immune response, can act to suppress autoreactive cells from proliferating, thus showing quantitatively how pathogenic infections can suppress autoimmune disease. We also show that over long periods of time this same effect can thin the repertoire of cells that defend against novel threats, leading to an age correlated vulnerability. This vulnerability is shown to be a consequence of system dynamics, not due to degradation of immune system components with age. Finally, modeling a specific tolerance mechanism that normally prevents autoimmune disease, in conjunction with models of the immune response and homeostasis we look at the consequences of the immune system mistakenly incorporating pathogenic molecules into its tolerizing mechanisms. The signature of this dynamic matches closely that of the dengue virus system.

  13. INNATE, ADAPTIVE AND INTRINSIC IMMUNITY IN HUMAN IMMUNODEFICIENCY VIRUS INFECTION

    Directory of Open Access Journals (Sweden)

    Suneth S. Perera

    2012-01-01

    Full Text Available The first line of defence of the innate immune system functions by recognizing highly conserved sets of molecular structures specific to the microbes, termed pathogen-associated molecular patterns, or PAMPs via the germ line-encoded receptors Pattern-Recognition Receptors (PRRs. In addition to the innate immune system, the vertebrates have also evolved a second line of defence termed adaptive immune system, which uses a diverse set of somatically rearranged receptors T-Cell Receptors (TCRs and B Cell Receptors (BCRs, which have the inherent ability to effectively recognise diverse antigens. The innate and adaptive immune systems are functionally tied in with the intrinsic immunity, which comprises of endogenous antiviral factors. Thus, this effective response to diverse microbial infections, including HIV, requires a coordinated interaction at several functional levels between innate, adaptive and intrinsic immune systems. This review provides a snapshot of roles played by the innate, adaptive and the intrinsic immune systems during HIV-infection, along with discussing recent developments highlighting the genomic basis of these responses and their regulation by micro-RNA (miRNAs.

  14. Immune System and Disorders

    Science.gov (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  15. Skin innate immune system

    Directory of Open Access Journals (Sweden)

    Berna Aksoy

    2013-06-01

    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  16. Tumors STING adaptive antitumor immunity.

    Science.gov (United States)

    Bronte, Vincenzo

    2014-11-20

    Immunotherapy is revolutionizing the treatment of cancer patients, but the molecular basis for tumor immunogenicity is unclear. In this issue of Immunity, Deng et al. (2014) and Woo et al. (2014) provide evidence suggesting that dendritic cells detect DNA from tumor cells via the STING-mediated, cytosolic DNA sensing pathway.

  17. Adaptive immune responses to Candida albicans infection.

    Science.gov (United States)

    Richardson, Jonathan P; Moyes, David L

    2015-01-01

    Fungal infections are becoming increasingly prevalent in the human population and contribute to morbidity and mortality in healthy and immunocompromised individuals respectively. Candida albicans is the most commonly encountered fungal pathogen of humans, and is frequently found on the mucosal surfaces of the body. Host defense against C. albicans is dependent upon a finely tuned implementation of innate and adaptive immune responses, enabling the host to neutralise the invading fungus. Central to this protection are the adaptive Th1 and Th17 cellular responses, which are considered paramount to successful immune defense against C. albicans infections, and enable tissue homeostasis to be maintained in the presence of colonising fungi. This review will highlight the recent advances in our understanding of adaptive immunity to Candida albicans infections.

  18. Energetics and the immune system

    Science.gov (United States)

    Reiches, Meredith W.; Prentice, Andrew M.; Moore, Sophie E.; Ellison, Peter T.

    2017-01-01

    Abstract Background and objectives: The human immune system is an ever-changing composition of innumerable cells and proteins, continually ready to respond to pathogens or insults. The cost of maintaining this state of immunological readiness is rarely considered. In this paper we aim to discern a cost to non-acute immune function by investigating how low levels of C-reactive protein (CRP) relate to other energetic demands and resources in adolescent Gambian girls. Methodology: Data from a longitudinal study of 66 adolescent girls was used to test hypotheses around investment in immune function. Non-acute (under 2 mg/L) CRP was used as an index of immune function. Predictor variables include linear height velocity, adiposity, leptin, and measures of energy balance. Results: Non-acute log CRP was positively associated with adiposity (β = 0.16, P resources and demands. We also find support for an adaptive association between the immune system and adipose tissue. PMID:28003312

  19. The Role of the p38 Pathway in Adaptive Immunity

    Institute of Scientific and Technical Information of China (English)

    Ryan Cook; Chia-Cheng Wu; Young Jun Kang; Jiahuai Han

    2007-01-01

    Since its discovery in 1993, the mitogen-activated protein (MAP) kinase p38 has attracted much attention for its role in a wide range of cellular processes, many of which involve the immune system. Although p38 has been heavily implicated in the function of all type immune cells, research has tended focus on its role in innate immunity.In this review we attempt to highlight some of the major discoveries that have been made regarding p38's role in adaptive immunity, and also to discuss the possible future implications of these discoveries.

  20. Adaptive Immunity to Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Françoise Stoll-Keller

    2009-09-01

    Full Text Available The precise role of adaptive immune responses in the clinical outcome of HCV infection is still only partially defined. Recent studies suggest that viral-host cell interactions during the acute phase of infection are essential for viral clearance or progression into chronic HCV infection. This review focuses on different aspects of the adaptive immune responses as determinants of the different outcomes of HCV infection, clearance or persistent infection, and outlines current concepts of HCV evasion strategies. Unravelling these important mechanisms of virus-host interaction will contribute to the development of novel strategies to prevent and control HCV infection.

  1. The evolution of adaptive immunity in vertebrates.

    Science.gov (United States)

    Hirano, Masayuki; Das, Sabyasachi; Guo, Peng; Cooper, Max D

    2011-01-01

    Approximately 500 million years ago, two types of recombinatorial adaptive immune systems (AISs) arose in vertebrates. The jawed vertebrates diversify their repertoire of immunoglobulin domain-based T and B cell antigen receptors mainly through the rearrangement of V(D)J gene segments and somatic hypermutation, but none of the fundamental AIS recognition elements in jawed vertebrates have been found in jawless vertebrates. Instead, the AIS of jawless vertebrates is based on variable lymphocyte receptors (VLRs) that are generated through recombinatorial usage of a large panel of highly diverse leucine-rich-repeat (LRR) sequences. Whereas the appearance of transposon-like, recombination-activating genes contributed uniquely to the origin of the AIS in jawed vertebrates, the use of activation-induced cytidine deaminase for receptor diversification is common to both the jawed and jawless vertebrates. Despite these differences in anticipatory receptor construction, the basic AIS design featuring two interactive T and B lymphocyte arms apparently evolved in an ancestor of jawed and jawless vertebrates within the context of preexisting innate immunity and has been maintained since as a consequence of powerful and enduring selection, most probably for pathogen defense purposes.

  2. The Immune System Game

    Science.gov (United States)

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  3. Visual computing model for immune system and medical system.

    Science.gov (United States)

    Gong, Tao; Cao, Xinxue; Xiong, Qin

    2015-01-01

    Natural immune system is an intelligent self-organizing and adaptive system, which has a variety of immune cells with different types of immune mechanisms. The mutual cooperation between the immune cells shows the intelligence of this immune system, and modeling this immune system has an important significance in medical science and engineering. In order to build a comprehensible model of this immune system for better understanding with the visualization method than the traditional mathematic model, a visual computing model of this immune system was proposed and also used to design a medical system with the immune system, in this paper. Some visual simulations of the immune system were made to test the visual effect. The experimental results of the simulations show that the visual modeling approach can provide a more effective way for analyzing this immune system than only the traditional mathematic equations.

  4. Readapting the adaptive immune response - therapeutic strategies for atherosclerosis.

    Science.gov (United States)

    Sage, Andrew P; Mallat, Ziad

    2017-01-04

    Cardiovascular diseases remain a major global health issue, with the development of atherosclerosis as a major underlying cause. Our treatment of cardiovascular disease has improved greatly over the past three decades, but much remains to be done reduce disease burden. Current priorities include reducing atherosclerosis advancement to clinically significant stages and preventing plaque rupture or erosion. Inflammation and involvement of the adaptive immune system influences all these aspects and therefore is one focus for future therapeutic development. The atherosclerotic vascular wall is now recognized to be invaded from both sides (arterial lumen and adventitia), for better or worse, by the adaptive immune system. Atherosclerosis is also affected at several stages by adaptive immune responses, overall providing many opportunities to target these responses and to reduce disease progression. Protective influences that may be defective in diseased individuals include humoral responses to modified LDL and regulatory T cell responses. There are many strategies in development to boost these pathways in humans, including vaccine-based therapies. The effects of various existing adaptive immune targeting therapies, such as blocking critical co-stimulatory pathways or B cell depletion, on cardiovascular disease are beginning to emerge with important consequences for both autoimmune disease patients and the potential for wider use of such therapies. Entering the translation phase for adaptive immune targeting therapies is an exciting and promising prospect.

  5. Human immune system variation.

    Science.gov (United States)

    Brodin, Petter; Davis, Mark M

    2017-01-01

    The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.

  6. Crosstalk between innate and adaptive immunity inhepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatitis B virus (HBV) infection is a major public health problem worldwide. HBV is not directly cytotoxic toinfected hepatocytes; the clinical outcome of infectionresults from complicated interactions between the virusand the host immune system. In acute HBV infection,initiation of a broad, vigorous immune response is responsiblefor viral clearance and self-limited inflammatoryliver disease. Effective and coordinated innate andadaptive immune responses are critical for viral clearanceand the development of long-lasting immunity. Chronichepatitis B patients fail to mount efficient innate andadaptive immune responses to the virus. In particular,HBV-specific cytotoxic T cells, which are crucial for HBVclearance, are hyporesponsiveness to HBV infection.Accumulating experimental evidence obtained fromthe development of animal and cell line models hashighlighted the importance of innate immunity in theearly control of HBV spread. The virus has evolvedimmune escape strategies, with higher HBV loads andHBV protein concentrations associated with increasingimpairment of immune function. Therefore, treatmentof HBV infection requires inhibition of HBV replicationand protein expression to restore the suppressedhost immunity. Complicated interactions exist notonly between innate and adaptive responses, but alsoamong innate immune cells and different components ofadaptive responses. Improved insight into these complexinteractions are important in designing new therapeuticstrategies for the treatment HBV infection. In thisreview, we summarize the current knowledge regardingthe cross-talk between the innate and adaptive immuneresponses and among different immunocytes in HBVinfection.

  7. Artificial Immune Systems (2010)

    CERN Document Server

    Greensmith, Julie; Aickelin, Uwe

    2010-01-01

    The human immune system has numerous properties that make it ripe for exploitation in the computational domain, such as robustness and fault tolerance, and many different algorithms, collectively termed Artificial Immune Systems (AIS), have been inspired by it. Two generations of AIS are currently in use, with the first generation relying on simplified immune models and the second generation utilising interdisciplinary collaboration to develop a deeper understanding of the immune system and hence produce more complex models. Both generations of algorithms have been successfully applied to a variety of problems, including anomaly detection, pattern recognition, optimisation and robotics. In this chapter an overview of AIS is presented, its evolution is discussed, and it is shown that the diversification of the field is linked to the diversity of the immune system itself, leading to a number of algorithms as opposed to one archetypal system. Two case studies are also presented to help provide insight into the m...

  8. Hosts are ahead in a marine host-parasite coevolutionary arms race: innate immune system adaptation in pipefish Syngnathus typhle against Vibrio phylotypes.

    Science.gov (United States)

    Roth, Olivia; Keller, Isabel; Landis, Susanne H; Salzburger, Walter; Reusch, Thorsten B H

    2012-08-01

    Microparasites have a higher evolutionary potential than their hosts due to an increased mutation rate and a shorter generation time that usually results in parasites being locally adapted to their sympatric hosts. This pattern may not apply to generalist pathogens as adaptation to sympatric host genotypes is disadvantageous due to a narrowing of the host range, in particular under strong gene flow among host populations. Under this scenario, we predict that the immune defense of hosts reveals adaptation to locally common pathogen phylotypes. This was tested in four host populations of the pipefish Syngnathus typhle and associated bacteria of the genus Vibrio. We investigated the population divergence among host and bacteria populations and verified that gene flow is higher among host populations than among parasite populations. Next, we experimentally assessed the strength of innate immune defense of pipefish hosts using in vitro assays that measured antimicrobial activity of blood plasma against sympatric and allopatric Vibrio phylotypes. Pipefish plasma displays stronger antimicrobial activity against sympatric Vibrio phylotypes compared to allopatric ones. This suggests that host defense is genetically adapted against local bacteria with a broad and unspecialized host spectrum, a situation that is typical for marine systems with weak host population structure.

  9. The immune system and hypertension.

    Science.gov (United States)

    Singh, Madhu V; Chapleau, Mark W; Harwani, Sailesh C; Abboud, Francois M

    2014-08-01

    A powerful interaction between the autonomic and the immune systems plays a prominent role in the initiation and maintenance of hypertension and significantly contributes to cardiovascular pathology, end-organ damage and mortality. Studies have shown consistent association between hypertension, proinflammatory cytokines and the cells of the innate and adaptive immune systems. The sympathetic nervous system, a major determinant of hypertension, innervates the bone marrow, spleen and peripheral lymphatic system and is proinflammatory, whereas the parasympathetic nerve activity dampens the inflammatory response through α7-nicotinic acetylcholine receptors. The neuro-immune synapse is bidirectional as cytokines may enhance the sympathetic activity through their central nervous system action that in turn increases the mobilization, migration and infiltration of immune cells in the end organs. Kidneys may be infiltrated by immune cells and mesangial cells that may originate in the bone marrow and release inflammatory cytokines that cause renal damage. Hypertension is also accompanied by infiltration of the adventitia and perivascular adipose tissue by inflammatory immune cells including macrophages. Increased cytokine production induces myogenic and structural changes in the resistance vessels, causing elevated blood pressure. Cardiac hypertrophy in hypertension may result from the mechanical afterload and the inflammatory response to resident or migratory immune cells. Toll-like receptors on innate immune cells function as sterile injury detectors and initiate the inflammatory pathway. Finally, abnormalities of innate immune cells and the molecular determinants of their activation that include toll-like receptor, adrenergic, cholinergic and AT1 receptors can define the severity of inflammation in hypertension. These receptors are putative therapeutic targets.

  10. Immune Adaptation to Environmental Influence: The Case of NK Cells and HCMV.

    Science.gov (United States)

    Rölle, Alexander; Brodin, Petter

    2016-03-01

    The immune system of an individual human is determined by heritable traits and a continuous process of adaptation to a broad variety of extrinsic, non-heritable factors such as viruses, bacteria, dietary components and more. Cytomegalovirus (CMV) successfully infects the majority of the human population and establishes latency, thereby exerting a life-long influence on the immune system of its host. CMV has been shown to influence the majority of immune parameters in healthy individuals. Here we focus on adaptive changes induced by CMV in subsets of Natural Killer (NK) cells, changes that question our very definition of adaptive and innate immunity by suggesting that adaptations of immune cells to environmental influences occur across the entire human immune system and not restricted to the classical adaptive branch of the immune system.

  11. Adaptive immunity in cancer immunology and therapeutics.

    Science.gov (United States)

    Spurrell, Emma L; Lockley, Michelle

    2014-01-01

    The vast genetic alterations characteristic of tumours produce a number of tumour antigens that enable the immune system to differentiate tumour cells from normal cells. Counter to this, tumour cells have developed mechanisms by which to evade host immunity in their constant quest for growth and survival. Tumour-associated antigens (TAAs) are one of the fundamental triggers of the immune response. They are important because they activate, via major histocompatibility complex (MHC), the T cell response, an important line of defense against tumourigenesis. However, the persistence of tumours despite host immunity implies that tumour cells develop immune avoidance. An example of this is the up-regulation of inhibitory immune checkpoint proteins, by tumours, which induces a form of self-tolerance. The majority of monoclonal antibodies in clinical practice have been developed to target tumour-specific antigens. More recently there has been research in the down-regulation of immune checkpoint proteins as a way of increasing anti-tumour immunity.

  12. Genetic adaptation of the antibacterial human innate immunity network

    Directory of Open Access Journals (Sweden)

    Lazarus Ross

    2011-07-01

    Full Text Available Abstract Background Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Results Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. Conclusions We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.

  13. Convergence of the innate and adaptive immunity during human aging

    Directory of Open Access Journals (Sweden)

    Branca Isabel Pereira

    2016-11-01

    Full Text Available Aging is associated with profound changes in the human immune system, a phenomenon referred to as immunosenescence. This complex immune remodeling affects the adaptive immune system and the CD8+ T cell compartment in particular, leading to the accumulation of terminally differentiated T cells, which can rapidly exert their effector functions at the expenses of a limited proliferative potential. In this review we will discuss evidence suggesting that senescent αβCD8+ T cells acquire the hallmarks of innate-like T cells and use recently acquired NK cell receptors as an alternative mechanism to mediate rapid effector functions. These cells concomitantly lose expression of co-stimulatory receptors and exhibit decreased TCR signaling suggesting a functional shift away from antigen specific activation. The convergence of innate and adaptive features in senescent T cells challenges the classic division between innate and adaptive immune systems. Innate-like T cells are particularly important for stress and tumor surveillance and we propose a new role for these cells in aging, where the acquisition of innate-like functions may represent a beneficial adaptation to an increased burden of malignancy with age, although it may also pose a higher risk of autoimmune disorders.

  14. Prognostic value of innate and adaptive immunity in colorectal cancer.

    Science.gov (United States)

    Grizzi, Fabio; Bianchi, Paolo; Malesci, Alberto; Laghi, Luigi

    2013-01-14

    Colorectal cancer (CRC) remains one of the major public health problems throughout the world. Originally depicted as a multi-step dynamical disease, CRC develops slowly over several years and progresses through cytologically distinct benign and malignant states, from single crypt lesions through adenoma, to malignant carcinoma with the potential for invasion and metastasis. Moving from histological observations since a long time, it has been recognized that inflammation and immunity actively participate in the pathogenesis, surveillance and progression of CRC. The advent of immunohistochemical techniques and of animal models has improved our understanding of the immune dynamical system in CRC. It is well known that immune cells have variable behavior controlled by complex interactions in the tumor microenvironment. Advances in immunology and molecular biology have shown that CRC is immunogenic and that host immune responses influence survival. Several lines of evidence support the concept that tumor stromal cells, are not merely a scaffold, but rather they influence growth, survival, and invasiveness of cancer cells, dynamically contributing to the tumor microenvironment, together with immune cells. Different types of immune cells infiltrate CRC, comprising cells of both the innate and adaptive immune system. A relevant issue is to unravel the discrepancy between the inhibitory effects on cancer growth exerted by the local immune response and the promoting effects on cancer proliferation, invasion, and dissemination induced by some types of inflammatory cells. Here, we sought to discuss the role played by innate and adaptive immune system in the local progression and metastasis of CRC, and the prognostic information that we can currently understand and exploit.

  15. The identification of lymphocyte-like cells and lymphoid-related genes in amphioxus indicates the twilight for the emergence of adaptive immune system.

    Directory of Open Access Journals (Sweden)

    Gonghua Huang

    Full Text Available To seek evidence of a primitive adaptive immune system (AIS before vertebrate, we examined whether lymphocytes or lymphocyte-like cells and the related molecules participating in the lymphocyte function existed in amphioxus. Anatomical analysis by electron microscopy revealed the presence of lymphocyte-like cells in gills, and these cells underwent morphological changes in response to microbial pathogens that are reminiscent of those of mammalian lymphocytes executing immune response to microbial challenge. In addition, a systematic comparative analysis of our cDNA database of amphioxus identified a large number of genes whose vertebrate counterparts are involved in lymphocyte function. Among these genes, several genes were found to be expressed in the vicinity of the lymphocyte-like cells by in situ hybridization and up-regulated after exposure to microbial pathogens. Our findings in the amphioxus indicate the twilight for the emergence of AIS before the invertebrate-vertebrate transition during evolution.

  16. Immune system simulation online

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

    2011-01-01

    MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno......-informatics methods to allow the simulation of the cardinal events of the antigenic recognition, going from single peptides to whole proteomes. The recognition process accounts for B cell-epitopes prediction through Parker-scale affinity estimation, class I and II HLA peptide prediction and binding through position...

  17. Yersinia enterocolitica targets cells of the innate and adaptive immune system by injection of Yops in a mouse infection model.

    Directory of Open Access Journals (Sweden)

    Martin Köberle

    2009-08-01

    Full Text Available Yersinia enterocolitica (Ye evades the immune system of the host by injection of Yersinia outer proteins (Yops via a type three secretion system into host cells. In this study, a reporter system comprising a YopE-beta-lactamase hybrid protein and a fluorescent staining sensitive to beta-lactamase cleavage was used to track Yop injection in cell culture and in an experimental Ye mouse infection model. Experiments with GD25, GD25-beta1A, and HeLa cells demonstrated that beta1-integrins and RhoGTPases play a role for Yop injection. As demonstrated by infection of splenocyte suspensions in vitro, injection of Yops appears to occur randomly into all types of leukocytes. In contrast, upon infection of mice, Yop injection was detected in 13% of F4/80(+, 11% of CD11c(+, 7% of CD49b(+, 5% of Gr1(+ cells, 2.3% of CD19(+, and 2.6% of CD3(+ cells. Taking the different abundance of these cell types in the spleen into account, the highest total number of Yop-injected cells represents B cells, particularly CD19(+CD21(+CD23(+ follicular B cells, followed by neutrophils, dendritic cells, and macrophages, suggesting a distinct cellular tropism of Ye. Yop-injected B cells displayed a significantly increased expression of CD69 compared to non-Yop-injected B cells, indicating activation of these cells by Ye. Infection of IFN-gammaR (receptor- and TNFRp55-deficient mice resulted in increased numbers of Yop-injected spleen cells for yet unknown reasons. The YopE-beta-lactamase hybrid protein reporter system provides new insights into the modulation of host cell and immune responses by Ye Yops.

  18. Cell-biological mechanisms regulating antigen presentation : Signaling towards adaptive immunity

    NARCIS (Netherlands)

    Compeer, E.B.

    2015-01-01

    We, humans, are exposed daily to millions of potential pathogens, through contact, inhalation, or ingestion. Our ability to avoid infection depends on our immune system, which consists of two distinct, yet interrelated and interacting subsystems: the innate and adaptive immune system. The adaptive i

  19. The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

    Directory of Open Access Journals (Sweden)

    Sara Gabrielli

    2016-01-01

    Full Text Available Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

  20. The immune system.

    Science.gov (United States)

    Nicholson, Lindsay B

    2016-10-31

    All organisms are connected in a complex web of relationships. Although many of these are benign, not all are, and everything alive devotes significant resources to identifying and neutralizing threats from other species. From bacteria through to primates, the presence of some kind of effective immune system has gone hand in hand with evolutionary success. This article focuses on mammalian immunity, the challenges that it faces, the mechanisms by which these are addressed, and the consequences that arise when it malfunctions.

  1. The Microbiome, Systemic Immune Function, and Allotransplantation.

    Science.gov (United States)

    Nellore, Anoma; Fishman, Jay A

    2016-01-01

    Diverse effects of the microbiome on solid organ transplantation are beginning to be recognized. In allograft recipients, microbial networks are disrupted by immunosuppression, nosocomial and community-based infectious exposures, antimicrobial therapies, surgery, and immune processes. Shifting microbial patterns, including acute infectious exposures, have dynamic and reciprocal interactions with local and systemic immune systems. Both individual microbial species and microbial networks have central roles in the induction and control of innate and adaptive immune responses, in graft rejection, and in ischemia-reperfusion injury. Understanding the diverse interactions between the microbiome and the immune system of allograft recipients may facilitate clinical management in the future.

  2. Multi-metal contamination with uranium trend impact on aquatic environment and consequences for fish immune system and adaptive responses

    Energy Technology Data Exchange (ETDEWEB)

    Le Guernic, A.; Gagnaire, B. [IRSN/PRP-ENV/SERIS/LECO (France); Sanchez, W. [Institut national de l' environnement industriel et des risques - INERIS (France); Betoulle, S. [Champagne Ardenne University (France)

    2014-07-01

    Human activities have conducted to an increase of concentrations of various metals in aquatic ecosystems, including uranium. Its extraction and use have been rapidly magnified because of its role in the nuclear fuel cycle. These activities have led to high concentrations of uranium in the aquatic environment and thus a potential risk to exposed organisms, including fish. Consequences can be observed through metabolic and physiological responses, called biomarkers. Some biomarkers are interesting in order to evaluate the effects of metal contamination, among other immunotoxicity markers, antioxidant defenses and genotoxicity. The aims of this study are: i) to investigate the effects of a multi-metal contamination on a fish, the three-spined stickleback, Gasterosteus aculeatus, and ii) to observe the adaptive capacity of fish due to a combination of stress (chemical stress and biological stress). To meet the first objective, six water bodies (ponds and lakes) located in two departments (Cantal and Haute-Vienne, France) were chosen according to their proximity to old uranium mines and to their levels of metal contamination related to chemical processes appeared during extraction. 240 three-spined sticklebacks were caged for 28 days in the six selected sites. A battery of biomarkers was measured in fish sampled after 14 and 28 of caging. The results for the Haute-Vienne department showed that caged fish in the pond with the highest uranium concentration (20 μg.L{sup -1}) presented the most DNA damage after 14 days of caging. Leukocyte phagocytosis (marker of immunotoxicity) of caged fish in this pond was lower at 14 days and greater at 28 days compared to other ponds without uranium. The multi-metal contamination negatively affected other parameters such as the condition index, oxidative activity, viability of lysosomal membrane and leukocytes distribution. In order to study the response of fish to a combined stress (chemical + biological) (objective ii), a second

  3. Immune System (For Parents)

    Science.gov (United States)

    ... infections, but the condition is usually not severe. Severe combined immunodeficiency (SCID) is also known as the "bubble boy disease" after a Texas boy with SCID who lived in a germ-free plastic bubble. SCID is a serious immune system disorder that occurs because of a lack of both ...

  4. Two forms of adaptive immunity in vertebrates: similarities and differences.

    Science.gov (United States)

    Kasahara, Masanori; Sutoh, Yoichi

    2014-01-01

    Unlike jawed vertebrates that use T-cell and B-cell receptors for antigen recognition, jawless vertebrates represented by lampreys and hagfish use variable lymphocyte receptors (VLRs) as antigen receptors. VLRs generate diversity comparable to that of gnathostome antigen receptors by assembling variable leucine-rich repeat modules. The discovery of VLR has revolutionized our understanding of how adaptive immunity emerged and highlighted the differences between the adaptive immune systems (AISs) of jawed and jawless vertebrates. However, emerging evidence also indicates that their AISs have much in common. Particularly striking is the conservation of lymphocyte lineages. The basic architecture of the AIS including the dichotomy of lymphocytes appears to have been established in a common ancestor of jawed and jawless vertebrates. We review here the current knowledge on the AIS of jawless vertebrates, emphasizing both the similarities to and differences from the AIS of jawed vertebrates.

  5. Bridging Innate and Adaptive Antitumor Immunity Targeting Glycans

    Science.gov (United States)

    Pashov, Anastas; Monzavi-Karbassi, Bejatolah; Raghava, Gajendra P. S.; Kieber-Emmons, Thomas

    2010-01-01

    Effective immunotherapy for cancer depends on cellular responses to tumor antigens. The role of major histocompatibility complex (MHC) in T-cell recognition and T-cell receptor repertoire selection has become a central tenet in immunology. Structurally, this does not contradict earlier findings that T-cells can differentiate between small hapten structures like simple glycans. Understanding T-cell recognition of antigens as defined genetically by MHC and combinatorially by T cell receptors led to the “altered self” hypothesis. This notion reflects a more fundamental principle underlying immune surveillance and integrating evolutionarily and mechanistically diverse elements of the immune system. Danger associated molecular patterns, including those generated by glycan remodeling, represent an instance of altered self. A prominent example is the modification of the tumor-associated antigen MUC1. Similar examples emphasize glycan reactivity patterns of antigen receptors as a phenomenon bridging innate and adaptive but also humoral and cellular immunity and providing templates for immunotherapies. PMID:20617150

  6. Innate and adaptive immune responses in HCV infections.

    Science.gov (United States)

    Heim, Markus H; Thimme, Robert

    2014-11-01

    Hepatitis C virus has been identified a quarter of a decade ago as a leading cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously during acute infection. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN) induced genes, and a delayed induction of adaptive immune responses. However, the majority of patients is unable to clear the virus and develops viral persistence in face of an ongoing innate and adaptive immune response. The virus has developed several strategies to escape these immune responses. For example, to escape innate immunity, the HCV NS3/4A protease can efficiently cleave and inactivate two important signalling molecules in the sensory pathways that react to HCV pathogen-associated molecular patterns (PAMPs) to induce IFNs, i.e., the mitochondrial anti-viral signalling protein (MAVS) and the Toll-IL-1 receptor-domain-containing adaptor-inducing IFN-β (TRIF). Despite these escape mechanisms, IFN-stimulated genes (ISGs) are induced in a large proportion of patients with chronic infection. Of note, chronically HCV infected patients with constitutive IFN-stimulated gene (ISG) expression have a poor response to treatment with pegylated IFN-α (PegIFN-α) and ribavirin. The mechanisms that protect HCV from IFN-mediated innate immune reactions are not entirely understood, but might involve blockade of ISG protein translation at the ribosome, localization of viral replication to cell compartments that are not accessible to anti-viral IFN-stimulated effector systems, or direct antagonism of effector systems by viral proteins. Escape from adaptive immune responses can be achieved by emergence of viral escape mutations that avoid recognition by antibodies and T cells. In addition, chronic infection is characterized by the presence of functionally and phenotypically altered NK and T cell responses that

  7. [Analysis of the relationships between the psychophysiological status and system of adaptive immunity in the conditions of 5-day dry immersion].

    Science.gov (United States)

    Nichiporuk, I A; Vasil'eva, G Iu; Rykova, M P; Antropova, E N; Berendeeva, T A; Ponomarev, S A; Morukov, B V

    2011-01-01

    Relationships of the T- and B-components of adaptive immunity and the psychophysiological status were studied in 14 volunteers for the experiment with 5-d dry immersion (DI) w/o countermeasures. Comparison of frequency of deviations in immunity parameters of psychologically different subjects demonstrated the highest frequency in non-anxious and extravert individuals on day-5 in DI. These differences in immune reactions as a function of psychological type and temperament point to existence of a neuroimmune typology and, therefore, the necessity of concurrent immunologic and psychological investigations in order to develop separate measures of rehabilitation from and prevention of stress in people with polar psychological status.

  8. Two separate mechanisms of enforced viral replication balance innate and adaptive immune activation.

    Science.gov (United States)

    Shaabani, Namir; Khairnar, Vishal; Duhan, Vikas; Zhou, Fan; Tur, Rita Ferrer; Häussinger, Dieter; Recher, Mike; Tumanov, Alexei V; Hardt, Cornelia; Pinschewer, Daniel; Christen, Urs; Lang, Philipp A; Honke, Nadine; Lang, Karl S

    2016-02-01

    The induction of innate and adaptive immunity is essential for controlling viral infections. Limited or overwhelming innate immunity can negatively impair the adaptive immune response. Therefore, balancing innate immunity separately from activating the adaptive immune response would result in a better antiviral immune response. Recently, we demonstrated that Usp18-dependent replication of virus in secondary lymphatic organs contributes to activation of the innate and adaptive immune responses. Whether specific mechanisms can balance innate and adaptive immunity separately remains unknown. In this study, using lymphocytic choriomeningitis virus (LCMV) and replication-deficient single-cycle LCMV vectors, we found that viral replication of the initial inoculum is essential for activating virus-specific CD8(+) T cells. In contrast, extracellular distribution of virus along the splenic conduits is necessary for inducing systemic levels of type I interferon (IFN-I). Although enforced virus replication is driven primarily by Usp18, B cell-derived lymphotoxin beta contributes to the extracellular distribution of virus along the splenic conduits. Therefore, lymphotoxin beta regulates IFN-I induction independently of CD8(+) T-cell activity. We found that two separate mechanisms act together in the spleen to guarantee amplification of virus during infection, thereby balancing the activation of the innate and adaptive immune system.

  9. Unique Features of Fish Immune Repertoires: Particularities of Adaptive Immunity Within the Largest Group of Vertebrates.

    Science.gov (United States)

    Magadan, Susana; Sunyer, Oriol J; Boudinot, Pierre

    2015-01-01

    Fishes (i.e., teleost fishes) are the largest group of vertebrates. Although their immune system is based on the fundamental receptors, pathways, and cell types found in all groups of vertebrates, fishes show a diversity of particular features that challenge some classical concepts of immunology. In this chapter, we discuss the particularities of fish immune repertoires from a comparative perspective. We examine how allelic exclusion can be achieved when multiple Ig loci are present, how isotypic diversity and functional specificity impact clonal complexity, how loss of the MHC class II molecules affects the cooperation between T and B cells, and how deep sequencing technologies bring new insights about somatic hypermutation in the absence of germinal centers. The unique coexistence of two distinct B-cell lineages respectively specialized in systemic and mucosal responses is also discussed. Finally, we try to show that the diverse adaptations of immune repertoires in teleosts can help in understanding how somatic adaptive mechanisms of immunity evolved in parallel in different lineages across vertebrates.

  10. Adaptive Immunity in Neurodegenerative and Neuropsychological Disorders.

    Science.gov (United States)

    Mosley, R Lee

    2015-12-01

    Neurodegenerative and neuropsychological disorders are becoming a greater proportion of the global disease burden; however the pathogenic mechanisms by which these disorders originate and contribute to disease progression are not well-described. Increasing evidence supports neuroinflammation as a common underlying component associated with the neuropathological processes that effect disease progression. This collection of articles explores the role of adaptive immunity in autoimmunity, neurodegeneration, neurotrauma, and psychological disorders. The section emphasizes the interactions of T cells with innate cellular responses within the CNS and the effects on neurological functions. One recurrent theme is that modified and aggregated self-proteins upregulate innate-mediated inflammation and provide a permissive environment for polarization of T cells to proinflammatory effector cells. Moreover, infiltration and reactivation of those T effector cells exacerbate neuroinflammation and oxidative stress to greater neurotoxic levels. Another recurrent theme in these disorders promotes diminished regulatory functions that reduce control over activated T effector cells and microglia, and ultimately augment proinflammatory conditions. Augmentation of regulatory control is discussed as therapeutic strategies to attenuate neuroinflammation, mitigate neurodegeneration or neuronal dysfunction, and lessen disease progression.

  11. Abdominal fat mass is associated with adaptive immune activation: the CODAM study

    NARCIS (Netherlands)

    Thewissen, M.M.; Damoiseaux, J.G.; Duijvestijn, A.M.; Greevenbroek, M.M.; Kallen, van der C.J.H.; Feskens, E.J.M.; Blaak, E.E.; Schalkwijk, C.G.; Stehouwer, C.D.A.; Cohen Tervaert, J.W.; Ferreira, I.

    2011-01-01

    Abdominal fat-related activation of the innate immune system and insulin resistance (IR) are implicated in the pathogenesis of cardiovascular diseases. Recent data support an important role of the adaptive immune system as well. In this study, we investigate the association between waist circumferen

  12. Inflammation and immune system interactions in atherosclerosis.

    Science.gov (United States)

    Legein, Bart; Temmerman, Lieve; Biessen, Erik A L; Lutgens, Esther

    2013-10-01

    Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 16.7 million deaths each year. The underlying cause of the majority of CVD is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall. Today's picture is far more complex. Atherosclerosis is considered a chronic inflammatory disease that results in the formation of plaques in large and mid-sized arteries. Both cells of the innate and the adaptive immune system play a crucial role in its pathogenesis. By transforming immune cells into pro- and anti-inflammatory chemokine- and cytokine-producing units, and by guiding the interactions between the different immune cells, the immune system decisively influences the propensity of a given plaque to rupture and cause clinical symptoms like myocardial infarction and stroke. In this review, we give an overview on the newest insights in the role of different immune cells and subtypes in atherosclerosis.

  13. A brief journey through the immune system.

    Science.gov (United States)

    Yatim, Karim M; Lakkis, Fadi G

    2015-07-07

    This review serves as an introduction to an Immunology Series for the Nephrologist published in CJASN. It provides a brief overview of the immune system, how it works, and why it matters to kidneys. This review describes in broad terms the main divisions of the immune system (innate and adaptive), their cellular and tissue components, and the ways by which they function and are regulated. The story is told through the prism of evolution in order to relay to the reader why the immune system does what it does and why imperfections in the system can lead to renal disease. Detailed descriptions of cell types, molecules, and other immunologic curiosities are avoided as much as possible in an effort to not detract from the importance of the broader concepts that define the immune system and its relationship to the kidney.

  14. Immune adaptive Gaussian mixture par ticle filter for state estimation

    Institute of Scientific and Technical Information of China (English)

    Wenlong Huang; Xiaodan Wang; Yi Wang; Guohong Li

    2015-01-01

    The particle filter (PF) is a flexible and powerful sequen-tial Monte Carlo (SMC) technique capable of modeling nonlinear, non-Gaussian, and nonstationary dynamical systems. However, the generic PF suffers from particle degeneracy and sample im-poverishment, which greatly affects its performance for nonlinear, non-Gaussian tracking problems. To deal with those issues, an improved PF is proposed. The algorithm consists of a PF that uses an immune adaptive Gaussian mixture model (IAGM) based immune algorithm to re-approximate the posterior density. At the same time, three immune antibody operators are embed in the new filter. Instead of using a resample strategy, the newest obser-vation and conditional likelihood are integrated into those immune antibody operators to update the particles, which can further im-prove the diversity of particles, and drive particles toward their close local maximum of the posterior probability. The improved PF algorithm can produce a closed-form expression for the posterior state distribution. Simulation results show the proposed algorithm can maintain the effectiveness and diversity of particles and avoid sample impoverishment, and its performance is superior to several PFs and Kalman filters.

  15. Multi-user cognitive radio network resource allocation based on the adaptive niche immune genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    Zu Yun-Xiao; Zhou Jie

    2012-01-01

    Multi-user cognitive radio network resource allocation based on the adaptive niche immune genetic algorithm is proposed,and a fitness function is provided.Simulations are conducted using the adaptive niche immune genetic algorithm,the simulated annealing algorithm,the quantum genetic algorithm and the simple genetic algorithm,respectively.The results show that the adaptive niche immune genetic algorithm performs better than the other three algorithms in terms of the multi-user cognitive radio network resource allocation,and has quick convergence speed and strong global searching capability,which effectively reduces the system power consumption and bit error rate.

  16. Multi-user cognitive radio network resource allocation based on the adaptive niche immune genetic algorithm

    Science.gov (United States)

    Zu, Yun-Xiao; Zhou, Jie

    2012-01-01

    Multi-user cognitive radio network resource allocation based on the adaptive niche immune genetic algorithm is proposed, and a fitness function is provided. Simulations are conducted using the adaptive niche immune genetic algorithm, the simulated annealing algorithm, the quantum genetic algorithm and the simple genetic algorithm, respectively. The results show that the adaptive niche immune genetic algorithm performs better than the other three algorithms in terms of the multi-user cognitive radio network resource allocation, and has quick convergence speed and strong global searching capability, which effectively reduces the system power consumption and bit error rate.

  17. Coevolutionary immune system dynamics driving pathogen speciation.

    Directory of Open Access Journals (Sweden)

    Kimberly J Schlesinger

    Full Text Available We introduce and analyze a within-host dynamical model of the coevolution between rapidly mutating pathogens and the adaptive immune response. Pathogen mutation and a homeostatic constraint on lymphocytes both play a role in allowing the development of chronic infection, rather than quick pathogen clearance. The dynamics of these chronic infections display emergent structure, including branching patterns corresponding to asexual pathogen speciation, which is fundamentally driven by the coevolutionary interaction. Over time, continued branching creates an increasingly fragile immune system, and leads to the eventual catastrophic loss of immune control.

  18. Inflammation and immune system alterations in frailty.

    Science.gov (United States)

    Yao, Xu; Li, Huifen; Leng, Sean X

    2011-02-01

    Frailty is an important geriatric syndrome characterized by multisystem dysregulation. Substantial evidence suggests heightened inflammatory state and significant immune system alterations in frailty. A heightened inflammatory state is marked by increases in levels of inflammatory molecules (interleukin 6 and C-reactive protein) and counts of white blood cell and its subpopulations, which may play an important role in the pathogenesis of frailty, directly or through its detrimental influence on other physiologic systems. Alterations in the innate immune system include decreased proliferation of the peripheral blood mononuclear cells and upregulated monocytic expression of specific stress-responsive inflammatory pathway genes. In the adaptive immune system, although little information is available about potential B-cell changes, significant alterations have been identified in the T-cell compartment, including increased counts of CD8+, CD8+CD28-, CCR5+T cells, above and beyond age-related senescent immune remodeling.

  19. Integrating innate and adaptive immune cells: Mast cells as crossroads between regulatory and effector B and T cells.

    Science.gov (United States)

    Mekori, Yoseph A; Hershko, Alon Y; Frossi, Barbara; Mion, Francesca; Pucillo, Carlo E

    2016-05-05

    A diversity of immune mechanisms have evolved to protect normal tissues from infection, but from immune damage too. Innate cells, as well as adaptive cells, are critical contributors to the correct development of the immune response and of tissue homeostasis. There is a dynamic "cross-talk" between the innate and adaptive immunomodulatory mechanisms for an integrated control of immune damage as well as the development of the immune response. Mast cells have shown a great plasticity, modifying their behavior at different stages of immune response through interaction with effector and regulatory populations of adaptive immunity. Understanding the interplays among T effectors, regulatory T cells, B cells and regulatory B cells with mast cells will be critical in the future to assist in the development of therapeutic strategies to enhance and synergize physiological immune-modulator and -suppressor elements in the innate and adaptive immune system.

  20. Neural regulation of innate and adaptive immunity in the gut

    NARCIS (Netherlands)

    Dhawan, S.

    2017-01-01

    This thesis investigates the role of neurotransmitters acetylcholine (ACh) and norepinephrine (NE), in modulating the innate and adaptive immune function in the intestine, during physiological and pathophysiological conditions. Furthermore, this thesis attempts to advance our current understanding o

  1. Null steering of adaptive beamforming using linear constraint minimum variance assisted by particle swarm optimization, dynamic mutated artificial immune system, and gravitational search algorithm.

    Science.gov (United States)

    Darzi, Soodabeh; Kiong, Tiong Sieh; Islam, Mohammad Tariqul; Ismail, Mahamod; Kibria, Salehin; Salem, Balasem

    2014-01-01

    Linear constraint minimum variance (LCMV) is one of the adaptive beamforming techniques that is commonly applied to cancel interfering signals and steer or produce a strong beam to the desired signal through its computed weight vectors. However, weights computed by LCMV usually are not able to form the radiation beam towards the target user precisely and not good enough to reduce the interference by placing null at the interference sources. It is difficult to improve and optimize the LCMV beamforming technique through conventional empirical approach. To provide a solution to this problem, artificial intelligence (AI) technique is explored in order to enhance the LCMV beamforming ability. In this paper, particle swarm optimization (PSO), dynamic mutated artificial immune system (DM-AIS), and gravitational search algorithm (GSA) are incorporated into the existing LCMV technique in order to improve the weights of LCMV. The simulation result demonstrates that received signal to interference and noise ratio (SINR) of target user can be significantly improved by the integration of PSO, DM-AIS, and GSA in LCMV through the suppression of interference in undesired direction. Furthermore, the proposed GSA can be applied as a more effective technique in LCMV beamforming optimization as compared to the PSO technique. The algorithms were implemented using Matlab program.

  2. Regional specialization within the intestinal immune system

    DEFF Research Database (Denmark)

    Mowat, Allan M.; Agace, William Winston

    2014-01-01

    The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly...... implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout...... the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease...

  3. The immune system vs. Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jensen, Peter Østrup; Givskov, Michael; Bjarnsholt, Thomas

    2010-01-01

    revealed both innate as well as adaptive immune responses to biofilms. On the other hand, measures launched by biofilm bacteria to achieve protection against the various immune responses have also been demonstrated. Whether particular immune responses to biofilm infections exist remains to be firmly...... established. However, because biofilm infections are often persistent (or chronic), an odd situation appears with the simultaneous activation of both arms of the host immune response, neither of which can eliminate the biofilm pathogen, but instead, in synergy, causes collateral tissue damage. Although...... the present review on the immune system vs. biofilm bacteria is focused on Pseudomonas aeruginosa (mainly because this is the most thoroughly studied), many of the same mechanisms are also seen with biofilm infections generated by other microorganisms....

  4. Neural regulation of innate and adaptive immunity in the gut

    OpenAIRE

    Dhawan, S.

    2017-01-01

    This thesis investigates the role of neurotransmitters acetylcholine (ACh) and norepinephrine (NE), in modulating the innate and adaptive immune function in the intestine, during physiological and pathophysiological conditions. Furthermore, this thesis attempts to advance our current understanding of the gut-brain immune axis, also known as the cholinergic anti-inflammatory pathway, coined largely due to the cholinergic nature of the vagus nerve.

  5. Biogenesis pathways of RNA guides in archaeal and bacterial CRISPR-Cas adaptive immunity

    NARCIS (Netherlands)

    Charpentier, Emmanuelle; Richter, Hagen; Oost, van der John; White, Malcolm F.

    2015-01-01

    CRISPR-Cas is an RNA-mediated adaptive immune system that defends bacteria and archaea against mobile genetic elements. Short mature CRISPR RNAs (crRNAs) are key elements in the interference step of the immune pathway. A CRISPR array composed of a series of repeats interspaced by spacer sequences

  6. Innate and adaptive immune responses in allergic contact dermatitis and autoimmune skin diseases.

    Science.gov (United States)

    Edele, Fanny; Esser, Philipp R; Lass, Christian; Laszczyk, Melanie N; Oswald, Eva; Strüh, Christian M; Rensing-Ehl, Anne; Martin, Stefan F

    2007-12-01

    Allergic contact dermatitis is induced by chemicals or metal ions. A hallmark of this T cell mediated skin disease is the activation of the innate immune system by contact allergens. This immune response results in inflammation and is a prerequisite for the activation of the adaptive immune system with tissue-specific migration of effector and regulatory T cells. Recent studies have begun to address in detail the innate immune cells as well as the innate receptors on these cells and the associated signaling pathways which lead to skin inflammation. We review here recent findings regarding innate and adaptive immune responses and immune regulation of contact dermatitis and other skin diseases as well as recent developments towards an in vitro assessment of the allergenic potential of chemicals. The elucidation of the innate inflammatory pathways, cellular components and mediators will help to identify new drug targets for more efficient treatment of allergic contact dermatitis and hopefully also for its prevention.

  7. Immune regulation by pericytes: modulating innate and adaptive immunity

    DEFF Research Database (Denmark)

    Navarro, Rocio; Compte, Marta; Álvarez-Vallina, Luis

    2016-01-01

    Pericytes (PC) are mural cells that surround endothelial cells (EC) in small blood vessels. PC have traditionally been endowed with structural functions, being essential for vessel maturation and stabilization. However, accumulating evidence suggest that PC also display immune properties. They ca...

  8. Functional demonstration of adaptive immunity in zebrafish using DNA vaccination

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lorenzen, Ellen; Einer-Jensen, Katja;

    studies have documented existence of a classical innate immune response, there is mainly indirect evidence of functional adaptive immunity. To address this aspect, groups of zebrafish were vaccinated with DNA-vaccines against the rhabdoviruses VHSV, IHNV and SVCV. Seven weeks later, the fish were...... challenged with SVCV by immersion. Despite some variability between replicate aquaria, there was a protective effect of the homologous vaccine and no effect of the heterologous vaccines. The results therefore confirm the existence of not only a well developed but also a fully functional adaptive immune...

  9. Macrophages Subvert Adaptive Immunity to Urinary Tract Infection.

    Directory of Open Access Journals (Sweden)

    Gabriela Mora-Bau

    2015-07-01

    Full Text Available Urinary tract infection (UTI is one of the most common bacterial infections with frequent recurrence being a major medical challenge. Development of effective therapies has been impeded by the lack of knowledge of events leading to adaptive immunity. Here, we establish conclusive evidence that an adaptive immune response is generated during UTI, yet this response does not establish sterilizing immunity. To investigate the underlying deficiency, we delineated the naïve bladder immune cell compartment, identifying resident macrophages as the most populous immune cell. To evaluate their impact on the establishment of adaptive immune responses following infection, we measured bacterial clearance in mice depleted of either circulating monocytes, which give rise to macrophages, or bladder resident macrophages. Surprisingly, mice depleted of resident macrophages, prior to primary infection, exhibited a nearly 2-log reduction in bacterial burden following secondary challenge compared to untreated animals. This increased bacterial clearance, in the context of a challenge infection, was dependent on lymphocytes. Macrophages were the predominant antigen presenting cell to acquire bacteria post-infection and in their absence, bacterial uptake by dendritic cells was increased almost 2-fold. These data suggest that bacterial uptake by tissue macrophages impedes development of adaptive immune responses during UTI, revealing a novel target for enhancing host responses to bacterial infection of the bladder.

  10. CD98 at the crossroads of adaptive immunity and cancer.

    Science.gov (United States)

    Cantor, Joseph M; Ginsberg, Mark H

    2012-03-15

    Adaptive immunity, a vertebrate specialization, adds memory and exquisite specificity to the basic innate immune responses present in invertebrates while conserving metabolic resources. In adaptive immunity, antigenic challenge requires extremely rapid proliferation of rare antigen-specific lymphocytes to produce large, clonally expanded effector populations that neutralize pathogens. Rapid proliferation and resulting clonal expansion are dependent on CD98, a protein whose well-conserved orthologs appear restricted to vertebrates. Thus, CD98 supports lymphocyte clonal expansion to enable protective adaptive immunity, an advantage that could account for the presence of CD98 in vertebrates. CD98 supports lymphocyte clonal expansion by amplifying integrin signals that enable proliferation and prevent apoptosis. These integrin-dependent signals can also provoke cancer development and invasion, anchorage-independence and the rapid proliferation of tumor cells. CD98 is highly expressed in many cancers and contributes to formation of tumors in experimental models. Strikingly, vertebrates, which possess highly conserved CD98 proteins, CD98-binding integrins and adaptive immunity, also display propensity towards invasive and metastatic tumors. In this Commentary, we review the roles of CD98 in lymphocyte biology and cancer. We suggest that the CD98 amplification of integrin signaling in adaptive immunity provides survival benefits to vertebrates, which, in turn, bear the price of increased susceptibility to cancer.

  11. Bridging Innate and Adaptive Antitumor Immunity Targeting Glycans

    Directory of Open Access Journals (Sweden)

    Anastas Pashov

    2010-01-01

    Full Text Available Effective immunotherapy for cancer depends on cellular responses to tumor antigens. The role of major histocompatibility complex (MHC in T-cell recognition and T-cell receptor repertoire selection has become a central tenet in immunology. Structurally, this does not contradict earlier findings that T-cells can differentiate between small hapten structures like simple glycans. Understanding T-cell recognition of antigens as defined genetically by MHC and combinatorially by T cell receptors led to the “altered self” hypothesis. This notion reflects a more fundamental principle underlying immune surveillance and integrating evolutionarily and mechanistically diverse elements of the immune system. Danger associated molecular patterns, including those generated by glycan remodeling, represent an instance of altered self. A prominent example is the modification of the tumor-associated antigen MUC1. Similar examples emphasize glycan reactivity patterns of antigen receptors as a phenomenon bridging innate and adaptive but also humoral and cellular immunity and providing templates for immunotherapies.

  12. Modelling Immune System: Principles, Models,Analysis and Perspectives

    Institute of Scientific and Technical Information of China (English)

    Xiang-hua Li; Zheng-xuan Wang; Tian-yang Lu; Xiang-jiu Che

    2009-01-01

    The biological immune system is a complex adaptive system. There are lots of benefits for building the model of the immune system. For biological researchers, they can test some hypotheses about the infection process or simulate the responses of some drugs. For computer researchers, they can build distributed, robust and fault tolerant networks inspired by the functions of the immune system. This paper provides a comprehensive survey of the literatures on modelling the immune system. From the methodology perspective, the paper compares and analyzes the existing approaches and models, and also demonstrates the focusing research effort on the future immune models in the next few years.

  13. Adaptation to High Grain Diets Proceeds Through Minimal Immune System Stimulation and Differences in Extracellular Matrix Protein Expression in A Model of Subacute Ruminal Acidosis in Non-lactating Dairy Cows

    Directory of Open Access Journals (Sweden)

    L. Dionissopoulos

    2012-01-01

    Full Text Available Problem statement: Subacute Ruminal Acidosis (SARA is a metabolic disorder affecting approximately 20% of all dairy cattle in North America. Although the presence of SARA has been described for some time, the etiology of the disorder remains uncertain. For example, many animals diagnosed with SARA seem to remodel and adapt their epithelium to accommodate the stresses imposed by SARA, but not before exacting a significant health and economic toll. Specifically, a search is on in which a desire to identify the system and associated pathways that are causative agents in the progression and development of SARA is evident. We hypothesize that adaptation to SARA is facilitated by the immune system. Approach: In order to answer of this question, 4 mature, non-lactating dairy cattle were transitioned from a High Fiber (HF; 0% grain diet to High Grain (HG; 65% grain diet. Having fed the HG diet for three weeks, the cattle were then transitioned back to the HF diet for an additional three weeks to facilitate adaptation. SARA was diagnosed by pH data only during the first week and not during the remaining weeks, indicating that adaptation to the HG diet took place within one week. Results: In this study, significant (pConclusion: These results indicate that the immune system is involved in the adaptation of the rumen epithelium to a HG diet, but to a lesser extent than was previously thought. This is the first time an attempt has been made to link the immune system and wound healing in the adaptation of the bovine rumen to a HG diet."""

  14. Featured Immune System Research

    Science.gov (United States)

    ... AMCase, an enzyme present in humans and other mammals, plays a key role in initiating protective immune ... Facilities Biosafety Laboratory Sites Rutgers University University of Alabama George Mason University Tufts University Tulane University Regional ...

  15. T Cell Adaptive Immunity Proceeds through Environment-Induced Adaptation from the Exposure of Cryptic Genetic Variation

    Science.gov (United States)

    Whitacre, James M.; Lin, Joseph; Harding, Angus

    2011-01-01

    Evolution is often characterized as a process involving incremental genetic changes that are slowly discovered and fixed in a population through genetic drift and selection. However, a growing body of evidence is finding that changes in the environment frequently induce adaptations that are much too rapid to occur by an incremental genetic search process. Rapid evolution is hypothesized to be facilitated by mutations present within the population that are silent or “cryptic” within the first environment but are co-opted or “exapted” to the new environment, providing a selective advantage once revealed. Although cryptic mutations have recently been shown to facilitate evolution in RNA enzymes, their role in the evolution of complex phenotypes has not been proven. In support of this wider role, this paper describes an unambiguous relationship between cryptic genetic variation and complex phenotypic responses within the immune system. By reviewing the biology of the adaptive immune system through the lens of evolution, we show that T cell adaptive immunity constitutes an exemplary model system where cryptic alleles drive rapid adaptation of complex traits. In naive T cells, normally cryptic differences in T cell receptor reveal diversity in activation responses when the cellular population is presented with a novel environment during infection. We summarize how the adaptive immune response presents a well studied and appropriate experimental system that can be used to confirm and expand upon theoretical evolutionary models describing how seemingly small and innocuous mutations can drive rapid cellular evolution. PMID:22363338

  16. Adaptation in CRISPR-Cas Systems.

    Science.gov (United States)

    Sternberg, Samuel H; Richter, Hagen; Charpentier, Emmanuelle; Qimron, Udi

    2016-03-17

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system in prokaryotes. The system preserves memories of prior infections by integrating short segments of foreign DNA, termed spacers, into the CRISPR array in a process termed adaptation. During the past 3 years, significant progress has been made on the genetic requirements and molecular mechanisms of adaptation. Here we review these recent advances, with a focus on the experimental approaches that have been developed, the insights they generated, and a proposed mechanism for self- versus non-self-discrimination during the process of spacer selection. We further describe the regulation of adaptation and the protein players involved in this fascinating process that allows bacteria and archaea to harbor adaptive immunity.

  17. SISTEMAS INMUNES ALTERNATIVOS Alternative Immune Systems

    Directory of Open Access Journals (Sweden)

    LUIS F. CADAVID

    Full Text Available El sistema inmune en animales es una red compleja de moléculas, células y tejidos que de manera conjunta mantienen la integridad fisiológica y genética de los organismos. Convencionalmente se ha considerado la existencia de dos clases de inmunidad, la innata y la adaptativa. La primera es ancestral, con variabilidad limitada y baja discriminación, mientras que la segunda es altamente variable, específica y restringida a vertebra-dos mandibulados. La inmunidad adaptativa se basa en receptores de antígeno que se rearreglan somáticamente para generar una diversidad casi ilimitada de moléculas. Este mecanismo de recombinación somática muy probablemente emergió como consecuencia de un evento de transferencia horizontal de transposones y transposasas bacterianas en el ancestro de los vertebrados mandibulados. El reciente descubrimiento en vertebrados no mandibulados e invertebrados de mecanismos alternativos de inmunidad adaptativa, sugiere que en el transcurso de la evolución distintos grupos animales han encontrado soluciones alternativas al problema del reconocimiento inmunológico.The immune system in animals is a complex network of molecules, cells and tissues that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless vertebrates and invertebrates of alternative adaptive immune mechanisms, suggests that during

  18. Diversity in the Immune System

    NARCIS (Netherlands)

    Borghans, J.A.M.; Boer, R.J. de

    2000-01-01

    Diversity is one of the key characteristics of the vertebrate immune system. Lymphocyte repertoires of at least 3x10⁷ different clonotypes protect humans against infections, while avoiding unwanted immune responses against self-peptides and innocuous antigens. It is this lymphocyte diversity that fo

  19. Let’s Tie the Knot: Marriage of Complement and Adaptive Immunity in Pathogen Evasion, for Better or Worse

    Science.gov (United States)

    Bennett, Kaila M.; Rooijakkers, Suzan H. M.; Gorham, Ronald D.

    2017-01-01

    The complement system is typically regarded as an effector arm of innate immunity, leading to recognition and killing of microbial invaders in body fluids. Consequently, pathogens have engaged in an arms race, evolving molecules that can interfere with proper complement responses. However, complement is no longer viewed as an isolated system, and links with other immune mechanisms are continually being discovered. Complement forms an important bridge between innate and adaptive immunity. While its roles in innate immunity are well-documented, its function in adaptive immunity is less characterized. Therefore, it is no surprise that the field of pathogenic complement evasion has focused on blockade of innate effector functions, while potential inhibition of adaptive immune responses (via complement) has been overlooked to a certain extent. In this review, we highlight past and recent developments on the involvement of complement in the adaptive immune response. We discuss the mechanisms by which complement aids in lymphocyte stimulation and regulation, as well as in antigen presentation. In addition, we discuss microbial complement evasion strategies, and highlight specific examples in the context of adaptive immune responses. These emerging ties between complement and adaptive immunity provide a catalyst for future discovery in not only the field of adaptive immune evasion but in elucidating new roles of complement. PMID:28197139

  20. Let's Tie the Knot: Marriage of Complement and Adaptive Immunity in Pathogen Evasion, for Better or Worse.

    Science.gov (United States)

    Bennett, Kaila M; Rooijakkers, Suzan H M; Gorham, Ronald D

    2017-01-01

    The complement system is typically regarded as an effector arm of innate immunity, leading to recognition and killing of microbial invaders in body fluids. Consequently, pathogens have engaged in an arms race, evolving molecules that can interfere with proper complement responses. However, complement is no longer viewed as an isolated system, and links with other immune mechanisms are continually being discovered. Complement forms an important bridge between innate and adaptive immunity. While its roles in innate immunity are well-documented, its function in adaptive immunity is less characterized. Therefore, it is no surprise that the field of pathogenic complement evasion has focused on blockade of innate effector functions, while potential inhibition of adaptive immune responses (via complement) has been overlooked to a certain extent. In this review, we highlight past and recent developments on the involvement of complement in the adaptive immune response. We discuss the mechanisms by which complement aids in lymphocyte stimulation and regulation, as well as in antigen presentation. In addition, we discuss microbial complement evasion strategies, and highlight specific examples in the context of adaptive immune responses. These emerging ties between complement and adaptive immunity provide a catalyst for future discovery in not only the field of adaptive immune evasion but in elucidating new roles of complement.

  1. Autophagy as a Stress Response Pathway in the Immune System.

    Science.gov (United States)

    Bhattacharya, Abhisek; Eissa, N Tony

    2015-01-01

    Macroautophagy, hereafter, referred to as autophagy, has long been regarded as a housekeeping pathway involved in intracellular degradation and energy recycling. These housekeeping and homeostatic functions are especially important during cellular stress, such as periods of nutrient deprivation. However, importance of autophagy extends far beyond its degradative functions. Recent evidence shows that autophagy plays an essential role in development, organization and functions of the immune system, and defects in autophagy lead to several diseases, including cancer and autoimmunity. In the immune system, autophagy is important in regulation of the innate and adaptive immune responses. This review focuses on the roles of autophagy in the adaptive immune system. We first introduce the autophagy pathway and provide a brief description of the major molecular players involved in autophagy. We then discuss the importance of autophagy as a stress integrator mechanism and provide relevant examples of this role of autophagy in adaptive immune cells. Then we proceed to describe how autophagy regulates development, activation and functions of different adaptive immune cells. In these contexts, we mention both degradative and non-degradative roles of autophagy, and illustrate their importance. We also discuss role of autophagy in antigen presenting cells, which play critical roles in the activation of adaptive immune cells. Further, we describe how autophagy regulates functions of different adaptive immune cells during infection, inflammation and autoimmunity.

  2. Adaptable Embedded Systems

    CERN Document Server

    Lisbôa, Carlos; Carro, Luigi

    2013-01-01

    As embedded systems become more complex, designers face a number of challenges at different levels: they need to boost performance, while keeping energy consumption as low as possible, they need to reuse existent software code, and at the same time they need to take advantage of the extra logic available in the chip, represented by multiple processors working together.  This book describes several strategies to achieve such different and interrelated goals, by the use of adaptability. Coverage includes reconfigurable systems, dynamic optimization techniques such as binary translation and trace reuse, new memory architectures including homogeneous and heterogeneous multiprocessor systems, communication issues and NOCs, fault tolerance against fabrication defects and soft errors, and finally, how one can combine several of these techniques together to achieve higher levels of performance and adaptability.  The discussion also includes how to employ specialized software to improve this new adaptive system, and...

  3. Adaptive Learning Management System

    Directory of Open Access Journals (Sweden)

    Violeta Moisa

    2013-06-01

    Full Text Available This article is an introduction to a new model for an adaptive Learning Management System. It presents the current e-learning standards and describes the elements that can be used to create the system: the sequencing control modes, sequencing rules, navigation controls, learning records and learning record stores. The model is based on artificial intelligent algorithms that analyze the data captured for each user and creates an adaptive navigation path through the learning content of the system, allowing each user to experience the content in different ways

  4. Arginine Metabolism in Myeloid Cells Shapes Innate and Adaptive Immunity

    Science.gov (United States)

    Rodriguez, Paulo C.; Ochoa, Augusto C.; Al-Khami, Amir A.

    2017-01-01

    Arginine metabolism has been a key catabolic and anabolic process throughout the evolution of the immune response. Accruing evidence indicates that arginine-catabolizing enzymes, mainly nitric oxide synthases and arginases, are closely integrated with the control of immune response under physiological and pathological conditions. Myeloid cells are major players that exploit the regulators of arginine metabolism to mediate diverse, although often opposing, immunological and functional consequences. In this article, we focus on the importance of arginine catabolism by myeloid cells in regulating innate and adaptive immunity. Revisiting this matter could result in novel therapeutic approaches by which the immunoregulatory nodes instructed by arginine metabolism can be targeted.

  5. The Immune System in Cancer Prevention, Development and Therapy.

    Science.gov (United States)

    Candeias, Serge M; Gaipl, Udo S

    2016-01-01

    The immune system plays a pivotal role in the maintenance of the integrity of an organism. Besides the protection against pathogens, it is strongly involved in cancer prevention, development and defense. This review focuses on how the immune system protects against infections and trauma and on its role in cancer development and disease. Focus is set on the interactions of the innate and adaptive immune system and tumors. The role of IFN-γ as a pleiotropic cytokine that plays a very important role at the interface of innate and adaptive immune systems in tumor development and induction of anti-tumor immune responses is outlined. Further, immune cells as prognostic and predictive markers of cancer will be discussed. Data are provided that even the brain as immune privileged organ is subjected to immune surveillance and consequently also brain tumors. Immune therapeutic approaches for glioblastoma multiforme, the most frequent and malignant brain tumor, based on vaccination with dendritic cells are outlined and application of hyperthermia in form of magnetic nanoparticles is discussed. We conclude that the immune system and developing tumors are intimately intertwined. Anti-tumor immune responses can be prominently boosted by multimodal therapies aiming on the one hand to induce immunogenic tumor cell death forms and on the other hand to actively counteract the immune suppressive microenvironment based on the tumor itself.

  6. STUDYING COMPLEX ADAPTIVE SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    John H. Holland

    2006-01-01

    Complex adaptive systems (cas) - systems that involve many components that adapt or learn as they interact - are at the heart of important contemporary problems. The study of cas poses unique challenges: Some of our most powerful mathematical tools, particularly methods involving fixed points, attractors, and the like, are of limited help in understanding the development of cas. This paper suggests ways to modify research methods and tools, with an emphasis on the role of computer-based models, to increase our understanding of cas.

  7. Chemical Tools To Monitor and Manipulate Adaptive Immune Responses.

    Science.gov (United States)

    Doran, Todd M; Sarkar, Mohosin; Kodadek, Thomas

    2016-05-18

    Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of "reawakening" the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between "good" and "bad" immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensively monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This Perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field.

  8. Cystatins in immune system.

    Science.gov (United States)

    Magister, Spela; Kos, Janko

    2013-01-01

    Cystatins comprise a large superfamily of related proteins with diverse biological activities. They were initially characterised as inhibitors of lysosomal cysteine proteases, however, in recent years some alternative functions for cystatins have been proposed. Cystatins possessing inhibitory function are members of three families, family I (stefins), family II (cystatins) and family III (kininogens). Stefin A is often linked to neoplastic changes in epithelium while another family I cystatin, stefin B is supposed to have a specific role in neuredegenerative diseases. Cystatin C, a typical type II cystatin, is expressed in a variety of human tissues and cells. On the other hand, expression of other type II cystatins is more specific. Cystatin F is an endo/lysosome targeted protease inhibitor, selectively expressed in immune cells, suggesting its role in processes related to immune response. Our recent work points on its role in regulation of dendritic cell maturation and in natural killer cells functional inactivation that may enhance tumor survival. Cystatin E/M expression is mainly restricted to the epithelia of the skin which emphasizes its prominent role in cutaneous biology. Here, we review the current knowledge on type I (stefins A and B) and type II cystatins (cystatins C, F and E/M) in pathologies, with particular emphasis on their suppressive vs. promotional function in the tumorigenesis and metastasis. We proposed that an imbalance between cathepsins and cystatins may attenuate immune cell functions and facilitate tumor cell invasion.

  9. Melatonin: Buffering the Immune System

    Directory of Open Access Journals (Sweden)

    Juan M. Guerrero

    2013-04-01

    Full Text Available Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

  10. Kicking off adaptive immunity: the discovery of dendritic cells

    OpenAIRE

    Katsnelson, Alla

    2006-01-01

    In 1973, Ralph Steinman and Zanvil Cohn discovered an unusual looking population of cells with an unprecedented ability to activate naive T cells. Dubbed “dendritic cells,” these cells are now known as the primary instigators of adaptive immunity.

  11. Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi

    NARCIS (Netherlands)

    Buffen, Kathrin; Oosting, Marije; Li, Yang; Kanneganti, Thirumala-Devi; Netea, Mihai G.; Joosten, Leo A. B.

    2016-01-01

    Inhibition of autophagy increases the severity of murine Lyme arthritis and human adaptive immune responses against B. burgdorferi. We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known regardi

  12. Adaptive immunity to rhinoviruses: sex and age matter

    Directory of Open Access Journals (Sweden)

    Pritchard Antonia L

    2010-12-01

    Full Text Available Abstract Background Rhinoviruses (RV are key triggers in acute asthma exacerbations. Previous studies suggest that men suffer from infectious diseases more frequently and with greater severity than women. Additionally, the immune response to most infections and vaccinations decreases with age. Most immune function studies do not account for such differences, therefore the aim of this study was to determine if the immune response to rhinovirus varies with sex or age. Methods Blood mononuclear cells were isolated from 63 healthy individuals and grouped by sex and age (≤50 years old and ≥52 years old. Cells were cultured with rhinovirus 16 at a multiplicity of infection of 1. The chemokine IP-10 was measured at 24 h as an index of innate immunity while IFNγ and IL-13 were measured at 5 days as an index of adaptive immunity. Results Rhinovirus induced IFNγ and IL-13 was significantly higher in ≤50 year old women than in age matched men (p 0.005. There was no sex or age based difference in rhinovirus induced IP-10 expression. Both IFNγ and IL-13 were negatively correlated with age in women but not in men. Conclusions This study suggests that pre-menopausal women have a stronger adaptive immune response to rhinovirus infection than men and older people, though the mechanisms responsible for these differences remain to be determined. Our findings highlight the importance of gender and age balance in clinical studies and in the development of new treatments and vaccines.

  13. Evolution of immune systems from self/not self to danger to artificial immune systems (AIS)

    Science.gov (United States)

    Cooper, Edwin L.

    2010-03-01

    This review will examine the evolution of immune mechanisms by emphasizing information from animal groups exclusive of all vertebrates. There will be a focus on concepts that propelled the immune system into prominent discourse in the life sciences. The self/not self hypothesis was crucial and so was the concern for immunologic memory or anamnesia, development of cancer, autoimmunity, and clonal selection. Now we may be able to deconstruct clonal selection since it is not applicable in the sense that it is not applicable to invertebrate mechanisms. Clonal selection seems to be purely as all evidence indicates a vertebrate strategy and therefore irrelevant to invertebrates. Some views may insist that anthropocentric mammalian immunologists utilized a tool to propel: the universal innate immune system of ubiquitous and plentiful invertebrates as an essential system for vertebrates. This was advantageous for all immunology; moreover innate immunity acquired an extended raison d'être. Innate immunity should help if there would be a failure of the adaptive immune system. Still to be answered are questions concerning immunologic surveillance that includes clonal selection. We can then ask does immunologic surveillance play a role in the survival of invertebrates that most universally seem to not develop cancer of vertebrates especially mammals; invertebrates only develop benign tumor. A recent proposal concerns an alternative explanation that is all embracing. Danger hypothesis operates in striking contrast to the self/not self hypothesis. This view holds that the immune system is adapted to intervene not because self is threatened but because of the system's sense of danger. This perception occurs by means of signals other than recognition of microbial pattern recognition molecules characteristic of invertebrates. Response to danger may be another way of analyzing innate immunity that does not trigger the production of clones and therefore does not rely entirely on the

  14. The Immune System in Hypertension

    Science.gov (United States)

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  15. miRNA-124 in Immune System and Immune Disorders

    OpenAIRE

    2016-01-01

    In recent years, miR-124 has emerged as a critical modulator of immunity and inflammation. Here, we summarize studies on the function and mechanism of miR-124 in the immune system and immunity-related diseases. They indicated that miR-124 exerts a crucial role in the development of immune system, regulation of immune responses, and inflammatory disorders. It is evident that miR-124 may serve as an informative diagnostic biomarker and therapeutic target in the future.

  16. Control of the adaptive immune response by tumor vasculature

    Directory of Open Access Journals (Sweden)

    Laetitia eMauge

    2014-03-01

    Full Text Available The endothelium is nowadays described as an entire organ that regulates various processes: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by abnormal vessel structure and permeability, and by specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intratumoral immune responses and contribute to the development of intratumoral immunosuppression, which is a major mechanism for promoting the development, progression and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of antitumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy.

  17. Adaptive CT scanning system

    Energy Technology Data Exchange (ETDEWEB)

    Sampayan, Stephen E.

    2016-11-22

    Apparatus, systems, and methods that provide an X-ray interrogation system having a plurality of stationary X-ray point sources arranged to substantially encircle an area or space to be interrogated. A plurality of stationary detectors are arranged to substantially encircle the area or space to be interrogated, A controller is adapted to control the stationary X-ray point sources to emit X-rays one at a time, and to control the stationary detectors to detect the X-rays emitted by the stationary X-ray point sources.

  18. Tactics used by HIV-1 to evade host innate, adaptive, and intrinsic immunities

    Institute of Scientific and Technical Information of China (English)

    LU Lu; YU Fei; DU Lan-ying; XU Wei; JIANG Shi-bo

    2013-01-01

    Objective To review the mechanisms by which HIV evades different components of the host immune system.Data sources This review is based on data obtained from published articles from 1991 to 2012.To perform the PubMed literature search,the following key words were input:HIV and immune evasion.Study selection Articles containing information related to HIV immune evasion were selected.Results Although HIV is able to induce vigorous antiviral immune responses,viral replication cannot be fully controlled,and neither pre-existing infected cells nor latent HIV infection can be completely eradicated.Like many other enveloped viruses,HIV can escape recognition by the innate and adaptive immune systems.Recent findings have demonstrated that HIV can also successfully evade host restriction factors,the components of intrinsic immune system,such as APOBEC3G (apolipoprotein B mRNA-editing enzyme,catalytic polypeptide-like 3G),TRIM5α (tripartite motif 5-α),tetherin,and SAMHD1 (SAM-domain HD-domain containing protein).Conclusions HIV immune evasion plays an important role in HIV pathcgenesis.Fully understanding the tactics deployed by HIV to evade various components of the host immune systems will allow for the development of novel strategies aimed toward the prevention and cure of HIV/AIDS.

  19. Autonomic nervous system and immune system interactions.

    Science.gov (United States)

    Kenney, M J; Ganta, C K

    2014-07-01

    The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological, and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines, and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease

  20. Is there a role for adaptive immunity in nonalcoholicsteatohepatitis?

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The growing diffusion of nonalcoholic fatty liver disease(NAFLD) is a consequence of the worldwide increasein the prevalence of obesity. Oxidative stress is widelyrecognized to play a pivotal role in NAFLD evolution tononalcoholic steatohepatitis (NASH). Here we reviewrecent evidence suggesting that oxidative stress-derivedantigens originating within fatty livers stimulate bothhumoral and cellular adaptive immune responses andthe possible mechanisms involved in sustaining hepaticinflammation in NASH.

  1. Is there a role for adaptive immunity in nonalcoholic steatohepatitis?

    Science.gov (United States)

    Sutti, Salvatore; Jindal, Aastha; Bruzzì, Stefania; Locatelli, Irene; Bozzola, Cristina; Albano, Emanuele

    2015-01-01

    The growing diffusion of nonalcoholic fatty liver disease (NAFLD) is a consequence of the worldwide increase in the prevalence of obesity. Oxidative stress is widely recognized to play a pivotal role in NAFLD evolution to nonalcoholic steatohepatitis (NASH). Here we review recent evidence suggesting that oxidative stress-derived antigens originating within fatty livers stimulate both humoral and cellular adaptive immune responses and the possible mechanisms involved in sustaining hepatic inflammation in NASH. PMID:26167244

  2. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?

    Directory of Open Access Journals (Sweden)

    Thomas Vorup-Jensen

    2012-11-01

    Full Text Available Multiple sclerosis is a disease of the central nervous system, resulting in the demyelination of neurons, causing mild to severe symptoms. Several anti-inflammatory treatments now play a significant role in ameliorating the disease. Glatiramer acetate (GA is a formulation of random polypeptide copolymers for the treatment of relapsing-remitting MS by limiting the frequency of attacks. While evidence suggests the influence of GA on inflammatory responses, the targeted molecular mechanisms remain poorly understood. Here, we review the multiple pharmacological modes-of-actions of glatiramer acetate in treatment of multiple sclerosis. We discuss in particular a newly discovered interaction between the leukocyte-expressed integrin αMβ2 (also called Mac-1, complement receptor 3, or CD11b/CD18 and perspectives on the GA co-polymers as an influence on the function of the innate immune system.

  3. SISTEMAS INMUNES ALTERNATIVOS - Alternative Immune Systems

    Directory of Open Access Journals (Sweden)

    Cadavid Gutierrez Luis Fernando

    2011-12-01

    Full Text Available El sistema inmune en animales es una red compleja de moléculas, células y tejidos que de manera conjunta mantienen la integridad fisiológica y genética de los organismos. Convencionalmente se ha considerado la existencia de dos clases de inmunidad, la innata y la adaptativa. La primera es ancestral, con variabilidad limitada y baja discriminación, mientras que la segunda es altamente variable, específica y restringida a vertebrados mandibulados. La inmunidad adaptativa se basa en receptores de antígeno que se rearreglan somáticamente para generar una diversidad casi ilimitada de moléculas. Este mecanismo de recombinación somática muy probablemente emergió como consecuencia de un evento de transferencia horizontal de transposones y transposasas bacterianas en el ancestro de los vertebrados mandibulados. El reciente descubrimiento en vertebrados no mandibulados e invertebrados de mecanismos alternativos de inmunidad adaptativa, sugiere que en el transcurso de la evolución distintos grupos animales han encontrado soluciones alternativas al problema del reconocimiento inmunológico. Palabras claves: Sistema inmune, evolución, VLR, Dscam, Alorreconocimiento ABSTRACT The immune system in animals is a complex network of molecules, cells and tissues that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of a horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless

  4. Diffuse endocrine system, neuroendocrine tumors and immunity: what's new?

    Science.gov (United States)

    Ameri, Pietro; Ferone, Diego

    2012-01-01

    During the last two decades, research into the modulation of immunity by the neuroendocrine system has flourished, unravelling significant effects of several neuropeptides, including somatostatin (SRIH), and especially cortistatin (CST), on immune cells. Scientists have learnt that the diffuse neuroendocrine system can regulate the immune system at all its levels: innate immunity, adaptive immunity, and maintenance of immune tolerance. Compelling studies with animal models have demonstrated that some neuropeptides may be effective in treating inflammatory disorders, such as sepsis, and T helper 1-driven autoimmune diseases, like Crohn's disease and rheumatoid arthritis. Here, the latest findings concerning the neuroendocrine control of the immune system are discussed, with emphasis on SRIH and CST. The second part of the review deals with the immune response to neuroendocrine tumors (NETs). The anti-NET immune response has been described in the last years and it is still being characterized, similarly to what is happening for several other types of cancer. In parallel with investigations addressing the mechanisms by which the immune system contrasts NET growth and spreading, ground-breaking clinical trials of dendritic cell vaccination as immunotherapy for metastatic NETs have shown in principle that the immune reaction to NETs can be exploited for treatment.

  5. Complex adaptive systems ecology

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2003-01-01

    In the following, I will analyze two articles called Complex Adaptive Systems EcologyI & II (Molin & Molin, 1997 & 2000). The CASE-articles are some of the more quirkyarticles that have come out of the Molecular Microbial Ecology Group - a groupwhere I am currently making observational studies....... They are the result of acooperation between Søren Molin, professor in the group, and his brother, JanMolin, professor at Department of Organization and Industrial Sociology atCopenhagen Business School. The cooperation arises from the recognition that bothmicrobial ecology and sociology/organization theory works...

  6. Detecting Anomalous Process Behaviour using Second Generation Artificial Immune Systems

    CERN Document Server

    Twycross, Jamie; Whitbrook, Amanda

    2010-01-01

    Artificial Immune Systems have been successfully applied to a number of problem domains including fault tolerance and data mining, but have been shown to scale poorly when applied to computer intrusion detec- tion despite the fact that the biological immune system is a very effective anomaly detector. This may be because AIS algorithms have previously been based on the adaptive immune system and biologically-naive mod- els. This paper focuses on describing and testing a more complex and biologically-authentic AIS model, inspired by the interactions between the innate and adaptive immune systems. Its performance on a realistic process anomaly detection problem is shown to be better than standard AIS methods (negative-selection), policy-based anomaly detection methods (systrace), and an alternative innate AIS approach (the DCA). In addition, it is shown that runtime information can be used in combination with system call information to enhance detection capability.

  7. Induction of mucosal immunity through systemic immunization: Phantom or reality?

    Science.gov (United States)

    Su, Fei; Patel, Girishchandra B; Hu, Songhua; Chen, Wangxue

    2016-04-02

    Generation of protective immunity at mucosal surfaces can greatly assist the host defense against pathogens which either cause disease at the mucosal epithelial barriers or enter the host through these surfaces. Although mucosal routes of immunization, such as intranasal and oral, are being intensely explored and appear promising for eliciting protective mucosal immunity in mammals, their application in clinical practice has been limited due to technical and safety related challenges. Most of the currently approved human vaccines are administered via systemic (such as intramuscular and subcutaneous) routes. Whereas these routes are acknowledged as being capable to elicit antigen-specific systemic humoral and cell-mediated immune responses, they are generally perceived as incapable of generating IgA responses or protective mucosal immunity. Nevertheless, currently licensed systemic vaccines do provide effective protection against mucosal pathogens such as influenza viruses and Streptococcus pneumoniae. However, whether systemic immunization induces protective mucosal immunity remains a controversial topic. Here we reviewed the current literature and discussed the potential of systemic routes of immunization for the induction of mucosal immunity.

  8. [The liver and the immune system].

    Science.gov (United States)

    Jakab, Lajos

    2015-07-26

    The liver is known to be the metabolic centre of the organism and is under the control of the central nervous system. It has a peculiar tissue structure and its anatomic localisation defines it as part of the immune system having an individual role in the defence of the organism. The determinant of its particular tissue build-up is the sinusoid system. In addition to hepatocytes, one cell row "endothelium", stellate cells close to the external surface, Kupffer cells tightly to its inner surface, as well as dendritic cells and other cell types (T and B lymphocytes, natural killer and natural killer T-cells, mast cells, granulocytes) are present. The multitudes and variety of cells make it possible to carry out the tasks according to the assignment of the organism. The liver is a member of the immune system having immune cells largely in an activated state. Its principal tasks are the assurance of the peripheral immune tolerance of the organism with the help of the haemopoetic cells and transforming growth factor-β. The liver takes part in the determination of the manner of the non-specific immune response of the organism. In addition to acute phase reaction of the organism, the liver has a role in the adaptive/specific immune response. These functions include retardation of the T and B lymphocytes and the defence against harmful pathogens. With the collaboration of transforming growth factor-β, immunoglobulins and their subclasses are inhibited just as the response of the T lymphocytes. The only exception is the undisturbed immunoglobulin A production. Particularly important is the intensive participation of the liver in the acute phase reaction of the organism, which is organised and guided by the coordinated functions of the cortico-hypothalamo-hypophysis-adrenal axis. Beside cellular elements, hormones, adhesion molecules, chemokines and cytokines are also involved in the cooperation with the organs. Acute phase reactants play a central role in these processes

  9. Adaptive immune response during hepatitis C virus infection.

    Science.gov (United States)

    Larrubia, Juan Ramón; Moreno-Cubero, Elia; Lokhande, Megha Uttam; García-Garzón, Silvia; Lázaro, Alicia; Miquel, Joaquín; Perna, Cristian; Sanz-de-Villalobos, Eduardo

    2014-04-07

    Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion. To impair HCV-specific T cell reactivity, HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. In this review, the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.

  10. Immunity Based Worm Detection System

    Institute of Scientific and Technical Information of China (English)

    HONG Zheng; WU Li-fa; WANG Yuan-yuan

    2007-01-01

    Current worm detection methods are unable to detect multi-vector polymorphic worms effectively.Based on negative selection mechanism of the immune system,a local network worm detection system that detects worms was proposed.Normal network service requests were represented by self-strings,and the detection system used self-strings to monitor the network for anomaly.According to the properties of worm propagation,a control center correlated the anomalies detected in the form of binary trees to ensure the accuracy of worm detection.Experiments show the system to be effective in detecting the traditional as well as multi-vector polymorphic worms.

  11. User-Centered Evaluation of Adaptive and Adaptable Systems

    NARCIS (Netherlands)

    Velsen, van Lex; Geest, van der Thea M.; Klaassen, Rob F.

    2009-01-01

    Adaptive and adaptable systems provide tailored output to various users in various contexts. While adaptive systems base their output on implicit inferences, adaptable systems use explicitly provided information. Since the presentation or output of these systems is adapted, standard user-centered ev

  12. [Obesity and the immune system].

    Science.gov (United States)

    Muñoz, M; Mazure, R A; Culebras, J M

    2004-01-01

    With an increased prevalence of obesity in developed countries, associated chronic diseases rise in a parallel way. Morbidity secondary to overweight and obesity include type 2 diabetes, dislipemia, hypertension, heart disease, cerebrovascular disease, cholelithiasis, osteoarthritis, heart insufficiency, sleep apnoea, menstrual changes, sterility and psychological alterations. There is also a greater susceptibility to suffer some types of cancer, infections, greater risk of bacteremia and a prolonged time of wound healing after surgical operations. All these factors indicate that obesity exerts negative effects upon the immune system. Immune changes found in obesity and their possible interrelations are described in this article. Changes produced during obesity affect both humoral and cellular immunity. It is known that adipose tissue, together with its role as energy reserve in form of triglycerides, has important endocrine functions, producing several hormones and other signal molecules. Immune response can be deeply affected by obesity, playing leptin an important role. Properties of leptin, alterations of leptin levels in different situations and its changes with different medical and surgical therapies for obesity are described in this article.

  13. Synthetic immunology: modulating the human immune system.

    Science.gov (United States)

    Geering, Barbara; Fussenegger, Martin

    2015-02-01

    Humans have manipulated the immune system to dampen or boost the immune response for thousands of years. As our understanding of fundamental immunology and biotechnological methodology accumulates, we can capitalize on this combined knowledge to engineer biological devices with the aim of rationally manipulating the immune response. We address therapeutic approaches based on the principles of synthetic immunology that either ameliorate disorders of the immune system by interfering with the immune response, or improve diverse pathogenic conditions by exploiting immune cell effector functions. We specifically highlight synthetic proteins investigated in preclinical and clinical trials, summarize studies that have used engineered immune cells, and finish with a discussion of possible future therapeutic concepts.

  14. Influenza, immune system, and pregnancy.

    Science.gov (United States)

    Raj, Renju S; Bonney, Elizabeth A; Phillippe, Mark

    2014-12-01

    Influenza is a major health problem worldwide. Both seasonal influenza and pandemics take a major toll on the health and economy of our country. The present review focuses on the virology and complex immunology of this RNA virus in general and in relation to pregnancy. The goal is to attempt to explain the increased morbidity and mortality seen in infection during pregnancy. We discuss elements of innate and adaptive immunity as well as placental cellular responses to infection. In addition, we delineate findings in animal models as well as human disease. Increased knowledge of maternal and fetal immunologic responses to influenza is needed. However, enhanced understanding of nonimmune, pregnancy-specific factors influencing direct interaction of the virus with host cells is also important for the development of more effective prevention and treatment options in the future.

  15. Dynamics of adaptive immunity against phage in bacterial populations

    CERN Document Server

    Bradde, Serena; Tesileanu, Tiberiu; Balasubramanian, Vijay

    2015-01-01

    The CRISPR (clustered regularly interspaced short palindromic repeats) mechanism allows bacteria to adaptively defend against phages by acquiring short genomic sequences (spacers) that target specific sequences in the viral genome. We propose a population dynamical model where immunity can be both acquired and lost. The model predicts regimes where bacterial and phage populations can co-exist, others where the populations oscillate, and still others where one population is driven to extinction. Our model considers two key parameters: (1) ease of acquisition and (2) spacer effectiveness in conferring immunity. Analytical calculations and numerical simulations show that if spacers differ mainly in ease of acquisition, or if the probability of acquiring them is sufficiently high, bacteria develop a diverse population of spacers. On the other hand, if spacers differ mainly in their effectiveness, their final distribution will be highly peaked, akin to a "winner-take-all" scenario, leading to a specialized spacer ...

  16. Future directions in bladder cancer immunotherapy: towards adaptive immunity.

    Science.gov (United States)

    Smith, Sean G; Zaharoff, David A

    2016-01-01

    The clinical management of bladder cancer has not changed significantly in several decades. In particular, intravesical bacillus Calmette-Guérin (BCG) immunotherapy has been a mainstay for high-risk nonmuscle invasive bladder cancer since the late 1970s/early 1980s. This is despite the fact that bladder cancer has the highest recurrence rates of any cancer and BCG immunotherapy has not been shown to induce a tumor-specific immune response. We and others have hypothesized that immunotherapies capable of inducing tumor-specific adaptive immunity are needed to impact bladder cancer morbidity and mortality. This article summarizes the preclinical and clinical development of bladder cancer immunotherapies with an emphasis on the last 5 years. Expected progress in the near future is also discussed.

  17. Biological Immune System Applications on Mobile Robot for Disabled People

    Directory of Open Access Journals (Sweden)

    Songmin Jia

    2014-01-01

    Full Text Available To improve the service quality of service robots for the disabled, immune system is applied on robot for its advantages such as diversity, dynamic, parallel management, self-organization, and self-adaptation. According to the immune system theory, local environment condition sensed by robot is considered an antigen while robot is regarded as B-cell and possible node as antibody, respectively. Antibody-antigen affinity is employed to choose the optimal possible node to ensure the service robot can pass through the optimal path. The paper details the immune system applications on service robot and gives experimental results.

  18. PD-1 blockade induces responses by inhibiting adaptive immune resistance

    Science.gov (United States)

    Tumeh, Paul C.; Harview, Christina L.; Yearley, Jennifer H.; Shintaku, I. Peter; Taylor, Emma J. M.; Robert, Lidia; Chmielowski, Bartosz; Spasic, Marko; Henry, Gina; Ciobanu, Voicu; West, Alisha N.; Carmona, Manuel; Kivork, Christine; Seja, Elizabeth; Cherry, Grace; Gutierrez, Antonio; Grogan, Tristan R.; Mateus, Christine; Tomasic, Gorana; Glaspy, John A.; Emerson, Ryan O.; Robins, Harlan; Pierce, Robert H.; Elashoff, David A.; Robert, Caroline; Ribas, Antoni

    2014-01-01

    Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types.1–5 One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8 T-cells (termed adaptive immune resistance).6,7 Here we show that pre-existing CD8 T-cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analyzed samples from 46 patients with metastatic melanoma obtained before and during anti-PD1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next generation sequencing for T-cell receptors (TCR). In serially sampled tumours, responding patients showed proliferation of intratumoural CD8+ T-cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8, PD1, and PD-L1 expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression following therapeutic PD-1 blockade requires pre-existing CD8+ T cells that are negatively regulated by PD-1/PD-L1 mediated adaptive immune resistance. PMID:25428505

  19. Dendritic Cells in Innate and Adaptive Immune Responses against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Artur Summerfield

    2009-11-01

    Full Text Available Dendritic cells (DC are major players in both innate and adaptive immune responses against influenza virus. These immune responses, as well as the important interface between the innate and adaptive systems, are orchestrated by specialized subsets of DC, including conventional steady-state DC, migratory DC and plasmacytoid DC. The characteristics and efficacy of the responses are dependent on the relative activity of these DC subsets, rendering DC crucial for the development of both naïve and memory immune responses. However, due to their critical role, DC also contribute to the immunopathological processes observed during acute influenza, such as that caused by the pathogenic H5N1 viruses. Therein, the role of different DC subsets in the induction of interferon type I, proinflammatory cytokine and chemokine responses is important for the outcome of interaction between the virus and host immune defences. The present review will present current knowledge on this area, relating to the importance of DC activity for the induction of efficacious humoral and cell-mediated immune responses. This will include the main viral elements associated with the triggering or inhibition of DC activation. Finally, the current knowledge on understanding how differences in various vaccines influence the manner of immune defence induction will be presented.

  20. The role of the innate and adaptive immune responses in Acanthamoeba keratitis.

    Science.gov (United States)

    Niederkorn, Jerry Y

    2002-01-01

    Infections of the corneal surface are an important cause of blindness. Protozoal, viral, bacterial, and helminthic infections of the cornea account for up to 9 million cases of corneal blindness. Free-living amoebae of the genus Acanthamoeba produce a progressive infection of the cornea called Acanthamoeba keratitis. Disease is usually transmitted by Acanthamoeba trophozoites bound to soft contact lenses. Infection of the cornea is initiated when the parasite binds to the corneal epithelial surface. Recrudescence can occur and suggests that the adaptive immune response is not aroused by corneal Acanthamoeba infections. Systemic immunization with Acanthamoeba antigens elicits robust Th1 cell-mediated immunity and serum IgG antibody, yet fails to prevent the development of Acanthamoeba keratitis. However, immunization via mucosal surfaces induces anti-Acanthamoeba IgA antibodies in the tears and provides solid protection against the development of Acanthamoeba keratitis. Unlike other immune effector mechanisms that rely on cytolysis, inflammation, release of toxic molecules, or the induction of host cell death, the adaptive immune apparatus prevents Acanthamoeba infections of the cornea by simply preventing the attachment of the parasite to the epithelial surface. The beauty of this mechanism lies in its exquisite simplicity and efficacy.

  1. Recognition of bacterial plant pathogens: local, systemic and transgenerational immunity.

    Science.gov (United States)

    Henry, Elizabeth; Yadeta, Koste A; Coaker, Gitta

    2013-09-01

    Bacterial pathogens can cause multiple plant diseases and plants rely on their innate immune system to recognize and actively respond to these microbes. The plant innate immune system comprises extracellular pattern recognition receptors that recognize conserved microbial patterns and intracellular nucleotide binding leucine-rich repeat (NLR) proteins that recognize specific bacterial effectors delivered into host cells. Plants lack the adaptive immune branch present in animals, but still afford flexibility to pathogen attack through systemic and transgenerational resistance. Here, we focus on current research in plant immune responses against bacterial pathogens. Recent studies shed light onto the activation and inactivation of pattern recognition receptors and systemic acquired resistance. New research has also uncovered additional layers of complexity surrounding NLR immune receptor activation, cooperation and sub-cellular localizations. Taken together, these recent advances bring us closer to understanding the web of molecular interactions responsible for coordinating defense responses and ultimately resistance.

  2. Editing at the crossroad of innate and adaptive immunity.

    Science.gov (United States)

    Turelli, Priscilla; Trono, Didier

    2005-02-18

    Genetic information can be altered through the enzymatic modification of nucleotide sequences. This process, known as editing, was originally identified in the mitochondrial RNA of trypanosomes and later found to condition events as diverse as neurotransmission and lipid metabolism in mammals. Recent evidence reveals that editing enzymes may fulfill one of their most essential roles in the defense against infectious agents: first, as the mediators of antibody diversification, a step crucial for building adaptive immunity, and second, as potent intracellular poisons for the replication of viruses. Exciting questions are raised, which take us to the depth of the intimate relations between vertebrates and the microbial underworld.

  3. Recognition of extracellular bacteria by NLRs and its role in the development of adaptive immunity

    Directory of Open Access Journals (Sweden)

    Jonathan eFerrand

    2013-10-01

    Full Text Available Innate immune recognition of bacteria is the first requirement for mounting an effective immune response able to control infection. Over the previous decade, the general paradigm was that extracellular bacteria were only sensed by cell surface-expressed Toll-like receptors (TLRs, whereas cytoplasmic sensors, including members of the Nod-like receptor (NLR family, were specific to pathogens capable of breaching the host cell membrane. It has become apparent, however, that intracellular innate immune molecules, such as the NLRs, play key roles in the sensing of not only intracellular, but also extracellular bacterial pathogens or their components. In this review, we will discuss the various mechanisms used by bacteria to activate NLR signaling in host cells. These mechanisms include bacterial secretion systems, pore-forming toxins and outer membrane vesicles. We will then focus on the influence of NLR activation on the development of adaptive immune responses in different cell types.

  4. Psychoneuroimmunology--cross-talk between the immune and nervous systems.

    Science.gov (United States)

    Ziemssen, Tjalf; Kern, Simone

    2007-05-01

    Psychoneuroimmunology is a relatively new field of study that investigates interactions between behaviour and the immune system, mediated by the endocrine and nervous systems. The immune and central nervous system (CNS) maintain extensive communication. On the one hand, the brain modulates the immune system by hardwiring sympathetic and parasympathetic nerves (autonomic nervous system) to lymphoid organs. On the other hand, neuroendocrine hormones such as corticotrophin-releasing hormone or substance P regulate cytokine balance. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and immune system-mediated disease.

  5. Multiple Limit Cycles in an Immune System

    Institute of Scientific and Technical Information of China (English)

    Xun-cheng Huang; Le-min Zhu; Minaya Villasana

    2008-01-01

    The nonlinear oscillatory phenomenon has been observed in the system of immune response, which corresponds to the limit cycles in the mathematical models. We prove that the system simulating an immune response studied by Huang has at least three limit cycles in the system. The conditions for the multiple limit cycles are useful in analyzing the nonlinear oscillation in immune response.

  6. Immune System Toxicity and Immunotoxicity Hazard Identification

    Science.gov (United States)

    Exposure to chemicals may alter immune system health, increasing the risk of infections, allergy and autoimmune diseases. The chapter provides a concise overview of the immune system, host factors that affect immune system heal, and the effects that xenobiotic exposure may have ...

  7. Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune Adipose Inflammation or Insulin Resistance in Obesity.

    Directory of Open Access Journals (Sweden)

    Manikandan Subramanian

    Full Text Available Obesity-induced inflammation in visceral adipose tissue (VAT is a major contributor to insulin resistance and type 2 diabetes. Whereas innate immune cells, notably macrophages, contribute to visceral adipose tissue (VAT inflammation and insulin resistance, the role of adaptive immunity is less well defined. To address this critical gap, we used a model in which endogenous activation of T cells was suppressed in obese mice by blocking MyD88-mediated maturation of CD11c+ antigen-presenting cells. VAT CD11c+ cells from Cd11cCre+Myd88fl/fl vs. control Myd88fl/fl mice were defective in activating T cells in vitro, and VAT T and B cell activation was markedly reduced in Cd11cCre+Myd88fl/fl obese mice. However, neither macrophage-mediated VAT inflammation nor systemic inflammation were altered in Cd11cCre+Myd88fl/fl mice, thereby enabling a focused analysis on adaptive immunity. Unexpectedly, fasting blood glucose, plasma insulin, and the glucose response to glucose and insulin were completely unaltered in Cd11cCre+Myd88fl/fl vs. control obese mice. Thus, CD11c+ cells activate VAT T and B cells in obese mice, but suppression of this process does not have a discernible effect on macrophage-mediated VAT inflammation or systemic glucose homeostasis.

  8. A cascade reaction network mimicking the basic functional steps of adaptive immune response

    Science.gov (United States)

    Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

    2015-10-01

    Biological systems use complex ‘information-processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

  9. Commentary on Special Issue : CNS Diseases and the Immune System

    NARCIS (Netherlands)

    't Hart, Bert A.; den Dunnen, Wilfred F.

    2013-01-01

    In an increasing number of central nervous system (CNS) diseases a pathogenic contribution of the immune system is proposed. However, the exact underlying mechanisms are often poorly understood. The collection of articles in this special issue presents a state-of-the-art review of adaptive and innat

  10. Innate and adaptive immune interactions at the fetal-maternal interface in healthy human pregnancy and preeclampsia

    Directory of Open Access Journals (Sweden)

    Peter eHsu

    2014-03-01

    Full Text Available Maternal immune tolerance of the fetus is indispensible for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal-maternal interface – the decidua, the site of implantation and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, preeclampsia. Within the innate immune system, decidual NK cells and antigen presenting cells (including dendritic cells and macrophages make up a large proportion of the decidual leukocyte population, and are thought to modulate vascular remodeling and trophoblast invasion. On the other hand, within the adaptive immune system, Foxp3+ regulatory T (Treg cells are crucial for ensuring immune tolerance towards the semi-allogeneic fetus. Additionally, another population of CD4+HLA-G+ suppressor T cells has also been identified as a potential player in the maintenance of immune tolerance. More recently, studies are beginning to unravel the potential interactions between the innate and the adaptive immune system within the decidua, that are required to maintain a healthy pregnancy. In this review, we discuss the recent advances exploring the complex crosstalk between the innate and the adaptive immune system during human pregnancy.

  11. The innate and adaptive immune response to avian influenza virus infections and vaccines

    Science.gov (United States)

    Protective immunity against viruses is mediated by the early innate immune responses and later on by the adaptive immune responses. The early innate immunity is designed to contain and limit virus replication in the host, primarily through cytokine and interferon production. Most all cells are cap...

  12. Research on Key Technologies of Self-adaptive Immune Monitoring of Bio-inspired Manufacturing System%类生物化制造系统自适应免疫监控关键技术研究

    Institute of Scientific and Technical Information of China (English)

    唐敦兵; 郑堃; 顾文斌; 汤定山

    2011-01-01

    利用生物免疫机制及人工免疫系统的相关算法,结合类生物化制造系统模型,建立了一套制造系统免疫监控系统,并运用层次分析模型给出了该免疫监控系统健康评估的策略.对模拟实验的结果进行了分析,结果表明,所设计的免疫监控系统对制造系统的内外环境干扰具有良好的自适应性,对系统的健康状态评估也与系统的实际状况相符,从而证明了该免疫监控系统的有效性.%Combining the control model of bio-inspired manufacturing system (BIMS) with the algorithms of artificial immune system (ALS), this paper established an immune monitoring system (IMS). Besides, this paper proposed the strategies of health assessment of manufacturing system with the help of analytic hierarchy process(AHP) model. Finally,a simulation experiment was carried out based on the IMS proposed herein, and the results show that the system has a good adaptability for the changes of internal and external environments of manufacturing system. It can also give a reasonable evaluation of the manufacturing system which can match the actual state very well.Therefore, the proposed IMS has good effectiveness and reliability.

  13. Genomics and the immune system.

    Science.gov (United States)

    Pipkin, Matthew E; Monticelli, Silvia

    2008-05-01

    While the hereditary information encoded in the Watson-Crick base pairing of genomes is largely static within a given individual, access to this information is controlled by dynamic mechanisms. The human genome is pervasively transcribed, but the roles played by the majority of the non-protein-coding genome sequences are still largely unknown. In this review we focus on insights to gene transcriptional regulation by placing special emphasis on genome-wide approaches, and on how non-coding RNAs, which derive from global transcription of the genome, in turn control gene expression. We review recent progress in the field with highlights on the immune system.

  14. A Recommender System based on Idiotypic Artificial Immune Networks

    CERN Document Server

    Cayzer, Steve

    2008-01-01

    The immune system is a complex biological system with a highly distributed, adaptive and self-organising nature. This paper presents an Artificial Immune System (AIS) that exploits some of these characteristics and is applied to the task of film recommendation by Collaborative Filtering (CF). Natural evolution and in particular the immune system have not been designed for classical optimisation. However, for this problem, we are not interested in finding a single optimum. Rather we intend to identify a sub-set of good matches on which recommendations can be based. It is our hypothesis that an AIS built on two central aspects of the biological immune system will be an ideal candidate to achieve this: Antigen-antibody interaction for matching and idiotypic antibody-antibody interaction for diversity. Computational results are presented in support of this conjecture and compared to those found by other CF techniques.

  15. A Recommender System based on the Immune Network

    CERN Document Server

    Steve, Cayzer

    2008-01-01

    The immune system is a complex biological system with a highly distributed, adaptive and self-organising nature. This paper presents an artificial immune system (AIS) that exploits some of these characteristics and is applied to the task of film recommendation by collaborative filtering (CF). Natural evolution and in particular the immune system have not been designed for classical optimisation. However, for this problem, we are not interested in finding a single optimum. Rather we intend to identify a sub-set of good matches on which recommendations can be based. It is our hypothesis that an AIS built on two central aspects of the biological immune system will be an ideal candidate to achieve this: Antigen - antibody interaction for matching and antibody - antibody interaction for diversity. Computational results are presented in support of this conjecture and compared to those found by other CF techniques.

  16. Complement system part II: role in immunity

    Directory of Open Access Journals (Sweden)

    Nicolas S. Merle

    2015-05-01

    Full Text Available The complement system has been considered for a long time as a simple lytic system, aimed to kill bacteria infecting the host organism. Nowadays this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing a direct killing by C5b-9 membrane attack complex by triggering inflammatory responses with the anaphylatoxins C3a and C5a and helps the mounting of an adaptive immune response, involving antigen presenting cells, T- and B- lymphocytes. But it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Also examples will be discussed, where inadequate complement activation becomes a disease cause, including atypical hemolytic uremic syndrome (aHUS, C3 glomerulopathies (C3G and systemic lupus erythematosus (SLE. Age related macular degeneration (AMD and cancer will be described as examples showing that complement contributes to a large variety of diseases, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target.

  17. Pathogenesis of innate immunity and adaptive immunity in the mouse model of experimental autoimmune uveitis.

    Science.gov (United States)

    Bi, Hong-Sheng; Liu, Zheng-Feng; Cui, Yan

    2015-05-01

    Experimental autoimmune uveitis, a well-established model for human uveitis, is similar to human uveitis in many pathological features. Studies concerning the mechanisms of experimental autoimmune uveitis would cast a light on the pathogenesis of human uveitis as well as the search for more effective therapeutic agents. The cellular components of innate immunity include natural killer cells, gamma delta T lymphocytes, antigen-presenting dendritic cells, phagocytic macrophages, and granulocytes. It is believed that T cells are central in the generation of human uveitis. It has already become clear that CD4(+) effecter cells that predominantly produce interleukin-17 (the so-called Th17 cells) may play an important role in uveitis. In addition, the occurrence and recurrence of uveitis depends on a complex interplay between the elements of innate and adaptive immunity.

  18. Natural selection drives Drosophila immune system evolution.

    Science.gov (United States)

    Schlenke, Todd A; Begun, David J

    2003-08-01

    Evidence from disparate sources suggests that natural selection may often play a role in the evolution of host immune system proteins. However, there have been few attempts to make general population genetic inferences on the basis of analysis of several immune-system-related genes from a single species. Here we present DNA polymorphism and divergence data from 34 genes thought to function in the innate immune system of Drosophila simulans and compare these data to those from 28 nonimmunity genes sequenced from the same lines. Several statistics, including average K(A)/K(S) ratio, average silent heterozygosity, and average haplotype diversity, significantly differ between the immunity and nonimmunity genes, suggesting an important role for directional selection in immune system protein evolution. In contrast to data from mammalian immunoglobulins and other proteins, we find no strong evidence for the selective maintenance of protein diversity in Drosophila immune system proteins. This may be a consequence of Drosophila's generalized innate immune response.

  19. Complement System Part II: Role in Immunity

    Science.gov (United States)

    Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.

    2015-01-01

    The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target. PMID:26074922

  20. Adaptive immunity against gut microbiota enhances apoE-mediated immune regulation and reduces atherosclerosis and western-diet-related inflammation.

    Science.gov (United States)

    Saita, Diego; Ferrarese, Roberto; Foglieni, Chiara; Esposito, Antonio; Canu, Tamara; Perani, Laura; Ceresola, Elisa Rita; Visconti, Laura; Burioni, Roberto; Clementi, Massimo; Canducci, Filippo

    2016-07-07

    Common features of immune-metabolic and inflammatory diseases such as metabolic syndrome, diabetes, obesity and cardiovascular diseases are an altered gut microbiota composition and a systemic pro-inflammatory state. We demonstrate that active immunization against the outer membrane protein of bacteria present in the gut enhances local and systemic immune control via apoE-mediated immune-modulation. Reduction of western-diet-associated inflammation was obtained for more than eighteen weeks after immunization. Immunized mice had reduced serum cytokine levels, reduced insulin and fasting glucose concentrations; and gene expression in both liver and visceral adipose tissue confirmed a reduced inflammatory steady-state after immunization. Moreover, both gut and atherosclerotic plaques of immunized mice showed reduced inflammatory cells and an increased M2 macrophage fraction. These results suggest that adaptive responses directed against microbes present in our microbiota have systemic beneficial consequences and demonstrate the key role of apoE in this mechanism that could be exploited to treat immune-metabolic diseases.

  1. Immune system modifications and feto-maternal immune tolerance

    Institute of Scientific and Technical Information of China (English)

    Song Dan; Shi Yichao

    2014-01-01

    Objective This review aimed at understanding pregnancy-induced changes in the maternal immune response and mechanisms for the establishment of feto-maternal tolerance.Data sources Articles cited in this review were obtained from PubMed in English from 2000 to 2014,and the search string included keywords such as feto-maternal tolerance,dendritic cells,macrophage,T regulatory cells,natural killer cells,cytokines and hormone.Study selection Articles regarding altered maternal immune response,including the proliferation and differentiation of the altered cells,and the production of cytokines and regulation of hormones in the feto-maternal interface were retrieved,reviewed and analyzed.Results The changes in immune cells and cytokines in the local uterine microenvironment and peripheral blood are correlated with the establishment of feto-maternal tolerance.The endocrine system regulates the maternal immune system,promoting modifications during pregnancy.In these regulatory networks,every factor is indispensible for others.Conclusions The integration and balance of these immune factors during pregnancy give rise to an environment that enables the fetus to escape rejection by the maternal immune system.This progress is complicated,and needs more comprehensive exploration and explanation.

  2. Integrating Innate and Adaptive Immunity for Intrusion Detection

    CERN Document Server

    Tedesco, Gianni; Aickelin, Uwe

    2010-01-01

    Network Intrusion Detection Systems (NDIS) monitor a network with the aim of discerning malicious from benign activity on that network. While a wide range of approaches have met varying levels of success, most IDS's rely on having access to a database of known attack signatures which are written by security experts. Nowadays, in order to solve problems with false positive alters, correlation algorithms are used to add additional structure to sequences of IDS alerts. However, such techniques are of no help in discovering novel attacks or variations of known attacks, something the human immune system (HIS) is capable of doing in its own specialised domain. This paper presents a novel immune algorithm for application to an intrusion detection problem. The goal is to discover packets containing novel variations of attacks covered by an existing signature base.

  3. Mast cells in allergy and autoimmunity: implications for adaptive immunity.

    Science.gov (United States)

    Gregory, Gregory D; Brown, Melissa A

    2006-01-01

    As in the fashion industry, trends in a particular area of scientific investigation often are fleeting but then return with renewed and enthusiastic interest. Studies of mast cell biology are good examples of this. Although dogma once relegated mast cells almost exclusively to roles in pathological inflammation associated with allergic disease, these cells are emerging as important players in a number of other physiological processes. Consequently, they are quickly becoming the newest "trendy" cell, both within and outside the field of immunology. As sources of a large array of pro- and anti-inflammatory mediators, mast cells also express cell surface molecules with defined functions in lymphocyte activation and trafficking. Here, we provide an overview of the traditional and newly appreciated contributions of mast cells to both innate and adaptive immune responses.

  4. Female postmating immune responses, immune system evolution and immunogenic males.

    Science.gov (United States)

    Morrow, Edward H; Innocenti, Paolo

    2012-08-01

    Females in many taxa experience postmating activation of their immune system, independently of any genital trauma or pathogenic attack arising from male-female genital contact. This response has always been interpreted as a product of natural selection as it either prepares the female immune system for antigens arising from an implanted embryo (in the case of placental mammals), or is a "pre-emptive strike" against infection or injury acquired during mating. While the first hypothesis has empirical support, the second is not entirely satisfactory. Recently, studies that have experimentally dissected the postmating responses of Drosophila melanogaster females point to a different explanation: male reproductive peptides/proteins that have evolved in response to postmating male-male competition are directly responsible for activating particular elements of the female immune system. Thus, in a broad sense, males may be said to be immunogenic to females. Here, we discuss a possible direct role of sexual selection/sexual conflict in immune system evolution, in contrast to indirect trade-offs with other life-history traits, presenting the available evidence from a range of taxa and proposing ways in which the competing hypotheses could be tested. The major implication of this review is that immune system evolution is not only a product of natural selection but also that sexual selection and potentially sexual conflict enforces a direct selective pressure. This is a significant shift, and will compel researchers studying immune system evolution and ecological immunity to look beyond the forces generated by parasites and pathogens to those generated by the male ejaculate.

  5. Immune System Inspired Strategies for Distributed Systems

    CERN Document Server

    Banerjee, Soumya

    2010-01-01

    Many components of the IS are constructed as modular units which do not need to communicate with each other such that the number of components increases but the size remains constant. However, a sub-modular IS architecture in which lymph node number and size both increase sublinearly with body size is shown to efficiently balance the requirements of communication and migration, consistent with experimental data. We hypothesize that the IS architecture optimizes the tradeoff between local search for pathogens and global response using antibodies. Similar to natural immune systems, physical space and resource are also important constraints on Artificial Immune Systems (AIS), especially distributed systems applications used to connect low-powered sensors using short-range wireless communication. AIS problems like distributed robot control will also require a sub-modular architecture to efficiently balance the tradeoff between local search for a solution and global response or proliferation of the solution betwee...

  6. Multifunctional host defense peptides: antimicrobial peptides, the small yet big players in innate and adaptive immunity.

    Science.gov (United States)

    Auvynet, Constance; Rosenstein, Yvonne

    2009-11-01

    The term 'antimicrobial peptides' refers to a large number of peptides first characterized on the basis of their antibiotic and antifungal activities. In addition to their role as endogenous antibiotics, antimicrobial peptides, also called host defense peptides, participate in multiple aspects of immunity (inflammation, wound repair, and regulation of the adaptive immune system) as well as in maintaining homeostasis. The possibility of utilizing these multifunctional molecules to effectively combat the ever-growing group of antibiotic-resistant pathogens has intensified research aimed at improving their antibiotic activity and therapeutic potential, without the burden of an exacerbated inflammatory response, but conserving their immunomodulatory potential. In this minireview, we focus on the contribution of small cationic antimicrobial peptides - particularly human cathelicidins and defensins - to the immune response and disease, highlighting recent advances in our understanding of the roles of these multifunctional molecules.

  7. Learning and Memory... and the Immune System

    Science.gov (United States)

    Marin, Ioana; Kipnis, Jonathan

    2013-01-01

    The nervous system and the immune system are two main regulators of homeostasis in the body. Communication between them ensures normal functioning of the organism. Immune cells and molecules are required for sculpting the circuitry and determining the activity of the nervous system. Within the parenchyma of the central nervous system (CNS),…

  8. The immune system and the impact of zinc during aging

    Directory of Open Access Journals (Sweden)

    Haase Hajo

    2009-06-01

    Full Text Available Abstract The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence.

  9. Inside the mucosal immune system.

    Directory of Open Access Journals (Sweden)

    Jerry R McGhee

    Full Text Available An intricate network of innate and immune cells and their derived mediators function in unison to protect us from toxic elements and infectious microbial diseases that are encountered in our environment. This vast network operates efficiently by use of a single cell epithelium in, for example, the gastrointestinal (GI and upper respiratory (UR tracts, fortified by adjoining cells and lymphoid tissues that protect its integrity. Perturbations certainly occur, sometimes resulting in inflammatory diseases or infections that can be debilitating and life threatening. For example, allergies in the eyes, skin, nose, and the UR or digestive tracts are common. Likewise, genetic background and environmental microbial encounters can lead to inflammatory bowel diseases (IBDs. This mucosal immune system (MIS in both health and disease is currently under intense investigation worldwide by scientists with diverse expertise and interests. Despite this activity, there are numerous questions remaining that will require detailed answers in order to use the MIS to our advantage. In this issue of PLOS Biology, a research article describes a multi-scale in vivo systems approach to determine precisely how the gut epithelium responds to an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α, given by the intravenous route. This article reveals a previously unknown pathway in which several cell types and their secreted mediators work in unison to prevent epithelial cell death in the mouse small intestine. The results of this interesting study illustrate how in vivo systems biology approaches can be used to unravel the complex mechanisms used to protect the host from its environment.

  10. Vitamin D and the Immune System

    OpenAIRE

    Aranow, Cynthia

    2011-01-01

    It is now clear that vitamin D has important roles in addition to its classic effects on calcium and bone homeostasis. As the vitamin D receptor is expressed on immune cells (B cells, T cells and antigen presenting cells) and these immunologic cells are all are capable of synthesizing the active vitamin D metabolite, vitamin D has the capability of acting in an autocrine manner in a local immunologic milieu. Vitamin D can modulate the innate and adaptive immune responses. Deficiency in vitami...

  11. A new hypothesis: some metastases are the result of inflammatory processes by adapted cells, especially adapted immune cells at sites of inflammation.

    Science.gov (United States)

    Shahriyari, Leili

    2016-01-01

    There is an old hypothesis that metastasis is the result of migration of tumor cells from the tumor to a distant site. In this article, we propose another mechanism for metastasis, for cancers that are initiated at the site of chronic inflammation. We suggest that cells at the site of chronic inflammation might become adapted to the inflammatory process, and these adaptations may lead to the initiation of an inflammatory tumor. For example, in an inflammatory tumor immune cells might be adapted to send signals of proliferation or angiogenesis, and epithelial cells might be adapted to proliferation (like inactivation of tumor suppressor genes). Therefore, we hypothesize that metastasis could be the result of an inflammatory process by adapted cells, especially adapted immune cells at the site of inflammation, as well as the migration of tumor cells with the help of activated platelets, which travel between sites of inflammation.  If this hypothesis is correct, then any treatment causing necrotic cell death may not be a good solution. Because necrotic cells in the tumor micro-environment or anywhere in the body activate the immune system to initiate the inflammatory process, and the involvement of adapted immune cells in the inflammatory processes leads to the formation and progression of tumors. Adapted activated immune cells send more signals of proliferation and/or angiogenesis than normal cells. Moreover, if there were adapted epithelial cells, they would divide at a much higher rate in response to the proliferation signals than normal cells. Thus, not only would the tumor come back after the treatment, but it would also grow more aggressively.

  12. Adaptive protection algorithm and system

    Science.gov (United States)

    Hedrick, Paul [Pittsburgh, PA; Toms, Helen L [Irwin, PA; Miller, Roger M [Mars, PA

    2009-04-28

    An adaptive protection algorithm and system for protecting electrical distribution systems traces the flow of power through a distribution system, assigns a value (or rank) to each circuit breaker in the system and then determines the appropriate trip set points based on the assigned rank.

  13. Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity

    Science.gov (United States)

    Klein, Theo; Viner, Rosa I.

    2016-01-01

    Adaptive immunity is the specialized defence mechanism in vertebrates that evolved to eliminate pathogens. Specialized lymphocytes recognize specific protein epitopes through antigen receptors to mount potent immune responses, many of which are initiated by nuclear factor-kappa B activation and gene transcription. Most, if not all, pathways in adaptive immunity are further regulated by post-translational modification (PTM) of signalling proteins, e.g. phosphorylation, citrullination, ubiquitination and proteolytic processing. The importance of PTMs is reflected by genetic or acquired defects in these pathways that lead to a dysfunctional immune response. Here we discuss the state of the art in targeted proteomics and systems biology approaches to dissect the PTM landscape specifically regarding ubiquitination and proteolysis in B- and T-cell activation. Recent advances have occurred in methods for specific enrichment and targeted quantitation. Together with improved instrument sensitivity, these advances enable the accurate analysis of often rare PTM events that are opaque to conventional proteomics approaches, now rendering in-depth analysis and pathway dissection possible. We discuss published approaches, including as a case study the profiling of the N-terminome of lymphocytes of a rare patient with a genetic defect in the paracaspase protease MALT1, a key regulator protease in antigen-driven signalling, which was manifested by elevated linear ubiquitination. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644975

  14. Can We Translate Vitamin D Immunomodulating Effect on Innate and Adaptive Immunity to Vaccine Response?

    Directory of Open Access Journals (Sweden)

    Pierre Olivier Lang

    2015-03-01

    Full Text Available Vitamin D (VitD, which is well known for its classic role in the maintenance of bone mineral density, has now become increasingly studied for its extra-skeletal roles. It has an important influence on the body’s immune system and modulates both innate and adaptive immunity and regulates the inflammatory cascade. In this review our aim was to describe how VitD might influence immune responsiveness and its potential modulating role in vaccine immunogenicity. In the first instance, we consider the literature that may provide molecular and genetic support to the idea that VitD status may be related to innate and/or adaptive immune response with a particular focus on vaccine immunogenicity and then discuss observational studies and controlled trials of VitD supplementation conducted in humans. Finally, we conclude with some knowledge gaps surrounding VitD and vaccine response, and that it is still premature to recommend “booster” of VitD at vaccination time to enhance vaccine response.

  15. Virulent Salmonella enterica serovar typhimurium evades adaptive immunity by preventing dendritic cells from activating T cells.

    Science.gov (United States)

    Tobar, Jaime A; Carreño, Leandro J; Bueno, Susan M; González, Pablo A; Mora, Jorge E; Quezada, Sergio A; Kalergis, Alexis M

    2006-11-01

    Dendritic cells (DCs) constitute the link between innate and adaptive immunity by directly recognizing pathogen-associated molecular patterns (PAMPs) in bacteria and by presenting bacterial antigens to T cells. Recognition of PAMPs renders DCs as professional antigen-presenting cells able to prime naïve T cells and initiate adaptive immunity against bacteria. Therefore, interfering with DC function would promote bacterial survival and dissemination. Understanding the molecular mechanisms that have evolved in virulent bacteria to evade activation of adaptive immunity requires the characterization of virulence factors that interfere with DC function. Salmonella enterica serovar Typhimurium, the causative agent of typhoid-like disease in the mouse, can prevent antigen presentation to T cells by avoiding lysosomal degradation in DCs. Here, we show that this feature of virulent Salmonella applies in vivo to prevent activation of adaptive immunity. In addition, this attribute of virulent Salmonella requires functional expression of a type three secretion system (TTSS) and effector proteins encoded within the Salmonella pathogenicity island 2 (SPI-2). In contrast to wild-type virulent Salmonella, mutant strains carrying specific deletions of SPI-2 genes encoding TTSS components or effectors proteins are targeted to lysosomes and are no longer able to prevent DCs from activating T cells in vitro or in vivo. SPI-2 mutant strains are attenuated in vivo, showing reduced tissue colonization and enhanced T-cell activation, which confers protection against a challenge with wild-type virulent Salmonella. Our data suggest that impairment of DC function by the activity of SPI-2 gene products is crucial for Salmonella pathogenesis.

  16. New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host

    Directory of Open Access Journals (Sweden)

    Yingru eLiu

    2011-03-01

    Full Text Available It is well known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host’s immune defenses, we propose that it also has the capacity to avoid inducing specific immune responses. In a mouse model of vaginal gonococcal infection, N. gonorrhoeae elicits Th17-driven inflammatory- immune responses, which recruit innate defense mechanisms including an influx of neutrophils. Concomitantly, N. gonorrhoeae suppresses Th1- and Th2-dependent adaptive immunity, including specific antibody responses, through a mechanism involving TGF-β and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with the generation of immune memory and protective immunity. Genital tract tissues are naturally rich in TGF-β, which fosters an immunosuppressive environment that is important in reproduction. In exploiting this niche, N. gonorrhoeae exemplifies a well-adapted pathogen that proactively elicits from its host innate responses that it can survive and concomitantly suppresses adaptive immunity. Comprehension of these mechanisms of gonococcal pathogenesis should allow the development of novel approaches to therapy and facilitate the development of an effective vaccine.

  17. Adaptive security systems -- Combining expert systems with adaptive technologies

    Energy Technology Data Exchange (ETDEWEB)

    Argo, P.; Loveland, R.; Anderson, K. [and others

    1997-09-01

    The Adaptive Multisensor Integrated Security System (AMISS) uses a variety of computational intelligence techniques to reason from raw sensor data through an array of processing layers to arrive at an assessment for alarm/alert conditions based on human behavior within a secure facility. In this paper, the authors give an overview of the system and briefly describe some of the major components of the system. This system is currently under development and testing in a realistic facility setting.

  18. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  19. Feeding Our Immune System: Impact on Metabolism

    Directory of Open Access Journals (Sweden)

    Isabelle Wolowczuk

    2008-01-01

    Full Text Available Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy.

  20. Metal-Based Nanoparticles and the Immune System: Activation, Inflammation, and Potential Applications.

    Science.gov (United States)

    Luo, Yueh-Hsia; Chang, Louis W; Lin, Pinpin

    2015-01-01

    Nanomaterials, including metal-based nanoparticles, are used for various biological and medical applications. However, metals affect immune functions in many animal species including humans. Different physical and chemical properties induce different cellular responses, such as cellular uptake and intracellular biodistribution, leading to the different immune responses. The goals of this review are to summarize and discuss the innate and adaptive immune responses triggered by metal-based nanoparticles in a variety of immune system models.

  1. Intestinal Epithelial Cell Regulation of Adaptive Immune Dysfunction in Human Type 1 Diabetes

    Science.gov (United States)

    Graves, Christina L.; Li, Jian; LaPato, Melissa; Shapiro, Melanie R.; Glover, Sarah C.; Wallet, Mark A.; Wallet, Shannon M.

    2017-01-01

    Environmental factors contribute to the initiation, progression, and maintenance of type 1 diabetes (T1D), although a single environmental trigger for disease has not been identified. Studies have documented the contribution of immunity within the gastrointestinal tract (GI) to the expression of autoimmunity at distal sites. Intestinal epithelial cells (IECs) regulate local and systemic immunologic homeostasis through physical and biochemical interactions with innate and adaptive immune populations. We hypothesize that a loss in the tolerance-inducing nature of the GI tract occurs within T1D and is due to altered IECs’ innate immune function. As a first step in addressing this hypothesis, we contrasted the global immune microenvironment within the GI tract of individuals with T1D as well as evaluated the IEC-specific effects on adaptive immune cell phenotypes. The soluble and cellular immune microenvironment within the duodenum, the soluble mediator profile of primary IECs derived from the same duodenal tissues, and the effect of the primary IECs’ soluble mediator profile on T-cell expansion and polarization were evaluated. Higher levels of IL-17C and beta-defensin 2 (BD-2) mRNA in the T1D-duodenum were observed. Higher frequencies of type 1 innate lymphoid cells (ILC1) and CD8+CXCR3+ T-cells (Tc1) were also observed in T1D-duodenal tissues, concomitant with lower frequencies of type 3 ILC (ILC3) and CD8+CCR6+ T-cells (Tc17). Higher levels of proinflammatory mediators (IL-17C and BD-2) in the absence of similar changes in mediators associated with homeostasis (interleukin 10 and thymic stromal lymphopoietin) were also observed in T1D-derived primary IEC cultures. T1D-derived IEC culture supernatants induced more robust CD8+ T-cell proliferation along with enhanced polarization of Tc1 populations, at the expense of Tc17 polarization, as well as the expansion of CXCR3+CCR6+/− Tregs, indicative of a Th1-like and less regulatory phenotype. These data demonstrate

  2. Borrelia burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts

    Science.gov (United States)

    Tracy, Karen E.; Baumgarth, Nicole

    2017-01-01

    Borrelia burgdorferi sensu lato species complex is capable of establishing persistent infections in a wide variety of species, particularly rodents. Infection is asymptomatic or mild in most reservoir host species, indicating successful co-evolution of the pathogen with its natural hosts. However, infected humans and other incidental hosts can develop Lyme disease, a serious inflammatory syndrome characterized by tissue inflammation of joints, heart, muscles, skin, and CNS. Although B. burgdorferi infection induces both innate and adaptive immune responses, they are ultimately ineffective in clearing the infection from reservoir hosts, leading to bacterial persistence. Here, we review some mechanisms by which B. burgdorferi evades the immune system of the rodent host, focusing in particular on the effects of innate immune mechanisms and recent findings suggesting that T-dependent B cell responses are subverted during infection. A better understanding of the mechanisms causing persistence in rodents may help to increase our understanding of the pathogenesis of Lyme disease and ultimately aid in the development of therapies that support effective clearance of the bacterial infection by the host’s immune system. PMID:28265270

  3. Adaptive ophthalmologic system

    Science.gov (United States)

    Olivier, Scot S.; Thompson, Charles A.; Bauman, Brian J.; Jones, Steve M.; Gavel, Don T.; Awwal, Abdul A.; Eisenbies, Stephen K.; Haney, Steven J.

    2007-03-27

    A system for improving vision that can diagnose monochromatic aberrations within a subject's eyes, apply the wavefront correction, and then enable the patient to view the results of the correction. The system utilizes a laser for producing a beam of light; a corrector; a wavefront sensor; a testing unit; an optic device for directing the beam of light to the corrector, to the retina, from the retina to the wavefront sensor, and to the testing unit; and a computer operatively connected to the wavefront sensor and the corrector.

  4. Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

    Science.gov (United States)

    Olsen, Ingar; Taubman, Martin A.; Singhrao, Sim K.

    2016-01-01

    Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer’s disease (AD). Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host’s adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions. In periodontitis, this bacterium inhibits the synthesis of IL-2 and increases humoral responses. This reduces the inflammatory responses related to T- and B-cell activation, and subsequent IFN-γ secretion by a subset of T cells. The T cells further suppress upregulation of programmed cell death-1 (PD-1)-receptor on CD+cells and its ligand PD-L1 on CD11b+-subset of T cells. IL-2 downregulates genes regulated by immune response and induces a cytokine pattern in which the Th17 lineage is favored, thereby modulating the Th17/T-regulatory cell (Treg) imbalance. The suppression of IFN-γ-stimulated release of interferon-inducible protein-10 (IP-10) chemokine ligands [ITAC (CXCL11) and Mig (CXCL9)] by P. gingivalis capsular serotypes triggers distinct T cell responses and contributes to local immune evasion by release of its outer membrane vesicles. In atherosclerosis, P. gingivalis reduces Tregs, transforms growth factor beta-1 (TGFβ-1), and causes imbalance in the Th17 lineage of the Treg population. In AD, P. gingivalis may affect the blood–brain barrier permeability and inhibit local IFN-γ response by preventing entry of immune cells into the brain. The scarcity of adaptive immune cells in AD neuropathology implies P. gingivalis infection of the brain likely causing impaired clearance of insoluble amyloid and inducing immunosuppression. By the effective manipulation of the armory of

  5. Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ingar Olsen

    2016-11-01

    Full Text Available Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer’s disease (AD. Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host’s adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions. In periodontitis, this bacterium inhibits the synthesis of IL-2 and increases humoral responses. This reduces the inflammatory responses related to T- and B-cell activation, and subsequent IFN-γ secretion by a subset of T cells. The T cells further suppress upregulation of programmed cell death-1 (PD-1-receptor on CD+cells and its ligand PD-L1 on CD11b+-subset of T cells. IL-2 downregulates genes regulated by immune response and induces a cytokine pattern in which the Th17 lineage is favored, thereby modulating the Th17/T-regulatory cell (Treg imbalance. The suppression of IFN-γ-stimulated release of interferon-inducible protein-10 (IP-10 chemokine ligands [ITAC (CXCL11 and Mig (CXCL9] by P. gingivalis capsular serotypes triggers distinct T cell responses and contributes to local immune evasion by release of its outer membrane vesicles. In atherosclerosis, P. gingivalis reduces Tregs, transforms growth factor beta-1 (TGFβ-1, and causes imbalance in the Th17 lineage of the Treg population. In AD, P. gingivalis may affect the blood–brain barrier permeability and inhibit local IFN-γ response by preventing entry of immune cells into the brain. The scarcity of adaptive immune cells in AD neuropathology implies P. gingivalis infection of the brain likely causing impaired clearance of insoluble amyloid and inducing immunosuppression. By the effective manipulation of

  6. Adaptive Instructional Systems

    Science.gov (United States)

    2005-09-01

    planning stage, which used the infbrmation obtained from the Phase I research to develop a plan for utilizing the tecnolog in the proposed system. 1.4...signifying that the trainee should push it, would be an example of a visul prompt. Auditory learners arc likened to having a tape recorder inside...they pushed on it too hard, The student would als be ale to query the simulator wth vera commands like "R’peat instrumtions" or "Rotor pedal descrition

  7. [Olive oil, immune system and infection].

    Science.gov (United States)

    Puertollano, M A; Puertollano, E; Alvarez de Cienfuegos, G; de Pablo Martínez, Manuel Antonio

    2010-01-01

    Polyunsaturated fatty acids contribute to the suppression of immune system functions. For this reason, n-3 polyunsaturated fatty acids have been applied in the resolution of inflammatory disorders. Although the inhibition of several immune functions promotes beneficial effects on the human health, this state may lead to a significant reduction of immune protection against infectious microorganisms (viruses, bacteria, fungi and parasites). Nevertheless, less attention has been paid to the action of olive oil in immunonutrition. Olive oil, a main constituent of the Mediterranean diet, is capable of modulating several immune functions, but it does not reduce host immune resistance to infectious microorganisms. Based on these criteria, we corroborate that olive oil administration may exert beneficial effects on the human health and especially on immune system, because it contributes to the reduction of typical inflammatory activity observed in patients suffering from autoimmune disorders, but without exacerbating the susceptibility to pathogen agents. The administration of olive oil in lipid emulsions may exert beneficial effects on the health and particularly on the immune system of immunocompromised patients. Therefore, this fact acquires a crucial importance in clinical nutrition. This review contributes to clarify the interaction between the administration of diets containing olive oil and immune system, as well as to determine the effect promoted by this essential component of Mediterranean diet in the immunomodulation against an infectious agent.

  8. Interactions between the immune system and bone

    OpenAIRE

    2011-01-01

    The relationship between the immune system, estrogen deficiency and bone loss is an intriguing and, as yet, unexplained challenge of the past two decades. Here we summarize the evidence that links immune cells, inflammation, cytokine production and osteoclast formation and activity with particular regard to humans.

  9. In Vivo Synthesis of Cyclic-di-GMP Using a Recombinant Adenovirus Preferentially Improves Adaptive Immune Responses against Extracellular Antigens.

    Science.gov (United States)

    Alyaqoub, Fadel S; Aldhamen, Yasser A; Koestler, Benjamin J; Bruger, Eric L; Seregin, Sergey S; Pereira-Hicks, Cristiane; Godbehere, Sarah; Waters, Christopher M; Amalfitano, Andrea

    2016-02-15

    There is a compelling need for more effective vaccine adjuvants to augment induction of Ag-specific adaptive immune responses. Recent reports suggested the bacterial second messenger bis-(3'-5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP) acts as an innate immune system modulator. We recently incorporated a Vibrio cholerae diguanylate cyclase into an adenovirus vaccine, fostering production of c-di-GMP as well as proinflammatory responses in mice. In this study, we recombined a more potent diguanylate cyclase gene, VCA0848, into a nonreplicating adenovirus serotype 5 (AdVCA0848) that produces elevated amounts of c-di-GMP when expressed in mammalian cells in vivo. This novel platform further improved induction of type I IFN-β and activation of innate and adaptive immune cells early after administration into mice as compared with control vectors. Coadministration of the extracellular protein OVA and the AdVCA0848 adjuvant significantly improved OVA-specific T cell responses as detected by IFN-γ and IL-2 ELISPOT, while also improving OVA-specific humoral B cell adaptive responses. In addition, we found that coadministration of AdVCA0848 with another adenovirus serotype 5 vector expressing the HIV-1-derived Gag Ag or the Clostridium difficile-derived toxin B resulted in significant inhibitory effects on the induction of Gag and toxin B-specific adaptive immune responses. As a proof of principle, these data confirm that in vivo synthesis of c-di-GMP stimulates strong innate immune responses that correlate with enhanced adaptive immune responses to concomitantly administered extracellular Ag, which can be used as an adjuvant to heighten effective immune responses for protein-based vaccine platforms against microbial infections and cancers.

  10. The Immune System of HIV-Exposed Uninfected Infants

    Science.gov (United States)

    Abu-Raya, Bahaa; Kollmann, Tobias R.; Marchant, Arnaud; MacGillivray, Duncan M.

    2016-01-01

    Infants born to human immunodeficiency virus (HIV) infected women are HIV-exposed but the majority remains uninfected [i.e., HIV-exposed uninfected (HEU)]. HEU infants suffer greater morbidity and mortality from infections compared to HIV-unexposed (HU) peers. The reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. This review comprehensively summarizes the current literature investigating the adaptive and innate immune system of HEU infants. HEU infants have altered cell-mediated immunity, including impaired T-cell maturation with documented hypo- as well as hyper-responsiveness to T-cell activation. And although prevaccination vaccine-specific antibody levels are often lower in HEU than HU, most HEU infants mount adequate humoral immune response following primary vaccination with diphtheria toxoid, haemophilus influenzae type b, whole cell pertussis, measles, hepatitis B, tetanus toxoid, and pneumococcal conjugate vaccines. However, HEU infants are often found to have lower absolute neutrophil counts as compared to HU infants. On the other hand, an increase of innate immune cytokine production and expression of co-stimulatory markers has been noted in HEU infants, but this increase appears to be restricted to the first few weeks of life. The immune system of HEU children beyond infancy remains largely unexplored. PMID:27733852

  11. Activation and Exhaustion of Adaptive Immune Cells in Hepatitis B Infection.

    Science.gov (United States)

    Gogoi, Dimpu; Borkakoty, Biswajyoti; Biswas, Dipankar; Mahanta, Jagadish

    2015-09-01

    In hepatitis B virus (HBV) infection, the immune reaction is responsible for viral clearance and preventing their spread within the host. However, the immune system is dysfunctional in patients with chronic HBV infection, leading to an inadequate immune response against the virus. A major factor contributing to inefficient immune function is the phenomenon of immune exhaustion. Hence, understanding immune activation and exhaustion during HBV infection is important, as it would provide insight in developing immunotherapy to control chronic HBV infection. The aim of this review is to highlight the existing information on immune effector functions and immune exhaustion in response to HBV infection.

  12. GALECTIN-1 AND ITS ROLE IN DEVELOPMENT OF INNATE AND ADAPTIVE IMMUNITY

    Directory of Open Access Journals (Sweden)

    V. D. Yakushina

    2012-01-01

    Full Text Available Abstract. Galectins comprise a family of β-galactoside-binding animal proteins, which are defined bycommon homologies of their carbohydrate-recognizing domaine (affinity for poly-N-acetyllactosamine. These lectins bind to cell surface glycans and extracellular matrix, thus influencing various cellular events, including cell cycle, adhesion, migration, proliferation and apoptosis. Moreover, galectins are able to exert intracellular effects, and participate, e.g., in signal transduction, by interacting with other nuclear and cytoplasmic proteins. Galectin-1 is considered to play a special role in functional regulation of immune cell activity. Thus protein is a factor of immunocompetent cell cooperation, thus being able to modulate immune reactions. In this respect, galectin-1 is considered as a potential agent or a target for new methods aimed to correct pathological processes associated with imbalance of immune system. This article provides an overview of works devoted to a possible role of galectin-1 in development of typical features of innate and adaptive immunity.

  13. STSV2 as a Model Crenarchaeal Virus for Studying Virus-Host Interactions and CRISPR-Cas Adaptive Immunity

    DEFF Research Database (Denmark)

    León Sobrino, Carlos

    , the archaea harbour their own viruses, which constitute an extraordinarily diverse group with exotic morphologies and unique features. Prokaryotes possess a variety of defence mechanisms. The CRISPR-Cas adaptive immune system is of great importance for archaea –84% of them possess it, compared to 45...... generate immune memory by inserting in its own genome short invader-derived DNA fragments forming a database –the CRISPR locus. Little was known about this system until recent years, and the generation of immune memory has been the most elusive step. In this work, the interactions of the spindle......-shaped monocaudavirus STSV2 and its host Sulfolobus islandicus REY15A were studied. This interaction produced, after several days, de novo CRISPR adaptation – that is, without any previous memory that can act as a trigger. We employed transcriptome sequencing to characterise the long-term progression...

  14. Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection

    Science.gov (United States)

    Nguyen, Philip V; Kafka, Jessica K; Ferreira, Victor H; Roth, Kristy; Kaushic, Charu

    2014-01-01

    The male and female reproductive tracts are complex microenvironments that have diverse functional demands. The immune system in the reproductive tract has the demanding task of providing a protective environment for a fetal allograft while simultaneously conferring protection against potential pathogens. As such, it has evolved a unique set of adaptations, primarily under the influence of sex hormones, which make it distinct from other mucosal sites. Here, we discuss the various components of the immune system that are present in both the male and female reproductive tracts, including innate soluble factors and cells and humoral and cell-mediated adaptive immunity under homeostatic conditions. We review the evidence showing unique phenotypic and functional characteristics of immune cells and responses in the male and female reproductive tracts that exhibit compartmentalization from systemic immunity and discuss how these features are influenced by sex hormones. We also examine the interactions among the reproductive tract, sex hormones and immune responses following HIV-1 infection. An improved understanding of the unique characteristics of the male and female reproductive tracts will provide insights into improving clinical treatments of the immunological causes of infertility and the design of prophylactic interventions for the prevention of sexually transmitted infections. PMID:24976268

  15. Information Fusion in the Immune System

    CERN Document Server

    Twycross, Jamie

    2010-01-01

    Biologically-inspired methods such as evolutionary algorithms and neural networks are proving useful in the field of information fusion. Artificial Immune Systems (AISs) are a biologically-inspired approach which take inspiration from the biological immune system. Interestingly, recent research has show how AISs which use multi-level information sources as input data can be used to build effective algorithms for real time computer intrusion detection. This research is based on biological information fusion mechanisms used by the human immune system and as such might be of interest to the information fusion community. The aim of this paper is to present a summary of some of the biological information fusion mechanisms seen in the human immune system, and of how these mechanisms have been implemented as AISs

  16. Weakened Immune System and Adult Vaccination

    Science.gov (United States)

    ... for Healthcare Professionals Weakened Immune System and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... up to age 26 years Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  17. [Immune system evolution. (From cells to humans)].

    Science.gov (United States)

    Belek, A S

    1992-01-01

    The great variety of cells and molecules observed in the mammalian immune system can be explained by stepwise acquisition of them during phylogeny. Self/nonself discrimination and cell-mediated immunity have been present since the early stages of evolution. Although some inducible antimicrobial molecules have been demonstrated in invertebrates, immunoglobulins appear in vertebrates. T and B cell diversity, development of the lymphoid organs, MHC molecules, complement and cytokines are the characteristics that appear through the evolution of vertebrates. Further knowledge that will be obtained from phylogenetic studies will improve our understanding of the immune system of human.

  18. Adaptive, dynamic, and resilient systems

    CERN Document Server

    Suri, Niranjan

    2015-01-01

    As the complexity of today's networked computer systems grows, they become increasingly difficult to understand, predict, and control. Addressing these challenges requires new approaches to building these systems. Adaptive, Dynamic, and Resilient Systems supplies readers with various perspectives of the critical infrastructure that systems of networked computers rely on. It introduces the key issues, describes their interrelationships, and presents new research in support of these areas.The book presents the insights of a different group of international experts in each chapter. Reporting on r

  19. Noncoding RNA danger motifs bridge innate and adaptive immunity and are potent adjuvants for vaccination

    OpenAIRE

    Wang, Lilin; Smith, Dan; Bot, Simona; Dellamary, Luis; Bloom, Amy; Bot, Adrian

    2002-01-01

    The adaptive immune response is triggered by recognition of T and B cell epitopes and is influenced by “danger” motifs that act via innate immune receptors. This study shows that motifs associated with noncoding RNA are essential features in the immune response reminiscent of viral infection, mediating rapid induction of proinflammatory chemokine expression, recruitment and activation of antigen-presenting cells, modulation of regulatory cytokines, subsequent differentiation of Th1 cells, iso...

  20. Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

    Science.gov (United States)

    Contreras, R. A.; Djouad, F.

    2016-01-01

    Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studied in vitro and in vivo in experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression. PMID:27847522

  1. Adaptive Maternal Immune Deviations as a Ground For Autism Spectrum Disorders Development in Children

    Directory of Open Access Journals (Sweden)

    Poletaev Alexander B.

    2014-08-01

    Full Text Available Autism is a vexed problem today. Overall, there is a high frequency of birth children (1:80 – 1:150 with late diagnosed autism spectrum disorders (ASD and this trend is getting progressively stronger. The causes for the currently increased frequency of ASD and the pathogenesis of ASD are not fully understood yet. One of the most likely mechanisms inducing ASD may be a maternal immune imprinting. This phenomenon is based on transplacental translocation of maternal antibodies of IgG class and, as a consequence, on the epigenetic “tuning” of immune system of the fetus and child. This mechanism provides development of child’s anti-infection resistance before meeting with microorganisms, but it can be also a cause of inborn pathology including the ASD appearance. The quantitative changes in maternal blood serum autoantibodies depend on a specific microbial population, or are induced by environmental chemical pollutants in association with some individual features of the maternal metabolism. These immune changes are adaptive in most cases for the maternal organism, but can be pathogenic for the fetus in some cases. We discuss in the present paper the possibilities to predict the risk from abnormal development of nervous system in fetus and early diagnosis of ASD in high-risk group of children.

  2. Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

    Directory of Open Access Journals (Sweden)

    R. A. Contreras

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studied in vitro and in vivo in experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression.

  3. [Biotherapy targeting the immune system].

    Science.gov (United States)

    Frenzel, Laurent

    2015-01-01

    The use of monoclonal antibody targeted therapy has changed the management of several diseases, including in hematology and immunology. The panel of the present available biotherapies allows a specific action at various stages of the immune response. Indeed, some of these molecules can target the naive T cell at the immunological synapse or the way of TH1, TH17 and regulatory T cell. Others may be more specific for the B cell and immunoglobulin. Some will even be active on both B and T cells.

  4. Obesity leptin and the immune system

    Directory of Open Access Journals (Sweden)

    Padiotis. K.

    2011-04-01

    Full Text Available The increasing prevalence of obesity in developed and developing countries raises a major health concern due to the fact that obesity and nutrition are associated with impaired immune responses. Overconsumption of nutrients alters several functions of the immune defence mechanisms leading to severe infection and chronic diseases. The hormone leptin, known to regulate energy balance has been proved to activate several components of signalling pathways having thus immunoregulatory activity. The aim of this paper is to present the connections between obesity, immune system mechanisms and the role of the adipocyte hormone leptin

  5. Nanoparticles for nasal delivery of vaccines : monitoring adaptive immune responses

    NARCIS (Netherlands)

    Keijzer, C.

    2013-01-01

    The continuous emergence of new pathogens and growing drug resistance of microorganisms asks for innovative vaccination strategies. An alternative to conventional multiple injection vaccines is the nasal route of vaccine delivery. The immune response induced following nasal antigen delivery depends

  6. Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search.

    Directory of Open Access Journals (Sweden)

    G Matthew Fricke

    2016-03-01

    Full Text Available Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated. Previous work suggests that T cell motion in the lymph node is similar to a Brownian random walk, however, no detailed analysis has definitively shown whether T cell movement is consistent with Brownian motion. Here, we provide a precise description of T cell motility in lymph nodes and a computational model that demonstrates how motility impacts T cell search efficiency. We find that both Brownian and Lévy walks fail to capture the complexity of T cell motion. Instead, T cell movement is better described as a correlated random walk with a heavy-tailed distribution of step lengths. Using computer simulations, we identify three distinct factors that contribute to increasing T cell search efficiency: 1 a lognormal distribution of step lengths, 2 motion that is directionally persistent over short time scales, and 3 heterogeneity in movement patterns. Furthermore, we show that T cells move differently in specific frequently visited locations that we call "hotspots" within lymph nodes, suggesting that T cells change their movement in response to the lymph node environment. Our results show that like foraging animals, T cells adapt to environmental cues, suggesting that adaption is a fundamental feature of biological search.

  7. SANA - Security Analysis in Internet Traffic through Artificial Immune Systems

    CERN Document Server

    Hilker, Michael

    2008-01-01

    The Attacks done by Viruses, Worms, Hackers, etc. are a Network Security-Problem in many Organisations. Current Intrusion Detection Systems have significant Disadvantages, e.g. the need of plenty of Computational Power or the Local Installation. Therefore, we introduce a novel Framework for Network Security which is called SANA. SANA contains an artificial Immune System with artificial Cells which perform certain Tasks in order to to support existing systems to better secure the Network against Intrusions. The Advantages of SANA are that it is efficient, adaptive, autonomous, and massively-distributed. In this Article, we describe the Architecture of the artificial Immune System and the Functionality of the Components. We explain briefly the Implementation and discuss Results.

  8. Immune system stimulation by probiotic microorganisms.

    Science.gov (United States)

    Ashraf, Rabia; Shah, Nagendra P

    2014-01-01

    Probiotic organisms are claimed to offer several functional properties including stimulation of immune system. This review is presented to provide detailed informations about how probiotics stimulate our immune system. Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, Bifidobacterium animalis Bb-12, Lactobacillus johnsonii La1, Bifidobacterium lactis DR10, and Saccharomyces cerevisiae boulardii are the most investigated probiotic cultures for their immunomodulation properties. Probiotics can enhance nonspecific cellular immune response characterized by activation of macrophages, natural killer (NK) cells, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in strain-specific and dose-dependent manner. Mixture and type (gram-positive and gram-negative) of probiotic organisms may induce different cytokine responses. Supplementation of probiotic organisms in infancy could help prevent immune-mediated diseases in childhood, whereas their intervention in pregnancy could affect fetal immune parameters, such as cord blood interferon (IFN)-γ levels, transforming growth factor (TGF)-β1 levels, and breast milk immunoglobulin (Ig)A. Probiotics that can be delivered via fermented milk or yogurt could improve the gut mucosal immune system by increasing the number of IgA(+) cells and cytokine-producing cells in the effector site of the intestine.

  9. Circadian Clocks in the Immune System.

    Science.gov (United States)

    Labrecque, Nathalie; Cermakian, Nicolas

    2015-08-01

    The immune system is a complex set of physiological mechanisms whose general aim is to defend the organism against non-self-bodies, such as pathogens (bacteria, viruses, parasites), as well as cancer cells. Circadian rhythms are endogenous 24-h variations found in virtually all physiological processes. These circadian rhythms are generated by circadian clocks, located in most cell types, including cells of the immune system. This review presents an overview of the clocks in the immune system and of the circadian regulation of the function of immune cells. Most immune cells express circadian clock genes and present a wide array of genes expressed with a 24-h rhythm. This has profound impacts on cellular functions, including a daily rhythm in the synthesis and release of cytokines, chemokines and cytolytic factors, the daily gating of the response occurring through pattern recognition receptors, circadian rhythms of cellular functions such as phagocytosis, migration to inflamed or infected tissue, cytolytic activity, and proliferative response to antigens. Consequently, alterations of circadian rhythms (e.g., clock gene mutation in mice or environmental disruption similar to shift work) lead to disturbed immune responses. We discuss the implications of these data for human health and the areas that future research should aim to address.

  10. Immune regulation in gut and cord : opportunities for directing the immune system

    NARCIS (Netherlands)

    de Roock, S.

    2012-01-01

    The gut is an important organ for the immune system. Microbes and immune cells interact directly or via epithelial cells. Both TH17 and Treg cells mature in this environment. The composition of the microbiota has an important influence on the immune homeostasis. Influencing the immune system via the

  11. Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

    Science.gov (United States)

    Crucian, B. E.; Mehta, S.; Stowe, R. P.; Uchakin, P.; Quiriarte, H.; Pierson, D.; Sams, C. F.

    2011-01-01

    This poster presentation reviews a study that is designed to address immune system dysregulation and the risk to crewmembers in long duration exploration class missions. This study will address these objectives: (1) Determine the status of adaptive immunity physiological stress, viral immunity, latent herpesvirus reactivation in astronauts during 6 month missions to the International Space Station; (2) determine the clinical risk related to immune dysregulation for exploration class spaceflight; and (3) determine an appropriate monitoring strategy for spaceflight-associated immune dysfunction that could be used for the evaluation of countermeasures. The study anticipates 17 subjects, and for this presentation, (midpoint study data) 10 subjects are reviewed.

  12. Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus.

    Science.gov (United States)

    Wolf, Susanne A; Steiner, Barbara; Wengner, Antje; Lipp, Martin; Kammertoens, Thomas; Kempermann, Gerd

    2009-09-01

    To understand the link between peripheral immune activation and neuronal precursor biology, we investigated the effect of T-cell activation on adult hippocampal neurogenesis in female C57Bl/6 mice. A peripheral adaptive immune response triggered by adjuvant-induced rheumatoid arthritis (2 microg/microl methylated BSA) or staphylococcus enterotoxin B (EC(50) of 0.25 microg/ml per 20 g body weight) was associated with a transient increase in hippocampal precursor cell proliferation and neurogenesis as assessed by immunohistochemistry and confocal microscopy. Both treatments were paralleled by an increase in corticosterone levels in the hippocampus 1- to 2-fold over the physiological amount measured by quantitative radioimmunoassay. In contrast, intraperitoneal administration of the innate immune response activator lipopolysaccaride (EC(50) of 0.5 microg/ml per 20 g body weight) led to a chronic 5-fold increase of hippocampal glucocorticoid levels and a decrease of adult neurogenesis. In vitro exposure of murine neuronal progenitor cells to corticosterone triggered either cell death at high (1.5 nM) or proliferation at low (0.25 nM) concentrations. This effect could be blocked using a viral vector system expressing a transdomain of the glucocorticoid receptor. We suggest an evolutionary relevant communication route for the brain to respond to environmental stressors like inflammation mediated by glucocorticoid levels in the hippocampus.

  13. Focusing on Ciona intestinalis (Tunicata innate immune system. Evolutionary implications

    Directory of Open Access Journals (Sweden)

    N Parrinello

    2009-03-01

    Full Text Available Phylogenetic analyses based on molecular data provide compelling evidence that ascidians are of critical importance for studying chordate immune system evolution. The Ciona intestinalis draft genome sequence allows searches for phylogenetic relationships, gene cloning and expression of immunorelevant molecules. Acidians lack of the pivotal components of the vertebrate recombinatory adaptive immunity, i.e., MHC, TCRs and dimeric immunoglobulins. However, bioinformatic sequence analyses recognized genic elements indicating the essential features of the Ig superfamily and ancestor proto-MHC genes, suggesting a primitive pre-duplication and pre-recombination status. C. intestinalis genes for individuality in the absence of MHC could encode diverse molecular markers, including a wide panel of complement factors that could be responsible for self-nonself discrimination. Genome analysis reveals a number of innate immunity vertebrate-like genes which encode Toll-like and virus receptors, complement pathways components and receptors, CD94/NK-receptor-like, lectins, TNF, IL1-R, collagens. However, pure homology seeking for vertebrate-specific immunorelevant molecules is of limited value, and functional screening methods may be a more promising approach for tracing the immune system evolution. C. intestinalis, which displays acute and chronic inflammatory reactions, is a model organism for studying innate immunity genes expression and functions.

  14. Certification Considerations for Adaptive Systems

    Science.gov (United States)

    Bhattacharyya, Siddhartha; Cofer, Darren; Musliner, David J.; Mueller, Joseph; Engstrom, Eric

    2015-01-01

    Advanced capabilities planned for the next generation of aircraft, including those that will operate within the Next Generation Air Transportation System (NextGen), will necessarily include complex new algorithms and non-traditional software elements. These aircraft will likely incorporate adaptive control algorithms that will provide enhanced safety, autonomy, and robustness during adverse conditions. Unmanned aircraft will operate alongside manned aircraft in the National Airspace (NAS), with intelligent software performing the high-level decision-making functions normally performed by human pilots. Even human-piloted aircraft will necessarily include more autonomy. However, there are serious barriers to the deployment of new capabilities, especially for those based upon software including adaptive control (AC) and artificial intelligence (AI) algorithms. Current civil aviation certification processes are based on the idea that the correct behavior of a system must be completely specified and verified prior to operation. This report by Rockwell Collins and SIFT documents our comprehensive study of the state of the art in intelligent and adaptive algorithms for the civil aviation domain, categorizing the approaches used and identifying gaps and challenges associated with certification of each approach.

  15. The Immune System: the ultimate fractionated cyber-physical system

    OpenAIRE

    Carolyn Talcott

    2013-01-01

    In this little vision paper we analyze the human immune system from a computer science point of view with the aim of understanding the architecture and features that allow robust, effective behavior to emerge from local sensing and actions. We then recall the notion of fractionated cyber-physical systems, and compare and contrast this to the immune system. We conclude with some challenges.

  16. HIV-1 and hijacking of the host immune system: the current scenario.

    Science.gov (United States)

    Imran, Muhammad; Manzoor, Sobia; Saalim, Muhammad; Resham, Saleha; Ashraf, Javed; Javed, Aneela; Waqar, Ahmed Bilal

    2016-10-01

    Human immunodeficiency virus (HIV) infection is a major health burden across the world which leads to the development of acquired immune deficiency syndrome (AIDS). This review article discusses the prevalence of HIV, its major routes of transmission, natural immunity, and evasion from the host immune system. HIV is mostly prevalent in Sub-Saharan Africa and low income countries. It is mostly transmitted by sharing syringe needles, blood transfusion, and sexual routes. The host immune system is categorized into three main types; the innate, the adaptive, and the intrinsic immune system. Regarding the innate immune system against HIV, the key players are mucosal membrane, dendritic cells (DCs), complement system, interferon, and host Micro RNAs. The major components of the adaptive immune system exploited by HIV are T cells mainly CD4+ T cells and B cells. The intrinsic immune system confronted by HIV involves (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) APOBEC3G, tripartite motif 5-α (TRIM5a), terherin, and (SAM-domain HD-domain containing protein) SAMHD1. HIV-1 efficiently interacts with the host immune system, exploits the host machinery, successfully replicates and transmits from one cell to another. Further research is required to explore evasion strategies of HIV to develop novel therapeutic approaches against HIV.

  17. Reciprocity in microbiome and immune system interactions and its implications in disease and health.

    Science.gov (United States)

    Nikoopour, Enayat; Singh, Bhagirath

    2014-01-01

    Adaptation of the whole microbial normal flora residing in a host to its natural habitat over an evolutionary peroid has resulted in peaceful coexistence with mutual benefits for both microbiota and host in steady state. This symbiotic relationship between host and microbiota has a significant impact on shaping the immune response in the host to achieve an immune tolerance to microbiota but retaining the ability to respond to invading pathogens. Perturbation of this balance by manipulation of microbial communities in the host can lead to immune dysregulation and susceptibility to diseases. By studying the host in the absence of microbiota or with alteration of microbiota the complexity of microbial impact on the immune system can be resolved. Conversely, the study of microbiota in the absence of immune system factors can show how the immune system contributes to preservation of the host-microbiota balance. The absence of molecules involved in innate or adaptive immunity in knockout models can perturb the balance between host and microbiota further adding to more immune dysregulation. A better understanding of Microbiome-immune system interaction provides a new opportunity to identify biomarkers and drug targets. This will allow the development of new therapeutic agents for modulating the immune system to improve health with little or no toxicity. The study of interplay between host and microbiota has a promising role in the design of therapeutic interventions for immunopathological diseases arising from imbalanced host and microbiota interactions.

  18. Neural Control of the Immune System

    Science.gov (United States)

    Sundman, Eva; Olofsson, Peder S.

    2014-01-01

    Neural reflexes support homeostasis by modulating the function of organ systems. Recent advances in neuroscience and immunology have revealed that neural reflexes also regulate the immune system. Activation of the vagus nerve modulates leukocyte cytokine production and alleviates experimental shock and autoimmune disease, and recent data have…

  19. Artificial immune system applications in computer security

    CERN Document Server

    Tan, Ying

    2016-01-01

    This book provides state-of-the-art information on the use, design, and development of the Artificial Immune System (AIS) and AIS-based solutions to computer security issues. Artificial Immune System: Applications in Computer Security focuses on the technologies and applications of AIS in malware detection proposed in recent years by the Computational Intelligence Laboratory of Peking University (CIL@PKU). It offers a theoretical perspective as well as practical solutions for readers interested in AIS, machine learning, pattern recognition and computer security. The book begins by introducing the basic concepts, typical algorithms, important features, and some applications of AIS. The second chapter introduces malware and its detection methods, especially for immune-based malware detection approaches. Successive chapters present a variety of advanced detection approaches for malware, including Virus Detection System, K-Nearest Neighbour (KNN), RBF networ s, and Support Vector Machines (SVM), Danger theory, ...

  20. Standard of hygiene and immune adaptation in newborn infants

    NARCIS (Netherlands)

    Kallionpaa, Henna; Laajala, Essi; Oling, Viveka; Harkonen, Taina; Tillmann, Vallo; Dorshakova, Natalya V.; Ilonen, Jorma; Landesmaki, Harri; Knip, Mikael; Lahesmaa, Riitta; Koski, Katriina; Koski, Matti; Ryhanen, Samppa; Siljander, Heli; Hamalainen, Anu-Maaria; Ormisson, Anne; Peet, Aleksandr; Ulich, Valentina; Kuzmicheva, Elena; Mokurov, Sergei; Markova, Svettana; Pylova, Svetlana; Isakova, Marina; Shakurova, Elena; Petrov, Vladimir; Karapetyan, Tatyana; Varlamova, Tatyana; Ilonen, Jorma; Kiviniemi, Minna; Alnek, Kristi; Janson, Helis; Uibo, Raivo; Salum, Tiit; von Mutius, Erika; Weber, Juliane; Ahlfors, Helena; Moulder, Robert; Nieminen, Janne; Ruohtula, Terhi; Vaarala, Outi; Honkanen, Hanna; Hyoty, Heikki; Kondrashova, Anita; Oikarinen, Sami; Harmsen, Hermie J. M.; De Goffau, Marcus C.; Welling, Gjalt; Alahuhta, Kirsi; Korhonen, Tuuli; Virtanen, Suvi M.

    2014-01-01

    The prevalence of immune-mediated diseases, such as allergies and type 1 diabetes, is on the rise in the developed world. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood

  1. AID and APOBECs span the gap between innate and adaptive immunity

    Directory of Open Access Journals (Sweden)

    Arnaud eMoris

    2014-10-01

    Full Text Available The AID/APOBEC cytidine deaminases participate in a diversity of biological processes from the regulation of protein expression to embryonic development and host defenses. In its classical role, AID mutates germline-encoded sequences of B cell receptors, a key aspect of adaptive immunity, and APOBEC1, mutates apoprotein B pre-mRNA, yielding two isoforms important for cellular function and plasma lipid metabolism. Investigations over the last ten years have uncovered a role of the APOBEC superfamily in intrinsic immunity against viruses and innate immunity against viral infection by deamination and mutation of viral genomes. Further, discovery in the area of HIV infection revealed that the HIV viral infectivity factor (Vif protein interacted with APOBEC3G, targeting it for proteosomal degradation, overriding its antiviral function. More recently, our and others’ work have uncovered that the AID and APOBEC cytidine deaminase family members have an even more direct link between activity against viral infection and induction and shaping of adaptive immunity than previous thought, including that of antigen processing for cytotoxic T lymphocyte (CTL activity and natural killer (NK cell activation. Newly ascribed functions of these cytodine deaminases will be discussed, including their newly identified roles in adaptive immunity, epigenetic regulation, and cell differentiation. Herein this review we discuss AID and APOBEC cytodine deaminases as a link between innate and adaptive immunity uncovered by recent studies.

  2. A Hybrid Approach Towards Intrusion Detection Based on Artificial Immune System and Soft Computing

    CERN Document Server

    Sanyal, Sugata

    2012-01-01

    A number of works in the field of intrusion detection have been based on Artificial Immune System and Soft Computing. Artificial Immune System based approaches attempt to leverage the adaptability, error tolerance, self- monitoring and distributed nature of Human Immune Systems. Whereas Soft Computing based approaches are instrumental in developing fuzzy rule based systems for detecting intrusions. They are computationally intensive and apply machine learning (both supervised and unsupervised) techniques to detect intrusions in a given system. A combination of these two approaches could provide significant advantages for intrusion detection. In this paper we attempt to leverage the adaptability of Artificial Immune System and the computation intensive nature of Soft Computing to develop a system that can effectively detect intrusions in a given network.

  3. ERIS adaptive optics system design

    Science.gov (United States)

    Marchetti, Enrico; Le Louarn, Miska; Soenke, Christian; Fedrigo, Enrico; Madec, Pierre-Yves; Hubin, Norbert

    2012-07-01

    The Enhanced Resolution Imager and Spectrograph (ERIS) is the next-generation instrument planned for the Very Large Telescope (VLT) and the Adaptive Optics facility (AOF). It is an AO assisted instrument that will make use of the Deformable Secondary Mirror and the new Laser Guide Star Facility (4LGSF), and it is planned for the Cassegrain focus of the telescope UT4. The project is currently in its Phase A awaiting for approval to continue to the next phases. The Adaptive Optics system of ERIS will include two wavefront sensors (WFS) to maximize the coverage of the proposed sciences cases. The first is a high order 40x40 Pyramid WFS (PWFS) for on axis Natural Guide Star (NGS) observations. The second is a high order 40x40 Shack-Hartmann WFS for single Laser Guide Stars (LGS) observations. The PWFS, with appropriate sub-aperture binning, will serve also as low order NGS WFS in support to the LGS mode with a field of view patrolling capability of 2 arcmin diameter. Both WFSs will be equipped with the very low read-out noise CCD220 based camera developed for the AOF. The real-time reconstruction and control is provided by a SPARTA real-time platform adapted to support both WFS modes. In this paper we will present the ERIS AO system in all its main aspects: opto-mechanical design, real-time computer design, control and calibrations strategy. Particular emphasis will be given to the system performance obtained via dedicated numerical simulations.

  4. The ERIS adaptive optics system

    Science.gov (United States)

    Marchetti, Enrico; Fedrigo, Enrico; Le Louarn, Miska; Madec, Pierre-Yves; Soenke, Christian; Brast, Roland; Conzelmann, Ralf; Delabre, Bernard; Duchateau, Michel; Frank, Christoph; Klein, Barbara; Amico, Paola; Hubin, Norbert; Esposito, Simone; Antichi, Jacopo; Carbonaro, Luca; Puglisi, Alfio; Quirós-Pacheco, Fernando; Riccardi, Armando; Xompero, Marco

    2014-07-01

    The Enhanced Resolution Imager and Spectrograph (ERIS) is the new Adaptive Optics based instrument for ESO's VLT aiming at replacing NACO and SINFONI to form a single compact facility with AO fed imaging and integral field unit spectroscopic scientific channels. ERIS completes the instrument suite at the VLT adaptive telescope. In particular it is equipped with a versatile AO system that delivers up to 95% Strehl correction in K band for science observations up to 5 micron It comprises high order NGS and LGS correction enabling the observation from exoplanets to distant galaxies with a large sky coverage thanks to the coupling of the LGS WFS with the high sensitivity of its visible WFS and the capability to observe in dust embedded environment thanks to its IR low order WFS. ERIS will be installed at the Cassegrain focus of the VLT unit hosting the Adaptive Optics Facility (AOF). The wavefront correction is provided by the AOF deformable secondary mirror while the Laser Guide Star is provided by one of the four launch units of the 4 Laser Guide Star Facility for the AOF. The overall layout of the ERIS AO system is extremely compact and highly optimized: the SPIFFI spectrograph is fed directly by the Cassegrain focus and both the NIX's (IR imager) and SPIFFI's entrance windows work as visible/infrared dichroics. In this paper we describe the concept of the ERIS AO system in detail, starting from the requirements and going through the estimated performance, the opto-mechanical design and the Real-Time Computer design.

  5. Promiscuity and the primate immune system.

    Science.gov (United States)

    Nunn, C L; Gittleman, J L; Antonovics, J

    2000-11-10

    The behavioral and ecological factors involved in immune system evolution remain poorly explored. We present a phylogenetic analysis of white blood cell counts in primates to test three hypotheses related to disease risk: increases in risk are expected with group size or population density, exposure to soil-borne pathogens, and mating promiscuity. White blood cell counts were significantly greater in species where females have more mating partners, indicating that the risk of sexually transmitted disease is likely to be a major factor leading to systematic differences in the primate immune system.

  6. Multifunctional antimicrobial proteins and peptides: natural activators of immune systems.

    Science.gov (United States)

    Niyonsaba, François; Nagaoka, Isao; Ogawa, Hideoki; Okumura, Ko

    2009-01-01

    In addition to the physical barrier of the stratum corneum, cutaneous innate immunity also includes the release of various humoral mediators, such as cytokines and chemokines, recruitment and activation of phagocytes, and the production of antimicrobial proteins/peptides (AMPs). AMPs form an innate epithelial chemical shield, which provides a front-line component in innate immunity to inhibit microbial invasion; however, this might be an oversimplification of the diverse functions of these molecules. In fact, apart from exhibiting a broad spectrum of microbicidal properties, it is increasingly evident that AMPs display additional activities that are related to the stimulation and modulation of the cutaneous immune system. These diverse functions include chemoattraction and activation of immune and/or inflammatory cells, the production and release of cytokines and chemokines, acceleration of angiogenesis, promotion of wound healing, neutralization of harmful microbial products, and bridging of both innate and adaptive immunity. Thus, better understanding of the functions of AMPs in skin and identification of their signaling mechanisms may offer new strategies for the development of potential therapeutics for the treatment of infection- and/or inflammation-related skin diseases. Here, we briefly outline the structure, regulation of expression, and multifunctional roles of principal skin-derived AMPs.

  7. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases.

  8. Long-term effects of early life microbiota disturbance on adaptive immunity in laying hens

    NARCIS (Netherlands)

    Simon, K.; Verwoolde, M.B.; Zhang, J.; Smidt, H.; Vries Reilingh, De G.; Kemp, B.; Lammers, A.

    2016-01-01

    Due to an interplay between intestinal microbiota and immune system, disruption of intestinal microbiota composition during immune development may have consequences for immune responses later in life. The present study investigated the effects of antibiotic treatment in the first weeks of life on

  9. Towards Adaptive Spoken Dialog Systems

    CERN Document Server

    Schmitt, Alexander

    2013-01-01

    In Monitoring Adaptive Spoken Dialog Systems, authors Alexander Schmitt and Wolfgang Minker investigate statistical approaches that allow for recognition of negative dialog patterns in Spoken Dialog Systems (SDS). The presented stochastic methods allow a flexible, portable and  accurate use.  Beginning with the foundations of machine learning and pattern recognition, this monograph examines how frequently users show negative emotions in spoken dialog systems and develop novel approaches to speech-based emotion recognition using hybrid approach to model emotions. The authors make use of statistical methods based on acoustic, linguistic and contextual features to examine the relationship between the interaction flow and the occurrence of emotions using non-acted  recordings several thousand real users from commercial and non-commercial SDS. Additionally, the authors present novel statistical methods that spot problems within a dialog based on interaction patterns. The approaches enable future SDS to offer m...

  10. Genotype-by-environment interactions and adaptation to local temperature affect immunity and fecundity in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Brian P Lazzaro

    2008-03-01

    Full Text Available Natural populations of most organisms harbor substantial genetic variation for resistance to infection. The continued existence of such variation is unexpected under simple evolutionary models that either posit direct and continuous natural selection on the immune system or an evolved life history "balance" between immunity and other fitness traits in a constant environment. However, both local adaptation to heterogeneous environments and genotype-by-environment interactions can maintain genetic variation in a species. In this study, we test Drosophila melanogaster genotypes sampled from tropical Africa, temperate northeastern North America, and semi-tropical southeastern North America for resistance to bacterial infection and fecundity at three different environmental temperatures. Environmental temperature had absolute effects on all traits, but there were also marked genotype-by-environment interactions that may limit the global efficiency of natural selection on both traits. African flies performed more poorly than North American flies in both immunity and fecundity at the lowest temperature, but not at the higher temperatures, suggesting that the African population is maladapted to low temperature. In contrast, there was no evidence for clinal variation driven by thermal adaptation within North America for either trait. Resistance to infection and reproductive success were generally uncorrelated across genotypes, so this study finds no evidence for a fitness tradeoff between immunity and fecundity under the conditions tested. Both local adaptation to geographically heterogeneous environments and genotype-by-environment interactions may explain the persistence of genetic variation for resistance to infection in natural populations.

  11. Genotype-by-Environment Interactions and Adaptation to Local Temperature Affect Immunity and Fecundity in Drosophila melanogaster

    Science.gov (United States)

    Lazzaro, Brian P.; Flores, Heather A.; Lorigan, James G.; Yourth, Christopher P.

    2008-01-01

    Natural populations of most organisms harbor substantial genetic variation for resistance to infection. The continued existence of such variation is unexpected under simple evolutionary models that either posit direct and continuous natural selection on the immune system or an evolved life history “balance” between immunity and other fitness traits in a constant environment. However, both local adaptation to heterogeneous environments and genotype-by-environment interactions can maintain genetic variation in a species. In this study, we test Drosophila melanogaster genotypes sampled from tropical Africa, temperate northeastern North America, and semi-tropical southeastern North America for resistance to bacterial infection and fecundity at three different environmental temperatures. Environmental temperature had absolute effects on all traits, but there were also marked genotype-by-environment interactions that may limit the global efficiency of natural selection on both traits. African flies performed more poorly than North American flies in both immunity and fecundity at the lowest temperature, but not at the higher temperatures, suggesting that the African population is maladapted to low temperature. In contrast, there was no evidence for clinal variation driven by thermal adaptation within North America for either trait. Resistance to infection and reproductive success were generally uncorrelated across genotypes, so this study finds no evidence for a fitness tradeoff between immunity and fecundity under the conditions tested. Both local adaptation to geographically heterogeneous environments and genotype-by-environment interactions may explain the persistence of genetic variation for resistance to infection in natural populations. PMID:18369474

  12. Mobilizing forces -CD4~+ helper T cells script adaptive immunity

    Institute of Scientific and Technical Information of China (English)

    Frédérick Masson; Gabrielle T Belz

    2010-01-01

    Traditionally, CD4~+ T cells have been understood to play a key role in 'helping' CD8~+ T cells undergo efficient activation and proliferation in response to foreign pathogens. This has been thought to be directed primarily by CD4~+ T cell interactions with dendritic cells (DCs) [1, 2] that convert 'unlicenced' DCs into DCs capable of implementing a full blown immune response ('licenced' DCs).

  13. The immune system in the aging human.

    Science.gov (United States)

    Rymkiewicz, Paulina Dominika; Heng, Yi Xiong; Vasudev, Anusha; Larbi, Anis

    2012-09-01

    With the improvement of medical care and hygienic conditions, there has been a tremendous increment in human lifespan. However, many of the elderly (>65 years) display chronic illnesses, and a majority requires frequent and longer hospitalization. The robustness of the immune system to eliminate or control infections is often eroded with advancing age. Nevertheless, some elderly individuals do cope better than others. The origin of these inter-individual differences may come from genetic, lifestyle conditions (nutrition, socio-economic parameters), as well as the type, number and recurrence of pathogens encountered during life. The theory we are supporting is that chronic infections, through life, will induce profound changes in the immune system probably due to unbalanced inflammatory profiles. Persistent viruses such a cytomegalovirus are not eliminated and are a driven force to immune exhaustion. Because of their age, elderly individuals may have seen more of these chronic stimulators and have experienced more reactivation episodes ultimately leading to shrinkage of their repertoire and overall immune robustness. This review integrates updates on immunity with advancing age and its impact on associated clinical conditions.

  14. Neuroendocrine-immune systems response to environmental stressors in the cephalopod Octopus vulgaris

    Directory of Open Access Journals (Sweden)

    Anna Di Cosmo

    2016-09-01

    Full Text Available Under a continuous changing environment, animals are challenged with stresses and stimuli which demanding adaptation at behavioral and physiological levels. The adaptation strategies are finely regulated by animal nervous, endocrine and immune systems. Although it’s been established by now the usage of integrative approach to the study the endocrine and nervous systems (neuroendocrine, yet our understanding of how they cooperate with the immune system remains far from complete. The possible role that immune system plays as a component of the network has only been recognized recently. Octopus vulgaris is an important member of cephalopods and is considered as a model species, with considerable information about the neuroendocrine and immune systems. In the current review, we anticipate to shed light on the complexity and cross talk among the three systems and how they cooperate in setting physiological response to stresses-stimuli in Octopus vulgaris as a target species and primary example.

  15. Neuroendocrine–Immune Systems Response to Environmental Stressors in the Cephalopod Octopus vulgaris

    Science.gov (United States)

    Di Cosmo, Anna; Polese, Gianluca

    2016-01-01

    Under a continuous changing environment, animals are challenged with stresses and stimuli which demanding adaptation at behavioral and physiological levels. The adaptation strategies are finely regulated by animal nervous, endocrine, and immune systems. Although it's been established by now the usage of integrative approach to the study the endocrine and nervous systems (neuroendocrine), yet our understanding of how they cooperate with the immune system remains far from complete. The possible role that immune system plays as a component of the network has only been recognized recently. Octopus vulgaris is an important member of cephalopods and is considered as a model species, with considerable information about the neuroendocrine and immune systems. In the current review, we anticipate to shed light on the complexity and cross talk among the three systems and how they cooperate in setting physiological response to stresses-stimuli in O. vulgaris as a target species and primary example. PMID:27733834

  16. Innate and adaptive immunity in bacteria: mechanisms of programmed genetic variation to fight bacteriophages.

    Science.gov (United States)

    Bikard, David; Marraffini, Luciano A

    2012-02-01

    Bacteria are constantly challenged by bacteriophages (viruses that infect bacteria), the most abundant microorganism on earth. Bacteria have evolved a variety of immunity mechanisms to resist bacteriophage infection. In response, bacteriophages can evolve counter-resistance mechanisms and launch a 'virus versus host' evolutionary arms race. In this context, rapid evolution is fundamental for the survival of the bacterial cell. Programmed genetic variation mechanisms at loci involved in immunity against bacteriophages generate diversity at a much faster rate than random point mutation and enable bacteria to quickly adapt and repel infection. Diversity-generating retroelements (DGRs) and phase variation mechanisms enhance the generic (innate) immune response against bacteriophages. On the other hand, the integration of small bacteriophage sequences in CRISPR loci provide bacteria with a virus-specific and sequence-specific adaptive immune response. Therefore, although using different molecular mechanisms, both prokaryotes and higher organisms rely on programmed genetic variation to increase genetic diversity and fight rapidly evolving infectious agents.

  17. Obesity, inflammation and the immune system.

    Science.gov (United States)

    de Heredia, Fátima Pérez; Gómez-Martínez, Sonia; Marcos, Ascensión

    2012-05-01

    Obesity shares with most chronic diseases the presence of an inflammatory component, which accounts for the development of metabolic disease and other associated health alterations. This inflammatory state is reflected in increased circulating levels of pro-inflammatory proteins, and it occurs not only in adults but also in adolescents and children. The chronic inflammatory response has its origin in the links existing between the adipose tissue and the immune system. Obesity, like other states of malnutrition, is known to impair the immune function, altering leucocyte counts as well as cell-mediated immune responses. In addition, evidence has arisen that an altered immune function contributes to the pathogenesis of obesity. This review attempts to briefly comment on the various plausible explanations that have been proposed for the phenomenon: (1) the obesity-associated increase in the production of leptin (pro-inflammatory) and the reduction in adiponectin (anti-inflammatory) seem to affect the activation of immune cells; (2) NEFA can induce inflammation through various mechanisms (such as modulation of adipokine production or activation of Toll-like receptors); (3) nutrient excess and adipocyte expansion trigger endoplasmic reticulum stress; and (4) hypoxia occurring in hypertrophied adipose tissue stimulates the expression of inflammatory genes and activates immune cells. Interestingly, data suggest a greater impact of visceral adipose tissue and central obesity, rather than total body fat, on the inflammatory process. In summary, there is a positive feedback loop between local inflammation in adipose tissue and altered immune response in obesity, both contributing to the development of related metabolic complications.

  18. Hippocampal adult neurogenesis: Does the immune system matter?

    Science.gov (United States)

    de Miranda, Aline Silva; Zhang, Cun-Jin; Katsumoto, Atsuko; Teixeira, Antônio Lúcio

    2017-01-15

    Adult hippocampal neurogenesis involves proliferation, survival, differentiation and integration of newborn neurons into pre-existing neuronal networks. Although its functional significance in the central nervous system (CNS) has not comprehensively elucidated, adult neurogenesis has been attributed a role in cognition, learning and memory. There is a growing body of evidence that CNS resident as well as peripheral immune cells participate in regulating hippocampal adult neurogenesis. Microglial cells are closely associated with neural stem/progenitor cell (NSPC) in the neurogenic niche engaged in a bidirectional communication with neurons, which may be important for adult neurogenesis. Microglial and neuronal crosstalk is mediated in part by CX3CL1/CX3CR1 signaling and a disruption in this pathway has been associated with impaired neurogenesis. It has been also reported that microglial neuroprotective or neurotoxic effects in adult neurogenesis occur in a context-dependent manner. Apart from microglia other brain resident and peripheral immune cells including pericytes, perivascular macrophages, mast cells and T-cells also modulate this phenomenon. It is worth mentioning that under some physiological circumstances such as normal aging there is a significant decrease in hippocampal neurogenesis. A role for innate and adaptive immune system in adult neurogenesis has been also reported during aging. Here, we review the current evidence regarding neuro-immune interactions in the regulation of neurogenesis under distinct conditions, including aging.

  19. Query Adaptive Image Retrieval System

    Directory of Open Access Journals (Sweden)

    Amruta Dubewar

    2014-03-01

    Full Text Available Images play a crucial role in various fields such as art gallery, medical, journalism and entertainment. Increasing use of image acquisition and data storage technologies have enabled the creation of large database. So, it is necessary to develop appropriate information management system to efficiently manage these collections and needed a system to retrieve required images from these collections. This paper proposed query adaptive image retrieval system (QAIRS to retrieve images similar to the query image specified by user from database. The goal of this system is to support image retrieval based on content properties such as colour and texture, usually encoded into feature vectors. In this system, colour feature extracted by various techniques such as colour moment, colour histogram and autocorrelogram and texture feature extracted by using gabor wavelet. Hashing technique is used to embed high dimensional image features into hamming space, where search can be performed by hamming distance of compact hash codes. Depending upon minimum hamming distance it returns the similar image to query image.

  20. Neutrophil-Mediated Regulation of Innate and Adaptive Immunity: The Role of Myeloperoxidase

    Directory of Open Access Journals (Sweden)

    Dragana Odobasic

    2016-01-01

    Full Text Available Neutrophils are no longer seen as leukocytes with a sole function of being the essential first responders in the removal of pathogens at sites of infection. Being armed with numerous pro- and anti-inflammatory mediators, these phagocytes can also contribute to the development of various autoimmune diseases and can positively or negatively regulate the generation of adaptive immune responses. In this review, we will discuss how myeloperoxidase, the most abundant neutrophil granule protein, plays a key role in the various functions of neutrophils in innate and adaptive immunity.

  1. Chasing the recipe for a pro-regenerative immune system

    Science.gov (United States)

    Pinto, Alexander R.; Rosenthal, Nadia A.

    2017-01-01

    Identification of the key ingredients and essential processes required to achieve perfect tissue regeneration in humans has so far remained elusive. Injury in vertebrates induces an obligatory wound response that will precede or overlap any regeneration specific program or scarring outcome. This process shapes the cellular and molecular landscape of the tissue, influencing the success of endogenous repair pathways or for potential clinical intervention. The involvement of immune cells is also required for aspects of development extending beyond the initial inflammatory phase of wounding. It has now become clear from amphibian, fish and mammalian models of tissue injury that the type of immune response and the profile of immune cells attending the site of injury can act as the gatekeepers that determine wound repair quality. The heterogeneity among innate and adaptive immune cell populations, along with the developmental origin of these cells, form key ingredients affecting the potential for downstream repair and the suppression of fibrosis. Cell-to-cell interactions between immune cells, such as macrophages and T cells, with stem cells and mesenchymal cells are critically important for shaping this process and these exchanges, are in turn influenced by the type of injury, tissue location and developmental stage of the organism. Developmentally, mouse cardiac regeneration is restricted to early stages of postnatal life where the balance of innate to adaptive immune cells may be poised towards regeneration. In the injured adult mouse liver, specific macrophage subsets improve repair while other bone marrow derived cells can exacerbate injury. Other studies using genetically diverse mice have shown enhanced regeneration in certain strains, restricted to specific tissues. This enhanced repair is linked with expression of genes such as Insulin-like Growth Factor- 1 (IGF-1) and activin (Act 1), that both play important roles in shaping the immune system. Immune cells are

  2. [Is the immune system our sixth sense? Relation between the immune and neuroendocrine systems].

    Science.gov (United States)

    Ferencík, M; Stvrtinová, V

    1997-04-01

    There is an overwhelming evidence that cytokines, peptide hormones and neurotransmitters, as well as their receptors, are present in the brain, endocrine and immune systems. The structure and pattern of synthesis of these peptides by leukocytes appear similar to those synthesized in the neuroendocrine system, although some differences exist. Once secreted, these peptide hormones may function as endogenous regulators inside of the each system and also in bidirectional communication between the immune and neuroendocrine systems. Such communication suggest an immunoregulatory role for the brain and a sensory function for the immune system which may sense stimuli that are not recognized by the central and peripheral nervous systems (noncognitive stimuli). The plasma hormone concentrations contributed by lymphocytes usually do not reach the levels required when the pituitary gland is the source, but because immune cells are mobile, they have the potential to deposit the hormone locally at the target site. Several immunoregulatory cytokines, including IL-1, IL-2, IL-6, IFN-gama and TNF are produced not only in the immune system but in the neuroendocrine system as well. They have profound effects on neuroendocrine functions especially on hypothalamic pituitary axes. Neuroendocrine influences that modulate the immune function mainly include mental and physical stress. It can reduce the resistance of organism to infectious diseases and malignancies by compromising the immune system directly or indirectly. The brain is not an immunologically privileged site and therefore may become the target of immunologic attacks resulting in neuroimmunological diseases with an autoimmune component. The impact of psychological and psychosocial factors on the immune system is studied by psychoneuroimmunology whereas neuroendocrine immunology is generally interested in the interactions between the immune and neuroendocrine systems under physiological and pathological conditions. The

  3. The immune system and skin cancer.

    Science.gov (United States)

    Yu, Sherry H; Bordeaux, Jeremy S; Baron, Elma D

    2014-01-01

    Carcinogenesis involves multiple mechanisms that disturb genomic integrity and encourage abnormal proliferation. The immune system plays an integral role in maintaining homeostasis and these mechanisms may arrest or enhance dysplasia. There exists a large body of evidence from organ transplantation literature supporting the significance of the immune suppression in the development of skin cancer. Nonmelanoma skin cancers are the most frequent neoplasms after organ transplantation, with organ transplant recipients having a 65-fold increase in squamous cell carcinoma incidence and 10-fold increase in basal cell carcinoma incidence. Similarly, UV-radiation (UVR) induced immunosuppression is correlated with the development of cutaneous malignancies in a dose-dependent manner. This was first shown several decades ago by Margaret Kripke, when transplanted tumors were rejected in mice with competent immune systems, but grew unchecked in immunosuppressed specimens. After UV exposure, chromophores initiate a cascade that leads to immunosuppression via derangement of Langerhans cells' antigen-presenting capacity. UV-irradiated Langerhans cells present antigens to Th2 cells, but fail to stimulate Th1 cells. A subset of T regulatory cells, specific for the antigen encountered after UVR, is also stimulated to proliferate. In general UV irradiation leads to a greater number of T regulatory cells and fewer effector T cells in the skin, shiftingthe balance from T-cell-mediated immunity to immunosuppression. These regulatory cells have the phenotype CD4+, CD25+, Foxp3+, CTLA-4+. These and many other changes in local immunity lead to a suppressed immune state, which allow for skin cancer development.

  4. Dendritic Cells under Hypoxia: How Oxygen Shortage Affects the Linkage between Innate and Adaptive Immunity.

    Science.gov (United States)

    Winning, Sandra; Fandrey, Joachim

    2016-01-01

    Dendritic cells (DCs) are considered as one of the main regulators of immune responses. They collect antigens, process them, and present typical antigenic structures to lymphocytes, thereby inducing an adaptive immune response. All these processes take place under conditions of oxygen shortage (hypoxia) which is often not considered in experimental settings. This review highlights how deeply hypoxia modulates human as well as mouse immature and mature dendritic cell functions. It tries to link in vitro results to actual in vivo studies and outlines how hypoxia-mediated shaping of dendritic cells affects the activation of (innate) immunity.

  5. Dendritic Cells under Hypoxia: How Oxygen Shortage Affects the Linkage between Innate and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Sandra Winning

    2016-01-01

    Full Text Available Dendritic cells (DCs are considered as one of the main regulators of immune responses. They collect antigens, process them, and present typical antigenic structures to lymphocytes, thereby inducing an adaptive immune response. All these processes take place under conditions of oxygen shortage (hypoxia which is often not considered in experimental settings. This review highlights how deeply hypoxia modulates human as well as mouse immature and mature dendritic cell functions. It tries to link in vitro results to actual in vivo studies and outlines how hypoxia-mediated shaping of dendritic cells affects the activation of (innate immunity.

  6. The immune system as the sixth sense.

    Science.gov (United States)

    Blalock, J E

    2005-02-01

    One of the truly remarkable discoveries in modern biology is the finding that the nervous system and immune system use a common chemical language for intra- and inter-system communication. This review will discuss some of the pivotal results that deciphered this chemical language. Specifically the nervous and immune systems produce a common set of peptide and nonpeptide neurotransmitters and cytokines that act on a common repertoire of receptors in the two systems. The paper will also review more recent studies that have delineated hardwired and humoral pathways for such bidirectional communication. This is discussed in the context of the idea that the sharing of ligands and receptors allows the immune system to serve as the sixth sense that notifies the nervous system of the presence of entities, such as viruses and bacteria, that are imperceptible to the classic senses. Lastly, this review will suggest ways to apply the newfound knowledge of the sixth sense to understand a placebo effect and to treat human disease.

  7. Delineating the deranged immune system in the antiphospholipid syndrome.

    Science.gov (United States)

    van den Hoogen, Lucas L; van Roon, Joël A G; Radstake, Timothy R D J; Fritsch-Stork, Ruth D E; Derksen, Ronald H W M

    2016-01-01

    The antiphospholipid syndrome (APS) is a systemic autoimmune disease that is characterized serologically by the presence of antiphospholipid antibodies (aPL) and clinically by vascular thrombosis and obstetric complications. The protein β2 glycoprotein I (β2GPI) is identified as the most important autoantigen in this syndrome. Activation of endothelial cells, thrombocytes and placental tissue by anti-β2GPI antibodies relates to the clinical manifestations of APS. This review describes genetic and environmental factors in relation to APS and summarizes the current knowledge on abnormalities in components of both the innate and adaptive immune system in APS. The role of dendritic cells, T-cells, B-cells, monocytes, neutrophils and NK-cells as well as the complement system in APS are discussed. Several gaps in our knowledge on the pathophysiology of APS are identified and a plea is made for future extensive immune cell profiling by a systems medicine approach in order to better unravel the pathogenesis of APS, to gain more insight in the role of the immune system in APS as well as having the potential to reveal biomarkers or novel therapeutic targets.

  8. Framework of Combined Adaptive and Non-adaptive Attitude Control System for a Helicopter Experimental System

    Institute of Scientific and Technical Information of China (English)

    Akira Inoue; Ming-Cong Deng

    2006-01-01

    This paper presents a framework of a combined adaptive and non-adaptive attitude control system for a helicopter experimental system. The design method is based on a combination of adaptive nonlinear control and non-adaptive nonlinear control. With regard to detailed attitude control system design, two schemes are shown for different application cases.

  9. TNF-alpha blockade by a dimeric TNF type I receptor molecule selectively inhibits adaptive immune responses.

    Science.gov (United States)

    Colagiovanni, D B; Suniga, M A; Frazier, J L; Edwards, C K; Fleshner, M; McCay, J A; White, K L; Shopp, G M

    2000-11-01

    Tumor necrosis factor-alpha (TNF-alpha) is a mediator of severe inflammatory processes, including rheumatoid arthritis. Suppression of TNF with a soluble type I or type II receptor molecule (TNF-RI or TNF-RII) has the potential to decrease cytokine levels and modulate inflammatory diseases in humans. However, it has recently been reported that treatment of mice with a TNF-RI:Fc immunoadhesin protein augmented Gram positive infections and subsequent mortality. To determine if TNF-alpha blockade with soluble TNF-alpha receptors might alter immune system function, assays were assessed in rodents treated with a dimeric form of the p55 TNF-RI, Tumor Necrosis Factor-binding protein (TNFbp). Administration of TNFbp resulted in suppression of primary and secondary IgG antibody responses and cell-mediated immune function. No treatment-related differences were detected in immune-enhancing assays or non-specific immune function parameters. Bacterial host resistance assays with Listeria monocytogenes, Staphylococcus aureus or Escherichia coli showed an increase in tissue colony counts only with L. monocytogenes challenged animals following TNFbp administration. These results suggest that TNFbp has the capacity to inhibit adaptive immune function in experimental animal models. Studies suggest that while reducing TNF-alpha is important in controlling cytokine-dependent disease states, maintenance of a threshold level may be critical for normal immune function.

  10. Influence of phthalates on in vitro innate and adaptive immune responses.

    Directory of Open Access Journals (Sweden)

    Juliana Frohnert Hansen

    Full Text Available Phthalates are a group of endocrine disrupting chemicals, suspected to influence the immune system. The aim of this study was to investigate the influence of phthalates on cytokine secretion from human peripheral blood mononuclear cells. Escherichia coli lipopolysaccharide and phytohemagglutinin-P were used for stimulation of monocytes/macrophages and T cells, respectively. Cells were exposed for 20 to 22 hours to either di-ethyl, di-n-butyl or mono-n-butyl phthalate at two different concentrations. Both diesters were metabolised to their respective monoester and influenced cytokine secretion from both monocytes/macrophages and T cells in a similar pattern: the secretion of interleukin (IL-6, IL-10 and the chemokine CXCL8 by monocytes/macrophages was enhanced, while tumour necrosis factor (TNF-α secretion by monocytes/macrophages was impaired, as was the secretion of IL-2 and IL-4, TNF-α and interferon-γ by T cells. The investigated phthalate monoester also influenced cytokine secretion from monocytes/macrophages similar to that of the diesters. In T cells, however, the effect of the monoester was different compared to the diesters. The influence of the phthalates on the cytokine secretion did not seem to be a result of cell death. Thus, results indicate that both human innate and adaptive immunity is influenced in vitro by phthalates, and that phthalates therefore may affect cell differentiation and regenerative and inflammatory processes in vivo.

  11. Influence of phthalates on in vitro innate and adaptive immune responses.

    Science.gov (United States)

    Hansen, Juliana Frohnert; Nielsen, Claus Henrik; Brorson, Marianne Møller; Frederiksen, Hanne; Hartoft-Nielsen, Marie-Louise; Rasmussen, Åse Krogh; Bendtzen, Klaus; Feldt-Rasmussen, Ulla

    2015-01-01

    Phthalates are a group of endocrine disrupting chemicals, suspected to influence the immune system. The aim of this study was to investigate the influence of phthalates on cytokine secretion from human peripheral blood mononuclear cells. Escherichia coli lipopolysaccharide and phytohemagglutinin-P were used for stimulation of monocytes/macrophages and T cells, respectively. Cells were exposed for 20 to 22 hours to either di-ethyl, di-n-butyl or mono-n-butyl phthalate at two different concentrations. Both diesters were metabolised to their respective monoester and influenced cytokine secretion from both monocytes/macrophages and T cells in a similar pattern: the secretion of interleukin (IL)-6, IL-10 and the chemokine CXCL8 by monocytes/macrophages was enhanced, while tumour necrosis factor (TNF)-α secretion by monocytes/macrophages was impaired, as was the secretion of IL-2 and IL-4, TNF-α and interferon-γ by T cells. The investigated phthalate monoester also influenced cytokine secretion from monocytes/macrophages similar to that of the diesters. In T cells, however, the effect of the monoester was different compared to the diesters. The influence of the phthalates on the cytokine secretion did not seem to be a result of cell death. Thus, results indicate that both human innate and adaptive immunity is influenced in vitro by phthalates, and that phthalates therefore may affect cell differentiation and regenerative and inflammatory processes in vivo.

  12. Surname Inherited Algorithm Research Based on Artificial Immune System

    Directory of Open Access Journals (Sweden)

    Jing Xie

    2013-06-01

    Full Text Available To keep the diversity of antibodies in artificial immune system evolution process, this paper puts forward a kind of increase simulation surname inheritance algorithm based on the clonal selection algorithm, and identification and forecast the Vibration Data about CA6140 horizontal  lathe machining slender shaft workpiece prone . The results show that the algorithm has the characteristics of flexible application, strong adaptability, an effective approach to improve efficiency of the algorithm, a good performance of global searching and broad application prospect.

  13. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children.

    Science.gov (United States)

    Strömbeck, Anna; Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Adlerberth, Ingegerd; Wold, Agnes E; Rudin, Anna

    2016-04-01

    There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles-mumps-rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3-5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination.

  14. The Immune System: the ultimate fractionated cyber-physical system

    Directory of Open Access Journals (Sweden)

    Carolyn Talcott

    2013-09-01

    Full Text Available In this little vision paper we analyze the human immune system from a computer science point of view with the aim of understanding the architecture and features that allow robust, effective behavior to emerge from local sensing and actions. We then recall the notion of fractionated cyber-physical systems, and compare and contrast this to the immune system. We conclude with some challenges.

  15. Immune system alterations in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Hovden, H; Frederiksen, J L; Pedersen, S W

    2013-01-01

    cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other...... give more insight into the disease. Markers from the classical complement pathway are elevated where its initiator C1q appears to derive primarily from motor neurons. Activated microglia and astrocytes are found in close proximity to dying motor neurons. Their activation status and proliferation......Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple...

  16. The Host Immune Response to Streptococcus pneumoniae: Bridging Innate and Adaptive Immunity

    Science.gov (United States)

    2006-07-06

    nonspecific manner and in the absence of germinal center formation, which is consistent with the observed lack of PC-specific memory (Wu et al., 2002...like receptor 9 by DNA from different bacterial species. Infect. Immun. 74: 940-946. Dasari, P., Nicholson, I.C., Hodge, G., Dandie, G.W., and Zola

  17. Dietary influence on pain via the immune system.

    Science.gov (United States)

    Totsch, Stacie K; Waite, Megan E; Sorge, Robert E

    2015-01-01

    Obesity rates are approaching epidemic proportions and are a significant factor in annual health care costs. In addition to cardiovascular comorbidities, the presence of diabetes and/or chronic pain is extremely high in this population of individuals. It is now well accepted that the cells of the innate (and adaptive) immune system mediate both acute and chronic pain through release of cytokines into the system. In this chapter, we outline the ways in which poor food choices and elevated adipose tissue (body fat) are likely to activate the immune system and increase inflammation and pain. In addition, we explore the ways in which a variety of foods (e.g., broccoli, ginger, grapes, and fish oils) may have anti-inflammatory effects via their direct action on cells in the immune system and on the subsequent release of inflammatory cytokines. Some foods (green tea, ginger, and broccoli) have been found to antagonize specific cell surface receptors, whereas others (grapes, soy proteins, tomatoes and ginseng) appear to reduce nuclear translocation of the major transcription factor NFκB, thereby reducing production of inflammatory cytokines. Together, we provide data in support of the use of diet interventions to reduce pain and inflammation in patients suffering from chronic pain or other inflammation-mediated disorders.

  18. An Immunized Aircraft Maneuver Selection System

    Science.gov (United States)

    Karr, Charles L.

    2003-01-01

    The objective of this project, as stated in the original proposal, was to develop an immunized aircraft maneuver selection (IAMS) system. The IAMS system was to be composed of computational and informational building blocks that resemble structures in natural immune systems. The ultimate goal of the project was to develop a software package that could be flight tested on aircraft models. This report describes the work performed in the first year of what was to have been a two year project. This report also describes efforts that would have been made in the final year to have completed the project, had it been continued for the final year. After introductory material is provided in Section 2, the end-of-year-one status of the effort is discussed in Section 3. The remainder of the report provides an accounting of first year efforts. Section 4 provides background information on natural immune systems while Section 5 describes a generic ar&itecture developed for use in the IAMS. Section 6 describes the application of the architecture to a system identification problem. Finally, Section 7 describes steps necessary for completing the project.

  19. Archaeal CRISPR-based immune systems

    DEFF Research Database (Denmark)

    Garrett, Roger A; Vestergaard, Gisle Alberg; Shah, Shiraz Ali

    2011-01-01

    CRISPR (clustered regularly interspaced short palindromic repeats)-based immune systems are essentially modular with three primary functions: the excision and integration of new spacers, the processing of CRISPR transcripts to yield mature CRISPR RNAs (crRNAs), and the targeting and cleavage...... of foreign nucleic acid. The primary target appears to be the DNA of foreign genetic elements, but the CRISPR/Cmr system that is widespread amongst archaea also specifically targets and cleaves RNA in vitro. The archaeal CRISPR systems tend to be both diverse and complex. Here we examine evidence...... of CRISPR loci and the evidence for intergenomic exchange of CRISPR systems....

  20. Age-Dependent Differences in Systemic and Cell-Autonomous Immunity to L. monocytogenes

    Directory of Open Access Journals (Sweden)

    Ashley M. Sherrid

    2013-01-01

    Full Text Available Host defense against infection can broadly be categorized into systemic immunity and cell-autonomous immunity. Systemic immunity is crucial for all multicellular organisms, increasing in importance with increasing cellular complexity of the host. The systemic immune response to Listeria monocytogenes has been studied extensively in murine models; however, the clinical applicability of these findings to the human newborn remains incompletely understood. Furthermore, the ability to control infection at the level of an individual cell, known as “cell-autonomous immunity,” appears most relevant following infection with L. monocytogenes; as the main target, the monocyte is centrally important to innate as well as adaptive systemic immunity to listeriosis. We thus suggest that the overall increased risk to suffer and die from L. monocytogenes infection in the newborn period is a direct consequence of age-dependent differences in cell-autonomous immunity of the monocyte to L. monocytogenes. We here review what is known about age-dependent differences in systemic innate and adaptive as well as cell-autonomous immunity to infection with Listeria monocytogenes.

  1. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus

    Science.gov (United States)

    Infection of pregnant cows with noncytopathic (ncp) BVDV induces rapid innate and adaptive immune responses resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent ...

  2. Stress responses sculpt the insect immune system, optimizing defense in an ever-changing world.

    Science.gov (United States)

    Adamo, Shelley Anne

    2017-01-01

    A whole organism, network approach can help explain the adaptive purpose of stress-induced changes in immune function. In insects, mediators of the stress response (e.g. stress hormones) divert molecular resources away from immune function and towards tissues necessary for fight-or-flight behaviours. For example, molecules such as lipid transport proteins are involved in both the stress and immune responses, leading to a reduction in disease resistance when these proteins are shifted towards being part of the stress response system. Stress responses also alter immune system strategies (i.e. reconfiguration) to compensate for resource losses that occur during fight-or flight events. In addition, stress responses optimize immune function for different physiological conditions. In insects, the stress response induces a pro-inflammatory state that probably enhances early immune responses.

  3. Is Echo a complex adaptive system?

    Science.gov (United States)

    Smith, R M; Bedau, M A

    2000-01-01

    We evaluate whether John Holland's Echo model exemplifies his theory of complex adaptive systems. After reviewing Holland's theory of complex adaptive systems and describing his Escho model, we describe and explain the characteristic evolutionary behavior observed in a series of Echo model runs. We conclude that Echo lacks the diversity of hierarchically organized aggregates that typify complex adaptive systems, and we explore possible explanations for this failure.

  4. Adaptive immune response in JAM-C-deficient mice: normal initiation but reduced IgG memory.

    Science.gov (United States)

    Zimmerli, Claudia; Lee, Boris P L; Palmer, Gaby; Gabay, Cem; Adams, Ralf; Aurrand-Lions, Michel; Imhof, Beat A

    2009-04-15

    We have recently shown that junctional adhesion molecule (JAM)-C-deficient mice have leukocytic pulmonary infiltrates, disturbed neutrophil homeostasis, and increased postnatal mortality. This phenotype was partially rescued when mice were housed in ventilated isolators, suggesting an inability to cope with opportunistic infections. In the present study, we further examined the adaptive immune responses in JAM-C(-/-) mice. We found that murine conventional dendritic cells express in addition to Mac-1 and CD11c also JAM-B as ligand for JAM-C. By in vitro adhesion assay, we show that murine DCs can interact with recombinant JAM-C via Mac-1. However, this interaction does not seem to be necessary for dendritic cell migration and function in vivo, even though JAM-C is highly expressed by lymphatic sinuses of lymph nodes. Nevertheless, upon immunization and boosting with a protein Ag, JAM-C-deficient mice showed decreased persistence of specific circulating Abs although the initial response was normal. Such a phenotype has also been observed in a model of Ag-induced arthritis, showing that specific IgG2a Ab titers are reduced in the serum of JAM-C(-/-) compared with wild-type mice. Taken together, these data suggest that JAM-C deficiency affects the adaptive humoral immune response against pathogens, in addition to the innate immune system.

  5. Lipoxin A₄ modulates adaptive immunity by decreasing memory B-cell responses via an ALX/FPR2-dependent mechanism.

    Science.gov (United States)

    Ramon, Sesquile; Bancos, Simona; Serhan, Charles N; Phipps, Richard P

    2014-02-01

    Specialized proresolving mediators are endogenous bioactive lipid molecules that play a fundamental role in the regulation of inflammation and its resolution. Lipoxins and other specialized proresolving mediators have been identified in important immunological tissues including bone marrow, spleen, and blood. Lipoxins regulate functions of the innate immune system including the promotion of monocyte recruitment and increase macrophage phagocytosis of apoptotic neutrophils. A major knowledge gap is whether lipoxins influence adaptive immune cells. Here, we analyzed the actions of lipoxin A₄ (LXA₄) and its receptor ALX/FPR2 on human and mouse B cells. LXA₄ decreased IgM and IgG production on activated human B cells through ALX/FPR2-dependent signaling, which downregulated NF-κB p65 nuclear translocation. LXA₄ also inhibited human memory B-cell antibody production and proliferation, but not naïve B-cell function. Lastly, LXA₄ decreased antigen-specific antibody production in an OVA immunization mouse model. To our knowledge, this is the first description of the actions of lipoxins on human B cells, demonstrating a link between resolution signals and adaptive immunity. Regulating antibody production is crucial to prevent unwanted inflammation. Harnessing the ability of lipoxins to decrease memory B-cell antibody production can be beneficial to threat inflammatory and autoimmune disorders.

  6. The immune system: role in hypertension.

    Science.gov (United States)

    Schiffrin, Ernesto L

    2013-05-01

    Over the past 20 years it has become recognized that low-grade inflammation plays a role in cardiovascular disease. More recently, participation of the innate and the adaptive immune response in mechanisms that contribute to inflammation in cardiovascular disease has been reported in atherosclerosis and hypertension. Different subsets of lymphocytes and their cytokines are involved in vascular remodelling and hypertensive renal disease as well as heart disease. Effector T cells including T-helper (Th) 1 (interferon-γ-producing) and Th2 lymphocytes (interleukin-4 producing), as well as Th17 (which produce interleukin-17), and T suppressor lymphocytes such as T regulatory cells, which express the transcription factor forkhead box P3, participate respectively as pro- and anti-inflammatory cells, and mediate effects of angiotensin II and mineralocorticoids. Involvement of immune mechanisms in cardiac, vascular, and renal changes in hypertension has been demonstrated in many experimental models, an example being the Dahl-salt sensitive rat and the spontaneously hypertensive rat. How activation of immunity is triggered remains unknown, but neoantigens could be generated by elevated blood pressure through damage-associated molecular pattern receptors or other mechanisms. When activated, Th1 may contribute to blood pressure elevation by affecting the kidney, vascular remodelling of blood vessels directly via effects of the cytokines produced, or through their effects on perivascular fat. T regulatory cells protect from blood pressure elevation acting on similar targets. These novel findings may open the way for new therapeutic approaches to improve outcomes in hypertension and cardiovascular disease in humans.

  7. Exploring the Homeostatic and Sensory Roles of the Immune System

    Science.gov (United States)

    Marques, Rafael Elias; Marques, Pedro Elias; Guabiraba, Rodrigo; Teixeira, Mauro Martins

    2016-01-01

    Immunology developed under the notion of the immune system exists to fight pathogens. Recently, the discovery of interactions with commensal microbiota that are essential to human health initiated a change in this old paradigm. Here, we argue that the immune system has major physiological roles extending far beyond defending the host. Immune and inflammatory responses share the core property of sensing, defining the immune system also as a sensory system. The inference with the immune system collects, interprets, and stores information, while creating an identity of self, places it in close relationship to the nervous system, which suggests that these systems may have a profound evolutionary connection. PMID:27065209

  8. Graphene Oxides Decorated with Carnosine as an Adjuvant To Modulate Innate Immune and Improve Adaptive Immunity in Vivo.

    Science.gov (United States)

    Meng, Chunchun; Zhi, Xiao; Li, Chao; Li, Chuanfeng; Chen, Zongyan; Qiu, Xusheng; Ding, Chan; Ma, Lijun; Lu, Hongmin; Chen, Di; Liu, Guangqing; Cui, Daxiang

    2016-02-23

    Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4(+) T and CD8(+) T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo.

  9. Immune system evolution among anthropoid primates: parasites, injuries and predators.

    Science.gov (United States)

    Semple, Stuart; Cowlishaw, Guy; Bennett, Peter M

    2002-05-22

    In this study we investigate whether present-day variation in a key component of the immune system (baseline leucocyte concentrations) represents evolutionary adaptation to ecological factors. In particular, we test three hypotheses, namely that leucocyte concentrations will be positively related to one of the following: risk of disease transmission between hosts, which is related to host abundance (hypothesis 1), risk of disease infection from the environment due to parasite viability and abundance (hypothesis 2), and risk of injury and subsequent infection, for example following attacks by predators (hypothesis 3). No support was found for hypothesis 1: neither population density nor group size were associated with variation in leucocyte concentrations. Hypothesis 2 was supported: for both sexes, lymphocyte and phagocyte concentrations were positively correlated with annual rainfall, as predicted if interspecific variation in the immune system is related to parasite prevalence (primates suffer higher rates of parasitism in wetter habitats). Support was also provided for hypothesis 3: for both males and females, platelet concentrations were negatively related to body mass, as predicted if injury risk affects immune system evolution, because animals with larger body mass have a relatively lower surface area available to injury. Additional support was provided for hypothesis 3 by the finding that for males, the sex which plays the active role in troop defence and retaliation against predators, concentration of platelets was positively correlated with rate of predation. In conclusion, our analysis suggests that the risk of disease infection from the environment and the risk of injury have played a key role in immune system evolution among anthropoid primates.

  10. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  11. Subversion of innate and adaptive immune activation induced by structurally modified lipopolysaccharide from Salmonella typhimurium.

    Science.gov (United States)

    Pastelin-Palacios, Rodolfo; Gil-Cruz, Cristina; Pérez-Shibayama, Christian I; Moreno-Eutimio, Mario A; Cervantes-Barragán, Luisa; Arriaga-Pizano, Lourdes; Ludewig, Burkhard; Cunningham, Adam F; García-Zepeda, Eduardo A; Becker, Ingeborg; Alpuche-Aranda, Celia; Bonifaz, Laura; Gunn, John S; Isibasi, Armando; López-Macías, Constantino

    2011-08-01

    Salmonella are successful pathogens that infect millions of people every year. During infection, Salmonella typhimurium changes the structure of its lipopolysaccharide (LPS) in response to the host environment, rendering bacteria resistant to cationic peptide lysis in vitro. However, the role of these structural changes in LPS as in vivo virulence factors and their effects on immune responses and the generation of immunity are largely unknown. We report that modified LPS are less efficient than wild-type LPS at inducing pro-inflammatory responses. The impact of this LPS-mediated subversion of innate immune responses was demonstrated by increased mortality in mice infected with a non-lethal dose of an attenuated S. typhimurium strain mixed with the modified LPS moieties. Up-regulation of co-stimulatory molecules on antigen-presenting cells and CD4(+) T-cell activation were affected by these modified LPS. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing specific antibody responses. Immunization with modified LPS moiety preparations combined with experimental antigens, induced an impaired Toll-like receptor 4-mediated adjuvant effect. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing immunity against challenge with virulent S. typhimurium. Hence, changes in S. typhimurium LPS structure impact not only on innate immune responses but also on both humoral and cellular adaptive immune responses.

  12. Subversion of innate and adaptive immune activation induced by structurally modified lipopolysaccharide from Salmonella typhimurium

    Science.gov (United States)

    Pastelin-Palacios, Rodolfo; Gil-Cruz, Cristina; Pérez-Shibayama, Christian I; Moreno-Eutimio, Mario A; Cervantes-Barragán, Luisa; Arriaga-Pizano, Lourdes; Ludewig, Burkhard; Cunningham, Adam F; García-Zepeda, Eduardo A; Becker, Ingeborg; Alpuche-Aranda, Celia; Bonifaz, Laura; Gunn, John S; Isibasi, Armando; López-Macías, Constantino

    2011-01-01

    Salmonella are successful pathogens that infect millions of people every year. During infection, Salmonella typhimurium changes the structure of its lipopolysaccharide (LPS) in response to the host environment, rendering bacteria resistant to cationic peptide lysis in vitro. However, the role of these structural changes in LPS as in vivo virulence factors and their effects on immune responses and the generation of immunity are largely unknown. We report that modified LPS are less efficient than wild-type LPS at inducing pro-inflammatory responses. The impact of this LPS-mediated subversion of innate immune responses was demonstrated by increased mortality in mice infected with a non-lethal dose of an attenuated S. typhimurium strain mixed with the modified LPS moieties. Up-regulation of co-stimulatory molecules on antigen-presenting cells and CD4+ T-cell activation were affected by these modified LPS. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing specific antibody responses. Immunization with modified LPS moiety preparations combined with experimental antigens, induced an impaired Toll-like receptor 4-mediated adjuvant effect. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing immunity against challenge with virulent S. typhimurium. Hence, changes in S. typhimurium LPS structure impact not only on innate immune responses but also on both humoral and cellular adaptive immune responses. PMID:21631497

  13. Amino acid catabolism: a pivotal regulator of innate and adaptive immunity.

    Science.gov (United States)

    McGaha, Tracy L; Huang, Lei; Lemos, Henrique; Metz, Richard; Mautino, Mario; Prendergast, George C; Mellor, Andrew L

    2012-09-01

    Enhanced amino acid catabolism is a common response to inflammation, but the immunologic significance of altered amino acid consumption remains unclear. The finding that tryptophan catabolism helped maintain fetal tolerance during pregnancy provided novel insights into the significance of amino acid metabolism in controlling immunity. Recent advances in identifying molecular pathways that enhance amino acid catabolism and downstream mechanisms that affect immune cells in response to inflammatory cues support the notion that amino acid catabolism regulates innate and adaptive immune cells in pathologic settings. Cells expressing enzymes that degrade amino acids modulate antigen-presenting cell and lymphocyte functions and reveal critical roles for amino acid- and catabolite-sensing pathways in controlling gene expression, functions, and survival of immune cells. Basal amino acid catabolism may contribute to immune homeostasis that prevents autoimmunity, whereas elevated amino acid catalytic activity may reinforce immune suppression to promote tumorigenesis and persistence of some pathogens that cause chronic infections. For these reasons, there is considerable interest in generating novel drugs that inhibit or induce amino acid consumption and target downstream molecular pathways that control immunity. In this review, we summarize recent developments and highlight novel concepts and key outstanding questions in this active research field.

  14. Pregnancy Associated with Systemic Lupus Erythematosus: Immune Tolerance in Pregnancy and Its Deficiency in Systemic Lupus Erythematosus—An Immunological Dilemma

    Directory of Open Access Journals (Sweden)

    Cristina Gluhovschi

    2015-01-01

    Full Text Available Pregnancy is a physiological condition that requires immune tolerance to the product of conception. Systemic lupus erythematosus (SLE is a disease with well-represented immune mechanisms that disturb immune tolerance. The association of pregnancy with systemic lupus erythematosus creates a particular immune environment in which the immune tolerance specific of pregnancy is required to coexist with alterations of the immune system caused by SLE. The main role is played by T regulatory (Treg cells, which attempt to regulate and adapt the immune system of the mother to the new conditions of pregnancy. Other components of the immune system also participate to maintain maternal-fetal immune tolerance. If the immune system of pregnant women with SLE is not able to maintain maternal immune tolerance to the fetus, pregnancy complications (miscarriage, fetal hypotrophy, and preterm birth or maternal complications (preeclampsia or activation of SLE, especially in conditions of lupus nephritis may occur. In certain situations this can be responsible for neonatal lupus. At the same time, it must be noted that during pregnancy, the immune system is able to achieve immune tolerance while maintaining the anti-infectious immune capacity of the mother. Immunological monitoring of pregnancy during SLE, as well as of the mother’s disease, is required. It is important to understand immune tolerance to grafts in transplant pathology.

  15. HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study.

    Science.gov (United States)

    Ovsyannikova, Inna G; Pankratz, V Shane; Salk, Hannah M; Kennedy, Richard B; Poland, Gregory A

    2014-09-01

    We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines.

  16. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints

    Science.gov (United States)

    Koyama, Shohei; Akbay, Esra A.; Li, Yvonne Y.; Herter-Sprie, Grit S.; Buczkowski, Kevin A.; Richards, William G.; Gandhi, Leena; Redig, Amanda J.; Rodig, Scott J.; Asahina, Hajime; Jones, Robert E.; Kulkarni, Meghana M.; Kuraguchi, Mari; Palakurthi, Sangeetha; Fecci, Peter E.; Johnson, Bruce E.; Janne, Pasi A.; Engelman, Jeffrey A.; Gangadharan, Sidharta P.; Costa, Daniel B.; Freeman, Gordon J.; Bueno, Raphael; Hodi, F. Stephen; Dranoff, Glenn; Wong, Kwok-Kin; Hammerman, Peter S.

    2016-01-01

    Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade. PMID:26883990

  17. Adaptive passive equivalence of uncertain Lü system

    Institute of Scientific and Technical Information of China (English)

    Qi Dong-Lian

    2006-01-01

    An adaptive passive strategy for controlling uncertain Lü system is proposed. Since the uncertain Lü system is minimum phase and the uncertain parameters are from a bounded compact set, the essential conditions are studied by which uncertain Lü system could be equivalent to a passive system, and the adaptive control law is given. Using passive theory, the uncertain Lü system could be globally asymptotically stabilized at different equilibria by the smooth state feedback.

  18. Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo

    Directory of Open Access Journals (Sweden)

    Thorsten Peters

    2012-01-01

    Full Text Available Absence of β2 integrins (CD11/CD18 leads to leukocyte-adhesion deficiency-1 (LAD1, a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−. CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT. In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl21 acetyl chicken γ globulin (NP21-CG, even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1.

  19. Mining the human gut microbiota for effector strains that shape the immune system.

    Science.gov (United States)

    Ahern, Philip P; Faith, Jeremiah J; Gordon, Jeffrey I

    2014-06-19

    The gut microbiota codevelops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community and immune system coregulation and to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed.

  20. The influence of Mineral Trioxide Aggregate (MTA) on adaptive immune responses to endodontic pathogens in mice

    Science.gov (United States)

    Rezende, Taia Maria Berto; Vieira, Leda Quercia; Sobrinho, Antônio Paulino Ribeiro; Oliveira, Ricardo Reis; Taubman, Martin A.; Kawai, Toshihisa

    2008-01-01

    This study assessed the influence of mineral trioxide aggregate (MTA) on adaptive immune responses. BALB/c mice were immunized with heat-killed Fusobacterium nucleatum (Fn) in MTA or other control adjuvants, and serum IgG responses to Fn were measured. Either Fn- or Peptostreptococcus anaerobius (Pa)-reactive memory T cells (Tm) were pre-incubated in vitro with/without MTA and restimulated with Fn or Pa. Tm proliferation and cytokine production were assessed. Compared to control groups, IgG-antibody responses were upregulated in mice immunized with Fn in MTA in a similar manner to animals immunized with Fn in Freund's adjuvant or aluminum hydroxide adjuvant. While MTA did not affect the upregulated expression of IL-10, TNF-α or RANKL by Tm, it suppressed the proliferation of Pa- or Fn-Tm and inhibited their production of Th1- or Th2-signature cytokines. MTA upregulated the adaptive humoral immune responses, but had little or no effect on pro- or anti-inflammatory cytokine production by Tm. PMID:18718367

  1. Role of microRNAs in the immune system, inflammation and cancer.

    Science.gov (United States)

    Raisch, Jennifer; Darfeuille-Michaud, Arlette; Nguyen, Hang Thi Thu

    2013-05-28

    MicroRNAs, a key class of gene expression regulators, have emerged as crucial players in various biological processes such as cellular proliferation and differentiation, development and apoptosis. In addition, microRNAs are coming to light as crucial regulators of innate and adaptive immune responses, and their abnormal expression and/or function in the immune system have been linked to multiple human diseases including inflammatory disorders, such as inflammatory bowel disease, and cancers. In this review, we discuss our current understanding of microRNAs with a focus on their role and mode of action in regulating the immune system during inflammation and carcinogenesis.

  2. The Roles of Orphan Nuclear Receptors in the Development and Function of the Immune System

    Institute of Scientific and Technical Information of China (English)

    Ivan Dzhagalov; Nu Zhang; You-Wen He

    2004-01-01

    Hormones and their receptors regulate cell growth, differentiation and apoptosis and also play important roles in immune function. Recent studies on the subfamily of the orphan nuclear receptors known as retinoid-acid related orphan receptors (ROR) have shed important insights on the roles of this group of nuclear proteins in the development and function of the immune system. RORα regulates inflammatory cytokine production in both innate and adaptive immune system while RORγ regulates the normal development of T lymphocyte repertoire and secondary lymphoid organs. Cellular & Molecular Immunology. 2004;1(6):401-407.

  3. The Roles of Orphan Nuclear Receptors in the Development and Function of the Immune System

    Institute of Scientific and Technical Information of China (English)

    IvanDzhagalov; NuZhang; You-WenHe

    2004-01-01

    Hormones and their receptors regulate cell growth, differentiation and apoptosis and also play important roles in immune function. Recent studies on the subfamily of the orphan nuclear receptors known as retinoid-acid related orphan receptors (ROR) have shed important insights on the roles of this group of nuclear proteins in the development and function of the immune system. RORα regulates inflammatory cytokine production in both innate and adaptive immune system while RORγ, regulates the normal development of T lymphocyte repertoire and secondary lymphoid organs. Cellular & Molecular Immunology. 2004;1(6):401-407.

  4. The role of the immune system in central nervous system plasticity after acute injury.

    Science.gov (United States)

    Peruzzotti-Jametti, L; Donegá, M; Giusto, E; Mallucci, G; Marchetti, B; Pluchino, S

    2014-12-26

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization.

  5. Intelligent Multimodal Signal Adaptation System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Micro Analysis and Design (MA&D) is pleased to submit this proposal to design an Intelligent Multimodal Signal Adaptation System. This system will dynamically...

  6. Operator adaptation to changes in system reliability under adaptable automation.

    Science.gov (United States)

    Chavaillaz, Alain; Sauer, Juergen

    2016-11-25

    This experiment examined how operators coped with a change in system reliability between training and testing. Forty participants were trained for 3 h on a complex process control simulation modelling six levels of automation (LOA). In training, participants either experienced a high- (100%) or low-reliability system (50%). The impact of training experience on operator behaviour was examined during a 2.5 h testing session, in which participants either experienced a high- (100%) or low-reliability system (60%). The results showed that most operators did not often switch between LOA. Most chose an LOA that relieved them of most tasks but maintained their decision authority. Training experience did not have a strong impact on the outcome measures (e.g. performance, complacency). Low system reliability led to decreased performance and self-confidence. Furthermore, complacency was observed under high system reliability. Overall, the findings suggest benefits of adaptable automation because it accommodates different operator preferences for LOA. Practitioner Summary: The present research shows that operators can adapt to changes in system reliability between training and testing sessions. Furthermore, it provides evidence that each operator has his/her preferred automation level. Since this preference varies strongly between operators, adaptable automation seems to be suitable to accommodate these large differences.

  7. IMMUNE SYSTEM MATURITY AND SENSITIVITY TO CHEMICAL EXPOSURE

    Science.gov (United States)

    It is well established that human diseases associated with abnormal immune function, including some common infectious diseases and asthma, are considerably more prevalent at younger ages. The immune system continues to mature after birth, and functional immaturity accounts for m...

  8. Innate and adaptive immune responses in migrating spring-run adult chinook salmon, Oncorhynchus tshawytscha

    Science.gov (United States)

    Dolan, Brian P.; Fisher, Kathleen M.; Colvin, Michael E.; Benda, Susan E.; Peterson, James T.; Kent, Michael L.; Schreck, Carl B.

    2016-01-01

    Adult Chinook salmon (Oncorhynchus tshawytscha) migrate from salt water to freshwater streams to spawn. Immune responses in migrating adult salmon are thought to diminish in the run up to spawning, though the exact mechanisms for diminished immune responses remain unknown. Here we examine both adaptive and innate immune responses as well as pathogen burdens in migrating adult Chinook salmon in the Upper Willamette River basin. Messenger RNA transcripts encoding antibody heavy chain molecules slightly diminish as a function of time, but are still present even after fish have successfully spawned. In contrast, the innate anti-bacterial effector proteins present in fish plasma rapidly decrease as spawning approaches. Fish also were examined for the presence and severity of eight different pathogens in different organs. While pathogen burden tended to increase during the migration, no specific pathogen signature was associated with diminished immune responses. Transcript levels of the immunosuppressive cytokines IL-10 and TGF beta were measured and did not change during the migration. These results suggest that loss of immune functions in adult migrating salmon are not due to pathogen infection or cytokine-mediated immune suppression, but is rather part of the life history of Chinook salmon likely induced by diminished energy reserves or hormonal changes which accompany spawning.

  9. Attack, parry and riposte: molecular fencing between the innate immune system and human herpesviruses.

    Science.gov (United States)

    Le-Trilling, V T K; Trilling, M

    2015-07-01

    Once individuals acquire one of the eight human-pathogenic herpesviruses, the upcoming relationship is predefined to last lifelong. Despite the fact that acute phases of herpesviral replication are usually confined and controlled by a concerted action of all branches of the healthy immune system, sterile immunity is never reached. To accomplish this, herpesviruses evolved the unique ability to outlast episodes of efficient immunity in a dormant state called latency and a remarkable array of immune antagonists which counteract most (if not all) relevant aspects of intrinsic, innate and adaptive immune responses. Certain psychological and physiological conditions (such as stress, immuno-suppression or pregnancy) predispose for viral reactivation which can lead to recurrent disease and virus spread. One important pillar of immunity is the innate immune system. The leading cytokines of the innate immune response are interferons (IFN). IFNs reinforce intrinsic immunity, induce a cell-intrinsic antiviral state and recruit and orchestrate adaptive immunity. Consistently, individuals lacking a functional IFN system suffer from otherwise harmless opportunists and live-attenuated vaccines. The selective pressure elicited by IFNs drove herpesviruses to evolve numerous IFN antagonistic gene products. A molecular in-depth understanding of (herpes-) viral IFN antagonists might allow the design of novel antiviral drugs which reconstitute IFN responses by blocking the antagonistic function and thereby help the host to help himself. Additionally, virus mutants lacking immune evasins constitute promising candidates for vaccine viruses. Here we summarize the current knowledge on IFN antagonistic strategies of the eight human herpesviruses and try to decipher common strategies.

  10. Prenatal Alcohol Exposure and the Developing Immune System.

    Science.gov (United States)

    Gauthier, Theresa W

    2015-01-01

    Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.

  11. Self-Adaptive Systems for Machine Intelligence

    CERN Document Server

    He, Haibo

    2011-01-01

    This book will advance the understanding and application of self-adaptive intelligent systems; therefore it will potentially benefit the long-term goal of replicating certain levels of brain-like intelligence in complex and networked engineering systems. It will provide new approaches for adaptive systems within uncertain environments. This will provide an opportunity to evaluate the strengths and weaknesses of the current state-of-the-art of knowledge, give rise to new research directions, and educate future professionals in this domain. Self-adaptive intelligent systems have wide application

  12. Web-Based Adaptive Testing System

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Due to the maturing of Internet technology, the adaptive testing can be utilized in the web-based environment and the examinee can take the test anywhere and any time. The purpose of the research is to apply item response theory (IRT), adaptive testing theory and web-service technique to construct an XML format itembank and a system of web-based adaptive testing (WAT) by the framework of three-tiered client server distance testing.

  13. Measuring the immune system: a comprehensive approach for the analysis of immune functions in humans.

    Science.gov (United States)

    Claus, Maren; Dychus, Nicole; Ebel, Melanie; Damaschke, Jürgen; Maydych, Viktoriya; Wolf, Oliver T; Kleinsorge, Thomas; Watzl, Carsten

    2016-10-01

    The immune system is essential to provide protection from infections and cancer. Disturbances in immune function can therefore directly affect the health of the affected individual. Many extrinsic and intrinsic factors such as exposure to chemicals, stress, nutrition and age have been reported to influence the immune system. These influences can affect various components of the immune system, and we are just beginning to understand the causalities of these changes. To investigate such disturbances, it is therefore essential to analyze the different components of the immune system in a comprehensive fashion. Here, we demonstrate such an approach which provides information about total number of leukocytes, detailed quantitative and qualitative changes in the composition of lymphocyte subsets, cytokine levels in serum and functional properties of T cells, NK cells and monocytes. Using samples from a cohort of 24 healthy volunteers, we demonstrate the feasibility of our approach to detect changes in immune functions.

  14. Write 'systemic small RNAs': read 'systemic immunity'

    NARCIS (Netherlands)

    Seifi Abdolabad, A.R.

    2011-01-01

    About 50 years ago, it was reported that pathogen-infected plants are less susceptible to a broad spectrum of the subsequent pathogen attacks. This form of induced resistance, which resembles the immunisation in mammalian cells, is called systemic acquired resistance (SAR). In the last 10 years, pla

  15. An Artificial Immune System Model for Multi Agents Resource Sharing in Distributed Environments

    Directory of Open Access Journals (Sweden)

    Tejbanta Singh Chingtham

    2010-08-01

    Full Text Available Natural Immune system plays a vital role in the survival of the all living being. It provides a mechanism to defend itself from external predates making it consistent systems, capable of adapting itself for survival incase of changes. The human immune system has motivated scientists and engineers for finding powerful information processing algorithms that has solved complex engineering tasks. This paper explores one of the various possibilities for solving problem in a Multiagent scenario wherein multiple robots are deployed to achieve agoal collectively. The final goal is dependent on the performance of individual robot and its survival without having to lose its energy beyond a predetermined threshold value by deploying an evolutionary computational technique otherwise called the artificial immune system that imitates the biological immune system.

  16. An Artificial Immune System Model for Multi-Agents Resource Sharing in Distributed Environments

    CERN Document Server

    Chingtham, Tejbanta Singh; Ghose, M K

    2011-01-01

    Natural Immune system plays a vital role in the survival of the all living being. It provides a mechanism to defend itself from external predates making it consistent systems, capable of adapting itself for survival incase of changes. The human immune system has motivated scientists and engineers for finding powerful information processing algorithms that has solved complex engineering tasks. This paper explores one of the various possibilities for solving problem in a Multiagent scenario wherein multiple robots are deployed to achieve a goal collectively. The final goal is dependent on the performance of individual robot and its survival without having to lose its energy beyond a predetermined threshold value by deploying an evolutionary computational technique otherwise called the artificial immune system that imitates the biological immune system.

  17. The Serum Complement System: A Simplified Laboratory Exercise to Measure the Activity of an Important Component of the Immune System

    Science.gov (United States)

    Inglis, Jordan E.; Radziwon, Kimberly A.; Maniero, Gregory D.

    2008-01-01

    The immune system is a vital physiological component that affords animals protection from disease and is composed of innate and adaptive mechanisms that rely on cellular and dissolved components. The serum complement system is a series of dissolved proteins that protect against a variety of pathogens. The activity of complement in serum can be…

  18. Role of Innate and Adaptive Immunity in Cardiac Injury and Repair

    OpenAIRE

    Epelman, Slava; Liu, Peter P; Mann, Douglas L.

    2015-01-01

    Despite significant advances, cardiovascular disease is the leading cause of world-wide mortality, highlighting an important yet unmet clinical need. Understanding the pathophysiological basis underlying cardiovascular tissue injury and repair in therefore of prime importance. Following cardiac tissue injury, the immune system plays an important and complex role throughout the acute inflammatory response and regenerative response. This review will summarize the role of the immune system in ca...

  19. The Role of the Immune System in Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Gisa Ellrichmann

    2013-01-01

    Full Text Available Huntington’s disease (HD is characterized by a progressive course of disease until death 15–20 years after the first symptoms occur and is caused by a mutation with expanded CAG repeats in the huntingtin (htt protein. Mutant htt (mhtt in the striatum is assumed to be the main reason for neurodegeneration. Knowledge about pathophysiology has rapidly improved discussing influences of excitotoxicity, mitochondrial damage, free radicals, and inflammatory mechanisms. Both innate and adaptive immune systems may play an important role in HD. Activation of microglia with expression of proinflammatory cytokines, impaired migration of macrophages, and deposition of complement factors in the striatum indicate an activation of the innate immune system. As part of the adaptive immune system, dendritic cells (DCs prime T-cell responses secreting inflammatory mediators. In HD, DCs may contain mhtt which brings the adaptive immune system into the focus of interest. These data underline an increasing interest in the peripheral immune system for pathomechanisms of HD. It is still unclear if neuroinflammation is a reactive process or if there is an active influence on disease progression. Further understanding the influence of inflammation in HD using mouse models may open various avenues for promising therapeutic approaches aiming at slowing disease progression or forestalling onset of disease.

  20. An Adaptive Nonlinear Filter for System Identification

    Directory of Open Access Journals (Sweden)

    Tokunbo Ogunfunmi

    2009-01-01

    Full Text Available The primary difficulty in the identification of Hammerstein nonlinear systems (a static memoryless nonlinear system in series with a dynamic linear system is that the output of the nonlinear system (input to the linear system is unknown. By employing the theory of affine projection, we propose a gradient-based adaptive Hammerstein algorithm with variable step-size which estimates the Hammerstein nonlinear system parameters. The adaptive Hammerstein nonlinear system parameter estimation algorithm proposed is accomplished without linearizing the systems nonlinearity. To reduce the effects of eigenvalue spread as a result of the Hammerstein system nonlinearity, a new criterion that provides a measure of how close the Hammerstein filter is to optimum performance was used to update the step-size. Experimental results are presented to validate our proposed variable step-size adaptive Hammerstein algorithm given a real life system and a hypothetical case.

  1. ADAPTIVE REGULATION OF HIGH ORDER NONHOLONOMIC SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The problem of adaptive regulation of a class of high-order parametric nonholonomic systems in chained-form was discussed. Using adding a power integrator technique and state scaling with discontinuous projection technique, a discontinuous adaptive dynamic controller was constructed. The controller guarantees the estimated value of unknown parameter is in the prescribed extent.

  2. Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women.

    Science.gov (United States)

    Gillespie, Shannon L; Porter, Kyle; Christian, Lisa M

    2016-04-01

    Pregnancy is a period of considerable physiological adaption in neuroendocrine, cardiovascular, as well as immune function. Understanding of typical changes in inflammatory immune responses during healthy pregnancy is incomplete. In addition, despite considerable racial difference in adverse pregnancy outcomes, data are lacking on potential racial differences in such adaptation. This repeated measures prospective cohort study included 37 Black and 39 White women who provided blood samples during early, mid-, and late pregnancy and 8-10 weeks postpartum. Peripheral blood mononuclear cells were incubated with lipopolysaccharide (LPS) for 24h and supernatants assayed by electrochemiluminescence to quantify interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β, and IL-8 production. While no changes were observed in IL-8 production over time, significant increases in IL-6, TNF-α, and IL-1β production were observed from early to late pregnancy, with subsequent declines approaching early pregnancy values at postpartum (pspregnancy (p=0.002) and marginally lower IL-1β production at postpartum (p=0.054). These data show a clear trajectory of change in the inflammatory immune response across pregnancy and postpartum. In this cohort of generally healthy women, Black and White women exhibited minimal differences in LPS-stimulated cytokine production across the perinatal period. Future prospective studies in Black and White women with healthy versus adverse outcomes (e.g., preeclampsia, preterm birth) would inform our understanding of the potential role of immune dysregulation in pregnant women and in relation to racial disparities in perinatal health.

  3. Multithreshold Segmentation Based on Artificial Immune Systems

    Directory of Open Access Journals (Sweden)

    Erik Cuevas

    2012-01-01

    Full Text Available Bio-inspired computing has lately demonstrated its usefulness with remarkable contributions to shape detection, optimization, and classification in pattern recognition. Similarly, multithreshold selection has become a critical step for image analysis and computer vision sparking considerable efforts to design an optimal multi-threshold estimator. This paper presents an algorithm for multi-threshold segmentation which is based on the artificial immune systems(AIS technique, also known as theclonal selection algorithm (CSA. It follows the clonal selection principle (CSP from the human immune system which basically generates a response according to the relationship between antigens (Ag, that is, patterns to be recognized and antibodies (Ab, that is, possible solutions. In our approach, the 1D histogram of one image is approximated through a Gaussian mixture model whose parameters are calculated through CSA. Each Gaussian function represents a pixel class and therefore a thresholding point. Unlike the expectation-maximization (EM algorithm, the CSA-based method shows a fast convergence and a low sensitivity to initial conditions. Remarkably, it also improves complex time-consuming computations commonly required by gradient-based methods. Experimental evidence demonstrates a successful automatic multi-threshold selection based on CSA, comparing its performance to the aforementioned well-known algorithms.

  4. Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry

    Science.gov (United States)

    Segerstrom, Suzanne C.; Miller, Gregory E.

    2004-01-01

    The present report meta-analyzes more than 300 empirical articles describing a relationship between psychological stress and parameters of the immune system in human participants. Acute stressors (lasting minutes) were associated with potentially adaptive upregulation of some parameters of natural immunity and downregulation of some functions of…

  5. The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster.

    Science.gov (United States)

    Prescott, Joseph; Safronetz, David; Haddock, Elaine; Robertson, Shelly; Scott, Dana; Feldmann, Heinz

    2013-10-01

    Pathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4(+) and CD8(+) T cells before infection with hantaviruses. Depletion resulted in inhibition of virus-specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster.

  6. FORMATION OF INNATE AND ADAPTIVE IMMUNE RESPONSE UNDER THE INFLUENCE OF DIFFERENT FLAVIVIRUS VACCINES

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    N. V. Krylova

    2015-01-01

    Full Text Available The review examines in a comparative perspective the key moments of formation of innate and adaptive immune responses to different types of current flavivirus vaccines: live attenuated against yellow fever virus and inactivated whole virus against tick-borne encephalitis virus. Particular attention is paid to the ability of these different vaccines, containing exogenous pathogen-associated molecular structures, to stimulate innate immunity. Live attenuated vaccine by infecting several subtypes of dendritic cells activates them through various pattern-recognition receptors, such as Tolland RIG-I-like receptors, which leads to significant production of proinflammatory cytokines, including interferon-α primary mediator of innate antiviral immunity. By simulating natural viral infection, this vaccine quickly spreads over the vascular network, and the dendritic cells, activated by it, migrate to the draining lymph nodes and trigger multiple foci of Tand B-cell activation. Inactivated vaccine stimulates the innate immunity predominantly at the injection site, and for the sufficient activation requires the presence in its composition of an adjuvant (aluminum hydroxide, which effects the formation and activation of inflammasomes, ensuring the formation and secretion of IL-1β and IL-18 that, in turn, trigger a cascade of cellular and humoral innate immune responses. We demonstrated the possibility of involvement in the induction of innate immunity, mediated by the inactivated vaccine, endogenous pathogenassociated molecular patterns (uric acid and host cell DNA, forming at the vaccine injection site. We discuss the triggering of Band T-cell responses by flavivirus vaccines that determine various duration of protection against various pathogens. A single injection of the live vaccine against yellow fever virus induces polyvalent adaptive immune response, including the production of cytotoxic T-lymphocytes, Th1and Th2-cells and neutralizing antibodies

  7. Anthrax lethal toxin-mediated killing of human and murine dendritic cells impairs the adaptive immune response.

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    Abdelkrim Alileche

    2005-10-01

    Full Text Available Many pathogens have acquired strategies to combat the immune response. Bacillus anthracis interferes with host defenses by releasing anthrax lethal toxin (LT, which inactivates mitogen-activated protein kinase pathways, rendering dendritic cells (DCs and T lymphocytes nonresponsive to immune stimulation. However, these cell types are considered resistant to killing by LT. Here we show that LT kills primary human DCs in vitro, and murine DCs in vitro and in vivo. Kinetics of LT-mediated killing of murine DCs, as well as cell death pathways induced, were dependent upon genetic background: LT triggered rapid necrosis in BALB/c-derived DCs, and slow apoptosis in C57BL/6-derived DCs. This is consistent with rapid and slow killing of LT-injected BALB/c and C57BL/6 mice, respectively. We present evidence that anthrax LT impairs adaptive immunity by specifically targeting DCs. This may represent an immune-evasion strategy of the bacterium, and contribute to anthrax disease progression. We also established that genetic background determines whether apoptosis or necrosis is induced by LT. Finally, killing of C57BL/6-derived DCs by LT mirrors that of human DCs, suggesting that C57BL/6 DCs represent a better model system for human anthrax than the prototypical BALB/c macrophages.

  8. Cross-talk between probiotic lactobacilli and host immune system.

    Science.gov (United States)

    Kemgang, T S; Kapila, S; Shanmugam, V P; Kapila, R

    2014-08-01

    The mechanism by which probiotic lactobacilli affect the immune system is strain specific. As the immune system is a multicompartmental system, each strain has its way to interact with it and induce a visible and quantifiable effect. This review summarizes the interplay existing between the host immune system and probiotic lactobacilli, that is, with emphasis on lactobacilli as a prototype probiotic genus. Several aspects including the bacterial-host cross-talk with the mucosal and systemic immune system are presented, as well as short sections on the competing effect towards pathogenic bacteria and their uses as delivery vehicle for antigens.

  9. Interactions of lactobacilli with the host immune system

    NARCIS (Netherlands)

    Meijerink, M.

    2011-01-01

    The aim of this thesis was to better understand the molecular mechanism of host res-ponses to probiotics. Probiotics can be used to stimulate or regulate immune responses in epithelial and immune cells of the intestinal mucosa and generate beneficial effects on the immune system. Carefully selected

  10. Systemic immune modulation induced by alcoholic beverage intake in obese-diabetes (db/db) mice.

    Science.gov (United States)

    Lee, Hyunah; Jang, Ik-Soon; Park, Junsoo; Kim, Seol-Hee; Baek, So-Young; Go, Sung-Ho; Lee, Seung-Hoon

    2013-03-01

    Alcohol over-consumption is generally immunosuppressive. In this study, the effects of single or repetitive alcohol administration on the systemic immunity of db/db mice were observed to clarify the possible mechanisms for the increased susceptibility of obese individuals to alcohol-related immunological health problems. Alcohol (as a form of commercially available 20% distilled-alcoholic beverage) was orally administered one-time or seven times over 2 weeks to db/db mice and normal C57BL/6J mice. Immunologic alterations were analyzed by observation of body weight and animal activity, along with proportional changes of splenocytes for natural killer cells, macrophages, and T and B lymphocytes. Modulation of plasma cytokine level and immune-related genes were also ascertained by micro-bead assay and a microarray method, respectively. The immune micro-environment of db/db mice was an inflammatory state and adaptive cellular immunity was significantly suppressed. Low-dose alcohol administration reversed the immune response, decreasing inflammatory responses and the increment of adaptive immunity mainly related to CD4(+) T cells, but not CD8(+) T cells, to normal background levels. Systemic immune modulation due to alcohol administration in the obese-diabetic mouse model may be useful in the understanding of the induction mechanism, which will aid the development of therapeutics for related secondary diseases.

  11. RNA-guided complex from a bacterial immune system enhances target recognition through seed sequence interactions

    NARCIS (Netherlands)

    Wiedenheft, Blake; van Duijn, Esther; Bultema, Jelle; Waghmare, Sakharam; Zhou, Kaihong; Barendregt, Arjan; Westphal, Wiebke; Heck, Albert; Boekema, Egbert; Dickman, Mark; Doudna, Jennifer A.

    2011-01-01

    Prokaryotes have evolved multiple versions of an RNA-guided adaptive immune system that targets foreign nucleic acids. In each case, transcripts derived from clustered regularly interspaced short palindromic repeats (CRISPRs) are thought to selectively target invading phage and plasmids in a sequenc

  12. Immunizing digital systems against electromagnetic interference

    Science.gov (United States)

    Ewing, P. D.; Korsah, K.; Antonescu, C.

    This paper discusses the development of the technical basis for acceptance criteria applicable to the immunization of digital systems against electromagnetic interference (EMI). The work is sponsored by the US Nuclear Regulatory Commission and stems from the safety-related issues that need to be addressed as a result of the application of digital instrumentation and control systems in nuclear power plants. Designers of digital circuits are incorporating increasingly higher clock frequencies and lower logic level voltages, thereby leading to potentially greater susceptibility of spurious interference being misinterpreted as legitimate logic. Development of the technical basis for acceptance criteria to apply to these digital systems centers around establishing good engineering practices to ensure that sufficient levels of electromagnetic compatibility (EMC) are maintained between the nuclear power plant's electronic and electromechanical systems. First, good EMC design and installation practices are needed to control the emissions from interference sources and thereby their impact on other nearby circuits and systems. Secondly, a test and evaluation program is needed to outline the EMI tests to be performed, the associated test methods to be followed, and adequate test limits to ensure that the circuit or system under test meets the recommended guidelines. Test and evaluation should be followed by periodic maintenance to assess whether the recommended EMI control practices continue to be adhered to as part of the routine operation of the nuclear power plant. By following these steps, the probability of encountering safety-related instrumentation problems associated with EMI will be greatly reduced.

  13. Sharing Knowledge in Adaptive Learning Systems

    NARCIS (Netherlands)

    Kravcik, Milos; Gasevic, Dragan

    2006-01-01

    Please, cite this publication as: Kravcik, M. & Gasevic, D. (2006). Sharing Knowledge in Adaptive Learning Systems. Proceedings of ICALT2006. July, Kerkrade, The Netherlands: IEEE. Retrieved July 30th, 2006, from http://dspace.learningnetworks.org

  14. ADAPTIVE GENERALIZED PREDICTIVE CONTROL OF SWITCHED SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    WANG Yi-jing; WANG Long

    2005-01-01

    The problem of adaptive generalized predictive control which consists of output prediction errors for a class of switched systems is studied. The switching law is determined by the output predictive errors of a finite number of subsystems. For the single subsystem and multiple subsystems cases, it is proved that the given direct algorithm of generalized predictive control guarantees the global convergence of the system. This algorithm overcomes the inherent drawbacks of the slow convergence and large transient errors for the conventional adaptive control.

  15. Cold stress and immunity: Do chickens adapt to cold by trading-off immunity for thermoregulation?

    NARCIS (Netherlands)

    Hangalapura, B.N.

    2006-01-01

    Future animal husbandry aims at enhanced animal welfare, with minimal use of preventive medical treatments. These husbandry conditions will resemble more natural or ecological conditions. Under such farming systems, animals will experience various kinds of stressors such as environmental (e.g. cold,

  16. The Innate Immune System in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Allal Boutajangout

    2013-01-01

    Full Text Available Alzheimer’s disease (AD is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloid β (Aβ peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT. Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4 (Potter and Wisniewski (2012, and Verghese et al. (2011. Recently, it has been reported by two groups independently that a rare functional variant (R47H of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs and are the resident macrophages of the central nervous system (CNS. In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD.

  17. Can the Immune System Perform a t-Test?

    Science.gov (United States)

    Faria, Bruno Filipe; Mostardinha, Patricia

    2017-01-01

    The self-nonself discrimination hypothesis remains a landmark concept in immunology. It proposes that tolerance breaks down in the presence of nonself antigens. In strike contrast, in statistics, occurrence of nonself elements in a sample (i.e., outliers) is not obligatory to violate the null hypothesis. Very often, what is crucial is the combination of (self) elements in a sample. The two views on how to detect a change seem challengingly different and it could seem difficult to conceive how immunological cellular interactions could trigger responses with a precision comparable to some statistical tests. Here it is shown that frustrated cellular interactions reconcile the two views within a plausible immunological setting. It is proposed that the adaptive immune system can be promptly activated either when nonself ligands are detected or self-ligands occur in abnormal combinations. In particular we show that cellular populations behaving in this way could perform location statistical tests, with performances comparable to t or KS tests, or even more general data mining tests such as support vector machines or random forests. In more general terms, this work claims that plausible immunological models should provide accurate detection mechanisms for host protection and, furthermore, that investigation on mechanisms leading to improved detection in “in silico” models can help unveil how the real immune system works. PMID:28046042

  18. Adaptive and Innate Immune Responses in Autism: Rationale for Therapeutic Use of Intravenous Immunoglobulin

    OpenAIRE

    Gupta, Sudhir; Samra, Daljeet; Agrawal, Sudhanshu

    2010-01-01

    Background Autism is a complex polygenic neurodevelopmental disorder characterized by deficits in communication and social interactions as well as specific stereotypical behaviors. Both genetic and environmental factors appear to contribute to the pathogenesis of autism. Accumulating data including changes in immune responses, linkage to major histocompatibility complex antigens, and the presence of autoantibodies to neural tissues/antigens suggest that the immune system plays an important ro...

  19. Innate immune cells in the pathogenesis of primary systemic vasculitis.

    Science.gov (United States)

    Misra, Durga Prasanna; Agarwal, Vikas

    2016-02-01

    Innate immune system forms the first line of defense against foreign substances. Neutrophils, eosinophils, erythrocytes, platelets, monocytes, macrophages, dendritic cells, γδ T cells, natural killer and natural killer T cells comprise the innate immune system. Genetic polymorphisms influencing the activation of innate immune cells predispose to development of vasculitis and influence its severity. Abnormally activated innate immune cells cross-talk with other cells of the innate immune system, present antigens more efficiently and activate T and B lymphocytes and cause tissue destruction via cell-mediated cytotoxicity and release of pro-inflammatory cytokines. These secreted cytokines further recruit other cells to the sites of vascular injury. They are involved in both the initiation as well as the perpetuation of vasculitis. Evidences suggest reversal of aberrant activation of immune cells in response to therapy. Understanding the role of innate immune cells in vasculitis helps understand the potential of therapeutic modulation of their activation to treat vasculitis.

  20. Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals.

    Directory of Open Access Journals (Sweden)

    Anne Roslev Bukh

    Full Text Available BACKGROUND: Microbial translocation may contribute to the immunopathogenesis in HIV infection. We investigated if microbial translocation and inflammation were associated with innate and adaptive immune responses in adults with HIV. METHODOLOGY/PRINCIPAL FINDINGS: This was an observational cohort study. Sera from HIV-infected and HIV-uninfected individuals were analyzed for microbial translocation (soluble CD14, lipopolysaccharides [LPS], endotoxin core antibody, and anti-α-galactosyl antibodies and inflammatory markers (high sensitivity C-reactive protein, IL-6, IL-1 receptor antagonist, soluble tumor necrosis factor receptor II, and IL-10 with enzyme-linked immunosorbent assays. Peripheral blood mononuclear cells (PBMC from HIV-infected persons and healthy controls (primed with single-stranded HIV-1-derived RNA were stimulated with LPS, and cytokine production was measured. Finally, HIV-infected patients were immunized with Prevnar 7vPnC±CpG 7909 followed by Pneumo Novum PPV-23. Effects of microbial translocation and inflammation on immunization were analyzed in a predictive regression model. We included 96 HIV-infected individuals, 76 on highly active antiretroviral therapy (HAART, 20 HAART-naive, and 50 healthy controls. Microbial translocation and inflammatory markers were higher among HIV-infected persons than controls. Cytokine levels following LPS stimulation were increased in PBMCs from HAART-naive compared to HAART-treated HIV-infected persons. Further, RNA-priming of PBMCs from controls acted synergistically with LPS to augment cytokine responses. Finally, high serum LPS levels predicted poor vaccine responses among HAART-naive, but not among HAART-treated HIV-infected individuals. CONCLUSIONS/SIGNIFICANCE: LPS acts synergistically with HIV RNA to stimulate innate immune responses in vitro and increasing serum LPS levels seem to predict poor antibody responses after vaccination among HAART-naive HIV-infected persons. Thus, our

  1. Innate Immunity in Systemic Sclerosis – Role of Toll-Like Receptors, Interferon, and the Potential Impact of Vitamin D

    Directory of Open Access Journals (Sweden)

    Ruxandra Ionescu

    2014-07-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune disease in which vascular damage and immune activation leads to excessive accumulation of extracellular matrix in the skin and internal organs. Although the focus has been on adaptive immunity in SSc, recent data suggest that innate immunity is critically important. The innate immune system, the first-line barrier against pathogens, modulates mechanisms which activate adaptive immunity. Dysregulation of the innate immune system and toll-like receptors (TLRs may link immune abnormalities and fibrosis in SSc. TLR signalling pathways might induce production of Type I interferon (IFN and other cytokines, and represent one of the mechanisms that initiate and develop autoimmunity and subsequent fibrosis. Vitamin D displays many immunomodulatory effects on both innate and adaptive immune responses. Active vitamin D will produce signals via vitamin D receptor and influences TLR stimulation, IFN response, and antimicrobial peptide production. Vitamin D deficiency has been associated with many autoimmune disorders, and can influence clinical phenotype and immune disorders in SSc patients.

  2. MicroRNAs of the immune system: roles in inflammation and cancer.

    Science.gov (United States)

    Davidson-Moncada, Jan; Papavasiliou, F Nina; Tam, Wayne

    2010-01-01

    MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary target mRNAs and either promoting their decay or inhibiting their translation. Most eukaryotic genomes studied encode miRNAs, which are processed from longer noncoding transcripts through pathways conserved from fungi to plants to animals. miRNAs are now understood to be key mediators of developmental transitions in a number of model organisms. With respect to the immune system, miRNAs affect all facets of immune system development, from hematopoiesis to activation in response to infection during both the innate and the adaptive immune response. At the same time, miRNA dysregulation is a central event in the development and pathophysiology of a number of cancers of the immune system. Here we will discuss our current understanding of this general regulatory mechanism, focusing on its involvement in inflammation and in oncogenesis.

  3. Neuroendocrine and Immune System Responses with Spaceflights

    Science.gov (United States)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  4. [Understanding of immune system by visualization of spatiotemporal regulation of immune cells in the entire body].

    Science.gov (United States)

    Tomura, Michio

    2013-01-01

    Immune system is high-dimensional integrated system distributed in the whole body. Many kinds of, total 10(11) of immune cells are regulated by receiving appropriate signals in appropriate places. We have been attempting to understand immune system by revealing spatiotemporal regulation of immune cells at the whole body level by "Visualization of immune response in vivo". Photoconvertible protein, "Kaede"-Tg mice allowed us to monitor cell-replacement and cell-movement in the whole body by marking cells with color of Kaede from green to red with exposure to violet light. It is applicable to small cell number populations in both lymphoid organs and also peripheral tissues under both normal and pathophysiological conditions. By using this system, we have demonstrated novel findings that "Naive CD4(+) T cell recirculation is an active process that they recirculate through lymphoid organs to seek limited niche for interacting with endogenous antigens and upregulate their function." and "Activated regulatory T cells emigrating from cutaneous immune response is responsible for termination of immune reponse." I will introduce these new tools of us and would like to discuss what is needed to understand immune system in the entire body.

  5. Aberrant Pregnancy Adaptations in the Peripheral Immune Response in Type 1 Diabetes: A Rat Model.

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    Bart Groen

    Full Text Available Despite tight glycemic control, pregnancy complication rate in type 1 diabetes patients is higher than in normal pregnancy. Other etiological factors may be responsible for the development of adverse pregnancy outcome. Acceptance of the semi-allogeneic fetus is accompanied by adaptations in the maternal immune-response. Maladaptations of the immune-response has been shown to contribute to pregnancy complications. We hypothesized that type 1 diabetes, as an autoimmune disease, may be associated with maladaptations of the immune-response to pregnancy, possibly resulting in pregnancy complications.We studied pregnancy outcome and pregnancy-induced immunological adaptations in a normoglycemic rat-model of type 1 diabetes, i.e. biobreeding diabetes-prone rats (BBDP; 5 non-pregnant rats, 7 pregnant day 10 rats and 6 pregnant day 18 rats , versus non-diabetic control rats (i.e. congenic non-diabetic biobreeding diabetes-resistant (BBDR; 6 non-pregnant rats, 6 pregnant day 10 rats and 6 pregnant day 18 rats and Wistar-rats (6 non-pregnant, 6 pregnant day 10 rats and 5 pregnant day 18 rats.We observed reduced litter size, lower fetal weight of viable fetuses and increased numbers of resorptions versus control rats. These complications are accompanied by various differences in the immune-response between BBDP and control rats in both pregnant and non-pregnant animals. The immune-response in non-pregnant BBDP-rats was characterized by decreased percentages of lymphocytes, increased percentages of effector T-cells, regulatory T-cells and natural killer cells, an increased Th1/Th2-ratio and activated monocytes versus Wistar and BBDR-rats. Furthermore, pregnancy-induced adaptations in BBDP-rats coincided with an increased Th1/Th2-ratio, a decreased mean fluorescence intensity CD161a/NKR-P1b ratio and no further activation of monocytes versus non-diabetic control rats.This study suggests that even in the face of strict normoglycemia, pregnancy complications

  6. Sublingual immunization with a subunit influenza vaccine elicits comparable systemic immune response as intramuscular immunization, but also induces local IgA and TH17 responses.

    Science.gov (United States)

    Gallorini, Simona; Taccone, Marianna; Bonci, Alessandra; Nardelli, Filomena; Casini, Daniele; Bonificio, Amanda; Kommareddy, Sushma; Bertholet, Sylvie; O'Hagan, Derek T; Baudner, Barbara C

    2014-04-25

    Influenza is a vaccine-preventable disease that remains a major health problem world-wide. Needle and syringe are still the primary delivery devices, and injection of liquid vaccine into the muscle is still the primary route of immunization. Vaccines could be more convenient and effective if they were delivered by the mucosal route. Elicitation of systemic and mucosal innate and adaptive immune responses, such as pathogen neutralizing antibodies (including mucosal IgA at the site of pathogen entry) and CD4(+) T-helper cells (especially the Th17 subset), have a critical role in vaccine-mediated protection. In the current study, a sublingual subunit influenza vaccine formulated with or without mucosal adjuvant was evaluated for systemic and mucosal immunogenicity and compared to intranasal and intramuscular vaccination. Sublingual administration of adjuvanted influenza vaccine elicited comparable antibody titers to those elicited by intramuscular immunization with conventional influenza vaccine. Furthermore, influenza-specific Th17 cells or neutralizing mucosal IgA were detected exclusively after mucosal immunization.

  7. Exercise and the immune system Ejercicio y sistema inmune

    Directory of Open Access Journals (Sweden)

    Domingo Caraballo Gracia

    2006-01-01

    Full Text Available It has been demonstrated that physical exercise, carried out at diverse intensities, modulates the function of different human body systems, and that it plays a major role in the immune response. Therefore, it is necessary to find out if these changes have benefic or harmful effects on the host adaptation against several pathogenic agents. The study of these physical-stress-induced changes might have a great impact on the comprehension and prevention of some diseases that involve activation of the immune system such as allergies, infections, immunodeficiencies and cancer. This article presents a review of current information concerning this area, with the purpose of providing concepts to help readers understand this biological phenomena and their implications in human health. Several immune response parameters have been studied during physical exercise, including their relationship with the stress-induced hormonal response and the profile of different hormones according to the intensity of physical activity. Also, changes in blood cell populations (lymphocytes, monocytes and neutrophils and the behavior of cytokines and the synthesis of specific immune globulins have been assessed. This knowledge has allowed to establish a relationship between the immune and neuroendocrine systems, which might explain the various changes in the immune response and the adaptation seen in physical activity, as well as the differences found at diverse exercise intensity and frequency levels. Se ha demostrado que el ejercicio hecho a diferentes intensidades cumple una función moduladora sobre diversos sistemas, y que su acción sobre la respuesta inmune es de gran importancia. Por lo tanto, es necesario esclarecer si estos cambios constituyen efectos benéficos o perjudiciales en cuanto a las adaptaciones del hospedero frente a diversos agentes patógenos. El estudio de estos cambios inducidos por el estrés físico puede tener un impacto grande en la comprensi

  8. Expression of the SLAM family of receptors adapter EAT-2 as a novel strategy for enhancing beneficial immune responses to vaccine antigens.

    Science.gov (United States)

    Aldhamen, Yasser A; Appledorn, Daniel M; Seregin, Sergey S; Liu, Chyong-jy J; Schuldt, Nathaniel J; Godbehere, Sarah; Amalfitano, Andrea

    2011-01-15

    Recent studies have shown that activation of the signaling lymphocytic activation molecule (SLAM) family of receptors plays an important role in several aspects of immune regulation. However, translation of this knowledge into a useful clinical application has not been undertaken. One important area where SLAM-mediated immune regulation may have keen importance is in the field of vaccinology. Because SLAM signaling plays such a critical role in the innate and adaptive immunity, we endeavored to develop a strategy to improve the efficacy of vaccines by incorporation of proteins known to be important in SLAM-mediated signaling. In this study, we hypothesized that coexpression of the SLAM adapter EWS-FLI1-activated transcript 2 (EAT-2) along with a pathogen-derived Ag would facilitate induction of beneficial innate immune responses, resulting in improved induction of Ag-specific adaptive immune responses. To test this hypothesis, we used rAd5 vector-based vaccines expressing murine EAT-2, or the HIV-1-derived Ag Gag. Compared with appropriate controls, rAd5 vectors expressing EAT-2 facilitated bystander activation of NK, NKT, B, and T cells early after their administration into animals. EAT-2 overexpression also augments the expression of APC (macrophages and dendritic cells) surface markers. Indeed, this multitiered activation of the innate immune system by vaccine-mediated EAT-2 expression enhanced the induction of Ag-specific cellular immune responses. Because both mice and humans express highly conserved EAT-2 adapters, our results suggest that human vaccination strategies that specifically facilitate SLAM signaling may improve vaccine potency when targeting HIV Ags specifically, as well as numerous other vaccine targets in general.

  9. Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets.

    Science.gov (United States)

    van Unen, Vincent; Li, Na; Molendijk, Ilse; Temurhan, Mine; Höllt, Thomas; van der Meulen-de Jong, Andrea E; Verspaget, Hein W; Mearin, M Luisa; Mulder, Chris J; van Bergen, Jeroen; Lelieveldt, Boudewijn P F; Koning, Frits

    2016-05-17

    Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We used high-dimensional mass cytometry to generate a system-wide view of the human mucosal immune system in health and disease. We distinguished 142 immune subsets and through computational applications found distinct immune subsets in peripheral blood mononuclear cells and intestinal biopsies that distinguished patients from controls. In addition, mucosal lymphoid malignancies were readily detected as well as precursors from which these likely derived. These findings indicate that an integrated high-dimensional analysis of the entire immune system can identify immune subsets associated with the pathogenesis of complex intestinal disorders. This might have implications for diagnostic procedures, immune-monitoring, and treatment of intestinal diseases and mucosal malignancies.

  10. The spleen in local and systemic regulation of immunity.

    Science.gov (United States)

    Bronte, Vincenzo; Pittet, Mikael J

    2013-11-14

    The spleen is the main filter for blood-borne pathogens and antigens, as well as a key organ for iron metabolism and erythrocyte homeostasis. Also, immune and hematopoietic functions have been recently unveiled for the mouse spleen, suggesting additional roles for this secondary lymphoid organ. Here we discuss the integration of the spleen in the regulation of immune responses locally and in the whole body and present the relevance of findings for our understanding of inflammatory and degenerative diseases and their treatments. We consider whether equivalent activities in humans are known, as well as initial therapeutic attempts to target the spleen for modulating innate and adaptive immunity.

  11. Quantitative Adaptation Analytics for Assessing Dynamic Systems of Systems.

    Energy Technology Data Exchange (ETDEWEB)

    Gauthier, John H.; Miner, Nadine E.; Wilson, Michael L.; Le, Hai D.; Kao, Gio K; Melander, Darryl J.; Longsine, Dennis Earl [Sandia National Laboratories, Unknown, Unknown; Vander Meer, Robert Charles,

    2015-01-01

    Our society is increasingly reliant on systems and interoperating collections of systems, known as systems of systems (SoS). These SoS are often subject to changing missions (e.g., nation- building, arms-control treaties), threats (e.g., asymmetric warfare, terrorism), natural environments (e.g., climate, weather, natural disasters) and budgets. How well can SoS adapt to these types of dynamic conditions? This report details the results of a three year Laboratory Directed Research and Development (LDRD) project aimed at developing metrics and methodologies for quantifying the adaptability of systems and SoS. Work products include: derivation of a set of adaptability metrics, a method for combining the metrics into a system of systems adaptability index (SoSAI) used to compare adaptability of SoS designs, development of a prototype dynamic SoS (proto-dSoS) simulation environment which provides the ability to investigate the validity of the adaptability metric set, and two test cases that evaluate the usefulness of a subset of the adaptability metrics and SoSAI for distinguishing good from poor adaptability in a SoS. Intellectual property results include three patents pending: A Method For Quantifying Relative System Adaptability, Method for Evaluating System Performance, and A Method for Determining Systems Re-Tasking.

  12. Complex and Adaptive Dynamical Systems A Primer

    CERN Document Server

    Gros, Claudius

    2011-01-01

    We are living in an ever more complex world, an epoch where human actions can accordingly acquire far-reaching potentialities. Complex and adaptive dynamical systems are ubiquitous in the world surrounding us and require us to adapt to new realities and the way of dealing with them. This primer has been developed with the aim of conveying a wide range of "commons-sense" knowledge in the field of quantitative complex system science at an introductory level, providing an entry point to this both fascinating and vitally important subject. The approach is modular and phenomenology driven. Examples of emerging phenomena of generic importance treated in this book are: -- The small world phenomenon in social and scale-free networks. -- Phase transitions and self-organized criticality in adaptive systems. -- Life at the edge of chaos and coevolutionary avalanches resulting from the unfolding of all living. -- The concept of living dynamical systems and emotional diffusive control within cognitive system theory. Techn...

  13. Complex and adaptive dynamical systems a primer

    CERN Document Server

    Gros, Claudius

    2007-01-01

    We are living in an ever more complex world, an epoch where human actions can accordingly acquire far-reaching potentialities. Complex and adaptive dynamical systems are ubiquitous in the world surrounding us and require us to adapt to new realities and the way of dealing with them. This primer has been developed with the aim of conveying a wide range of "commons-sense" knowledge in the field of quantitative complex system science at an introductory level, providing an entry point to this both fascinating and vitally important subject. The approach is modular and phenomenology driven. Examples of emerging phenomena of generic importance treated in this book are: -- The small world phenomenon in social and scale-free networks. -- Phase transitions and self-organized criticality in adaptive systems. -- Life at the edge of chaos and coevolutionary avalanches resulting from the unfolding of all living. -- The concept of living dynamical systems and emotional diffusive control within cognitive system theory. Techn...

  14. The two sides of complement C3d: evolution of electrostatics in a link between innate and adaptive immunity.

    Directory of Open Access Journals (Sweden)

    Chris A Kieslich

    Full Text Available The interaction between complement fragment C3d and complement receptor 2 (CR2 is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of -1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic "hot-spots". Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic "hot-spots" at the two functional sites of C3d, while the surface of CR2 lacks electrostatic "hot-spots" despite its excessively positive nature. We propose that the electrostatic "hot-spots" of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2, which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3

  15. The two sides of complement C3d: evolution of electrostatics in a link between innate and adaptive immunity.

    Science.gov (United States)

    Kieslich, Chris A; Morikis, Dimitrios

    2012-01-01

    The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of -1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic "hot-spots". Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic "hot-spots" at the two functional sites of C3d, while the surface of CR2 lacks electrostatic "hot-spots" despite its excessively positive nature. We propose that the electrostatic "hot-spots" of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2), which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3d, after the

  16. [Psychoneuroimmunology--regulation of immunity at the systemic level].

    Science.gov (United States)

    Boranić, Milivoj; Sabioncello, Ante; Gabrilovac, Jelka

    2008-01-01

    Innate and acquired immune reactions are controlled by their intrinsic regulatory mechanisms, ie. by an array of cytokines that mediate communication among cells of the immune system itself and with other cells and tissues, e. g. in areas of inflammation. In addition, the immune system is also subjected to systemic regulation by the vegetative and endocrine systems since immune cells express receptors for neurotransmitters and hormones. Neuroendocrine signals may enhance or suppress the immune reaction, accelerate or slow it, but do not affect specificity. Various stressful factors, including the psychosocial ones, affect immunity. In turn, cytokines generated by the immune system influence hormonal secretion and central nervous system, producing specific behavioral changes (the "sickness behavior") accompanying infectious and inflammatory diseases. That includes somnolence, loss of apetite, depression or anxiety and decrease of cognitive abilities, attention and memory. Local immune systems in skin and mucosa are also subjected to systemic neuroendocrine regulation and possess intrinsic neuroregulatory networks as well. These mechanisms render skin and respiratory and digestive tracts responsive to various forms of stress. Examples are neurodermitis, asthma and ulcerative colitis. In children, the immune and the neuroendocrine systems are still developing, particularly in fetal, neonatal and early infant periods, and exposure to stressful experiences at that time may result in late consequences in the form of deficient immunity or greater risks for allergic or autoimmune reactions. Recognition of the participation of neuroendocrine mechanisms in regulation of immunity helps us understand alterations and disturbances of immune reactions under the influence of stressful factors but so far has not produced reliable therapeutic implications. Psychosocial interventions involving the child and its family may be useful.

  17. Pressure Induced Changes in Adaptive Immune Function in Belugas (Delphinapterus leucas; implications for dive physiology and health

    Directory of Open Access Journals (Sweden)

    Laura A Thompson

    2016-09-01

    Full Text Available Increased pressure, associated with diving, can alter cell function through several mechanisms and has been shown to impact immune functions performed by peripheral blood mononuclear cells (PBMC in humans. While marine mammals possess specific adaptations which protect them from dive related injury, it is unknown how their immune system is adapted to the challenges associated with diving. The purpose of this study was to measure PBMC activation (IL2R expression and Concanavalin A induced lymphocyte proliferation (BrdU incorporation in belugas following in vitro pressure exposures during baseline, Out of Water Examination (OWE and capture/release conditions. Beluga blood samples (n=4 were obtained from animals at the Mystic Aquarium and from free ranging animals in Alaska (n=9. Human blood samples (n=4 (Biological Specialty Corporation were run for comparison. In vivo catecholamines and cortisol were measured in belugas to characterize the neuroendocrine response. Comparison of cellular responses between controls and pressure exposed cells, between conditions in belugas, between belugas and humans as well as between dive profiles, were run using mixed generalized linear models (α=0.05. Cortisol was significantly higher in wild belugas and OWE samples as compared with baseline for aquarium animals. Both IL2R expression and proliferation displayed significant pressure induced changes, and these responses varied between conditions in belugas. Both belugas and humans displayed increased IL2R expression, while lymphocyte proliferation decreased for aquarium animals and increased for humans and wild belugas. Results suggest beluga PBMC function is altered during diving and changes may represent dive adaptation as the response differs from humans, a non-dive adapted mammal. In addition, characteristics of a dive (i.e., duration, depth as well as neuroendocrine activity can alter the response of beluga cells, potentially impacting the ability of animals

  18. 5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.

    Directory of Open Access Journals (Sweden)

    Adriana Secatto

    Full Text Available 5-Lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO(-/- mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO(-/- mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.

  19. APF-guided adaptive immune network algorithm for robot path planning

    Institute of Scientific and Technical Information of China (English)

    Mingxin YUAN; Sunan WANG; Canyang WU; Kunpeng LI

    2009-01-01

    Inspired by the mechanism of Jerne's idiotypic network hypothesis, a new adaptive immune network algorithm (AINA) is presented through the stimulation and suppression between the antigen and antibody by taking the environment and robot behavior as antigen and antibody respectively. A guiding weight is defined based on the artificial potential field (APF) method, and the guiding weight is combined with antibody vitality to construct a new antibody selection operator, which improves the searching efficiency. In addition, an updating operator of antibody vi-tality is provided based on the Baldwin effect, which results in a positive feedback mechanism of search and accelerates the convergence of the immune network. The simulation and experimental results show that the proposed algorithm is characterized by high searching speed, good convergence performance and strong planning ability, which solves the path planning well in complicated environments.

  20. Immune response induction in the central nervous system

    DEFF Research Database (Denmark)

    Owens, Trevor; Babcock, Alicia

    2002-01-01

    The primary function of the immune response is protection of the host against infection with pathogens, including viruses. Since viruses can infect any tissue of the body, including the central nervous system (CNS), it is logical that cells of the immune system should equally have access to all...... tissues. Nevertheless, the brain and spinal cord are noted for their lack of immune presence. Relative to other organ systems, the CNS appears immunologically privileged. Furthermore, when immune responses do occur in the CNS, they are frequently associated with deleterious effects such as inflammatory...

  1. Evolution of JAK-STAT pathway components: mechanisms and role in immune system development.

    Directory of Open Access Journals (Sweden)

    Clifford Liongue

    Full Text Available BACKGROUND: Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK-Signal transducer and activator of transcription (STAT pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP, Protein inhibitors against Stats (PIAS, and Suppressor of cytokine signaling (SOCS proteins across a diverse range of organisms. RESULTS: Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components. CONCLUSION: Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.

  2. The Effects of Environment and Physiological Cyclicity on the Immune System of Viperinae

    Directory of Open Access Journals (Sweden)

    Lorand Kobolkuti

    2012-01-01

    Full Text Available One of the important aspects of species’ survival is connected with global climate changes, which also conditions the epidemiology of infectious diseases. Poikilotherms are exposed, as other species, to climatic influence, especially due to their physiological peculiarities such as important stages of their life cycle: hibernation, shedding, and active phase. The immune system serves as an accurate indicator of the health status and stress levels in these species. This study aimed to monitor the changes of innate (leukocyte subpopulations and total immune globulins and adaptive immunity (in vitro leukocyte blast transformation of two viper species, V. berus berus and V. ammodytes ammodytes, endemic in Europe and spread in different regions of Romania during their three major life cycles, hibernation, shedding, and active phase. The results indicated that seasonal variance and cycle rather than species and regional distribution influence the functionality of the immune system.

  3. Invited essay: Cognitive influences on the psychological immune system.

    Science.gov (United States)

    Rachman, S J

    2016-12-01

    The construct of the psychological immune system is described and analysed. The direct and indirect cognitive influences on the system are discussed, and the implications of adding a cognitive construal to the influential model of a behavioural immune system are considered. The psychological immune system has two main properties: defensive and healing. It encompasses a good amount of health-related phenomena that is outside the scope of the behavioural model or the biological immune system. Evidence pertaining to the psychological immune system includes meta-analyses of the associations between psychological variables such as positive affect/wellbeing and diseases and mortality, and associations between wellbeing and positive health. The results of long-term prospective studies are consistent with the conclusions drawn from the meta-analyses. Laboratory investigations of the effects of psychological variables on the biological immune system show that negative affect can slow wound-healing, and positive affect can enhance resistance to infections, for example in experiments involving the introduction of the rhinovirus and the influenza A virus. A number of problems concerning the assessment of the functioning of the psychological immune system are considered, and the need to develop techniques for determining when the system is active or not, is emphasized. This problem is particularly challenging when trying to assess the effects of the psychological immune system during a prolonged psychological intervention, such as a course of resilience training.

  4. Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies.

    Science.gov (United States)

    Sideras, K; Braat, H; Kwekkeboom, J; van Eijck, C H; Peppelenbosch, M P; Sleijfer, S; Bruno, M

    2014-05-01

    Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials.

  5. Selection for brain size impairs innate, but not adaptive immune responses.

    Science.gov (United States)

    Kotrschal, Alexander; Kolm, Niclas; Penn, Dustin J

    2016-03-16

    Both the brain and the immune system are energetically demanding organs, and when natural selection favours increased investment into one, then the size or performance of the other should be reduced. While comparative analyses have attempted to test this potential evolutionary trade-off, the results remain inconclusive. To test this hypothesis, we compared the tissue graft rejection (an assay for measuring innate and acquired immune responses) in guppies (Poecilia reticulata) artificially selected for large and small relative brain size. Individual scales were transplanted between pairs of fish, creating reciprocal allografts, and the rejection reaction was scored over 8 days (before acquired immunity develops). Acquired immune responses were tested two weeks later, when the same pairs of fish received a second set of allografts and were scored again. Compared with large-brained animals, small-brained animals of both sexes mounted a significantly stronger rejection response to the first allograft. The rejection response to the second set of allografts did not differ between large- and small-brained fish. Our results show that selection for large brain size reduced innate immune responses to an allograft, which supports the hypothesis that there is a selective trade-off between investing into brain size and innate immunity.

  6. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity

    Science.gov (United States)

    Cissé, Yasmine M.; Russart, Kathryn L.G.; Nelson, Randy J.

    2017-01-01

    Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 9 weeks, then paired in full factorial design, mated, and thereafter housed under dark nights. Offspring were gestated and reared in dark nights, then tested as adults for cell-mediated and humoral immunity. Maternal exposure to dLAN dampened delayed type hypersensitivity (DTH) responses in male offspring. Maternal and paternal exposure to dLAN reduced DTH responses in female offspring. IgG antibodies to a novel antigen were elevated in offspring of dams exposed to dLAN. Paternal exposure to dLAN decreased splenic endocrine receptor expression and global methylation in a parental sex-specific manner. Together, these data suggest that exposure to dLAN has transgenerational effects on endocrine-immune function that may be mediated by global alterations in the epigenetic landscape of immune tissues. PMID:28361901

  7. Mapping the effects of drugs on the immune system.

    Science.gov (United States)

    Kidd, Brian A; Wroblewska, Aleksandra; Boland, Mary R; Agudo, Judith; Merad, Miriam; Tatonetti, Nicholas P; Brown, Brian D; Dudley, Joel T

    2016-01-01

    Understanding how drugs affect the immune system has consequences for treating disease and minimizing unwanted side effects. Here we present an integrative computational approach for predicting interactions between drugs and immune cells in a system-wide manner. The approach matches gene sets between transcriptional signatures to determine their similarity. We apply the method to model the interactions between 1,309 drugs and 221 immune cell types and predict 69,995 interactions. The resulting immune-cell pharmacology map is used to predict how five drugs influence four immune cell types in humans and mice. To validate the predictions, we analyzed patient records and examined cell population changes from in vivo experiments. Our method offers a tool for screening thousands of interactions to identify relationships between drugs and the immune system.

  8. Influence of Phthalates on in vitro Innate and Adaptive Immune Responses

    DEFF Research Database (Denmark)

    Hansen, Juliana Frohnert; Nielsen, Claus Henrik; Brorson, Marianne Møller

    2015-01-01

    from both monocytes/macrophages and T cells in a similar pattern: the secretion of interleukin (IL)-6, IL-10 and the chemokine CXCL8 by monocytes/macrophages was enhanced, while tumour necrosis factor (TNF)-α secretion by monocytes/macrophages was impaired, as was the secretion of IL-2 and IL-4, TNF...... not seem to be a result of cell death. Thus, results indicate that both human innate and adaptive immunity is influenced in vitro by phthalates, and that phthalates therefore may affect cell differentiation and regenerative and inflammatory processes in vivo....

  9. Endocrine and Local IGF-I in the Bony Fish Immune System

    Directory of Open Access Journals (Sweden)

    Anne-Constance Franz

    2016-01-01

    Full Text Available A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived, which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

  10. The immune system: a new look at pain

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun-hua; HUANG Yu-guang

    2006-01-01

    Objective To review the relationship between the immune system and the mechanism of pain.Data sources Related researches published in the period of 1987-2005 were systematically reviewed.Study selection Articles about the immune system and pain were selected.Data extraction Data were mainly extracted from 74 articles which are listed in the reference section of this review.Results Pain was classically viewed as being mediated solely by neurons. However, growing evidence has showed the possible relationships between the immune system and the central nervous system. In this article, we reviewed the role of the immune system in the development of pain, together with the importance of the glia in this process. These findings suggest a novel approach to pain control in the future.Conclusions The immune system plays a potential but important role in the development of pain.

  11. Tumor-Associated Glycans and Immune Surveillance

    OpenAIRE

    Anastas Pashov; Behjatolah Monzavi-Karbassi; Thomas Kieber-Emmons

    2013-01-01

    Changes in cell surface glycosylation are a hallmark of the transition from normal to inflamed and neoplastic tissue. Tumor-associated carbohydrate antigens (TACAs) challenge our understanding of immune tolerance, while functioning as immune targets that bridge innate immune surveillance and adaptive antitumor immunity in clinical applications. T-cells, being a part of the adaptive immune response, are the most popular component of the immune system considered for targeting tumor cells. Howev...

  12. The molecular choreography of IRF4 and IRF8 with immune system partners.

    Science.gov (United States)

    Singh, Harinder; Glasmacher, Elke; Chang, Abraham B; Vander Lugt, Bryan

    2013-01-01

    The transcription factors IRF4 and IRF8 represent immune-specific members of the interferon regulatory family. They play major roles in controlling the development and functioning of innate and adaptive cells. Genes encoding these factors appear to have been coopted by the immune system via gene duplication and divergence of regulatory and protein coding sequences to enable the acquisition of unique molecular properties and functions. Unlike other members of the IRF family, IRF4 and IRF8 do not activate transcription of Type 1 interferon genes or positively regulate interferon-induced gene expression. Instead, they bind to unusual composite Ets-IRF or AP-1-IRF elements with specific Ets or AP-1 family transcription factors, respectively, and regulate the expression of diverse sets of immune response genes in innate as well as adaptive cells.

  13. Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function

    Science.gov (United States)

    2017-01-01

    Idiopathic chronic inflammatory conditions (ICIC) such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR) of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system's thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way) resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system's compartmentalization in the pathogenesis of ICIC. The CDR concept's relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function. PMID:28246613

  14. Adaptation in the auditory system: an overview

    Directory of Open Access Journals (Sweden)

    David ePérez-González

    2014-02-01

    Full Text Available The early stages of the auditory system need to preserve the timing information of sounds in order to extract the basic features of acoustic stimuli. At the same time, different processes of neuronal adaptation occur at several levels to further process the auditory information. For instance, auditory nerve fiber responses already experience adaptation of their firing rates, a type of response that can be found in many other auditory nuclei and may be useful for emphasizing the onset of the stimuli. However, it is at higher levels in the auditory hierarchy where more sophisticated types of neuronal processing take place. For example, stimulus-specific adaptation, where neurons show adaptation to frequent, repetitive stimuli, but maintain their responsiveness to stimuli with different physical characteristics, thus representing a distinct kind of processing that may play a role in change and deviance detection. In the auditory cortex, adaptation takes more elaborate forms, and contributes to the processing of complex sequences, auditory scene analysis and attention. Here we review the multiple types of adaptation that occur in the auditory system, which are part of the pool of resources that the neurons employ to process the auditory scene, and are critical to a proper understanding of the neuronal mechanisms that govern auditory perception.

  15. The University Immune System: Overcoming Resistance to Change

    Science.gov (United States)

    Gilley, Ann; Godek, Marisha; Gilley, Jerry W.

    2009-01-01

    A university, similar to any other organization, has an immune system that erects a powerful barrier against change. This article discusses the university immune system and what can be done to counteract its negative effects and thereby allow change to occur.

  16. Breakdown of the innate immune system by bacterial proteases

    NARCIS (Netherlands)

    Laarman, A.J.

    2011-01-01

    Bacteria have developed many strategies to circumvent our immune system to survive and colonize human tissues. One of these strategies is by secreting proteases that specifically target the innate immune system. Aureolysin is a metalloprotease from Staphylococcus aureus which target the main compone

  17. The reaction of the immune system of fish to vaccination

    NARCIS (Netherlands)

    Lamers, C.H.J.

    1985-01-01

    The studies presented in this thesis deal with the effect of bacterial antigens of Yersinia ruckeri and Aeromonashydrophila on the immune system of carp. The antigens were administered by injection or by bath treatment. The effect on the immune system was studied by measuring the numbers of antibody

  18. How Ebola and Marburg Viruses Battle the Immune System

    Science.gov (United States)

    2007-07-01

    adaptive immunity) • Late (fever, malaise, gastrointestinal distress, possible septicaemia, LPS?) B cell (?) CD8+ T cell Hepatocytes CD4+ T cell • High...specific antibodies; mitigation of virus-induced coagulation deficits using recombinant nematode anticoagulant protein c2; antisense compounds or small

  19. Activation of innate immunity during systemic Candida infections

    NARCIS (Netherlands)

    Ifrim, D.C.

    2015-01-01

    Despite the increased knowledge on the mechanisms of Candida recognition and the networks of innate and adaptive host defense activated during infection, much remains to be learned regarding the distinctive modulatory effects of Candida spp on host immune responses. We showed that the chronic exposu

  20. The ERIS Adaptive Optics System

    CERN Document Server

    Riccardi, A; Agapito, G; Antichi, J; Biliotti, V; Blain, C; Briguglio, R; Busoni, L; Carbonaro, L; Di Rico, G; Giordano, C; Pinna, E; Puglisi, A; Spanò, P; Xompero, M; Baruffolo, A; Kasper, M; Egner, S; Valles, M Suàrez; Soenke, C; Downing, M; Reyes, J

    2016-01-01

    ERIS is the new AO instrument for VLT-UT4 led by a Consortium of Max-Planck Institut fuer Extraterrestrische Physik, UK-ATC, ETH-Zurich, ESO and INAF. The ERIS AO system provides NGS mode to deliver high contrast correction and LGS mode to extend high Strehl performance to large sky coverage. The AO module includes NGS and LGS wavefront sensors and, with VLT-AOF Deformable Secondary Mirror and Laser Facility, will provide AO correction to the high resolution imager NIX (1-5um) and the IFU spectrograph SPIFFIER (1-2.5um). In this paper we present the preliminary design of the ERIS AO system and the estimated correction performance.

  1. The ERIS adaptive optics system

    Science.gov (United States)

    Riccardi, A.; Esposito, S.; Agapito, G.; Antichi, J.; Biliotti, V.; Blain, C.; Briguglio, R.; Busoni, L.; Carbonaro, L.; Di Rico, G.; Giordano, C.; Pinna, E.; Puglisi, A.; Spanò, P.; Xompero, M.; Baruffolo, A.; Kasper, M.; Egner, S.; Suàrez Valles, M.; Soenke, C.; Downing, M.; Reyes, J.

    2016-07-01

    ERIS is the new AO instrument for VLT-UT4 led by a Consortium of Max-Planck Institut fuer Extraterrestrische Physik, UK-ATC, ETH-Zurich, ESO and INAF. The ERIS AO system provides NGS mode to deliver high contrast correction and LGS mode to extend high Strehl performance to large sky coverage. The AO module includes NGS and LGS wavefront sensors and, with VLT-AOF Deformable Secondary Mirror and Laser Facility, will provide AO correction to the high resolution imager NIX (1-5um) and the IFU spectrograph SPIFFIER (1-2.5um). In this paper we present the preliminary design of the ERIS AO system and the estimated correction performance.

  2. Fuzzy-Immune PID Control for AMB Systems

    Institute of Scientific and Technical Information of China (English)

    SU Yixin; LI Xuan; ZHOU Zude; CHEN Youping; ZHANG Danhong

    2006-01-01

    In order to improve the dynamic performance of active magnetic bearing systems with highly nonlinear and naturally unstable dynamics, a new nonlinear fuzzy-immune proportional-integral-derivative (PID) controller is proposed by combining the immune feedback law with linear PID control. This controller consists of a PID controller and a basic immune proportional controller in cascaded connection, the nonlinear function of the immune proportional controller is realized by using fuzzy reasoning. Simulation results demonstrate that the active magnetic bearing system with the proposed controller has better dynamic performance and disturbance rejection ability than using the linear PID controller.

  3. The subversion of the immune system by Francisella tularensis

    Directory of Open Access Journals (Sweden)

    Catharine eBosio

    2011-02-01

    Full Text Available Francisella tularensis is a highly virulent bacterial pathogen and the causative agent of tularemia. Perhaps the most impressive feature of this bacterium is its ability to cause lethal disease following inoculation of as few as 15 organisms. This remarkable virulence is, in part, attributed to the ability of this microorganism to evade, disrupt and modulate host immune responses. The objective of this review is to discuss the mechanisms utilized by F. tularensis to evade and inhibit innate and adaptive immune responses. The capability of F. tularensis to interfere with developing immunity in the host was appreciated decades ago. Early studies in humans were the first to demonstrate the ability of F. tularensis to suppress innate immunity. This work noted that humans suffering from tularemia failed to respond to a secondary challenge of endotoxin isolated from unrelated bacteria. Further, anecdotal observations of individuals becoming repeatedly infected with virulent strains of F. tularensis suggests that this bacterium also interferes with the generation of adequate adaptive immunity. Recent advances utilizing the mouse model for in vivo studies and human cells for in vitro work have identified specific bacterial and host compounds that play a role in mediating ubiquitous suppression of the host immune response. Compilation of this work will undoubtedly aid in enhancing our understanding of the myriad of mechanisms utilized by virulent F. tularensis for successful infection, colonization and pathogenesis in the mammalian host.

  4. Evolving Systems and Adaptive Key Component Control

    Science.gov (United States)

    Frost, Susan A.; Balas, Mark J.

    2009-01-01

    We propose a new framework called Evolving Systems to describe the self-assembly, or autonomous assembly, of actively controlled dynamical subsystems into an Evolved System with a higher purpose. An introduction to Evolving Systems and exploration of the essential topics of the control and stability properties of Evolving Systems is provided. This chapter defines a framework for Evolving Systems, develops theory and control solutions for fundamental characteristics of Evolving Systems, and provides illustrative examples of Evolving Systems and their control with adaptive key component controllers.

  5. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

    Science.gov (United States)

    Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

    2016-05-01

    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

  6. Self-Adaptation in Evolving Systems

    CERN Document Server

    Stephens, C R; Mora, J; Waelbroeck, H

    1997-01-01

    A theoretical and experimental analysis is made of the effects of self-adaptation in a simple evolving system. Specifically, we consider the effects of coding the mutation and crossover probabilities of a genetic algorithm evolving in certain model fitness landscapes. The resultant genotype-phenotype mapping is degenerate, there being no direct selective advantage for one probability versus another. We show that the action of mutation and crossover breaks this degeneracy leading to an induced symmetry breaking among the genotypic synonyms. We demonstrate that this induced symmetry breaking allows the system to self-adapt in a time dependent environment.

  7. Adaptive control of solar energy collector systems

    CERN Document Server

    Lemos, João M; Igreja, José M

    2014-01-01

    This book describes methods for adaptive control of distributed-collector solar fields: plants that collect solar energy and deliver it in thermal form. Controller design methods are presented that can overcome difficulties found in these type of plants:they are distributed-parameter systems, i.e., systems with dynamics that depend on space as well as time;their dynamics is nonlinear, with a bilinear structure;there is a significant level of uncertainty in plant knowledge.Adaptive methods form the focus of the text because of the degree of uncertainty in the knowledge of plant dynamics. Parts

  8. Environmentally-adapted local energy systems

    Energy Technology Data Exchange (ETDEWEB)

    Moe, N.; Oefverholm, E. [NUTEK, Stockholm (Sweden); Andersson, Owe [EKAN Gruppen (Sweden); Froste, H. [Swedish Environmental Protection Agency, Stockholm (Sweden)

    1997-10-01

    Energy companies, municipalities, property companies, firms of consultants, environmental groups and individuals are examples of players working locally to shape environmentally adapted energy systems. These players have needed information making them better able to make decisions on cost-efficient, environmentally-adapted energy systems. This book answers many of the questions they have put. The volume is mainly based on Swedish handbooks produced by the Swedish National Board for Industrial and Technical Development, NUTEK, together with the Swedish Environmental Protection Agency. These handbooks have been used in conjunction with municipal energy planning, local Agenda 21 work, to provide a basis for deciding on concrete local energy systems. The contents in brief: -The book throws new light on the concept of energy efficiency; -A section on the environment compares how air-polluting emissions vary with different methods of energy production; -A section contains more than 40 ideas for measures which can be profitable, reduce energy consumption and the impact on the environment all at the same time; -The book gives concrete examples of new, alternative and environmentally-adapted local energy systems. More efficient use of energy is included as a possible change of energy system; -The greatest emphasis is laid upon alternative energy systems for heating. It may be heating in a house, block of flats, office building or school; -Finally, there are examples of environmentally-adapted local energy planning.

  9. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    Science.gov (United States)

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  10. An Adaptive Multimodal Biometrics System using PSO

    Directory of Open Access Journals (Sweden)

    Ola M. Aly

    2013-08-01

    Full Text Available Multimodal biometric systems which fuse information from a number of biometrics, are gaining more attentions lately because they are able to overcome limitations in unimodal biometric systems. These systems are suited for high security applications. Most of the proposed multibiometric systems offer one level of security. In this paper a new approach for adaptive combination of multiple biometrics has been proposed to ensure multiple levels of security. The score level fusion rule is adapted using (PSO Particle Swarm Optimization to ensure the desired system performance corresponding to the desired level of security. The experimental results prove that the proposed multimodal biometric system is appropriate for applications that require different levels of security.

  11. Autopolyreactivity Confers a Holistic Role in the Immune System.

    Science.gov (United States)

    Avrameas, S

    2016-04-01

    In this review, we summarize and discuss some key findings from the study of naturally occurring autoantibodies. The B-cell compartment of the immune system appears to recognize almost all endogenous and environmental antigens. This ability is accomplished principally through autopolyreactive humoral and cellular immune receptors. This extended autopolyreactivity (1) along immunoglobulin gene recombination contributes to the immune system's ability to recognize a very large number of self and non-self constituents; and (2) generates a vast immune network that creates communication channels between the organism's interior and exterior. Thus, the immune system continuously evolves depending on the internal and external stimuli it encounters. Furthermore, this far-reaching network's existence implies activities resembling those of classical biological factors or activities that modulate the function of other classical biological factors. A few such antibodies have already been found. Another important concept is that natural autoantibodies are highly dependent on the presence or absence of commensal microbes in the organism. These results are in line with past and recent findings showing the fundamental influence of the microbiota on proper immune system development, and necessitate the existence of a host-microbe homeostasis. This homeostasis requires that the participating humoral and cellular receptors are able to recognize self-antigens and commensal microbes without damaging them. Autopolyreactive immune receptors expressing low affinity for both types of antigens fulfil this role. The immune system appears to play a holistic role similar to that of the nervous system.

  12. SATZ An Adaptive Sentence Segmentation System

    CERN Document Server

    Palmer, D D

    1995-01-01

    This paper provides a detailed description of the sentence segmentation system first introduced in cmp-lg/9411022. It provides results of systematic experiments involving sentence boundary determination, including context size, lexicon size, and single-case texts. Also included are the results of successfully adapting the system to German and French. The source code for the system is available as a compressed tar file at ftp://cs-tr.CS.Berkeley.EDU/pub/cstr/satz.tar.Z .

  13. Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection.

    Science.gov (United States)

    Stevens, Natalie E; Hatjopolous, Antoinette; Fraser, Cara K; Alsharifi, Mohammed; Diener, Kerrilyn R; Hayball, John D

    2016-07-06

    Passive immunotherapy may have particular benefits for the treatment of severe influenza infection in at-risk populations, however little is known of the impact of passive immunotherapy on the formation of memory responses to the virus. Ideally, passive immunotherapy should attenuate the severity of infection while still allowing the formation of adaptive responses to confer protection from future exposure. In this study, we sought to determine if administration of influenza-specific ovine polyclonal antibodies could inhibit adaptive immune responses in a murine model of lethal influenza infection. Ovine polyclonal antibodies generated against recombinant PR8 (H1N1) hemagglutinin exhibited potent prophylactic capacity and reduced lethality in an established influenza infection, particularly when administered intranasally. Surviving mice were also protected against reinfection and generated normal antibody and cytotoxic T lymphocyte responses to the virus. The longevity of ovine polyclonal antibodies was explored with a half-life of over two weeks following a single antibody administration. These findings support the development of an ovine passive polyclonal antibody therapy for treatment of severe influenza infection which does not affect the formation of subsequent acquired immunity to the virus.

  14. The immune system and inflammation in breast cancer.

    Science.gov (United States)

    Jiang, Xinguo; Shapiro, David J

    2014-01-25

    During different stages of tumor development the immune system can either identify and destroy tumors, or promote their growth. Therapies targeting the immune system have emerged as a promising treatment modality for breast cancer, and immunotherapeutic strategies are being examined in preclinical and clinical models. However, our understanding of the complex interplay between cells of the immune system and breast cancer cells is incomplete. In this article, we review recent findings showing how the immune system plays dual host-protective and tumor-promoting roles in breast cancer initiation and progression. We then discuss estrogen receptor α (ERα)-dependent and ERα-independent mechanisms that shield breast cancers from immunosurveillance and enable breast cancer cells to evade immune cell induced apoptosis and produce an immunosuppressive tumor microenvironment. Finally, we discuss protumorigenic inflammation that is induced during tumor progression and therapy, and how inflammation promotes more aggressive phenotypes in ERα positive breast cancers.

  15. Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

    Directory of Open Access Journals (Sweden)

    Manns Michael P

    2007-06-01

    Full Text Available Abstract Spontaneous clearance of hepatitis C virus (HCV has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100.000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

  16. Engineered Murine HSCs Reconstitute Multi-lineage Hematopoiesis and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Yi-Fen Lu

    2016-12-01

    Full Text Available Hematopoietic stem cell (HSC transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients. Single-cell analysis shows that following engraftment in the bone marrow niche, these engineered HSCs further specify to a hybrid cell type, in which distinct gene regulatory networks of hematopoietic stem/progenitors and differentiated hematopoietic lineages are co-expressed. Our work demonstrates engineering of fully functional HSCs via modulation of genetic programs that govern self-renewal and lineage priming.

  17. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus.

    Science.gov (United States)

    Hansen, Thomas R; Smirnova, Natalia P; Webb, Brett T; Bielefeldt-Ohmann, Helle; Sacco, Randy E; Van Campen, Hana

    2015-06-01

    Infection of pregnant cows with noncytopathic (ncp) bovine viral diarrhea virus (BVDV) induces rapid innate and adaptive immune responses, resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent infection with ncpBVDV in the fetus has been attributed to the inability to mount an immune response before 90-150 days of gestational age. The result is 'immune tolerance', persistent viral replication and shedding of ncpBVDV. In contrast, we describe the chronic upregulation of fetal Type I interferon (IFN) pathway genes and the induction of IFN-γ pathways in fetuses of cows infected on day 75 of gestation. Persistently infected (PI) fetal IFN-γ concentrations also increased at day 97 at the peak of fetal viremia and IFN-γ mRNA was significantly elevated in fetal thymus, liver and spleen 14-22 days post maternal inoculation. PI fetuses respond to ncpBVDV infection through induction of Type I IFN and IFN-γ activated genes leading to a reduction in ncpBVDV titer. We hypothesize that fetal infection with BVDV persists because of impaired induction of IFN-γ in the face of activated Type I IFN responses. Clarification of the mechanisms involved in the IFN-associated pathways during BVDV fetal infection may lead to better detection methods, antiviral compounds and selection of genetically resistant breeding animals.

  18. DESIGN PATTERNS FOR SELF ADAPTIVE SYSTEMS ENGINEERING

    Directory of Open Access Journals (Sweden)

    Yousef Abuseta

    2015-07-01

    Full Text Available Self adaptation has been proposed to overcome the complexity of today's software systems which results from the uncertainty issue. Aspects of uncertainty include changing systems goals, changing resource availability and dynamic operating conditions. Feedback control loops have been recognized as vital elements for engineering self-adaptive systems. However, despite their importance, there is still a lack of systematic way of the design of the interactions between the different components comprising one particular feedback control loop as well as the interactions between components from different control loops . Most existing approaches are either domain specific or too abstract to be useful. In addition, the issue of multiple control loops is often neglected and consequently self adaptive systems are often designed around a single loop. In this paper we propose a set of design patterns for modeling and designing self adaptive software systems based on MAPE-K. Control loop of IBM architecture blueprint which takes into account the multiple control loops issue. A case study is presented to illustrate the applicability of the proposed design patterns.

  19. Between Scylla and Charybdis: the role of the human immune system in the pathogenesis of hepatitis C.

    Science.gov (United States)

    Spengler, Ulrich; Nischalke, Hans Dieter; Nattermann, Jacob; Strassburg, Christian P

    2013-11-28

    Hepatitis C virus (HCV) frequently elicits only mild immune responses so that it can often establish chronic infection. In this case HCV antigens persist and continue to stimulate the immune system. Antigen persistence then leads to profound changes in the infected host's immune responsiveness, and eventually contributes to the pathology of chronic hepatitis. This topic highlight summarizes changes associated with chronic hepatitis C concerning innate immunity (interferons, natural killer cells), adaptive immune responses (immunoglobulins, T cells, and mechanisms of immune regulation (regulatory T cells). Our overview clarifies that a strong anti-HCV immune response is frequently associated with acute severe tissue damage. In chronic hepatitis C, however, the effector arms of the immune system either become refractory to activation or take over regulatory functions. Taken together these changes in immunity may lead to persistent liver damage and cirrhosis. Consequently, effector arms of the immune system will not only be considered with respect to antiviral defence but also as pivotal mechanisms of inflammation, necrosis and progression to cirrhosis. Thus, avoiding Scylla - a strong, sustained antiviral immune response with inital tissue damage - takes the infected host to virus-triggered immunopathology, which ultimately leads to cirrhosis and liver cancer - the realm of Charybdis.

  20. Investigating the adaptive immune response in influenza and secondary bacterial pneumonia and nanoparticle based therapeutic delivery

    Science.gov (United States)

    Chakravarthy, Krishnan V.

    In early 2000, influenza and its associated complications were the 7 th leading cause of death in the United States[1-4]. As of today, this major health problem has become even more of a concern, with the possibility of a potentially devastating avian flu (H5N1) or swine flu pandemic (H1N1). According to the Centers for Disease Control (CDC), over 10 countries have reported transmission of influenza A (H5N1) virus to humans as of June 2006 [5]. In response to this growing concern, the United States pledged over $334 million dollars in international aid for battling influenza[1-4]. The major flu pandemic of the early 1900's provided the first evidence that secondary bacterial pneumonia (not primary viral pneumonia) was the major cause of death in both community and hospital-based settings. Secondary bacterial infections currently account for 35-40% mortality following a primary influenza viral infection [1, 6]. The first component of this work addresses the immunological mechanisms that predispose patients to secondary bacterial infections following a primary influenza viral infection. By assessing host immune responses through various immune-modulatory tools, such as use of volatile anesthetics (i.e. halothane) and Apilimod/STA-5326 (an IL-12/Il-23 transcription blocker), we provide experimental evidence that demonstrates that the overactive adaptive Th1 immune response is critical in mediating increased susceptibility to secondary bacterial infections. We also present data that shows that suppressing the adaptive Th1 immune response enhances innate immunity, specifically in alveolar macrophages, by favoring a pro anti-bacterial phenotype. The second component of this work addresses the use of nanotechnology to deliver therapeutic modalities that affect the primary viral and associated secondary bacterial infections post influenza. First, we used surface functionalized quantum dots for selective targeting of lung alveolar macrophages both in vitro and in vivo

  1. IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms.

    Directory of Open Access Journals (Sweden)

    Brian Wan-Chi Tse

    Full Text Available Interleukin(IL-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM/B4H7-luc. RM1 and RM1(BM/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4. IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4(+ and CD8(+ T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1(-/- mice or in mice depleted of CD4(+ and/or CD8(+ cells than in normal mice. The tumors in RAG1(-/- mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.

  2. Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function

    Directory of Open Access Journals (Sweden)

    Silvana Balzar

    2017-01-01

    Full Text Available Idiopathic chronic inflammatory conditions (ICIC such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system’s thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system’s compartmentalization in the pathogenesis of ICIC. The CDR concept’s relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function.

  3. Towards a Conceptual Framework for Innate Immunity

    CERN Document Server

    Twycross, Jamie

    2010-01-01

    Innate immunity now occupies a central role in immunology. However, artificial immune system models have largely been inspired by adaptive not innate immunity. This paper reviews the biological principles and properties of innate immunity and, adopting a conceptual framework, asks how these can be incorporated into artificial models. The aim is to outline a meta-framework for models of innate immunity.

  4. New insights into innate immune control of systemic candidiasis.

    Science.gov (United States)

    Lionakis, Michail S

    2014-08-01

    Systemic infection caused by Candida species is the fourth leading cause of nosocomial bloodstream infection in modern hospitals and carries high morbidity and mortality despite antifungal therapy. A recent surge of immunological studies in the mouse models of systemic candidiasis and the parallel discovery and phenotypic characterization of inherited genetic disorders in antifungal immune factors that are associated with enhanced susceptibility or resistance to the infection have provided new insights into the cellular and molecular basis of protective innate immune responses against Candida. In this review, the new developments in our understanding of how the mammalian immune system responds to systemic Candida challenge are synthesized and important future research directions are highlighted.

  5. Evaluation of mucosal and systemic immune responses elicited by GPI-0100- adjuvanted influenza vaccine delivered by different immunization strategies.

    Directory of Open Access Journals (Sweden)

    Heng Liu

    Full Text Available Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN or the intrapulmonary (IPL route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.

  6. Galectins as self/non-self recognition receptors in innate and adaptive immunity: An unresolved paradox

    Directory of Open Access Journals (Sweden)

    Gerardo R. Vasta

    2012-07-01

    Full Text Available Galectins are characterized by their binding affinity for ß-galactosides, a unique binding site sequence motif, and wide taxonomic distribution and structural conservation in vertebrates, invertebrates, protista, and fungi. Since their initial description, galectins were considered to bind endogenous (self glycans and mediate developmental processes and cancer. In the past few years, however, numerous studies have described the diverse effects of galectins on cells involved in both innate and adaptive immune responses, and the mechanistic aspects of their regulatory roles in immune homeostasis. More recently, however, evidence has accumulated to suggest that galectins also bind exogenous (non-self glycans on the surface of potentially pathogenic microbes, parasites, and fungi, suggesting that galectins can function as pattern recognition receptors (PRRs in innate immunity. Thus, a perplexing paradox arises by the fact that galectins also recognize lactosamine-containing glycans on the host cell surface during developmental processes and regulation of immune responses. According to the currently accepted model for non-self recognition, PRRs recognize pathogens via highly conserved microbial surface molecules of wide distribution such as LPS or peptidoglycan (pathogen-associated molecular patterns; PAMPs, which are absent in the host. Hence, this would not apply to galectins, which apparently bind similar self/non-self molecular patterns on host and microbial cells. This paradox underscores first, an oversimplification in the use of the PRR/PAMP terminology. Second, and most importantly, it reveals significant gaps in our knowledge about the diversity of the host galectin repertoire, and the subcellular targeting, localization, and secretion. Furthermore, our knowledge about the structural and biophysical aspects of their interactions with the host and microbial carbohydrate moieties is fragmentary, and warrants further investigation.

  7. An adaptive strategy for controlling chaotic system

    Institute of Scientific and Technical Information of China (English)

    曹一家; 张红先

    2003-01-01

    This paper presents an adaptive strategy for controlling chaotic systems. By employing the phase space reconstruction technique in nonlinear dynamical systems theory, the proposed strategy transforms the nonlinear system into canonical form, and employs a nonlinear observer to estimate the uncertainties and disturbances of the nonlinear system, and then establishes a state-error-like feedback law. The developed control scheme allows chaos control in spite of modeling errors and parametric variations. The effectiveness of the proposed approach has been demonstrated through its applications to two well-known chaotic systems : Duffing oscillator and Rǒssler chaos.

  8. An adaptive strategy for controlling chaotic system.

    Science.gov (United States)

    Cao, Yi-Jia; Hang, Hong-Xian

    2003-01-01

    This paper presents an adaptive strategy for controlling chaotic systems. By employing the phase space reconstruction technique in nonlinear dynamical systems theory, the proposed strategy transforms the nonlinear system into canonical form, and employs a nonlinear observer to estimate the uncertainties and disturbances of the nonlinear system, and then establishes a state-error-like feedback law. The developed control scheme allows chaos control in spite of modeling errors and parametric variations. The effectiveness of the proposed approach has been demonstrated through its applications to two well-known chaotic systems: Duffing oscillator and Rössler chaos.

  9. An adaptive strategy for controlling chaotic system

    Institute of Scientific and Technical Information of China (English)

    曹一家; 张红先

    2003-01-01

    This paper presents an adaptive strategy for controlling chaotic systems. By employing the phase space reconstruction technique in nonlinear dynamical systems theory, the proposed strategy transforms the nonlinear system into canonical form, and employs a nonlinear observer to estimate the uncertainties and disturbances of the nonlinear system, and then establishes a state-error-like feedback law. The developed control scheme allows chaos control in spite of modeling errors and parametric variations. The effectiveness of the proposed approach has been demonstrated through its applications to two well-known chaotic systems: Duffing oscillator and Rossler chaos.

  10. Nociception and role of immune system in pain.

    Science.gov (United States)

    Verma, Vivek; Sheikh, Zeeshan; Ahmed, Ahad S

    2015-09-01

    Both pain and inflammation are protective responses. However, these self-limiting conditions (with well-established negative feedback loops) become pathological if left uncontrolled. Both pain and inflammation can interact with each other in a multi-dimensional manner. These interactions are known to create an array of 'difficult to manage' pathologies. This review explains in detail the role of immune system and the related cells in peripheral sensitization and neurogenic inflammation. Various neuro-immune interactions are analyzed at peripheral, sensory and central nervous system levels. Innate immunity plays a critical role in central sensitization and in establishing acute pain as chronic condition. Moreover, inflammatory mediators also exhibit psychological effects, thus contributing towards the emotional elements associated with pain. However, there is also a considerable anti-inflammatory and analgesic role of immune system. This review also attempts to enlist various novel pharmacological approaches that exhibit their actions through modification of neuro-immune interface.

  11. Adaptive immune neuroprotection in G93A-SOD1 amyotrophic lateral sclerosis mice.

    Directory of Open Access Journals (Sweden)

    Rebecca Banerjee

    Full Text Available BACKGROUND: Innate neuroimmune dysfunction is a pathobiological feature of amyotrophic lateral sclerosis (ALS. However, links, if any, between disease and adaptive immunity are poorly understood. Thus, the role of T cell immunity in disease was investigated in human G93A superoxide dismutase 1 (SOD1 transgenic (Tg mice and subsequently in ALS patients. METHODS AND FINDINGS: Quantitative and qualitative immune deficits in lymphoid cell and T cell function were seen in G93A-SOD1 Tg mice. Spleens of Tg animals showed reductions in size, weight, lymphocyte numbers, and morphological deficits at terminal stages of disease compared to their wild-type (Wt littermates. Spleen sizes and weights of pre-symptomatic Tg mice were unchanged, but deficits were readily seen in T cell proliferation coincident with increased annexin-V associated apoptosis and necrosis of lymphocytes. These lymphoid deficits paralleled failure of Copolymer-1 (COP-1 immunization to affect longevity. In addition, among CD4(+ T cells in ALS patients, levels of CD45RA(+ (naïve T cells were diminished, while CD45RO(+ (memory T cells were increased compared to age-matched caregivers. In attempts to correct mutant SOD1 associated immune deficits, we reconstituted SOD1 Tg mice with unfractionated naïve lymphocytes or anti-CD3 activated CD4(+CD25(+ T regulatory cells (Treg or CD4(+CD25(- T effector cells (Teff from Wt donor mice. While naive lymphocytes failed to enhance survival, both polyclonal-activated Treg and Teff subsets delayed loss of motor function and extended survival; however, only Treg delayed neurological symptom onset, whereas Teff increased latency between disease onset and entry into late stage. CONCLUSIONS: A profound and progressive immunodeficiency is operative in G93A-SOD1 mice and is linked to T cell dysfunction and the failure to elicit COP-1 neuroprotective immune responses. In preliminary studies T cell deficits were also observed in human ALS. These findings

  12. A cognitive computational model inspired by the immune system response.

    Science.gov (United States)

    Abdo Abd Al-Hady, Mohamed; Badr, Amr Ahmed; Mostafa, Mostafa Abd Al-Azim

    2014-01-01

    The immune system has a cognitive ability to differentiate between healthy and unhealthy cells. The immune system response (ISR) is stimulated by a disorder in the temporary fuzzy state that is oscillating between the healthy and unhealthy states. However, modeling the immune system is an enormous challenge; the paper introduces an extensive summary of how the immune system response functions, as an overview of a complex topic, to present the immune system as a cognitive intelligent agent. The homogeneity and perfection of the natural immune system have been always standing out as the sought-after model we attempted to imitate while building our proposed model of cognitive architecture. The paper divides the ISR into four logical phases: setting a computational architectural diagram for each phase, proceeding from functional perspectives (input, process, and output), and their consequences. The proposed architecture components are defined by matching biological operations with computational functions and hence with the framework of the paper. On the other hand, the architecture focuses on the interoperability of main theoretical immunological perspectives (classic, cognitive, and danger theory), as related to computer science terminologies. The paper presents a descriptive model of immune system, to figure out the nature of response, deemed to be intrinsic for building a hybrid computational model based on a cognitive intelligent agent perspective and inspired by the natural biology. To that end, this paper highlights the ISR phases as applied to a case study on hepatitis C virus, meanwhile illustrating our proposed architecture perspective.

  13. Immune System Dysregulation in First-Onset Postpartum Psychosis

    NARCIS (Netherlands)

    Bergink, Veerle; Burgerhout, Karin M.; Weigelt, Karin; Pop, Victor J.; de Wit, Harm; Drexhage, Roos C.; Kushner, Steven A.; Drexhage, Hemmo A.

    2013-01-01

    Background: Accumulating evidence suggests that dysregulation of the immune system represents an important vulnerability factor for mood disorders. Postpartum psychosis (PP) is a severe mood disorder occurring within 4 weeks after delivery, a period of heightened immune responsiveness and an altered

  14. Processing and Linguistics Properties of Adaptable Systems

    Directory of Open Access Journals (Sweden)

    Dumitru TODOROI

    2006-01-01

    Full Text Available Continuation and development of the research in Adaptable Programming Initialization [Tod-05.1,2,3] is presented. As continuation of [Tod-05.2,3] in this paper metalinguistic tools used in the process of introduction of new constructions (data, operations, instructions and controls are developed. The generalization schemes of evaluation of adaptable languages and systems are discussed. These results analogically with [Tod-05.2,3] are obtained by the team, composed from the researchers D. Todoroi [Tod-05.4], Z. Todoroi [ZTod-05], and D. Micusa [Mic-03]. Presented results will be included in the book [Tod-06].

  15. Two Perspectives on Information System Adaptation

    DEFF Research Database (Denmark)

    Jensen, Tina Blegind; Kjærgaard, Annemette; Svejvig, Per

    Institutional theory has proven to be a central analytical perspective for investigating the role of larger social and historical structures of Information System (IS) adaptation. However, it does not explicitly account for how organizational actors make sense of and enact IS in their local context...... for investigating the phenomenon of IS adaptation. Furthermore, we explore a combination of the two theories with a case study in a health care setting where an Electronic Patient Record (EPR) system was introduced and used by a group of doctors. The empirical case provides evidence of how existing institutional...... structures influenced the doctors' sensemaking of the EPR system. Additionally, it illustrates how the doctors made sense of the EPR system in practice. The paper outlines that: 1) institutional theory has its explanatory power at the organizational field and organizational/group level of analysis focusing...

  16. Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections

    Institute of Scientific and Technical Information of China (English)

    DEWAN Sheilesh Kumar; ZHENG Song-bai; XIA Shi-jin; BILL Kalionis

    2012-01-01

    Objective To review the senescent remodeling of the immune system with aging and its relevance to the increased susceptibility of the elderly to infectious diseases,along with an outlook on emerging immunological biomarkers.Data sources The data selected were from PubMed with relevant published articles in English or French from 1995 to the present.Searches were made using the terms “immunosenescence” and “aging” paired with the following:“innate immunity”,“T-cell”,“B-cell”,“adaptive immunity” and “biomarkers“.Articles were reviewed for additional citations and some information was gathered from web searches.Study selection Articles on aging of both the innate and adaptive immunity were reviewed,with special attention to the remodeling effect on the ability of the immune system to fight infectious diseases.Articles related to biomarkers of immunosenescence were selected with the goal of identifying immunological biomarkers predisposing the elderly to infections.Results Innate immunity is generally thought to be relatively well preserved or enhanced during aging compared with adaptive immunity which manifests more profound alterations.However,evidence,particularly in the last decade,reveals that both limbs of the immune system undergo profound remodeling with aging.Reported data on adaptive immunity is consistent and changes are well established but conflicting results about innate immunity were reported between in vivo and in vitro studies,as well as between murine and human studies.Epidemiological data suggests increased predisposition of the elderly to infections,but no compelling scientific evidence has directly linked senescent immune remodeling to this increased susceptibility.Recently,growing interest in identifying immunological biomarkers and defining “immune risk phenotypes/profiles” (IRP) has been expressed.Identification of biomarkers is in its early days and few potential biomarkers have been identified,with the Swedish

  17. The Role of Plasmacytoid Dendritic Cells in Innate and Adaptive Immune Responses against Alpha Herpes Virus Infections

    Directory of Open Access Journals (Sweden)

    Philipp Schuster

    2011-01-01

    Full Text Available In 1999, two independent groups identified plasmacytoid dendritic cells (PDC as major type I interferon- (IFN- producing cells in the blood. Since then, evidence is accumulating that PDC are a multifunctional cell population effectively coordinating innate and adaptive immune responses. This paper focuses on the role of different immune cells and their interactions in the surveillance of alpha herpes virus infections, summarizes current knowledge on PDC surface receptors and their role in direct cell-cell contacts, and develops a risk factor model for the clinical implications of herpes simplex and varicella zoster virus reactivation. Data from studies involving knockout mice and cell-depletion experiments as well as human studies converge into a “spider web”, in which the direct and indirect crosstalk between many cell populations tightly controls acute, latent, and recurrent alpha herpes virus infections. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses more extensively than previously thought.

  18. Novel Link Adaptation Schemes for OFDM System

    Institute of Scientific and Technical Information of China (English)

    LEI Ming; CAI Peng; XU Yue-shan; ZHANG Ping

    2003-01-01

    Orthogonal Frequency Division Multiplexing (OFDM) is the most promising technique supporting the high data rate transmission. The combination of the link adaptation and OFDM can further increase the spectral efficiency. In this paper, we put forward two link adaptation schemes for OFDM system which have the advantages of both flexibility and practicability. Both of the two novel link adaptation schemes are based on the iterative mechanism to allocate the bit and power to subcarriers according to their channel gains and noisy levels which are assumed to be already known at the transmitter. The candidate modulation modes are determined freely before the link adaptation schemes are performed. The distinction between the two novel link adaptation schemes is that in the novel scheme A, the modulation mode is upgraded to the neighboring higher-order mode, while in the novel scheme B the modulation is upgraded to the genuine optimal mode. Therefore, the novel scheme A has the advantage of lower complexity and the novel scheme B has the advantage of higher spectral efficiency.

  19. Activation of the Arabidopsis thaliana immune system by combinations of common ACD6 alleles.

    Directory of Open Access Journals (Sweden)

    Marco Todesco

    2014-07-01

    Full Text Available A fundamental question in biology is how multicellular organisms distinguish self and non-self. The ability to make this distinction allows animals and plants to detect and respond to pathogens without triggering immune reactions directed against their own cells. In plants, inappropriate self-recognition results in the autonomous activation of the immune system, causing affected individuals to grow less well. These plants also suffer from spontaneous cell death, but are at the same time more resistant to pathogens. Known causes for such autonomous activation of the immune system are hyperactive alleles of immune regulators, or epistatic interactions between immune regulators and unlinked genes. We have discovered a third class, in which the Arabidopsis thaliana immune system is activated by interactions between natural alleles at a single locus, ACCELERATED CELL DEATH 6 (ACD6. There are two main types of these interacting alleles, one of which has evolved recently by partial resurrection of a pseudogene, and each type includes multiple functional variants. Most previously studies hybrid necrosis cases involve rare alleles found in geographically unrelated populations. These two types of ACD6 alleles instead occur at low frequency throughout the range of the species, and have risen to high frequency in the Northeast of Spain, suggesting a role in local adaptation. In addition, such hybrids occur in these populations in the wild. The extensive functional variation among ACD6 alleles points to a central role of this locus in fine-tuning pathogen defenses in natural populations.

  20. Micromanagement of the immune system by microRNAs.

    Science.gov (United States)

    Lodish, Harvey F; Zhou, Beiyan; Liu, Gwen; Chen, Chang-Zheng

    2008-02-01

    MicroRNAs (miRNAs) are an abundant class of evolutionarily conserved small non-coding RNAs that are thought to control gene expression by targeting mRNAs for degradation or translational repression. Emerging evidence suggests that miRNA-mediated gene regulation represents a fundamental layer of genetic programmes at the post-transcriptional level and has diverse functional roles in animals. Here, we provide an overview of the mechanisms by which miRNAs regulate gene expression, with specific focus on the role of miRNAs in regulating the development of immune cells and in modulating innate and adaptive immune responses.

  1. The impact of T cell intrinsic antigen adaptation on peripheral immune tolerance.

    Directory of Open Access Journals (Sweden)

    Nevil J Singh

    2006-10-01

    Full Text Available Overlapping roles have been ascribed for T cell anergy, clonal deletion, and regulation in the maintenance of peripheral immunological tolerance. A measurement of the individual and additive impacts of each of these processes on systemic tolerance is often lacking. In this report we have used adoptive transfer strategies to tease out the unique contribution of T cell intrinsic receptor calibration (adaptation in the maintenance of tolerance to a systemic self-antigen. Adoptively transferred naïve T cells stably calibrated their responsiveness to a persistent self-antigen in both lymphopenic and T cell-replete hosts. In the former, this state was not accompanied by deletion or suppression, allowing us to examine the unique contribution of adaptation to systemic tolerance. Surprisingly, adapting T cells could chronically help antigen-expressing B cells, leading to polyclonal hypergammaglobulinemia and pathology, in the form of mild arthritis. The helper activity mediated by CD40L and cytokines was evident even if the B cells were introduced after extended adaptation of the T cells. In contrast, in the T cell-replete host, neither arthritis nor autoantibodies were induced. The containment of systemic pathology required host T cell-mediated extrinsic regulatory mechanisms to synergize with the cell intrinsic adaptation process. These extrinsic mechanisms prevented the effector differentiation of the autoreactive T cells and reduced their precursor frequency, in vivo.

  2. Modeling evolution and immune system by cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Bezzi, M. [Scuola Internazionale Superiore di Studi Avanzati, Trieste (Italy); Istituto Nazionale di Fisica della Materia, Florence (Italy)

    2001-07-01

    In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section.

  3. Understanding the vertebrate immune system: insights from the reptilian perspective.

    Science.gov (United States)

    Zimmerman, L M; Vogel, L A; Bowden, R M

    2010-03-01

    Reptiles are ectothermic amniotes, providing the key link between ectothermic anamniotic fishes and amphibians, and endothermic amniotic birds and mammals. A greater understanding of reptilian immunity will provide important insights into the evolutionary history of vertebrate immunity as well as the growing field of eco-immunology. Like mammals, reptile immunity is complex and involves innate, cell-mediated and humoral compartments but, overall, there is considerably less known about immune function in reptiles. We review the current literature on each branch of the reptilian immune system, placing this information in context to other vertebrates. Further, we identify key areas that are prime for research as well as areas that are lagging because of lack of reagents in non-model systems.

  4. Clonal Selection Based Artificial Immune System for Generalized Pattern Recognition

    Science.gov (United States)

    Huntsberger, Terry

    2011-01-01

    The last two decades has seen a rapid increase in the application of AIS (Artificial Immune Systems) modeled after the human immune system to a wide range of areas including network intrusion detection, job shop scheduling, classification, pattern recognition, and robot control. JPL (Jet Propulsion Laboratory) has developed an integrated pattern recognition/classification system called AISLE (Artificial Immune System for Learning and Exploration) based on biologically inspired models of B-cell dynamics in the immune system. When used for unsupervised or supervised classification, the method scales linearly with the number of dimensions, has performance that is relatively independent of the total size of the dataset, and has been shown to perform as well as traditional clustering methods. When used for pattern recognition, the method efficiently isolates the appropriate matches in the data set. The paper presents the underlying structure of AISLE and the results from a number of experimental studies.

  5. ADAPTING LINUX AS MOBILE OPERATING SYSTEM

    Directory of Open Access Journals (Sweden)

    Kaushik Velusamy

    2013-01-01

    Full Text Available In this fast growing world, people are increasingly mobile; everything is fast, connected and highly secured. All these have put up the requirements on mobile devices and leads to several features being added in the mobile operating systems and its architecture. The development of the next generation software platform based on Linux for mobile phones provides enhanced user experience, power management, cloud support and openness in the design. In spite of many studies on Linux, the investigations on the challenges and benefits of reusing and adapting the Linux kernel to mobile platforms is very less. In this study, a study on architecture of the Linux, its adaptations for a mobile operating system, requirements and analysis for Linux mobile phones, comparison with android and solution technologies to satisfy the requirements for a Linux mobile operating system are analysed and discussed."

  6. Adaptive vibration isolation system for diesel engine

    Institute of Scientific and Technical Information of China (English)

    YANG Tie-jun; ZHANG Xin-yu; XIAO You-hong; HUANG Jin-e; LIU Zhi-gang

    2004-01-01

    An active two-stage isolation mounting, on which servo-hydraulic system is used as the actuator (secondary vibration source) and a diesel engine is used as primary vibration source, has been built. The upper mass of the mounting is composed of a 495diesel and an electrical eddy current dynamometer. The lower mass is divided into four small masses to which servo-hydraulic actuator and rubber isolators are attached. According to the periodical characteristics of diesel vibration signals, a multi-point adaptive strategy based on adaptive comb filtered algorithm is applied to active multi-direction coupled vibrations control for the engine. The experimental results demonstrate that a good suppression in the effective range of phase compensation in secondary path (within 100Hz) at different operation conditions is achieved, and verify that this strategy is effective. The features of the active system, the development activities carried out on the system and experimental results are discussed in the paper.

  7. T cells and the humoral immune system

    NARCIS (Netherlands)

    W.B. van Muiswinkel (Willem)

    1975-01-01

    textabstractLymphoid cells and macrophages play an important role in the development and rnaintance of humoral and cellular immunity in mammals. The lymphoid cells in the peripheral lymphoid organs are divided into two major classes: (1) thymus-derived lymphocytes or T cells and (2) bursa-equivalent

  8. Conceptual development of the immune system as a sixth sense.

    Science.gov (United States)

    Blalock, J Edwin; Smith, Eric M

    2007-01-01

    Understanding how and why the immune and nervous systems communicate in a bidirectional pathway has been fundamental to the development of the psychoneuroimmunology (PNI) field. This review will discuss some of the pivotal results that found the nervous and immune systems use a common chemical language for intra and inter-system communication. Specifically the nervous and immune systems produce a common set of peptide and nonpeptide neurotransmitters and cytokines that provides a common repertoire of receptors and ligands between the two systems. These studies led to the concept that through the sharing of ligands and receptors the immune system could serve as a sixth sense to detect things the body cannot otherwise hear, see, smell, taste or touch. Pathogens, tumors, and allergens are detected with great sensitivity and specificity by the immune system. As a sixth sense the immune system is a means to signal and mobilize the body to respond to these types of challenges. The paper will also review in a chronological manner some of the PNI-related studies important to validating the sixth sense concept. Finally, the review will suggest ways to apply the new found knowledge of the sixth sense to understanding a placebo effect and developing new therapeutic approaches for treatment of human diseases.

  9. Adaptive Embedded Digital System for Plasma Diagnostics

    Science.gov (United States)

    González, Angel; Rodríguez, Othoniel; Mangual, Osvaldo; Ponce, Eduardo; Vélez, Xavier

    2014-05-01

    An Adaptive Embedded Digital System to perform plasma diagnostics using electrostatic probes was developed at the Plasma Engineering Laboratory at Polytechnic University of Puerto Rico. The system will replace the existing instrumentation at the Laboratory, using reconfigurable hardware to minimize the equipment and software needed to perform diagnostics. The adaptability of the design resides on the possibility of replacing the computational algorithm on the fly, allowing to use the same hardware for different probes. The system was prototyped using Very High Speed Integrated Circuits Hardware Description Language (VHDL) into an Field Programmable Gate Array (FPGA) board. The design of the Embedded Digital System includes a Zero Phase Digital Filter, a Derivative Unit, and a Computational Unit designed using the VHDL-2008 Support Library. The prototype is able to compute the Plasma Electron Temperature and Density from a Single Langmuir probe. The system was tested using real data previously acquired from a single Langmuir probe. The plasma parameters obtained from the embedded system were compared with results computed using matlab yielding excellent matching. The new embedded system operates on 4096 samples versus 500 on the previous system, and completes its computations in 26 milliseconds compared with about 15 seconds on the previous system.

  10. Analytical tools for the study of cellular glycosylation in the immune system

    Directory of Open Access Journals (Sweden)

    Yvette eVan Kooyk

    2013-12-01

    Full Text Available It is becoming increasingly clear that glycosylation plays important role in intercellular communication within the immune system. Glycosylation-dependent interactions are crucial for the innate and adaptive immune system and regulate immune cell trafficking, synapse formation, activation, and survival. These functions take place by the cis or trans interaction of lectins with glycans. Classical immunological and biochemical methods have been used for the study of lectin function; however, the investigation of their counterparts, glycans, requires very specialized methodologies that have been extensively developed in the past decade within the Glycobiology scientific community. This Mini-Review intends to summarize the available technology for the study of glycan biosynthesis, its regulation and characterization for their application to the study of glycans in Immunology.

  11. Innate immune and adaptive immune responses in fungal infections%真菌感染中的先天免疫和适应性免疫反应

    Institute of Scientific and Technical Information of China (English)

    宋营改; 任翊

    2013-01-01

    宿主对致病真菌感染的免疫反应基于免疫细胞的功能可塑性,免疫细胞无论是个体还是群体,其表型或功能特征都具有可变性.利用表型分群的方法可以加深对真菌感染后免疫反应的认识,探讨导致细胞表型变化的影响因素,以及变化后的结果.在抗真菌感染中宿主先天免疫和适应性免疫同等重要,最佳的免疫反应结果在于促炎和抗炎反应的平衡,细胞免疫反应和体液免疫反应的平衡.%The functional plasticity of immune cells is the foundation of immunity in the interaction between host and fungal pathogens. The phenotypes or functional character of single cells or cell groups can vary. However, phenotyping can be used to understand a host's immune response after a fungal infection, what factors cause the phenotypes of immune cells to change, and the results of these changes. Innate immunity and adaptive immunity are both believed to be equally important in fungal infections. The best immune response is based on a balance of proinflammatory and anti-inflammatory responses and a balance of cell immunity and humoral immunity.

  12. Optimizing Mining Association Rules for Artificial Immune System based Classification

    Directory of Open Access Journals (Sweden)

    SAMEER DIXIT

    2011-08-01

    Full Text Available The primary function of a biological immune system is to protect the body from foreign molecules known as antigens. It has great pattern recognition capability that may be used to distinguish between foreigncells entering the body (non-self or antigen and the body cells (self. Immune systems have many characteristics such as uniqueness, autonomous, recognition of foreigners, distributed detection, and noise tolerance . Inspired by biological immune systems, Artificial Immune Systems have emerged during the last decade. They are incited by many researchers to design and build immune-based models for a variety of application domains. Artificial immune systems can be defined as a computational paradigm that is inspired by theoretical immunology, observed immune functions, principles and mechanisms. Association rule mining is one of the most important and well researched techniques of data mining. The goal of association rules is to extract interesting correlations, frequent patterns, associations or casual structures among sets of items in thetransaction databases or other data repositories. Association rules are widely used in various areas such as inventory control, telecommunication networks, intelligent decision making, market analysis and risk management etc. Apriori is the most widely used algorithm for mining the association rules. Other popular association rule mining algorithms are frequent pattern (FP growth, Eclat, dynamic itemset counting (DIC etc. Associative classification uses association rule mining in the rule discovery process to predict the class labels of the data. This technique has shown great promise over many other classification techniques. Associative classification also integrates the process of rule discovery and classification to build the classifier for the purpose of prediction. The main problem with the associative classification approach is the discovery of highquality association rules in a very large space of

  13. Adaptive Immunity in Ankylosing Spondylitis: Phenotype and Functional Alterations of T-Cells before and during Infliximab Therapy

    Directory of Open Access Journals (Sweden)

    Balázs Szalay

    2012-01-01

    Flow cytometry was used to determine T-cell subsets in peripheral blood and their intracellular signaling during activation. The prevalence of Th2 and Th17 cells responsible for the regulation of adaptive immunity was higher in AS than in 9 healthy controls. Although IFX therapy improved patients' condition, immune phenotype did not normalize. Cytoplasmic and mitochondrial calcium responses of CD4+ and CD8+ cells to a specific activation were delayed, while NO generation was increased in AS. NO generation normalized sooner upon IFX than calcium response. These results suggest an abnormal immune phenotype with functional disturbances of CD4+ and CD8+ cells in AS.

  14. A Holistic and Immune System inspired Security Framework

    OpenAIRE

    Mwakalinga, G. Jeffy; Yngström, Louise; Kowalski, Stewart

    2009-01-01

    This paper presents a Framework for adaptive information security systems for securing information systems. Information systems today are vulnerable and not adaptive to the dynamic environments because initial development of these systems focused on computer technology and communications protocol only. Most research in information security does not consider culture of users, system environments and does not pay enough attention to the enemies of information systems. As a result, users serve t...

  15. The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.

    Science.gov (United States)

    Masi, Anne; Glozier, Nicholas; Dale, Russell; Guastella, Adam J

    2017-04-01

    Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.

  16. [The role of the immune system in hereditary demyelinating neuropathies].

    Science.gov (United States)

    Mäurer, M; Toyka, K V; Martini, R

    2005-06-01

    Hereditary neuropathies, e.g., Charcot-Marie-Tooth (CMT) disease, are inherited diseases of the peripheral nervous system causing chronic progressive motor and sensory dysfunction. Most neuropathies are due to mutations in myelin genes such as PMP22, P0, and the gap junction protein Cx32. Myelin mutant mice are regarded as suitable animal models for several forms of hereditary neuropathies and are important neurobiological tools for the evaluation of pathogenetic and therapeutic concepts in hereditary neuropathies. Using these animal models we could recently show that the immune system is involved in the pathogenesis of hereditary neuropathies. Due to the phenotypic similarities we also consider the immune system important for human inherited neuropathies, in particular since several case reports demonstrate a beneficial effect of immune therapies in patients with hereditary neuropathies. In this review we compare findings from animal models and human disease to elucidate the role of the immune system in hereditary neuropathies.

  17. Dynamic detection for computer virus based on immune system

    Institute of Scientific and Technical Information of China (English)

    LI Tao

    2008-01-01

    Inspired by biological immune system,a new dynamic detection model for computer virus based on immune system is proposed.The quantitative description of the model is given.The problem of dynamic description for self and nonself in a computer virus immune system is solved,which reduces the size of self set.The new concept of dynamic tolerance,as well as the new mechanisms of gene evolution and gene coding for immature detectors is presented,improving the generating efficiency of mature detectors,reducing the false-negative and false-positive rates.Therefore,the difficult problem,in which the detector training cost is exponentially related to the size of self-set in a traditional computer immune system,is thus overcome.The theory analysis and experimental results show that the proposed model has better time efficiency and detecting ability than the classic model ARTIS.

  18. Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances.

    Science.gov (United States)

    Haapakoski, Rita; Ebmeier, Klaus P; Alenius, Harri; Kivimäki, Mika

    2016-04-01

    The inflammation theory of depression, proposed over 20years ago, was influenced by early studies on T cell responses and since then has been a stimulus for numerous research projects aimed at understanding the relationship between immune function and depression. Observational studies have shown that indicators of immunity, especially C reactive protein and proinflammatory cytokines, such as interleukin 6, are associated with an increased risk of depressive disorders, although the evidence from randomized trials remains limited and only few studies have assessed the interplay between innate and adaptive immunity in depression. In this paper, we review current knowledge on the interactions between central and peripheral innate and adaptive immune molecules and the potential role of immune-related activation of microglia, inflammasomes and indoleamine-2,3-dioxygenase in the development of depressive symptoms. We highlight how combining basic immune methods with more advanced 'omics' technologies would help us to make progress in unravelling the complex associations between altered immune function and depressive disorders, in the identification of depression-specific biomarkers and in developing immunotherapeutic treatment strategies that take individual variability into account.

  19. Understanding Supply Networks from Complex Adaptive Systems

    Directory of Open Access Journals (Sweden)

    Jamur Johnas Marchi

    2014-10-01

    Full Text Available This theoretical paper is based on complex adaptive systems (CAS that integrate dynamic and holistic elements, aiming to discuss supply networks as complex systems and their dynamic and co-evolutionary processes. The CAS approach can give clues to understand the dynamic nature and co-evolution of supply networks because it consists of an approach that incorporates systems and complexity. This paper’s overall contribution is to reinforce the theoretical discussion of studies that have addressed supply chain issues, such as CAS.

  20. ADAPTIVE CONTROL AND IDENTIFICATION OF CHAOTIC SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    LI ZHI; HAN CHONG-ZHAO

    2001-01-01

    A novel adaptive control and identification on-line method is proposed for a class of chaotic system with uncertain parameters. We prove that, using the presented method, a controller and identifier is developed which can remove chaos in nonlinear systems and make the system asymptotically stabilizing to an arbitrarily desired smooth orbit. And at the same time, estimates to uncertain parameters converge to their true values. The advantage of our method over the existing result is that the controller and identifier is directly constructed by analytic formula without knowing unknown bounds about uncertain parameters in advance. A computer simulation example is given to validate the proposed approach.

  1. Semantic models for adaptive interactive systems

    CERN Document Server

    Hussein, Tim; Lukosch, Stephan; Ziegler, Jürgen; Calvary, Gaëlle

    2013-01-01

    Providing insights into methodologies for designing adaptive systems based on semantic data, and introducing semantic models that can be used for building interactive systems, this book showcases many of the applications made possible by the use of semantic models.Ontologies may enhance the functional coverage of an interactive system as well as its visualization and interaction capabilities in various ways. Semantic models can also contribute to bridging gaps; for example, between user models, context-aware interfaces, and model-driven UI generation. There is considerable potential for using

  2. Hyperthermia on skin immune system and its application in the treatment of HPV-infected skin diseases

    Institute of Scientific and Technical Information of China (English)

    Gao Xinghua; Chen Hongduo

    2014-01-01

    In this paper,the effects of hyperthermia on cells and immune system are introduced briefly. The mechanism of action of hyperthermia on human papilloma virus (HPV)-infected skin diseases was elaborated as an example in this paper. Many studies have proved that hyperthermia affects a number of cellular and molecu-lar constitutes in the skin immune system,involving both innate and adaptive immune responses;the efficacy of hyperthermia in treating some infectious and cancerous conditions has been validated and applied in clinics, while molecular mechanisms of hyperthermia affecting the immunereaction is still unclear.

  3. Hyperthermia on skin immune system and its application in the treatment of HPV-infected skin diseases

    Institute of Scientific and Technical Information of China (English)

    Gao Xinghua; Chen Hongduo

    2014-01-01

    In this paper, the effects of hyperthermia on cells and immune system are introduced briefly. The mechanism of action of hyperthermia on human papilloma virus (HPV)-infected skin diseases was elaborated as an example in this paper. Many studies have proved that hyperthermia affects a number of cellular and molecu- lar constitutes in the skin immune system, involving both innate and adaptive immune responses; the efficacy of hyperthermia in treating some infectious and cancerous conditions has been validated and applied in clinics, while molecular mechanisms of hyperthermia affecting the immunereaction is still unclear.

  4. Characterising the CRISPR immune system in Archaea using genome sequence analysis

    DEFF Research Database (Denmark)

    Shah, Shiraz Ali

    Archaea, a group of microorganisms distinct from bacteria and eukaryotes, are equipped with an adaptive immune system called the CRISPR system, which relies on an RNA interference mechanism to combat invading viruses and plasmids. Using a genome sequence analysis approach, the four components...... of archaeal genomic CRISPR loci were analysed, namely, repeats, spacers, leaders and cas genes. Based on analysis of spacer sequences it was predicted that the immune system combats viruses and plasmids by targeting their DNA. Furthermore, analysis of repeats, leaders and cas genes revealed that CRISPR...... systems exist as distinct families which have key differences between themselves. Closely related organisms were seen harbouring different CRISPR systems, while some distantly related species carried similar systems, indicating frequent horizontal exchange. Moreover, it was found that cas genes of Type I...

  5. Active chinese mistletoe lectin-55 enhances colon cancer surveillance through regulating innate and adaptive immune responses

    Institute of Scientific and Technical Information of China (English)

    Yan-Hui Ma; Wei-Zhi Cheng; Fang Gong; An-Lun Ma; Qi-Wen Yu; Ji-Ying Zhang; Chao-Ying Hu; Xue-Hua Chen; Dong-Qing Zhang

    2008-01-01

    AIM:To investigate the potential role of Active Chinese mistletoe lectin-55 (ACML-55) in tumor immune surveillance.METHODS:In this study,an experimental model was established by hypodermic inoculating the colon cancer cell line CT26 (5×105 cells) into BALB/c mice.The experimental treatment was orally administered with ACML-55 or PBS,followed by the inoculation of colon cancer cell line CT26.Intracellular cytokine staining was used to detect IFN-y production by tumor antigen specific CD8+ T cells.FACS analysis was employed to profile composition and activation of CD4+,CD8+,γδ T and NK cells.RESULTS:Our results showed,compared to PBS treated mice,ACML-55 treatment significantly delayed colon cancer development in colon cancer-bearing Balb/c mice in vivo.Treatment with ACML-55 enhanced both Ag specific activation and proliferation of CD4+ and CD8+ T cells,and increased the number of tumor Ag specific CD8+ T cells,it was more important to increase the frequency of tumor Ag specific IFN-γ producing-CD8+ T cells.Interestingly,ACML-55 treatment also showed increased cell number of NK,and γδT cells,indicating the role of ACML-55 in activation of innate lymphooltes.CONCLUSION:Our results demonstrate that ACML-55therapy can enhance function in immune surveillance in colon cancer-bearing mice through regulating both innate and adaptive immune responses.

  6. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Ryohei; Eeden, Stephan F. van, E-mail: Stephan.vanEeden@hli.ubc.ca

    2011-12-15

    Emerging epidemiological evidence suggests that exposure to particulate matter (PM) air pollution increases the risk of cardiovascular events but the exact mechanism by which PM has adverse effects is still unclear. Alveolar macrophages (AM) play a major role in clearing and processing inhaled PM. This comprehensive review of research findings on immunological interactions between AM and PM provides potential pathophysiological pathways that interconnect PM exposure with adverse cardiovascular effects. Coarse particles (10 {mu}m or less, PM{sub 10}) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 {mu}m or less, PM{sub 2.5}) and ultrafine particles (0.1 {mu}m or less, UFP) induce via reactive oxygen species generation by transition metals and/or polyaromatic hydrocarbons. The innate immune responses are characterized by activation of transcription factors [nuclear factor (NF)-{kappa}B and activator protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1{beta}, IL-6, and tumor necrosis factor-{alpha}] production. In addition to the conventional opsonin-dependent phagocytosis by AM, PM can also be endocytosed by an opsonin-independent pathway via scavenger receptors. Activation of scavenger receptors negatively regulates the TLR4-NF-{kappa}B pathway. Internalized particles are subsequently subjected to adaptive immunity involving major histocompatibility complex class II (MHC II) expression, recruitment of costimulatory molecules, and the modulation of the T helper (Th) responses. AM show atypical antigen presenting cell maturation in which phagocytic activity decreases while both MHC II and costimulatory molecules remain unaltered. PM drives AM towards a Th1 profile but secondary responses in a Th1- or Th-2 up-regulated milieu drive the response in favor of a Th2 profile.

  7. Next generation intelligent environments ambient adaptive systems

    CERN Document Server

    Nothdurft, Florian; Heinroth, Tobias; Minker, Wolfgang

    2016-01-01

    This book covers key topics in the field of intelligent ambient adaptive systems. It focuses on the results worked out within the framework of the ATRACO (Adaptive and TRusted Ambient eCOlogies) project. The theoretical background, the developed prototypes, and the evaluated results form a fertile ground useful for the broad intelligent environments scientific community as well as for industrial interest groups. The new edition provides: Chapter authors comment on their work on ATRACO with final remarks as viewed in retrospective Each chapter has been updated with follow-up work emerging from ATRACO An extensive introduction to state-of-the-art statistical dialog management for intelligent environments Approaches are introduced on how Trust is reflected during the dialog with the system.

  8. HIV and Malnutrition: Effects on Immune System

    Directory of Open Access Journals (Sweden)

    Shalini Duggal

    2012-01-01

    Full Text Available HIV or human immunodeficiency virus infection has assumed worldwide proportions and importance in just a span of 25 years. Continuous research is being done in many parts of the world regarding its treatment and vaccine development, and a lot of money has flown into this. However, fully understanding the mechanisms of immune depletion has still not been possible. The focus has also been on improving the quality of life of people living with HIV/AIDS through education, counselling, and nutritional support. Malnutrition further reduces the capacity of the body to fight this infection by compromising various immune parameters. Knowledge of essential components of nutrition and incorporating them in the management goes a long way in improving quality of life and better survival in HIV-infected patients.

  9. Adaptive stabilization for cascade nonlinear systems

    Institute of Scientific and Technical Information of China (English)

    陈岚萍; 王洪元; 吴波

    2004-01-01

    An adaptive controller of full state feedback for certain cascade nonlinear systems achieving input-to-state stability with respect to unknown bounded disturbance is designed using backstepping and control Lyapunov function (CLF)techniques. We show that unknown bounded disturbance can be estimated by update laws, which requires less information on unknown disturbance, as a part of stabilizing control. The design method achieves the desired property: global robust stability. Our contribution is illustrated with the example of a disturbed pendulum.

  10. Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria.

    Science.gov (United States)

    Huang, Jing; Li, Xiangming; Coelho-dos-Reis, Jordana G A; Zhang, Min; Mitchell, Robert; Nogueira, Raquel Tayar; Tsao, Tiffany; Noe, Amy R; Ayala, Ramses; Sahi, Vincent; Gutierrez, Gabriel M; Nussenzweig, Victor; Wilson, James M; Nardin, Elizabeth H; Nussenzweig, Ruth S; Tsuji, Moriya

    2015-12-01

    In this study, we developed human immune system (HIS) mice that possess functional human CD4+ T cells and B cells, named HIS-CD4/B mice. HIS-CD4/B mice were generated by first introducing HLA class II genes, including DR1 and DR4, along with genes encoding various human cytokines and human B cell activation factor (BAFF) to NSG mice by adeno-associated virus serotype 9 (AAV9) vectors, followed by engrafting human hematopoietic stem cells (HSCs). HIS-CD4/B mice, in which the reconstitution of human CD4+ T and B cells resembles to that of humans, produced a significant level of human IgG against Plasmodium falciparum circumsporozoite (PfCS) protein upon immunization. CD4+ T cells in HIS-CD4/B mice, which possess central and effector memory phenotypes like those in humans, are functional, since PfCS protein-specific human CD4+ T cells secreting IFN-γ and IL-2 were detected in immunized HIS-CD4/B mice. Lastly, PfCS protein-immunized HIS-CD4/B mice were protected from in vivo challenge with transgenic P. berghei sporozoites expressing the PfCS protein. The immune sera collected from protected HIS-CD4/B mice reacted against transgenic P. berghei sporozoites expressing the PfCS protein and also inhibited the parasite invasion into hepatocytes in vitro. Taken together, these studies show that our HIS-CD4/B mice could mount protective human anti-malaria immunity, consisting of human IgG and human CD4+ T cell responses both specific for a human malaria antigen.

  11. The role of the innate immune system in granulomatous disorders

    Directory of Open Access Journals (Sweden)

    Helen Josephine Petersen

    2013-05-01

    Full Text Available The dynamic structure of the granuloma serves to protect the body from microbiological challenge. This organised aggregate of immune cells seeks to contain this challenge and protect against dissemination, giving host immune cells a chance to eradicate the threat. A number of systemic diseases are characterised by this specialised inflammatory process and granulomas have been shown to develop at multiple body sites and in various tissues. Central to this process is the macrophage and the arms of the innate immune response. This review seeks to explore how the innate immune response drives this inflammatory process in a contrast of diseases, particularly those with a component of immunodeficiency. By understanding the genes and inflammatory mechanisms behind this specialised immune response, will guide research in in the development of novel therapeutics to combat granulomatous diseases.

  12. Immune system responses and fitness costs associated with consumption of bacteria in larvae of Trichoplusia ni

    Directory of Open Access Journals (Sweden)

    Heckel David G

    2007-12-01

    Full Text Available Abstract Background Insects helped pioneer, and persist as model organisms for, the study of specific aspects of immunity. Although they lack an adaptive immune system, insects possess an innate immune system that recognizes and destroys intruding microorganisms. Its operation under natural conditions has not been well studied, as most studies have introduced microbes to laboratory-reared insects via artificial mechanical wounding. One of the most common routes of natural exposure and infection, however, is via food; thus, the role of dietary microbial communities in herbivorous insect immune system evolution invites study. Here, we examine the immune system response and consequences of exposing a lepidopteran agricultural pest to non-infectious microorganisms via simple oral consumption. Results Immune system response was compared between Trichoplusia ni larvae reared on diets with or without non-pathogenic bacteria (Escherichia coli and Micrococcus luteus. Two major immune response-related enzymatic activities responded to diets differently – phenoloxidase activity was inhibited in the bacteria-fed larvae, whereas general antibacterial activity was enhanced. Eight proteins were highly expressed in the hemolymph of the bacteria fed larvae, among them immune response related proteins arylphorin, apolipophorin III and gloverin. Expression response among 25 putative immune response-related genes were assayed via RT-qPCR. Seven showed more than fivefold up regulation in the presence of bacterial diet, with 22 in total being differentially expressed, among them apolipophorin III, cecropin, gallerimycin, gloverin, lysozyme, and phenoloxidase inhibiting enzyme. Finally, potential life-history trade-offs were studied, with pupation time and pupal mass being negatively affected in bacteria fed larvae. Conclusion The presence of bacteria in food, even if non-pathogenic, can trigger an immune response cascade with life history tradeoffs. Trichoplusia ni

  13. An Architecture for Alert Correlation Inspired By a Comprehensive Model of Human Immune System

    Directory of Open Access Journals (Sweden)

    Mehdi Bateni

    2014-11-01

    Full Text Available Alert correlation is the process of analyzing, relating and fusing the alerts generated by one or more Intrusion Detection Systems (IDS in order to provide a high-level and comprehensive view of the security situation of the system or network. Different approaches, such as rule-based, prerequisites consequences-based, learning-based and similarity-based approach are used in correlation process. In this paper, a new AIS-inspired architecture is presented for alert correlation. Different aspects of human immune system (HIS are considered to design iCorrelator. Its three-level structure is inspired by three types of responses in human immune system: the innate immune system's response, the adaptive immune system's primary response, and the adaptive immune system's secondary response. iCorrelator also uses the concepts of Danger theory to decrease the computational complexity of the correlation process without considerable accuracy degradation. By considering the importance of signals in Danger theory, a new alert selection policy is introduced. It is named Enhanced Random Directed Time Window (ERDTW and is used to classify time slots to Relevant (Dangerous and Irrelevant (Safe slots based on the context information gathered during previous correlations. iCorrelator is evaluated using the DARPA 2000 dataset and a netForensics honeynet data. Completeness, soundness, false correlation rate and the execution time are investigated. Results show that iCorrelator generates attack graph with an acceptable accuracy that is comparable to the best known solutions. Moreover, inspiring by the Danger theory and using context information, the computational complexity of the correlation process is decreased considerably and makes it more applicable to online correlation.

  14. Traumatic spinal cord injury in mice with human immune systems.

    Science.gov (United States)

    Carpenter, Randall S; Kigerl, Kristina A; Marbourg, Jessica M; Gaudet, Andrew D; Huey, Devra; Niewiesk, Stefan; Popovich, Phillip G

    2015-09-01

    Mouse models have provided key insight into the cellular and molecular control of human immune system function. However, recent data indicate that extrapolating the functional capabilities of the murine immune system into humans can be misleading. Since immune cells significantly affect neuron survival and axon growth and also are required to defend the body against infection, it is important to determine the pathophysiological significance of spinal cord injury (SCI)-induced changes in human immune system function. Research projects using monkeys or humans would be ideal; however, logistical and ethical barriers preclude detailed mechanistic studies in either species. Humanized mice, i.e., immunocompromised mice reconstituted with human immune cells, can help overcome these barriers and can be applied in various experimental conditions that are of interest to the SCI community. Specifically, newborn NOD-SCID-IL2rg(null) (NSG) mice engrafted with human CD34(+) hematopoietic stem cells develop normally without neurological impairment. In this report, new data show that when mice with human immune systems receive a clinically-relevant spinal contusion injury, spontaneous functional recovery is indistinguishable from that achieved after SCI using conventional inbred mouse strains. Moreover, using routine immunohistochemical and flow cytometry techniques, one can easily phenotype circulating human immune cells and document the composition and distribution of these cells in the injured spinal cord. Lesion pathology in humanized mice is typical of mouse contusion injuries, producing a centralized lesion epicenter that becomes occupied by phagocytic macrophages and lymphocytes and enclosed by a dense astrocytic scar. Specific human immune cell types, including three distinct subsets of human monocytes, were readily detected in the blood, spleen and liver. Future studies that aim to understand the functional consequences of manipulating the neuro-immune axis after SCI

  15. Complex Adaptive Systems of Systems (CASOS) engineering environment.

    Energy Technology Data Exchange (ETDEWEB)

    Detry, Richard Joseph; Linebarger, John Michael; Finley, Patrick D.; Maffitt, S. Louise; Glass, Robert John, Jr.; Beyeler, Walter Eugene; Ames, Arlo Leroy

    2012-02-01

    Complex Adaptive Systems of Systems, or CASoS, are vastly complex physical-socio-technical systems which we must understand to design a secure future for the nation. The Phoenix initiative implements CASoS Engineering principles combining the bottom up Complex Systems and Complex Adaptive Systems view with the top down Systems Engineering and System-of-Systems view. CASoS Engineering theory and practice must be conducted together to develop a discipline that is grounded in reality, extends our understanding of how CASoS behave and allows us to better control the outcomes. The pull of applications (real world problems) is critical to this effort, as is the articulation of a CASoS Engineering Framework that grounds an engineering approach in the theory of complex adaptive systems of systems. Successful application of the CASoS Engineering Framework requires modeling, simulation and analysis (MS and A) capabilities and the cultivation of a CASoS Engineering Community of Practice through knowledge sharing and facilitation. The CASoS Engineering Environment, itself a complex adaptive system of systems, constitutes the two platforms that provide these capabilities.

  16. Antibody complementarity-determining regions (CDRs: a bridge between adaptive and innate immunity.

    Directory of Open Access Journals (Sweden)

    Elena Gabrielli

    Full Text Available BACKGROUND: It has been documented that, independently from the specificity of the native antibody (Ab for a given antigen (Ag, complementarity determining regions (CDR-related peptides may display differential antimicrobial, antiviral and antitumor activities. METHODOLOGY/PRINCIPAL FINDINGS: In this study we demonstrate that a synthetic peptide with sequence identical to V(HCDR3 of a mouse monoclonal Ab (mAb specific for difucosyl human blood group A is easily taken up by macrophages with subsequent stimulation of: i proinflammatory cytokine production; ii PI3K-Akt pathway and iii TLR-4 expression. Significantly, V(HCDR3 exerts therapeutic effect against systemic candidiasis without possessing direct candidacidal properties. CONCLUSIONS/SIGNIFICANCE: These results open a new scenario about the possibility that, beyond the half life of immunoglobulins, Ab fragments may effectively influence the antiinfective cellular immune response in a way reminiscent of regulatory peptides of innate immunity.

  17. The role of Toll-like receptors and adaptive immunity in the development of protective or pathological immune response triggered by the Trypanosoma cruzi protozoan.

    Science.gov (United States)

    Pellegrini, Andrea; Guiñazu, Natalia; Giordanengo, Laura; Cano, Roxana Carolina; Gea, Susana

    2011-12-01

    Trypanosoma cruzi, the causal agent of Chagas disease, is an intracellular protozoan parasite that predominantly invades macrophages and cardiomyocytes, leading to persistent infection. Several members of the Toll-like receptor family are crucial for innate immunity to infection and are involved in maintaining tissue homeostasis. This review focuses on recent experimental findings of the innate and adaptive immune response in controlling the parasite and/or in generating heart and liver tissue injury. We also describe the importance of the host's genetic background in the outcome of the disease and emphasize the importance of studying the response to specific parasite antigens. Understanding the dual participation of the immune response may contribute to the design of new therapies for Chagas disease.

  18. Social networks as embedded complex adaptive systems.

    Science.gov (United States)

    Benham-Hutchins, Marge; Clancy, Thomas R

    2010-09-01

    As systems evolve over time, their natural tendency is to become increasingly more complex. Studies in the field of complex systems have generated new perspectives on management in social organizations such as hospitals. Much of this research appears as a natural extension of the cross-disciplinary field of systems theory. This is the 15th in a series of articles applying complex systems science to the traditional management concepts of planning, organizing, directing, coordinating, and controlling. In this article, the authors discuss healthcare social networks as a hierarchy of embedded complex adaptive systems. The authors further examine the use of social network analysis tools as a means to understand complex communication patterns and reduce medical errors.

  19. Complex and adaptive dynamical systems a primer

    CERN Document Server

    Gros, Claudius

    2013-01-01

    Complex system theory is rapidly developing and gaining importance, providing tools and concepts central to our modern understanding of emergent phenomena. This primer offers an introduction to this area together with detailed coverage of the mathematics involved. All calculations are presented step by step and are straightforward to follow. This new third edition comes with new material, figures and exercises. Network theory, dynamical systems and information theory, the core of modern complex system sciences, are developed in the first three chapters, covering basic concepts and phenomena like small-world networks, bifurcation theory and information entropy. Further chapters use a modular approach to address the most important concepts in complex system sciences, with the emergence and self-organization playing a central role. Prominent examples are self-organized criticality in adaptive systems, life at the edge of chaos, hypercycles and coevolutionary avalanches, synchronization phenomena, absorbing phase...

  20. EBV Infection of Mice with Reconstituted Human Immune System Components.

    Science.gov (United States)

    Münz, Christian

    2015-01-01

    Epstein-Barr virus (EBV) was discovered 50 years ago as the first candidate human tumor virus. Since then, we have realized that this human γ-herpesvirus establishes persistent infection in the majority of adult humans, but fortunately causes EBV-associated diseases only in few individuals. This is an incredible success story of the human immune system, which controls EBV infection and its transforming capacity for decades. A better understanding of this immune control would not only benefit patients with EBV-associated malignancies, but could also provide clues how to establish such a potent, mostly cell-mediated immune control against other pathogens and tumors. However, the functional relevance of EBV-specific immune responses can only be addressed in vivo, and mice with reconstituted human immune system components (huMice) constitute a small animal model to interrogate the protective value of immune compartments during EBV infection, but also might provide a platform to test EBV-specific vaccines. This chapter will summarize the insights into EBV immunobiology that have already been gained in these models and provide an outlook into promising future avenues to develop this in vivo model of EBV infection and human immune responses further.

  1. Theory of an Immune System Retrovirus.

    Science.gov (United States)

    1986-07-23

    expected strong dependence on the rate of virus produccion as well as the very powerful effect of immunization via the increase of Bo cells.* 4. -4...for the non-linear produccion term YP’= Y’ tdt’(Q(t’)) 2 = 2 ’ftdt it Y(t’)B (t’)z(t’)dt’ (A7) where Y’= Y "’’¥6 YpF = Y>(B YTY’) and now Z =fty(t

  2. Melanoma: oncogenic drivers and the immune system

    Science.gov (United States)

    Karachaliou, Niki; Pilotto, Sara; Teixidó, Cristina; Viteri, Santiago; González-Cao, María; Riso, Aldo; Morales-Espinosa, Daniela; Molina, Miguel Angel; Chaib, Imane; Santarpia, Mariacarmela; Richardet, Eduardo; Bria, Emilio

    2015-01-01

    Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches. PMID:26605311

  3. Probing the phenomenon of trained immunity in invertebrates during a transgenerational study, using brine shrimp Artemia as a model system.

    Science.gov (United States)

    Norouzitallab, Parisa; Baruah, Kartik; Biswas, Priyanka; Vanrompay, Daisy; Bossier, Peter

    2016-02-15

    The invertebrate's innate immune system was reported to show some form of adaptive features, termed trained immunity. However, the memory characteristics of innate immune system and the mechanisms behind such phenomena remain unclear. Using the invertebrate model Artemia, we verified the possibility or impossibility of trained immunity, examining the presence or absence of enduring memory against homologous and heterologous antigens (Vibrio spp.) during a transgenerational study. We also determined the mechanisms behind such phenomenon. Our results showed the occurrence of memory and partial discrimination in Artemia's immune system, as manifested by increased resistance, for three successive generations, of the progenies of Vibrio-exposed ancestors towards a homologous bacterial strain, rather than to a heterologous strain. This increased resistance phenotype was associated with elevated levels of hsp70 and hmgb1 signaling molecules and alteration in the expression of key innate immunity-related genes. Our results also showed stochastic pattern in the acetylation and methylation levels of H4 and H3K4me3 histones, respectively, in the progenies whose ancestors were challenged. Overall results suggest that innate immune responses in invertebrates have the capacity to be trained, and epigenetic reprogramming of (selected) innate immune effectors is likely to have central place in the mechanisms leading to trained immunity.

  4. Molecular players involved in the interaction between beneficial bacteria and the immune system

    Directory of Open Access Journals (Sweden)

    Arancha eHevia

    2015-11-01

    Full Text Available The human gastrointestinal tract is a very complex ecosystem, in which there is a continuous interaction between nutrients, host cells, and microorganisms. The gut microbiota comprises trillions of microbes that have been selected during evolution on the basis of their functionality and capacity to survive in, and adapt to, the intestinal environment. Host bacteria and our immune system constantly sense and react to one another. In this regard, commensal microbes contribute to gut homeostasis, whereas the necessary responses are triggered against enteropathogens. Some representatives of our gut microbiota have beneficial effects on human health. Some of the most important roles of these microbes are to help to maintain the integrity of the mucosal barrier, to provide nutrients such as vitamins, or to protect against pathogens. In addition, the interaction between commensal microbiota and the mucosal immune system is crucial for proper immune function. This process is mainly performed via the pattern recognition receptors of epithelial cells, such as Toll-like or Nod-like receptors, which are able to recognize the molecular effectors that are produced by intestinal microbes. These effectors mediate processes that can ameliorate certain inflammatory gut disorders, discriminate between beneficial and pathogenic bacteria, or increase the number of immune cells or their pattern recognition receptors. This review intends to summarize the molecular players produced by probiotic bacteria, notably Lactobacillus and Bifidobacterium strains, but also other very promising potential probiotics, which affect the human immune system.

  5. Coincident helminth infection modulates systemic inflammation and immune activation in active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Parakkal Jovvian George

    Full Text Available Helminth infections are known to modulate innate and adaptive immune responses in active and latent tuberculosis (TB. However, the role of helminth infections in modulating responses associated with inflammation and immune activation (reflecting disease activity and/or severity in TB is not known.We measured markers of inflammation and immune activation in active pulmonary TB individuals (ATB with co-incidental Strongyloides stercoralis (Ss infection. These included systemic levels of acute phase proteins, matrix metalloproteinases and their endogenous inhibitors and immune activation markers. As a control, we measured the systemic levels of the same molecules in TB-uninfected individuals (NTB with or without Ss infection.Our data confirm that ATB is associated with elevated levels of the various measured molecules when compared to those seen in NTB. Our data also reveal that co-incident Ss infection in ATB individuals is associated with significantly decreased circulating levels of acute phase proteins, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases as well as the systemic immune activation markers, sCD14 and sCD163. These changes are specific to ATB since they are absent in NTB individuals with Ss infection.Our data therefore reveal a profound effect of Ss infection on the markers associated with TB disease activity and severity and indicate that co-incidental helminth infections might dampen the severity of TB disease.

  6. ADAPTIVE SYSTEMS THEORY: SOME BASIC CONCEPTS, METHODS AND RESULTS

    Institute of Scientific and Technical Information of China (English)

    GUO Lei

    2003-01-01

    The adaptive systems theory to be presented in this paper consists of two closely related parts: adaptive estimation (or filtering, prediction) and adaptive control of dynamical systems. Both adaptive estimation and control are nonlinear mappings of the on-line observed signals of dynamical systems, where the main features are the uncertainties in both the system's structure and external disturbances, and the non-stationarity and dependency of the system signals. Thus, a key difficulty in establishing a mathematical theory of adaptive systems lies in how to deal with complicated nonlinear stochastic dynamical systems which describe the adaptation processes. In this paper, we will illustrate some of the basic concepts, methods and results through some simple examples. The following fundamental questions will be discussed: How much information is needed for estimation? How to deal with uncertainty by adaptation? How to analyze an adaptive system? What are the convergence or tracking performances of adaptation? How to find the proper rate of adaptation in some sense? We will also explore the following more fundamental questions: How much uncertainty can be dealt with by adaptation ? What are the limitations of adaptation ? How does the performance of adaptation depend on the prior information ? We will partially answer these questions by finding some "critical values" and establishing some "Impossibility Theorems" for the capability of adaptation, for several basic classes of nonlinear dynamical control systems with either parametric or nonparametric uncertainties.

  7. Optimal approximation of linear systems by artificial immune response

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper puts forward a novel artificial immune response algorithm for optimal approximation of linear systems. A quaternion model of artificial immune response is proposed for engineering computing. The model abstracts four elements, namely, antigen, antibody, reaction rules among antibodies, and driving algorithm describing how the rules are applied to antibodies, to simulate the process of immune response. Some reaction rules including clonal selection rules, immunological memory rules and immune regulation rules are introduced. Using the theorem of Markov chain, it is proofed that the new model is convergent. The experimental study on the optimal approximation of a stable linear system and an unstable one show that the approximate models searched by the new model have better performance indices than those obtained by some existing algorithms including the differential evolution algorithm and the multi-agent genetic algorithm.

  8. Intranasal Immunization with Influenza Virus-Like Particles Containing Membrane-Anchored Cholera Toxin B or Ricin Toxin B Enhances Adaptive Immune Responses and Protection against an Antigenically Distinct Virus.

    Science.gov (United States)

    Ji, Xianliang; Ren, Zhiguang; Xu, Na; Meng, Lingnan; Yu, Zhijun; Feng, Na; Sang, Xiaoyu; Li, Shengnan; Li, Yuanguo; Wang, Tiecheng; Zhao, Yongkun; Wang, Hualei; Zheng, Xuexing; Jin, Hongli; Li, Nan; Yang, Songtao; Cao, Jinshan; Liu, Wensen; Gao, Yuwei; Xia, Xianzhu

    2016-04-21

    Vaccination is the most effective means to prevent influenza virus infection, although current approaches are associated with suboptimal efficacy. Here, we generated virus-like particles (VLPs) composed of the hemagglutinin (HA), neuraminidase (NA) and matrix protein (M1) of A/Changchun/01/2009 (H1N1) with or without either membrane-anchored cholera toxin B (CTB) or ricin toxin B (RTB) as molecular adjuvants. The intranasal immunization of mice with VLPs containing membrane-anchored CTB or RTB elicited stronger humoral and cellular immune responses when compared to mice immunized with VLPs alone. Administration of VLPs containing CTB or RTB significantly enhanced virus-specific systemic and mucosal antibody responses, hemagglutination inhibiting antibody titers, virus neutralizing antibody titers, and the frequency of virus-specific IFN-γ and IL-4 secreting splenocytes. VLPs with and without CTB or RTB conferred complete protection against lethal challenge with a mouse-adapted homologous virus. When challenged with an antigenically distinct H1N1 virus, all mice immunized with VLPs containing CTB or RTB survived whereas mice immunized with VLPs alone showed only partial protection (80% survival). Our results suggest that membrane-anchored CTB and RTB possess strong adjuvant properties when incorporated into an intranasally-delivered influenza VLP vaccine. Chimeric influenza VLPs containing CTB or RTB may represent promising vaccine candidates for improved immunological protection against homologous and antigenically distinct influenza viruses.

  9. Maintenance of systemic immune functions prevents accelerated presbycusis.

    Science.gov (United States)

    Iwai, Hiroshi; Baba, Susumu; Omae, Mariko; Lee, Shinryu; Yamashita, Toshio; Ikehara, Susumu

    2008-05-07

    There is no effective therapy for progressive hearing loss such as presbycusis, the causes of which remain poorly understood because of the difficulty of separating genetic and environmental contributions. In the present study, we show that the age-related dysfunctions of the systemic immune system in an animal model of accelerated presbycusis (SAMP1, senescence-accelerated mouse P1) can be corrected by allogeneic bone marrow transplantation (BMT). We also demonstrate that this presbycusis can be prevented; BMT protects the recipients from age-related hearing impairment and the degeneration of spiral ganglion cells (SGCs) as well as the dysfunctions of T lymphocytes, which have a close relation to immune senescence. No donor cells are infiltrated to the spiral ganglia, confirming that this experimental system using BMT is connected to the systemic immune system and does not contribute to transdifferentiation or fusion by donor hematopoietic stem cells (HSCs), or to the direct maintenance of ganglion cells by locally infiltrated donor immunocompetent cells. Therefore, another procedure which attempts to prevent the age-related dysfunctions of the recipient immune system is the inoculation of syngeneic splenocytes from young donors. These mice show no development of hearing loss, compared with the recipient mice with inoculation of saline or splenocytes from old donors. Our studies on the relationship between age-related systemic immune dysfunctions and neurodegeneration mechanisms open up new avenues of treatment for presbycusis, for which there is no effective therapy.

  10. Effects of gastrointestinal nematode infection on the ruminant immune system.

    Science.gov (United States)

    Gasbarre, L C

    1997-11-01

    Gastrointestinal (GI) nematodes of ruminants evoke a wide variety of immune responses in their hosts. In terms of specific immune responses directed against parasite antigens, the resulting immune responses may vary from those that give strong protection from reinfection after a relatively light exposure (e.g. Oesophagostomum radiatum) to responses that are very weak and delayed in their onset (e.g. Ostertagia ostertagi). The nature of these protective immune responses has been covered in another section of the workshop and the purpose of this section will be to explore the nature of changes that occur in the immune system of infected animals and to discuss the effect of GI nematode infections upon the overall immunoresponsiveness of the host. The discussion will focus primarily on Ostertagia ostertagi because this parasite has received the most attention in published studies. The interaction of Ostertagia and the host immune system presents what appears to be an interesting contradiction. Protective immunity directed against the parasite is slow to arise and when compared to some of the other GI nematodes, is relatively weak. Although responses that reduce egg output in the feces or increase the number of larvae undergoing inhibition may occur after a relatively brief exposure (3-4 months), immune responses which reduce the number of parasites that can establish in the host are not evident until the animal's second year. Additionally, even older animals that have spent several seasons on infected pastures will have low numbers of Ostertagia in their abomasa, indicating that sterilizing immune responses against the parasite are uncommon. In spite of this apparent lack of specific protective immune responses, infections with Ostertagia induce profound changes in the host immune system. These changes include a tremendous expansion of both the number of lymphocytes in the local lymph nodes and the number of lymphoid cells in the mucosa of the abomasum. This expansion

  11. Fat:A matter of disturbance for the immune system

    Institute of Scientific and Technical Information of China (English)

    Alessandro; Federico; Elena; D’Aiuto; Francesco; Borriello; Giusi; Barra; Antonietta; Gerarda; Gravina; Marco; Romano; Raffaele; De; Palma

    2010-01-01

    Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. There is compelling evidence that both overnutrition and undernutrition negatively interfere with the immune system. Overnutrition has been found to increase susceptibility to the development of inflammatory diseases, autoimmune diseases and cancer. In the regulation of immune and in? ammatory ...

  12. Allergic contact dermatitis: immune system involvement and distinctive clinical cases.

    Science.gov (United States)

    Imbesi, S; Minciullo, P L; Isola, S; Gangemi, S

    2011-01-01

    The aim of this review is drawing the attention to the contact dermatitis, an inflammatory skin condition due to pro-inflammatory and toxic factors able to activate the skin innate immunity (irritant contact dermatitis) or caused by a T-cell- mediated hypersensitivity reaction (allergic contact dermatitis). The immune system involvement and a variety of clinical pictures are described in order to better diagnose, prevent and treat allergic contact dermatitis.

  13. Evasion of the human innate immune system by dengue virus

    OpenAIRE

    Pagni, Sarah; Fernandez-Sesma, Ana

    2012-01-01

    Dengue virus is a worldwide health problem, with billions of people at risk annually. Dengue virus causes a spectrum of diseases, namely dengue fever, dengue hemorrhagic fever and dengue shock syndrome with the latter two being linked to death. Understanding how dengue is able to evade the immune system and cause enhanced severity of disease is the main topics of interest in the Fernandez-Sesma laboratory at Mount Sinai School of Medicine. Using primary human immune cells, our group investiga...

  14. Complex and adaptive dynamical systems a primer

    CERN Document Server

    Gros, Claudius

    2015-01-01

    This primer offers readers an introduction to the central concepts that form our modern understanding of complex and emergent behavior, together with detailed coverage of accompanying mathematical methods. All calculations are presented step by step and are easy to follow. This new fourth edition has been fully reorganized and includes new chapters, figures and exercises. The core aspects of modern complex system sciences are presented in the first chapters, covering network theory, dynamical systems, bifurcation and catastrophe theory, chaos and adaptive processes, together with the principle of self-organization in reaction-diffusion systems and social animals. Modern information theoretical principles are treated in further chapters, together with the concept of self-organized criticality, gene regulation networks, hypercycles and coevolutionary avalanches, synchronization phenomena, absorbing phase transitions and the cognitive system approach to the brain. Technical course prerequisites are the standard ...

  15. Progress with the lick adaptive optics system

    Energy Technology Data Exchange (ETDEWEB)

    Gavel, D T; Olivier, S S; Bauman, B; Max, C E; Macintosh, B

    2000-03-01

    Progress and results of observations with the Lick Observatory Laser Guide Star Adaptive Optics System are presented. This system is optimized for diffraction-limited imaging in the near infrared, 1-2 micron wavelength bands. We describe our development efforts in a number of component areas including, a redesign of the optical bench layout, the commissioning of a new infrared science camera, and improvements to the software and user interface. There is also an ongoing effort to characterize the system performance with both natural and laser guide stars and to fold this data into a refined system model. Such a model can be used to help plan future observations, for example, predicting the point-spread function as a function of seeing and guide star magnitude.

  16. Adaptable data management for systems biology investigations

    Directory of Open Access Journals (Sweden)

    Burdick David

    2009-03-01

    Full Text Available Abstract Background Within research each experiment is different, the focus changes and the data is generated from a continually evolving barrage of technologies. There is a continual introduction of new techniques whose usage ranges from in-house protocols through to high-throughput instrumentation. To support these requirements data management systems are needed that can be rapidly built and readily adapted for new usage. Results The adaptable data management system discussed is designed to support the seamless mining and analysis of biological experiment data that is commonly used in systems biology (e.g. ChIP-chip, gene expression, proteomics, imaging, flow cytometry. We use different content graphs to represent different views upon the data. These views are designed for different roles: equipment specific views are used to gather instrumentation information; data processing oriented views are provided to enable the rapid development of analysis applications; and research project specific views are used to organize information for individual research experiments. This management system allows for both the rapid introduction of new types of information and the evolution of the knowledge it represents. Conclusion Data management is an important aspect of any research enterprise. It is the foundation on which most applications are built, and must be easily extended to serve new functionality for new scientific areas. We have found that adopting a three-tier architecture for data management, built around distributed standardized content repositories, allows us to rapidly develop new applications to support a diverse user community.

  17. Immune System Approaches to Intrusion Detection - A Review

    CERN Document Server

    Kim, Jungwon; Aickelin, Uwe; Greensmith, Julie; Tedesco, Gianni; Twycross, Jamie

    2008-01-01

    The use of artificial immune systems in intrusion detection is an appealing concept for two reasons. Firstly, the human immune system provides the human body with a high level of protection from invading pathogens, in a robust, self-organised and distributed manner. Secondly, current techniques used in computer security are not able to cope with the dynamic and increasingly complex nature of computer systems and their security. It is hoped that biologically inspired approaches in this area, including the use of immune-based systems will be able to meet this challenge. Here we review the algorithms used, the development of the systems and the outcome of their implementation. We provide an introduction and analysis of the key developments within this field, in addition to making suggestions for future research.

  18. Artificial immune system via Euclidean Distance Minimization for anomaly detection in bearings

    Science.gov (United States)

    Montechiesi, L.; Cocconcelli, M.; Rubini, R.

    2016-08-01

    In recent years new diagnostics methodologies have emerged, with particular interest into machinery operating in non-stationary conditions. In fact continuous speed changes and variable loads make non-trivial the spectrum analysis. A variable speed means a variable characteristic fault frequency related to the damage that is no more recognizable in the spectrum. To overcome this problem the scientific community proposed different approaches listed in two main categories: model-based approaches and expert systems. In this context the paper aims to present a simple expert system derived from the mechanisms of the immune system called Euclidean Distance Minimization, and its application in a real case of bearing faults recognition. The proposed method is a simplification of the original process, adapted by the class of Artificial Immune Systems, which proved to be useful and promising in different application fields. Comparative results are provided, with a complete explanation of the algorithm and its functioning aspects.

  19. Toward a molecular understanding of adaptive immunity:A chronology, Part II

    Directory of Open Access Journals (Sweden)

    Kendall A Smith

    2012-11-01

    Full Text Available By 1980 it was obvious that to more fully understand adaptive immunity, one needed to somehow reduce the tremendous complexity of antigen recognition by T cell populations. Thus, there were two developments that resulted in a paradigm shift in immunology, one being the generation of monoclonal antibodies, and the other the development of monoclonal functional antigen-specific T cell lines. For the first time, the cellular reagents became available to ask new questions as to how individual cells comprising the complex cell populations recognize and respond to changes in their molecular environments. The first successful generation of monoclonal T cells depended upon the understanding that antigen renders cells responsive to the antigen non-specific T cell growth factor that came to be termed interleukin-2 (IL-2, which could then be used in propagating large numbers of the progeny of single cells, which in turn could then be used for molecular analyses. Monoclonal functional human T cells were used to immunize mice to generate clone-specific (clonotypic monoclonal antibodies, which then permitted the first biochemical characterizations of the antigen recognition elements of the T cell antigen receptor complex. Moreover, the use of monoclonal cytolytic and helper/inducer human T cell clones essentially proved that the T cell-specific molecules T4 and T8 functioned as accessory molecules in antigen recognition by defining MHC class II or class I restriction respectively. As well, the expression of the T3 molecules, found to be common to all T cells, were shown further to be obligatory for functional antigen-specific T cell signaling. The monoclonal IL-2-dependent T cells were also instrumental in the isolation and purification of the IL-2 molecule to homogeneity, the first interleukin molecule to be identified and characterized. These advances then led to the generation of pure radiolabeled IL-2 molecules that were used to identify the first

  20. Adaptive stimulus optimization for sensory systems neuroscience.

    Science.gov (United States)

    DiMattina, Christopher; Zhang, Kechen

    2013-01-01

    In this paper, we review several lines of recent work aimed at developing practical methods for adaptive on-line stimulus generation for sensory neurophysiology. We consider various experimental paradigms where on-line stimulus optimization is utilized, including the classical optimal stimulus paradigm where the goal of experiments is to identify a stimulus which maximizes neural responses, the iso-response paradigm which finds sets of stimuli giving rise to constant responses, and the system identification paradigm where the experimental goal is to estimate and possibly compare sensory processing models. We discuss various theoretical and practical aspects of adaptive firing rate optimization, including optimization with stimulus space constraints, firing rate adaptation, and possible network constraints on the optimal stimulus. We consider the problem of system identification, and show how accurate estimation of non-linear models can be highly dependent on the stimulus set used to probe the network. We suggest that optimizing stimuli for accurate model estimation may make it possible to successfully identify non-linear models which are otherwise intractable, and summarize several recent studies of this type. Finally, we present a two-stage stimulus design procedure which combines the dual goals of model estimation and model comparison and may be especially useful for system identification experiments where the appropriate model is unknown beforehand. We propose that fast, on-line stimulus optimization enabled by increasing computer power can make it practical to move sensory neuroscience away from a descriptive paradigm and toward a new paradigm of real-time model estimation and comparison.