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Sample records for immune defense strategies

  1. Host-pathogen interactions between the human innate immune system and Candida albicans—understanding and modeling defense and evasion strategies

    PubMed Central

    Dühring, Sybille; Germerodt, Sebastian; Skerka, Christine; Zipfel, Peter F.; Dandekar, Thomas; Schuster, Stefan

    2015-01-01

    The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given. PMID:26175718

  2. Lymphoma: Immune Evasion Strategies

    PubMed Central

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care. PMID:25941795

  3. Immune defense against pneumonic plague

    PubMed Central

    Smiley, Stephen T.

    2009-01-01

    Summary Yersinia pestis is one of the world's most virulent human pathogens. Inhalation of this Gram-negative bacterium causes pneumonic plague, a rapidly progressing and usually fatal disease. Extensively antibiotic-resistant strains of Y. pestis exist and have significant potential for exploitation as agents of terrorism and biowarfare. Subunit vaccines comprised of the Y. pestis F1 and LcrV proteins are well-tolerated and immunogenic in humans but cannot be tested for efficacy, because pneumonic plague outbreaks are uncommon and intentional infection of humans is unethical. In animal models, F1/LcrV-based vaccines protect mice and cynomolgus macaques but have failed, thus far, to adequately protect African green monkeys. We lack an explanation for this inconsistent efficacy. We also lack reliable correlate assays for protective immunity. These deficiencies are hampering efforts to improve vaccine efficacy. Here, I review the immunology of pneumonic plague, focusing on evidence that humoral and cellular defense mechanisms collaborate to defend against pulmonary Y. pestis infection. PMID:18837787

  4. Improving immunization strategies

    NASA Astrophysics Data System (ADS)

    Gallos, Lazaros K.; Liljeros, Fredrik; Argyrakis, Panos; Bunde, Armin; Havlin, Shlomo

    2007-04-01

    We introduce an immunization method where the percentage of required vaccinations for immunity are close to the optimal value of a targeted immunization scheme of highest degree nodes. Our strategy retains the advantage of being purely local, without the need for knowledge on the global network structure or identification of the highest degree nodes. The method consists of selecting a random node and asking for a neighbor that has more links than himself or more than a given threshold and immunizing him. We compare this method to other efficient strategies on three real social networks and on a scale-free network model and find it to be significantly more effective.

  5. Disease Tolerance as a Defense Strategy

    PubMed Central

    Medzhitov, Ruslan; Schneider, David S.; Soares, Miguel P.

    2013-01-01

    The immune system protects from infections primarily by detecting and eliminating the invading pathogens; however, the host organism can also protect itself from infectious diseases by reducing the negative impact of infections on host fitness. This ability to tolerate a pathogens presence is a distinct host defense strategy, which has been largely overlooked in animal and human studies. Introduction of the notion of disease tolerance into the conceptual toolkit of immunology will expand our understanding of infectious diseases and host pathogen interactions. Analysis of disease tolerance mechanisms should provide new approaches for the treatment of infections and other diseases. PMID:22363001

  6. Defense strategies used by two sympatric vineyard moth pests.

    PubMed

    Vogelweith, Fanny; Thiry, Denis; Moret, Yannick; Colin, Elose; Motreuil, Sbastien; Moreau, Jrme

    2014-05-01

    Natural enemies including parasitoids are the major biological cause of mortality among phytophagous insects. In response to parasitism, these insects have evolved a set of defenses to protect themselves, including behavioral, morphological, physiological and immunological barriers. According to life history theory, resources are partitioned to various functions including defense, implying trade-offs among defense mechanisms. In this study we characterized the relative investment in behavioral, physical and immunological defense systems in two sympatric species of Tortricidae (Eupoecilia ambiguella, Lobesia botrana) which are important grapevine moth pests. We also estimated the parasitism by parasitoids in natural populations of both species, to infer the relative success of the investment strategies used by each moth. We demonstrated that larvae invest differently in defense systems according to the species. Relative to L. botrana, E. ambiguella larvae invested more into morphological defenses and less into behavioral defenses, and exhibited lower basal levels of immune defense but strongly responded to immune challenge. L. botrana larvae in a natural population were more heavily parasitized by various parasitoid species than E. ambiguella, suggesting that the efficacy of defense strategies against parasitoids is not equal among species. These results have implications for understanding of regulation in communities, and in the development of biological control strategies for these two grapevine pests. PMID:24662468

  7. Immunization Strategies Against Henipaviruses

    PubMed Central

    Geisbert, Thomas W.; Xu, Kai; Nikolov, Dimitar B.; Wang, Lin-Fa; Middleton, Deborah; Pallister, Jackie; Bossart, Katharine N.

    2015-01-01

    Hendra virus and Nipah virus are recently discovered and closely related emerging viruses that now comprise the genus henipavirus within the subfamily Paramyxoviridae and are distinguished by their broad species tropism and ability to cause fatal disease in a wide variety of mammalian hosts including humans. The high mortality associated with human and animal henipavirus infections has highlighted the importance and necessity of developing effective immunization strategies. The development of suitable animal models of henipavirus infection and pathogenesis has been critical for testing the efficacy of potential therapeutic approaches. Several henipavirus challenge models have been used and recent successes in both active and passive immunization strategies against henipaviruses have been reported which have all targeted the viral envelope glycoproteins. PMID:22481140

  8. Secretory immunity in defense against cariogenic mutans streptococci.

    PubMed

    Russell, M W; Hajishengallis, G; Childers, N K; Michalek, S M

    1999-01-01

    Specific immune defense against cariogenic mutans streptococci is provided largely by salivary secretory IgA antibodies, which are generated by the common mucosal immune system. This system is functional in newborn infants, who develop salivary IgA antibodies as they become colonized by oral microorganisms. The mechanisms of action of salivary IgA antibodies include interference with sucrose-independent and sucrose- dependent attachment of mutans streptococci to tooth surfaces, as well as possible inhibition of metabolic activities. The goal of protecting infants against colonization by mutans streptococci might be accomplished by applying new strategies of mucosal immunization that would induce salivary IgA antibodies without the complications of parenteral immunization. Strategies of mucosal immunization against mutans streptococci currently under development include the use of surface adhesins and glucosyltransferase as key antigens, which are being incorporated into novel mucosal vaccine delivery systems and adjuvants. The oral application of preformed, genetically engineered antibodies to mutans streptococcal antigens also offers new prospects for passive immunization against dental caries. PMID:9831775

  9. Cutaneous Immune Defenses Against Staphylococcus aureus Infections

    PubMed Central

    Choi, Ji Hae; Seo, Ho Seong; Lim, Sang Young; Park, Kyungho

    2014-01-01

    Staphylococcus aureus (S. aureus) is a virulent bacterium that abundantly colonizes inflammatory skin diseases. Since S. aureus infections occur in an impaired skin barrier, it is important to understand the protective mechanism through cutaneous immune responses against S. aureus infections and the interaction with Staphylococcal virulence factors. In this review, we summarize not only the pathogenesis and key elements of S. aureus skin infections, but also the cutaneous immune system against its infections and colonization. The information obtained from this area may provide the groundwork for further immunomodulatory therapies or vaccination strategies to prevent S. aureus infections. PMID:26064853

  10. Topical immunization strategies.

    PubMed

    Czerkinsky, C; Holmgren, J

    2010-11-01

    Research has yielded an abundance of vaccine candidates against mucosal infections, but only few mucosal vaccines have been registered for human use. Extensive research is being carried out to identify new and safe adjuvants for mucosal immunization, novel delivery systems, including live vectors and reporter molecules for tissue- and cell-specific targeting of vaccine antigens. If these candidates are to reach those in need, several lessons from clinical and field research carried out under resource-poor settings must be considered. These lessons include the need to develop new vaccines that can be administered topically onto the skin or to the mucosa, without needles or expensive delivery devices. Such topical vaccines must be able to protect all age groups at risk, be safe and effective in immunocompromised people, and be able to contain epidemics following complex emergencies. The anatomical compartmentalization of immune responses imposes constraints on the selection of topical route(s) of vaccine administration and on strategies for measuring these responses, especially in young infants. Thus, the selection of any particular route of immunization is critical when designing and formulating vaccines against organ-specific infections. PMID:20861833

  11. Finding a Better Immunization Strategy

    NASA Astrophysics Data System (ADS)

    Chen, Yiping; Paul, Gerald; Havlin, Shlomo; Liljeros, Fredrik; Stanley, H. Eugene

    2008-08-01

    The problem of finding the best strategy to immunize a population or a computer network with a minimal number of immunization doses is of current interest. It has been accepted that the targeted strategies on most central nodes are most efficient for model and real networks. We present a newly developed graph-partitioning strategy which requires 5% to 50% fewer immunization doses compared to the targeted strategy and achieves the same degree of immunization of the network. We explicitly demonstrate the effectiveness of our proposed strategy on several model networks and also on real networks.

  12. Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses

    PubMed Central

    Mogensen, Trine H.

    2009-01-01

    Summary: The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs). Among the PRRs, the Toll-like receptors have been studied most extensively. Upon PAMP engagement, PRRs trigger intracellular signaling cascades ultimately culminating in the expression of a variety of proinflammatory molecules, which together orchestrate the early host response to infection, and also is a prerequisite for the subsequent activation and shaping of adaptive immunity. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response. Moreover, pathogenic microbes have developed sophisticated molecular strategies to subvert host defenses by interfering with molecules involved in inflammatory signaling. This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response. Moreover, medical implications are discussed, including the role of PRRs in primary immunodeficiencies and in the pathogenesis of infectious and autoimmune diseases, as well as the possibilities for translation into clinical and therapeutic applications. PMID:19366914

  13. The equal effectiveness of different defensive strategies

    PubMed Central

    Zhang, Shuang; Zhang, Yuxin; Ma, Keming

    2015-01-01

    Plants have evolved a variety of defensive strategies to resist herbivory, but at the interspecific level, the relative effectiveness of these strategies has been poorly evaluated. In this study, we compared the level of herbivory between species that depend on ants as indirect defenders and species that rely primarily on their own direct defenses. Using a dataset of 871 species and 1,405 data points, we found that in general, ant-associated species had levels of herbivory equal to those of species that are unattractive to ants; the pattern was unaffected by plant life form, climate and phylogenetic relationships between species. Interestingly, species that offer both food and nesting spaces for ants suffered significantly lower herbivory compared to species that offer either food or nesting spaces only or no reward for ants. A negative relationship between herbivory and latitude was detected, but the pattern can be changed by ants. These findings suggest that, at the interspecific level, the effectiveness of different defensive strategies may be equal. Considering the effects of herbivory on plant performance and fitness, the equal effectiveness of different defensive strategies may play an important role in the coexistence of various species at the community scale. PMID:26267426

  14. Pattern Recognition Receptors in Innate Immunity, Host Defense, and Immunopathology

    ERIC Educational Resources Information Center

    Suresh, Rahul; Mosser, David M.

    2013-01-01

    Infection by pathogenic microbes initiates a set of complex interactions between the pathogen and the host mediated by pattern recognition receptors. Innate immune responses play direct roles in host defense during the early stages of infection, and they also exert a profound influence on the generation of the adaptive immune responses that ensue.

  15. Pattern Recognition Receptors in Innate Immunity, Host Defense, and Immunopathology

    ERIC Educational Resources Information Center

    Suresh, Rahul; Mosser, David M.

    2013-01-01

    Infection by pathogenic microbes initiates a set of complex interactions between the pathogen and the host mediated by pattern recognition receptors. Innate immune responses play direct roles in host defense during the early stages of infection, and they also exert a profound influence on the generation of the adaptive immune responses that ensue.…

  16. Pattern recognition receptors in innate immunity, host defense, and immunopathology

    PubMed Central

    Suresh, Rahul

    2013-01-01

    Infection by pathogenic microbes initiates a set of complex interactions between the pathogen and the host mediated by pattern recognition receptors. Innate immune responses play direct roles in host defense during the early stages of infection, and they also exert a profound influence on the generation of the adaptive immune responses that ensue. An improved understanding of the pattern recognition receptors that mediate innate responses and their downstream effects after receptor ligation has the potential to lead to new ways to improve vaccines and prevent autoimmunity. This review focuses on the control of innate immune activation and the role that innate immune receptors play in helping to maintain tissue homeostasis. PMID:24292903

  17. Immune Evasion Strategies of Glioblastoma

    PubMed Central

    Razavi, Seyed-Mostafa; Lee, Karen E.; Jin, Benjamin E.; Aujla, Parvir S.; Gholamin, Sharareh; Li, Gordon

    2016-01-01

    Glioblastoma (GBM) is the most devastating brain tumor, with associated poor prognosis. Despite advances in surgery and chemoradiation, the survival of afflicted patients has not improved significantly in the past three decades. Immunotherapy has been heralded as a promising approach in treatment of various cancers; however, the immune privileged environment of the brain usually curbs the optimal expected response in central nervous system malignancies. In addition, GBM cells create an immunosuppressive microenvironment and employ various methods to escape immune surveillance. The purpose of this review is to highlight the strategies by which GBM cells evade the host immune system. Further understanding of these strategies and the biology of this tumor will pave the way for developing novel immunotherapeutic approaches for treatment of GBM. PMID:26973839

  18. Systemic Bacterial Infection and Immune Defense Phenotypes in Drosophila Melanogaster

    PubMed Central

    Khalil, Sarah; Jacobson, Eliana; Chambers, Moria C.; Lazzaro, Brian P.

    2015-01-01

    The fruit fly Drosophila melanogaster is one of the premier model organisms for studying the function and evolution of immune defense. Many aspects of innate immunity are conserved between insects and mammals, and since Drosophila can readily be genetically and experimentally manipulated, they are powerful for studying immune system function and the physiological consequences of disease. The procedure demonstrated here allows infection of flies by introduction of bacteria directly into the body cavity, bypassing epithelial barriers and more passive forms of defense and allowing focus on systemic infection. The procedure includes protocols for the measuring rates of host mortality, systemic pathogen load, and degree of induction of the host immune system. This infection procedure is inexpensive, robust and quantitatively repeatable, and can be used in studies of functional genetics, evolutionary life history, and physiology. PMID:25992475

  19. Bacteria- and IMD Pathway-Independent Immune Defenses against Plasmodium falciparum in Anopheles gambiae

    PubMed Central

    Blumberg, Benjamin J.; Trop, Stefanie; Das, Suchismita; Dimopoulos, George

    2013-01-01

    The mosquito Anopheles gambiae uses its innate immune system to control bacterial and Plasmodium infection of its midgut tissue. The activation of potent IMD pathway-mediated anti-Plasmodium falciparum defenses is dependent on the presence of the midgut microbiota, which activate this defense system upon parasite infection through a peptidoglycan recognition protein, PGRPLC. We employed transcriptomic and reverse genetic analyses to compare the P. falciparum infection-responsive transcriptomes of septic and aseptic mosquitoes and to determine whether bacteria-independent anti-Plasmodium defenses exist. Antibiotic treated aseptic mosquitoes mounted molecular immune responses representing a variety of immune functions upon P. falciparum infection. Among other immune factors, our analysis uncovered a serine protease inhibitor (SRPN7) and Clip-domain serine protease (CLIPC2) that were transcriptionally induced in the midgut upon P. falciparum infection, independent of bacteria. We also showed that SRPN7 negatively and CLIPC2 positively regulate the anti-Plasmodium defense, independently of the midgut-associated bacteria. Co-silencing assays suggested that these two genes may function together in a signaling cascade. Neither gene was regulated, nor modulated, by infection with the rodent malaria parasite Plasmodium berghei, suggesting that SRPN7 and CLIPC2 are components of a defense system with preferential activity towards P. falciparum. Further analysis using RNA interference determined that these genes do not regulate the anti-Plasmodium defense mediated by the IMD pathway, and both factors act as agonists of the endogenous midgut microbiota, further demonstrating the lack of functional relatedness between these genes and the bacteria-dependent activation of the IMD pathway. This is the first study confirming the existence of a bacteria-independent, anti-P. falciparum defense. Further exploration of this anti-Plasmodium defense will help clarify determinants of immune specificity in the mosquito, and expose potential gene and/or protein targets for malaria intervention strategies based on targeting the parasite in the mosquito vector. PMID:24019865

  20. Mosquito Defense Strategies against Viral Infection.

    PubMed

    Cheng, Gong; Liu, Yang; Wang, Penghua; Xiao, Xiaoping

    2016-03-01

    Mosquito-borne viral diseases are a major concern of global health and result in significant economic losses in many countries. As natural vectors, mosquitoes are very permissive to and allow systemic and persistent arbovirus infection. Intriguingly, persistent viral propagation in mosquito tissues neither results in dramatic pathological sequelae nor impairs the vectorial behavior or lifespan, indicating that mosquitoes have evolved mechanisms to tolerate persistent infection and developed efficient antiviral strategies to restrict viral replication to nonpathogenic levels. Here we provide an overview of recent progress in understanding mosquito antiviral immunity and advances in the strategies by which mosquitoes control viral infection in specific tissues. PMID:26626596

  1. Immunity and defense in pea aphids, Acyrthosiphon pisum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent genomic analyses of arthropod defense mechanisms suggest conservation of key elements underlying responses to pathogens, parasites, and stresses. At the center of pathogen-induced immune response are signaling pathways triggered by the recognition of fungal, bacterial, and viral signatures. T...

  2. T CellMediated Host Immune Defenses in the Lung

    PubMed Central

    Chen, Kong; Kolls, Jay K.

    2014-01-01

    Evidence has increasingly shown that the lungs are a major site of immune regulation. A robust and highly regulated immune response in the lung protects the host from pathogen infection, whereas an inefficient or deleterious response can lead to various pulmonary diseases. Many cell types, such as epithelial cells, dendritic cells, macrophages, neutrophils, eosinophils, and B and T lymphocytes, contribute to lung immunity. This review focuses on the recent advances in understanding how T lymphocytes mediate pulmonary host defenses against bacterial, viral, and fungal pathogens. PMID:23516986

  3. Immunity and other defenses in pea aphids, Acyrthosiphon pisum

    PubMed Central

    2010-01-01

    Background Recent genomic analyses of arthropod defense mechanisms suggest conservation of key elements underlying responses to pathogens, parasites and stresses. At the center of pathogen-induced immune responses are signaling pathways triggered by the recognition of fungal, bacterial and viral signatures. These pathways result in the production of response molecules, such as antimicrobial peptides and lysozymes, which degrade or destroy invaders. Using the recently sequenced genome of the pea aphid (Acyrthosiphon pisum), we conducted the first extensive annotation of the immune and stress gene repertoire of a hemipterous insect, which is phylogenetically distantly related to previously characterized insects models. Results Strikingly, pea aphids appear to be missing genes present in insect genomes characterized to date and thought critical for recognition, signaling and killing of microbes. In line with results of gene annotation, experimental analyses designed to characterize immune response through the isolation of RNA transcripts and proteins from immune-challenged pea aphids uncovered few immune-related products. Gene expression studies, however, indicated some expression of immune and stress-related genes. Conclusions The absence of genes suspected to be essential for the insect immune response suggests that the traditional view of insect immunity may not be as broadly applicable as once thought. The limitations of the aphid immune system may be representative of a broad range of insects, or may be aphid specific. We suggest that several aspects of the aphid life style, such as their association with microbial symbionts, could facilitate survival without strong immune protection. PMID:20178569

  4. Genetic constraints and sexual dimorphism in immune defense.

    PubMed

    Rolff, Jens; Armitage, Sophie A O; Coltman, David W

    2005-08-01

    The absence of continued evolutionary change despite the presence of genetic variation and directional selection is very common. Genetic correlations between traits can reduce the evolvability of traits. One intriguing example might be found in a sexual conflict over sexually dimorphic traits: a common genetic architecture constrains the response to selection on a trait subjected to sexually asymmetric selection pressures. Here we show that males and females of the mealworm beetle Tenebrio molitor differ in the quantitative genetic architecture of four traits related to immune defense and condition. Moreover, high genetic correlations between the sexes constitute a genetic constraint to the evolution of sexual dimorphism in immune defense. Our results suggest a general mechanism by which sexual conflict can promote evolutionary stasis. We furthermore show negative genetic correlations, strong indications of trade-offs, between immune traits for two pairs of traits in females. PMID:16329251

  5. Stop or move: Defensive strategies in humans.

    PubMed

    Bastos, Aline F; Vieira, Andre S; Oliveira, Jose M; Oliveira, Leticia; Pereira, Mirtes G; Figueira, Ivan; Erthal, Fatima S; Volchan, Eliane

    2016-04-01

    Threatening cues and surrounding contexts trigger specific defensive response patterns. Potential threat evokes attentive immobility; attack evokes flight when escape is available and immobility when escape is blocked. Tonic immobility installs when threat is overwhelming and life-risky. In humans, reduced body sway characterizes attentive and tonic immobility, the former with bradycardia, and the later with expressive tachycardia. Here, we investigate human defensive strategies in the presence or absence of an escape route. We employed pictures depicting a man carrying a gun and worked with participants exposed to urban violence. In pictures simulating more possibility of escape, the gun was directed away from the observer; in those simulating higher risk and less chance of escape, the gun was directed toward the observer. Matched control pictures depicted similar layouts, but a non-lethal object substituted the gun. Posturographic and electrocardiographic recordings were collected. Amplitude of sway and heart rate were higher for gun directed-away and lower for gun direct-toward. Compared to their respective matched controls, there was a general increase in the amplitude of sway for the gun directed-away pictures; and a reduction in back-and-forth sway and in heart rate for gun directed-toward pictures. Taken together, those measures suggest that, when exposed to threat invading their margin of safety in a context indicating possible escape route, humans, as non-human species, engage in active escape, resembling the flight stage of the defensive cascade. When facing threat indicating less possibility of escape, humans present an immobile response with bradycardia. PMID:26802729

  6. Efficient immunization strategies to prevent financial contagion

    NASA Astrophysics Data System (ADS)

    Kobayashi, Teruyoshi; Hasui, Kohei

    2014-01-01

    Many immunization strategies have been proposed to prevent infectious viruses from spreading through a network. In this work, we study efficient immunization strategies to prevent a default contagion that might occur in a financial network. An essential difference from the previous studies on immunization strategy is that we take into account the possibility of serious side effects. Uniform immunization refers to a situation in which banks are ``vaccinated'' with a common low-risk asset. The riskiness of immunized banks will decrease significantly, but the level of systemic risk may increase due to the de-diversification effect. To overcome this side effect, we propose another immunization strategy, called counteractive immunization, which prevents pairs of banks from failing simultaneously. We find that counteractive immunization can efficiently reduce systemic risk without altering the riskiness of individual banks.

  7. Efficient immunization strategies to prevent financial contagion.

    PubMed

    Kobayashi, Teruyoshi; Hasui, Kohei

    2014-01-01

    Many immunization strategies have been proposed to prevent infectious viruses from spreading through a network. In this work, we study efficient immunization strategies to prevent a default contagion that might occur in a financial network. An essential difference from the previous studies on immunization strategy is that we take into account the possibility of serious side effects. Uniform immunization refers to a situation in which banks are "vaccinated" with a common low-risk asset. The riskiness of immunized banks will decrease significantly, but the level of systemic risk may increase due to the de-diversification effect. To overcome this side effect, we propose another immunization strategy, called counteractive immunization, which prevents pairs of banks from failing simultaneously. We find that counteractive immunization can efficiently reduce systemic risk without altering the riskiness of individual banks. PMID:24452277

  8. Regulation of lung immunity and host defense by the intestinal microbiota

    PubMed Central

    Samuelson, Derrick R.; Welsh, David A.; Shellito, Judd E.

    2015-01-01

    Every year in the United States approximately 200,000 people die from pulmonary infections, such as influenza and pneumonia, or from lung disease that is exacerbated by pulmonary infection. In addition, respiratory diseases such as, asthma, affect 300 million people worldwide. Therefore, understanding the mechanistic basis for host defense against infection and regulation of immune processes involved in asthma are crucial for the development of novel therapeutic strategies. The identification, characterization, and manipulation of immune regulatory networks in the lung represents one of the biggest challenges in treatment of lung associated disease. Recent evidence suggests that the gastrointestinal (GI) microbiota plays a key role in immune adaptation and initiation in the GI tract as well as at other distal mucosal sites, such as the lung. This review explores the current research describing the role of the GI microbiota in the regulation of pulmonary immune responses. Specific focus is given to understanding how intestinal “dysbiosis” affects lung health. PMID:26500629

  9. Innate Immunity and antimicrobial defense systems in psoriasis

    PubMed Central

    Büchau, Amanda S.; Gallo, Richard L.

    2009-01-01

    Psoriasis is a chronic inflammatory disorder that is mediated by elements of the innate and adaptive immune systems. Its characteristic features in the skin consist of inflammatory changes in both dermis and epidermis, with abnormal keratinocyte differentiation and proliferation. Despite the elucidation of many aspects of psoriasis pathogenesis, some puzzling questions remain to be answered. A major question currently debated is if psoriasis is a primary abnormality of the epidermal keratinocyte or a reflection of dysregulated bone-marrow derived immunocytes. In this review we will focus on understanding the role of the innate immune system in psoriasis and how this provides a rational solution to address the origin of this multifactorial disease. Innate immunity is non-specific and genetically-based. It protects the body against the constant risk of pathogens through the use of rapidly mobilized defenses that are able to recognize and kill a wide variety of threats (bacteria, fungi, viruses, etc.). The key mechanisms of innate immune responses are the existence of receptors to recognize pathogens, and the production of factors that kill pathogens, such as antimicrobial peptides and proteins. Any combination of excessive sensitivity of the innate detection system, or dysregulation of the response system, can manifest both an epidermal phenotype and abnormal T-cell function. Thus, the multidimensional action of the innate immune system, its triggers, and its recently understood role in T-cell function, argue for an important role for innate mechanisms of recognition and response in the pathogenesis of psoriasis. PMID:18021900

  10. Flexible defense strategies: competition modifies investment in behavioral vs. morphological defenses.

    PubMed

    Teplitsky, Céline; Laurila, Anssi

    2007-07-01

    Competition is predicted to affect the expression of inducible defenses, but because costs of behavioral and morphological antipredator defenses differ along resource gradients, its effects on defenses may depend on the traits considered. We tested the predictions from different defense models in tadpoles of the common frog Rana temporaria, which exhibit both types of defenses. In an outdoor experiment, we exposed the tadpoles to nonlethal predators (Aeshna dragonfly larvae) and to a gradient of intraspecific competition. Morphological responses did not follow any of the expected patterns, since investment in defense was not affected by resource level. Instead, tail depth decreased in the absence of predators. Behavioral defenses followed a state-dependent model. Overall, the defense strategy of the tadpoles revealed a shift from morphological and behavioral defenses at low tadpole density to morphological defense only at high density. This difference probably reflects the different efficiency of the defenses. Hiding is an effective means of defense, but it is unsustainable when resources are scarce. Morphological responses become more important with increasing density to compensate for the increase in behavioral risk-taking. Our results indicate that competition can strongly affect reaction norms of inducible defenses and highlight the importance of integrating ecological parameters that affect the cost-benefit balance of phenotypic plasticity. PMID:17645010

  11. Dynamical immunization strategy for seasonal epidemics

    NASA Astrophysics Data System (ADS)

    Yan, Shu; Tang, Shaoting; Pei, Sen; Jiang, Shijin; Zheng, Zhiming

    2014-08-01

    The topic of finding an effective strategy to halt virus in a complex network is of current interest. We propose an immunization strategy for seasonal epidemics that occur periodically. Based on the local information of the infection status from the previous epidemic season, the selection of vaccinated nodes is optimized gradually. The evolution of vaccinated nodes during iterations demonstrates that the immunization tends to locate in both global hubs and local hubs. We analyze the epidemic prevalence using a heterogeneous mean-field method, and we present numerical simulations of our model. This immunization performs better than some other previously known strategies. Our work highlights an alternative direction in immunization for seasonal epidemics.

  12. Herbivores can select for mixed defensive strategies in plants.

    PubMed

    Carmona, Diego; Fornoni, Juan

    2013-01-01

    Resistance and tolerance are the most important defense mechanisms against herbivores. Initial theoretical studies considered both mechanisms functionally redundant, but more recent empirical studies suggest that these mechanisms may complement each other, favoring the presence of mixed defense patterns. However, the expectation of redundancy between tolerance and resistance remains unsupported. In this study, we tested this assumption following an ecological genetics field experiment in which the presence/absence of two herbivores (Lema daturaphila and Epitrix parvula) of Datura stramonium were manipulated. In each of three treatments, genotypic selection analyses were performed and selection patterns compared. Our results indicated that selection on resistance and tolerance was significantly different between the two folivores. Tolerance and resistance are not redundant defense strategies in D. stramonium but instead functioned as complementary defenses against both beetle species, favoring the evolution of a mixed defense strategy. Although each herbivore was selected for different defense strategies, the observed average tolerance and resistance were closer to the adaptive peak predicted against E. parvula and both beetles together. In our experimental population, natural selection imposed by herbivores can favor the evolution of mixed defense strategies in plants, accounting for the presence of intermediate levels of tolerance and resistance. PMID:23171270

  13. Pulse immunization -- polio eradication strategy.

    PubMed

    1994-09-30

    India has 10% of the reported cases of poliomyelitis each year, and the capital city, Delhi, contributes 6% of these. The trans-Yamuna region of Delhi has the highest incidence of the disease in the world. Yet, the World Health Organization (WHO) predicts that polio will be eradicated from India in 3 years and from the world by the year 2000. Thus, the WHO is working with the government of Delhi to implement a new "pulse immunization" program. Pulse immunization is thought to be the only way to eradicate the disease in conditions with unsafe water and poor sewage disposal. Pulse immunization requires simultaneous mass vaccination (over 2-3 days) with oral polio vaccine (OPV) of all children in the susceptible age group. This mass immunization is repeated twice a year with a 6-8 week interval between doses. Pulse immunization must be continued for 3-4 years to prevent resurgence of the disease. In Delhi, the first Sundays of October and December 1994 have been earmarked for the effort which will reach 3 million children under age of 3 years. The most difficult part of the effort will be to see that mothers bring their children to receive the immunization from one of 4000 vaccination booths. Pulse immunization can be administered to children regardless of their previous vaccination status and regardless of whether they are ill or healthy at the time. One pitfall of the program which must be considered to ensure its success is the infrastructure needed to provide refrigerated transportation of the OPV to the site of use. Even minor temperature changes can destroy the effectiveness of the OPV, so it is essential to protect the vaccine. It is ironic that while Delhi, with all of its problems, attempts to provide a cold chain-dependent mass immunization, efforts in the US to commence a new national vaccine program have been questioned because of the ability and cost-effectiveness of maintaining the cold chain. If the US has trouble maintaining the cold chain, will the government of Delhi have the resources to be successful in its efforts? PMID:12179217

  14. Inverse targeting An effective immunization strategy

    NASA Astrophysics Data System (ADS)

    Schneider, C. M.; Mihaljev, T.; Herrmann, H. J.

    2012-05-01

    We propose a new method to immunize populations or computer networks against epidemics which is more efficient than any continuous immunization method considered before. The novelty of our method resides in the way of determining the immunization targets. First we identify those individuals or computers that contribute the least to the disease spreading measured through their contribution to the size of the largest connected cluster in the social or a computer network. The immunization process follows the list of identified individuals or computers in inverse order, immunizing first those which are most relevant for the epidemic spreading. We have applied our immunization strategy to several model networks and two real networks, the Internet and the collaboration network of high-energy physicists. We find that our new immunization strategy is in the case of model networks up to 14%, and for real networks up to 33% more efficient than immunizing dynamically the most connected nodes in a network. Our strategy is also numerically efficient and can therefore be applied to large systems.

  15. Comparison of immunization strategies in geographical networks

    NASA Astrophysics Data System (ADS)

    Wang, Bing; Aihara, Kazuyuki; Kim, Beom Jun

    2009-10-01

    The epidemic spread and immunizations in geographically embedded scale-free (SF) and Watts-Strogatz (WS) networks are numerically investigated. We make a realistic assumption that it takes time which we call the detection time, for a vertex to be identified as infected, and implement two different immunization strategies: one is based on connection neighbors (CN) of the infected vertex with the exact information of the network structure utilized and the other is based on spatial neighbors (SN) with only geographical distances taken into account. We find that the decrease of the detection time is crucial for a successful immunization in general. Simulation results show that for both SF networks and WS networks, the SN strategy always performs better than the CN strategy, especially for more heterogeneous SF networks at long detection time. The observation is verified by checking the number of the infected nodes being immunized. We found that in geographical space, the distance preferences in the network construction process and the geographically decaying infection rate are key factors that make the SN immunization strategy outperforms the CN strategy. It indicates that even in the absence of the full knowledge of network connectivity we can still stop the epidemic spread efficiently only by using geographical information as in the SN strategy, which may have potential applications for preventing the real epidemic spread.

  16. Trade-offs between acquired and innate immune defenses in humans.

    PubMed

    McDade, Thomas W; Georgiev, Alexander V; Kuzawa, Christopher W

    2016-01-01

    Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

  17. Trade-offs between acquired and innate immune defenses in humans

    PubMed Central

    McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

    2016-01-01

    Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

  18. Ecological immunology in a fluctuating environment: an integrative analysis of tree swallow nestling immune defense

    PubMed Central

    Pigeon, Gabriel; Blisle, Marc; Garant, Dany; Cohen, Alan A; Pelletier, Fanie

    2013-01-01

    Evolutionary ecologists have long been interested by the link between different immune defenses and fitness. Given the importance of a proper immune defense for survival, it is important to understand how its numerous components are affected by environmental heterogeneity. Previous studies targeting this question have rarely considered more than two immune markers. In this study, we measured seven immune markers (response to phytohemagglutinin (PHA), hemolysis capacity, hemagglutination capacity, plasma bactericidal capacity, percentage of lymphocytes, percentage of heterophils, and percentage of eosinophils) in tree swallow (Tachycineta bicolor) nestlings raised in two types of agro-ecosystems of contrasted quality and over 2 years. First, we assessed the effect of environmental heterogeneity (spatial and temporal) on the strength and direction of correlations between immune measures. Second, we investigated the effect of an immune score integrating information from several immune markers on individual performance (including growth, mass at fledging and parasite burden). Both a multivariate and a pair-wise approach showed variation in relationships between immune measures across years and habitats. We also found a weak association between the integrated score of nestling immune function and individual performance, but only under certain environmental conditions. We conclude that the ecological context can strongly affect the interpretation of immune defenses in the wild. Given that spatiotemporal variations are likely to affect individual immune defenses, great caution should be used when generalizing conclusions to other study systems. PMID:23610646

  19. What lies beneath: belowground defense strategies in plants.

    PubMed

    De Coninck, Barbara; Timmermans, Pieter; Vos, Christine; Cammue, Bruno P A; Kazan, Kemal

    2015-02-01

    Diseases caused by soil-borne pathogens result worldwide in significant yield losses in economically important crops. In contrast to foliar diseases, relatively little is known about the nature of root defenses against these pathogens. This review summarizes the current knowledge on root infection strategies, root-specific preformed barriers, pathogen recognition, and defense signaling. Studies reviewed here suggest that many commonalities as well as differences exist in defense strategies employed by roots and foliar tissues during pathogen attack. Importantly, in addition to pathogens, plant roots interact with a plethora of non-pathogenic and symbiotic microorganisms. Therefore, a good understanding of how plant roots interact with the microbiome would be particularly important to engineer resistance to root pathogens without negatively altering root-beneficial microbe interactions. PMID:25307784

  20. Digital Medical Imaging: Implementation Strategy for the Defense Medical Establishment

    NASA Astrophysics Data System (ADS)

    Goeringer, Fred; Mun, Seong K.; Kerlin, Barbara D.

    1989-05-01

    In formulating an Implementation strategy for digital medical imaging, three interrelated thrusts have emerged for the Defense Medical Establishment. These thrusts- (1) Totally filmless medical imaging on the battlefield, (2) Teleradiology, and (3) DIN/PACS for peacetime military health care- have significant implications in their fully developed form as resource savers and quality improvers for the unique aspects of military health care .

  1. Phylogenetic escalation and decline of plant defense strategies

    PubMed Central

    Agrawal, Anurag A.; Fishbein, Mark

    2008-01-01

    As the basal resource in most food webs, plants have evolved myriad strategies to battle consumption by herbivores. Over the past 50 years, plant defense theories have been formulated to explain the remarkable variation in abundance, distribution, and diversity of secondary chemistry and other defensive traits. For example, classic theories of enemy-driven evolutionary dynamics have hypothesized that defensive traits escalate through the diversification process. Despite the fact that macroevolutionary patterns are an explicit part of defense theories, phylogenetic analyses have not been previously attempted to disentangle specific predictions concerning (i) investment in resistance traits, (ii) recovery after damage, and (iii) plant growth rate. We constructed a molecular phylogeny of 38 species of milkweed and tested four major predictions of defense theory using maximum-likelihood methods. We did not find support for the growth-rate hypothesis. Our key finding was a pattern of phyletic decline in the three most potent resistance traits (cardenolides, latex, and trichomes) and an escalation of regrowth ability. Our neontological approach complements more common paleontological approaches to discover directional trends in the evolution of life and points to the importance of natural enemies in the macroevolution of species. The finding of macroevolutionary escalating regowth ability and declining resistance provides a window into the ongoing coevolutionary dynamics between plants and herbivores and suggests a revision of classic plant defense theory. Where plants are primarily consumed by specialist herbivores, regrowth (or tolerance) may be favored over resistance traits during the diversification process. PMID:18645183

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

    PubMed

    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. PMID:26423359

  3. Strategy for child immunization in Malaysian plantations.

    PubMed

    Sinniah, D; Rajeswari, B; Harun, F; Maniam, C R

    1994-01-01

    An outline is given of a simple cost-effective strategy aimed at the immunization of all children and pregnant women residing in the plantation sector of Malaysia. It is based on a partnership between government, nongovernmental organizations and the private sector, and is supported by UNICEF. PMID:7945748

  4. Immune evasion strategies used by Helicobacter pylori

    PubMed Central

    Lina, Taslima T; Alzahrani, Shatha; Gonzalez, Jazmin; Pinchuk, Irina V; Beswick, Ellen J; Reyes, Victor E

    2014-01-01

    Helicobacter pylori (H. pylori) is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than half of humankind. Infection with this bacterium is commonly acquired during childhood. Once infected, people carry the bacteria for decades or even for life, if not treated. Persistent infection with this pathogen causes gastritis, peptic ulcer disease and is also strongly associated with the development of gastric cancer. Despite induction of innate and adaptive immune responses in the infected individual, the host is unable to clear the bacteria. One widely accepted hallmark of H. pylori is that it successfully and stealthily evades host defense mechanisms. Though the gastric mucosa is well protected against infection, H. pylori is able to reside under the mucus, attach to gastric epithelial cells and cause persistent infection by evading immune responses mediated by host. In this review, we discuss how H. pylori avoids innate and acquired immune response elements, uses gastric epithelial cells as mediators to manipulate host T cell responses and uses virulence factors to avoid adaptive immune responses by T cells to establish a persistent infection. We also discuss in this review how the genetic diversity of this pathogen helps for its survival. PMID:25278676

  5. An engineered innate immune defense protects grapevines from Pierce disease.

    PubMed

    Dandekar, Abhaya M; Gouran, Hossein; Ibez, Ana Mara; Uratsu, Sandra L; Agero, Cecilia B; McFarland, Sarah; Borhani, Yasmin; Feldstein, Paul A; Bruening, George; Nascimento, Rafael; Goulart, Luiz R; Pardington, Paige E; Chaudhary, Anu; Norvell, Meghan; Civerolo, Edwin; Gupta, Goutam

    2012-03-01

    We postulated that a synergistic combination of two innate immune functions, pathogen surface recognition and lysis, in a protein chimera would lead to a robust class of engineered antimicrobial therapeutics for protection against pathogens. In support of our hypothesis, we have engineered such a chimera to protect against the gram-negative Xylella fastidiosa (Xf), which causes diseases in multiple plants of economic importance. Here we report the design and delivery of this chimera to target the Xf subspecies fastidiosa (Xff), which causes Pierce disease in grapevines and poses a great threat to the wine-growing regions of California. One domain of this chimera is an elastase that recognizes and cleaves MopB, a conserved outer membrane protein of Xff. The second domain is a lytic peptide, cecropin B, which targets conserved lipid moieties and creates pores in the Xff outer membrane. A flexible linker joins the recognition and lysis domains, thereby ensuring correct folding of the individual domains and synergistic combination of their functions. The chimera transgene is fused with an amino-terminal signal sequence to facilitate delivery of the chimera to the plant xylem, the site of Xff colonization. We demonstrate that the protein chimera expressed in the xylem is able to directly target Xff, suppress its growth, and significantly decrease the leaf scorching and xylem clogging commonly associated with Pierce disease in grapevines. We believe that similar strategies involving protein chimeras can be developed to protect against many diseases caused by human and plant pathogens. PMID:22355130

  6. Immunization in urban areas: issues and strategies.

    PubMed Central

    Atkinson, S. J.; Cheyne, J.

    1994-01-01

    In the past, immunization programmes have focused primarily on rural areas. However, with the recognition of the increasing numbers of urban poor, it is timely to review urban immunization activities. This update addresses two questions: Is there any need to be concerned about urban immunization and, if so, is more of the same kind of rural EPI activity needed or are there specific urban issues that need specific urban strategies? Vaccine-preventable diseases have specific urban patterns that require efficacious vaccines for younger children, higher target coverage levels, and particular focus to ensure national and global eradication of poliomyelitis. Although aggregate coverage levels are higher in urban than rural areas, gaps are masked since capital cities are better covered than other urban areas and the coverage in the poorest slum and periurban areas within cities is as bad as or worse than that in rural areas. Difficult access to immunization services in terms of distance, costs, and time can still be the main barrier in some parts of the city. Mobilization and motivation strategies in urban areas should make use of the mass media and workplace networks as well as the traditional word-of-mouth strategies. Use of community health workers has been successful in some urban settings. Management issues concern integration of the needs of the poor into a coherent city health plan, coordination of different health providers, and clear lines of responsibility for addressing the needs of new, urbanizing areas. PMID:8205637

  7. Vaccination Strategies for Mucosal Immune Responses

    PubMed Central

    Ogra, Pearay L.; Faden, Howard; Welliver, Robert C.

    2001-01-01

    Mucosal administration of vaccines is an important approach to the induction of appropriate immune responses to microbial and other environmental antigens in systemic sites and peripheral blood as well as in most external mucosal surfaces. The development of specific antibody- or T-cell-mediated immunologic responses and the induction of mucosally induced systemic immunologic hyporesponsiveness (oral or mucosal tolerance) depend on complex sets of immunologic events, including the nature of the antigenic stimulation of specialized lymphoid structures in the host, antigen-induced activation of different populations of regulatory T cells (Th1 versus Th2), and the expression of proinflammatory and immunoregulatory cytokines. Availability of mucosal vaccines will provide a painless approach to deliver large numbers of vaccine antigens for human immunization. Currently, an average infant will receive 20 to 25 percutaneous injections for vaccination against different childhood infections by 18 months of age. It should be possible to develop for human use effective, nonliving, recombinant, replicating, transgenic, and microbial vector- or plant-based mucosal vaccines to prevent infections. Based on the experience with many dietary antigens, it is also possible to manipulate the mucosal immune system to induce systemic tolerance against environmental, dietary, and possibly other autoantigens associated with allergic and autoimmune disorders. Mucosal immunity offers new strategies to induce protective immune responses against a variety of infectious agents. Such immunization may also provide new prophylactic or therapeutic avenues in the control of autoimmune diseases in humans. PMID:11292646

  8. Unmasking host and microbial strategies in the Agrobacterium-plant defense tango

    PubMed Central

    Hwang, Elizabeth E.; Wang, Melinda B.; Bravo, Janis E.; Banta, Lois M.

    2015-01-01

    Coevolutionary forces drive adaptation of both plant-associated microbes and their hosts. Eloquently captured in the Red Queen Hypothesis, the complexity of each plantpathogen relationship reflects escalating adversarial strategies, but also external biotic and abiotic pressures on both partners. Innate immune responses are triggered by highly conserved pathogen-associated molecular patterns, or PAMPs, that are harbingers of microbial presence. Upon cell surface receptor-mediated recognition of these pathogen-derived molecules, host plants mount a variety of physiological responses to limit pathogen survival and/or invasion. Successful pathogens often rely on secretion systems to translocate host-modulating effectors that subvert plant defenses, thereby increasing virulence. Host plants, in turn, have evolved to recognize these effectors, activating what has typically been characterized as a pathogen-specific form of immunity. Recent data support the notion that PAMP-triggered and effector-triggered defenses are complementary facets of a convergent, albeit differentially regulated, set of immune responses. This review highlights the key players in the plants recognition and signal transduction pathways, with a focus on the aspects that may limit Agrobacterium tumefaciens infection and the ways it might overcome those defenses. Recent advances in the field include a growing appreciation for the contributions of cytoskeletal dynamics and membrane trafficking to the regulation of these exquisitely tuned defenses. Pathogen counter-defenses frequently manipulate the interwoven hormonal pathways that mediate host responses. Emerging systems-level analyses include host physiological factors such as circadian cycling. The existing literature indicates that varying or even conflicting results from different labs may well be attributable to environmental factors including time of day of infection, temperature, and/or developmental stage of the host plant. PMID:25873923

  9. Cellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens

    PubMed Central

    Randow, Felix; MacMicking, John D.; James, Leo C.

    2013-01-01

    Our prevailing view of vertebrate host defense is strongly shaped by the notion of a specialized set of immune cells as sole guardians of antimicrobial resistance. Yet this view greatly underestimates a capacity for most cell lineagesthe majority of which fall outside the traditional province of the immune systemto defend themselves against infection. This ancient and ubiquitous form of host protection is termed cell-autonomous immunity and operates across all three domains of life. Here, we discuss the organizing principles that govern cellular self-defense and how intracellular compartmentalization has shaped its activities to provide effective protection against a wide variety of microbial pathogens. PMID:23661752

  10. Incompatibility between plant-derived defensive chemistry and immune response of two sphingid herbivores.

    PubMed

    Lampert, Evan C; Bowers, M Deane

    2015-01-01

    Herbivorous insects use several different defenses against predators and parasites, and tradeoffs among defensive traits may occur if these traits are energetically demanding. Chemical defense and immune response potentially can interact, and both can be influenced by host plant chemistry. Two closely related caterpillars in the lepidopteran family Sphingidae are both attacked by the same specialist endoparasitoid species but have mostly non-overlapping host plant ranges that differ in secondary chemistry. Ceratomia catalpae is a specialist on Catalpa and also will feed on Chilopsis, which both produce iridoid glycosides. Ceratomia undulosa consumes members of the Oleaceae, which produce seco-iridoid glycosides. Immune response of the two species on a typical host plant species (Catalpa bignonioides for C. catalpa; Fraxinus americana for C. undulosa) was compared using a melanization assay, and did not differ. In a second experiment, the iridoid glycoside catalpol was added to the diets of both insects, and growth rate, mass, chemical defense, and immune response were evaluated. Increased dietary catalpol weakened the immune response of C. undulosa and altered the development rate of C. catalpae by prolonging the third instar and accelerating the fourth instar. Catalpol sequestration was negatively correlated with immune response of C. catalpae, while C. undulosa was unable to sequester catalpol. These results show that immune response can be negatively influenced by increasing concentrations of sequestered defensive compounds. PMID:25516226

  11. The middle ear immune defense changes with age.

    PubMed

    Nielsen, Michelle Christine; Friis, Morten; Martin-Bertelsen, Tomas; Winther, Ole; Friis-Hansen, Lennart; Cay-Thomasen, Per

    2016-01-01

    Otitis media is a common disease in childhood. In adults, the disease is relatively rare, but more frequently associated with complications. Possible reasons for this discrepancy are age-related differences in pathogen exposure, anatomy of the Eustachian tube and immune system. The objective of this study was to analyze the relationship between age and the mucosal immune system in the middle ear. It is hypothesized that genes involved in the middle ear immune system will change with age. A comprehensive assessment of these genetic differences using the techniques of complementary DNA has not been performed. Complementary DNA microarray technology was used to identify immune-related genes differentially expressed between the normal middle ear mucosa of young (10days old) and adult rats (80days old). Data were analyzed using tools of bioinformatics. A total of 260 age-related genes were identified, of which 51 genes were involved in the middle ear mucosal immune system. Genes related to the innate immune system, including alpha-defensin, calcium-binding proteins S100A9 and S100A8, were upregulated in young rats, whereas genes related to the adaptive immune system, including CD3 molecules, zeta-chain T-cell receptor-associated protein kinase and linker of activated T-cells, were upregulated in the adult. This study concludes that the normal middle ear immune system changes with age. Genes related to the innate immune system are upregulated in young rats, whereas genes related to the adaptive immune system are upregulated in adults. PMID:25563239

  12. Strategy alternatives for homeland air and cruise missile defense.

    PubMed

    Murphy, Eric M; Payne, Michael D; Vanderwoude, Glenn W

    2010-10-01

    Air and cruise missile defense of the U.S. homeland is characterized by a requirement to protect a large number of critical assets nonuniformly dispersed over a vast area with relatively few defensive systems. In this article, we explore strategy alternatives to make the best use of existing defense resources and suggest this approach as a means of reducing risk while mitigating the cost of developing and acquiring new systems. We frame the issue as an attacker-defender problem with simultaneous moves. First, we outline and examine the relatively simple problem of defending comparatively few locations with two surveillance systems. Second, we present our analysis and findings for a more realistic scenario that includes a representative list of U.S. critical assets. Third, we investigate sensitivity to defensive strategic choices in the more realistic scenario. As part of this investigation, we describe two complementary computational methods that, under certain circumstances, allow one to reduce large computational problems to a more manageable size. Finally, we demonstrate that strategic choices can be an important supplement to material solutions and can, in some cases, be a more cost-effective alternative. PMID:20626693

  13. Plant mating system transitions drive the macroevolution of defense strategies

    PubMed Central

    Campbell, Stuart A.; Kessler, André

    2013-01-01

    Understanding the factors that shape macroevolutionary patterns in functional traits is a central goal of evolutionary biology. Alternative strategies of sexual reproduction (inbreeding vs. outcrossing) have divergent effects on population genetic structure and could thereby broadly influence trait evolution. However, the broader evolutionary consequences of mating system transitions remain poorly understood, with the exception of traits related to reproduction itself (e.g., pollination). Across a phylogeny of 56 wild species of Solanaceae (nightshades), we show here that the repeated, unidirectional transition from ancestral self-incompatibility (obligate outcrossing) to self-compatibility (increased inbreeding) leads to the evolution of an inducible (vs. constitutive) strategy of plant resistance to herbivores. We demonstrate that inducible and constitutive defense strategies represent evolutionary alternatives and that the magnitude of the resulting macroevolutionary tradeoff is dependent on the mating system. Loss of self-incompatibility is also associated with the evolution of increased specificity in induced plant resistance. We conclude that the evolution of sexual reproductive variation may have profound effects on plant–herbivore interactions, suggesting a new hypothesis for the evolution of two primary strategies of plant defense. PMID:23431190

  14. Probing the Unknowns in Cytokinin-Mediated Immune Defense in Arabidopsis with Systems Biology Approaches

    PubMed Central

    Naseem, Muhammad; Kunz, Meik; Dandekar, Thomas

    2014-01-01

    Plant hormones involving salicylic acid (SA), jasmonic acid (JA), ethylene (Et), and auxin, gibberellins, and abscisic acid (ABA) are known to regulate host immune responses. However, plant hormone cytokinin has the potential to modulate defense signaling including SA and JA. It promotes plant pathogen and herbivore resistance; underlying mechanisms are still unknown. Using systems biology approaches, we unravel hub points of immune interaction mediated by cytokinin signaling in Arabidopsis. High-confidence Arabidopsis proteinprotein interactions (PPI) are coupled to changes in cytokinin-mediated gene expression. Nodes of the cellular interactome that are enriched in immune functions also reconstitute sub-networks. Topological analyses and their specific immunological relevance lead to the identification of functional hubs in cellular interactome. We discuss our identified immune hubs in light of an emerging model of cytokinin-mediated immune defense against pathogen infection in plants. PMID:24558299

  15. Control Systems Cyber Security:Defense in Depth Strategies

    SciTech Connect

    David Kuipers; Mark Fabro

    2006-05-01

    Information infrastructures across many public and private domains share several common attributes regarding IT deployments and data communications. This is particularly true in the control systems domain. A majority of the systems use robust architectures to enhance business and reduce costs by increasing the integration of external, business, and control system networks. However, multi-network integration strategies often lead to vulnerabilities that greatly reduce the security of an organization, and can expose mission-critical control systems to cyber threats. This document provides guidance and direction for developing ‘defense-in-depth’ strategies for organizations that use control system networks while maintaining a multi-tier information architecture that requires: Maintenance of various field devices, telemetry collection, and/or industrial-level process systems Access to facilities via remote data link or modem Public facing services for customer or corporate operations A robust business environment that requires connections among the control system domain, the external Internet, and other peer organizations.

  16. Immune Evasion Strategies of Trypanosoma cruzi

    PubMed Central

    Flávia Nardy, Ana; Freire-de-Lima, Célio Geraldo; Morrot, Alexandre

    2015-01-01

    Microbes have evolved a diverse range of strategies to subvert the host immune system. The protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, provides a good example of such adaptations. This parasite targets a broad spectrum of host tissues including both peripheral and central lymphoid tissues. Rapid colonization of the host gives rise to a systemic acute response which the parasite must overcome. The parasite in fact undermines both innate and adaptive immunity. It interferes with the antigen presenting function of dendritic cells via an action on host sialic acid-binding Ig-like lectin receptors. These receptors also induce suppression of CD4+ T cells responses, and we presented evidence that the sialylation of parasite-derived mucins is required for the inhibitory effects on CD4 T cells. In this review we highlight the major mechanisms used by Trypanosoma cruzi to overcome host immunity and discuss the role of parasite colonization of the central thymic lymphoid tissue in chronic disease. PMID:26240832

  17. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation

    PubMed Central

    Muralidharan, Sujatha; Mandrekar, Pranoti

    2013-01-01

    Extensive research in the past decade has identified innate immune recognition receptors and intracellular signaling pathways that culminate in inflammatory responses. Besides its role in cytoprotection, the importance of cell stress in inflammation and host defense against pathogens is emerging. Recent studies have shown that proteins in cellular stress responses, including the heat shock response, ER stress response, and DNA damage response, interact with and regulate signaling intermediates involved in the activation of innate and adaptive immune responses. The effect of such regulation by cell stress proteins may dictate the inflammatory profile of the immune response during infection and disease. In this review, we describe the regulation of innate immune cell activation by cell stress pathways, present detailed descriptions of the types of stress response proteins and their crosstalk with immune signaling intermediates that are essential in host defense, and illustrate the relevance of these interactions in diseases characteristic of aberrant immune responses, such as chronic inflammatory diseases, autoimmune disorders, and cancer. Understanding the crosstalk between cellular stress proteins and immune signaling may have translational implications for designing more effective regimens to treat immune disorders. PMID:23990626

  18. Inducible defenses stay up late: temporal patterns of immune gene expression in Tenebrio molitor.

    PubMed

    Johnston, Paul R; Makarova, Olga; Rolff, Jens

    2014-06-01

    The course of microbial infection in insects is shaped by a two-stage process of immune defense. Constitutive defenses, such as engulfment and melanization, act immediately and are followed by inducible defenses, archetypically the production of antimicrobial peptides, which eliminate or suppress the remaining microbes. By applying RNAseq across a 7-day time course, we sought to characterize the long-lasting immune response to bacterial challenge in the mealworm beetle Tenebrio molitor, a model for the biochemistry of insect immunity and persistent bacterial infection. By annotating a hybrid de novo assembly of RNAseq data, we were able to identify putative orthologs for the majority of components of the conserved insect immune system. Compared with Tribolium castaneum, the most closely related species with a reference genome sequence and a manually curated immune system annotation, the T. molitor immune gene count was lower, with lineage-specific expansions of genes encoding serine proteases and their countervailing inhibitors accounting for the majority of the deficit. Quantitative mapping of RNAseq reads to the reference assembly showed that expression of genes with predicted functions in cellular immunity, wound healing, melanization, and the production of reactive oxygen species was transiently induced immediately after immune challenge. In contrast, expression of genes encoding antimicrobial peptides or components of the Toll signaling pathway and iron sequestration response remained elevated for at least 7 days. Numerous genes involved in metabolism and nutrient storage were repressed, indicating a possible cost of immune induction. Strikingly, the expression of almost all antibacterial peptides followed the same pattern of long-lasting induction, regardless of their spectra of activity, signaling possible interactive roles in vivo. PMID:24318927

  19. Inducible Defenses Stay Up Late: Temporal Patterns of Immune Gene Expression in Tenebrio molitor

    PubMed Central

    Johnston, Paul R; Makarova, Olga; Rolff, Jens

    2014-01-01

    The course of microbial infection in insects is shaped by a two-stage process of immune defense. Constitutive defenses, such as engulfment and melanization, act immediately and are followed by inducible defenses, archetypically the production of antimicrobial peptides, which eliminate or suppress the remaining microbes. By applying RNAseq across a 7-day time course, we sought to characterize the long-lasting immune response to bacterial challenge in the mealworm beetle Tenebrio molitor, a model for the biochemistry of insect immunity and persistent bacterial infection. By annotating a hybrid de novo assembly of RNAseq data, we were able to identify putative orthologs for the majority of components of the conserved insect immune system. Compared with Tribolium castaneum, the most closely related species with a reference genome sequence and a manually curated immune system annotation, the T. molitor immune gene count was lower, with lineage-specific expansions of genes encoding serine proteases and their countervailing inhibitors accounting for the majority of the deficit. Quantitative mapping of RNAseq reads to the reference assembly showed that expression of genes with predicted functions in cellular immunity, wound healing, melanization, and the production of reactive oxygen species was transiently induced immediately after immune challenge. In contrast, expression of genes encoding antimicrobial peptides or components of the Toll signaling pathway and iron sequestration response remained elevated for at least 7 days. Numerous genes involved in metabolism and nutrient storage were repressed, indicating a possible cost of immune induction. Strikingly, the expression of almost all antibacterial peptides followed the same pattern of long-lasting induction, regardless of their spectra of activity, signaling possible interactive roles in vivo. PMID:24318927

  20. Salivary defense proteins: their network and role in innate and acquired oral immunity.

    PubMed

    Fbin, Tibor Kroly; Hermann, Pter; Beck, Anita; Fejrdy, Pl; Fbin, Gbor

    2012-01-01

    There are numerous defense proteins present in the saliva. Although some of these molecules are present in rather low concentrations, their effects are additive and/or synergistic, resulting in an efficient molecular defense network of the oral cavity. Moreover, local concentrations of these proteins near the mucosal surfaces (mucosal transudate), periodontal sulcus (gingival crevicular fluid) and oral wounds and ulcers (transudate) may be much greater, and in many cases reinforced by immune and/or inflammatory reactions of the oral mucosa. Some defense proteins, like salivary immunoglobulins and salivary chaperokine HSP70/HSPAs (70 kDa heat shock proteins), are involved in both innate and acquired immunity. Cationic peptides and other defense proteins like lysozyme, bactericidal/permeability increasing protein (BPI), BPI-like proteins, PLUNC (palate lung and nasal epithelial clone) proteins, salivary amylase, cystatins, prolin-rich proteins, mucins, peroxidases, statherin and others are primarily responsible for innate immunity. In this paper, this complex system and function of the salivary defense proteins will be reviewed. PMID:22605979

  1. Salivary Defense Proteins: Their Network and Role in Innate and Acquired Oral Immunity

    PubMed Central

    Fbin, Tibor Kroly; Hermann, Pter; Beck, Anita; Fejrdy, Pl; Fbin, Gbor

    2012-01-01

    There are numerous defense proteins present in the saliva. Although some of these molecules are present in rather low concentrations, their effects are additive and/or synergistic, resulting in an efficient molecular defense network of the oral cavity. Moreover, local concentrations of these proteins near the mucosal surfaces (mucosal transudate), periodontal sulcus (gingival crevicular fluid) and oral wounds and ulcers (transudate) may be much greater, and in many cases reinforced by immune and/or inflammatory reactions of the oral mucosa. Some defense proteins, like salivary immunoglobulins and salivary chaperokine HSP70/HSPAs (70 kDa heat shock proteins), are involved in both innate and acquired immunity. Cationic peptides and other defense proteins like lysozyme, bactericidal/permeability increasing protein (BPI), BPI-like proteins, PLUNC (palate lung and nasal epithelial clone) proteins, salivary amylase, cystatins, prolin-rich proteins, mucins, peroxidases, statherin and others are primarily responsible for innate immunity. In this paper, this complex system and function of the salivary defense proteins will be reviewed. PMID:22605979

  2. A unique host defense pathway: TRIF mediates both antiviral and antibacterial immune responses

    PubMed Central

    Hyun, Jinhee; Kanagavelu, Saravana; Fukata, Masayuki

    2012-01-01

    Both anti-viral and anti-bacterial host defense mechanisms involve TRIF signaling. TRIF provides early clearance of pathogens and coordination of a local inflammatory ensemble through an interferon cascade, while it may trigger organ damage. The multipotentiality of TRIF-mediated immune machinery may direct the fate of our continuous battle with microbes. PMID:23116944

  3. Host Defense Peptides as Effector Molecules of the Innate Immune Response: A Sledgehammer for Drug Resistance?

    PubMed Central

    Steinstraesser, Lars; Kraneburg, Ursula M.; Hirsch, Tobias; Kesting, Marco; Steinau, Hans-Ulrich; Jacobsen, Frank; Al-Benna, Sammy

    2009-01-01

    Host defense peptides can modulate the innate immune response and boost infection-resolving immunity, while dampening potentially harmful pro-inflammatory (septic) responses. Both antimicrobial and/or immunomodulatory activities are an integral part of the process of innate immunity, which itself has many of the hallmarks of successful anti-infective therapies, namely rapid action and broad-spectrum antimicrobial activities. This gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections. This review details the role and activities of these peptides, and examines their applicability as development candidates for use against bacterial infections. PMID:19865528

  4. Optimal defense strategies in an idealized microbial food web under trade-off between competition and defense.

    PubMed

    Vge, Selina; Storesund, Julia E; Giske, Jarl; Thingstad, T Frede

    2014-01-01

    Trophic mechanisms that can generate biodiversity in food webs include bottom-up (growth rate regulating) and top-down (biomass regulating) factors. The top-down control has traditionally been analyzed using the concepts of "Keystone Predation" (KP) and "Killing-the-Winner" (KtW), predominately occuring in discussions of macro- and micro-biological ecology, respectively. Here we combine the classical diamond-shaped food web structure frequently discussed in KP analyses and the KtW concept by introducing a defense strategist capable of partial defense. A formalized description of a trade-off between the defense-strategist's competitive and defensive ability is included. The analysis reveals a complex topology of the steady state solution with strong relationships between food web structure and the combination of trade-off, defense strategy and the system's nutrient content. Among the results is a difference in defense strategies corresponding to maximum biomass, production, or net growth rate of invading individuals. The analysis thus summons awareness that biomass or production, parameters typically measured in field studies to infer success of particular biota, are not directly acted upon by natural selection. Under coexistence with a competition specialist, a balance of competitive and defensive ability of the defense strategist was found to be evolutionarily stable, whereas stronger defense was optimal under increased nutrient levels in the absence of the pure competition specialist. The findings of success of different defense strategies are discussed with respect to SAR11, a highly successful bacterial clade in the pelagic ocean. PMID:24999739

  5. Optimal Defense Strategies in an Idealized Microbial Food Web under Trade-Off between Competition and Defense

    PubMed Central

    Vge, Selina; Storesund, Julia E.; Giske, Jarl; Thingstad, T. Frede

    2014-01-01

    Trophic mechanisms that can generate biodiversity in food webs include bottom-up (growth rate regulating) and top-down (biomass regulating) factors. The top-down control has traditionally been analyzed using the concepts of Keystone Predation (KP) and Killing-the-Winner (KtW), predominately occuring in discussions of macro- and micro-biological ecology, respectively. Here we combine the classical diamond-shaped food web structure frequently discussed in KP analyses and the KtW concept by introducing a defense strategist capable of partial defense. A formalized description of a trade-off between the defense-strategist's competitive and defensive ability is included. The analysis reveals a complex topology of the steady state solution with strong relationships between food web structure and the combination of trade-off, defense strategy and the system's nutrient content. Among the results is a difference in defense strategies corresponding to maximum biomass, production, or net growth rate of invading individuals. The analysis thus summons awareness that biomass or production, parameters typically measured in field studies to infer success of particular biota, are not directly acted upon by natural selection. Under coexistence with a competition specialist, a balance of competitive and defensive ability of the defense strategist was found to be evolutionarily stable, whereas stronger defense was optimal under increased nutrient levels in the absence of the pure competition specialist. The findings of success of different defense strategies are discussed with respect to SAR11, a highly successful bacterial clade in the pelagic ocean. PMID:24999739

  6. Passive Antibody Administration (Immediate Immunity) as a Specific Defense Against Biological Weapons

    PubMed Central

    2002-01-01

    The potential threat of biological warfare with a specific agent is proportional to the susceptibility of the population to that agent. Preventing disease after exposure to a biological agent is partially a function of the immunity of the exposed individual. The only available countermeasure that can provide immediate immunity against a biological agent is passive antibody. Unlike vaccines, which require time to induce protective immunity and depend on the hosts ability to mount an immune response, passive antibody can theoretically confer protection regardless of the immune status of the host. Passive antibody therapy has substantial advantages over antimicrobial agents and other measures for postexposure prophylaxis, including low toxicity and high specific activity. Specific antibodies are active against the major agents of bioterrorism, including anthrax, smallpox, botulinum toxin, tularemia, and plague. This article proposes a biological defense initiative based on developing, producing, and stockpiling specific antibody reagents that can be used to protect the population against biological warfare threats. PMID:12141970

  7. Innate immune evasion strategies of influenza viruses

    PubMed Central

    Hale, Benjamin G; Albrecht, Randy A; Garca-Sastre, Adolfo

    2010-01-01

    Influenza viruses are globally important human respiratory pathogens. These viruses cause seasonal epidemics and occasional worldwide pandemics, both of which can vary significantly in disease severity. The virulence of a particular influenza virus strain is partly determined by its success in circumventing the host immune response. This article briefly reviews the innate mechanisms that host cells have evolved to resist virus infection, and outlines the plethora of strategies that influenza viruses have developed in order to counteract such powerful defences. The molecular details of this virushost interplay are summarized, and the ways in which research in this area is being applied to the rational design of protective vaccines and novel antivirals are discussed. PMID:20020828

  8. Quantifying the coevolutionary potential of multistep immune defenses.

    PubMed

    Nuismer, Scott L; Dybdahl, Mark F

    2016-02-01

    Coevolutionary models often assume host infection by parasites depends on a single bout of molecular recognition. As detailed immunological studies accumulate, however, it becomes increasingly apparent that the outcome of host-parasite interactions more generally depends on complex multiple step infection processes. For example, in plant and animal innate immunity, recognition steps are followed by downstream effector steps that kill recognized parasites, with the outcome depending on an escalatory molecular arms race. Here, we explore the consequences of such multistep infection processes for coevolution using a genetically explicit model. Model analyses reveal that polymorphism is much greater at recognition loci than effector loci, that host-genotype by parasite-genotype (Gh Gp ) interactions are larger for the recognition step, and that the recognition step contributes more to local adaptation than the effector step. These results suggest that (1) local adaptation is more likely when fitness measures are related to recognition versus downstream effectors, (2) effector loci, while mechanistically important, are less likely to harbor the Gh Gp variation that fuels coevolution, and (3) recognition loci are better candidates for genomic hotspots of coevolution. PMID:26792644

  9. Antimicrobial responses of teleost phagocytes and innate immune evasion strategies of intracellular bacteria.

    PubMed

    Grayfer, Leon; Hodgkinson, Jordan W; Belosevic, Miodrag

    2014-04-01

    During infection, macrophage lineage cells eliminate infiltrating pathogens through a battery of antimicrobial responses, where the efficacy of these innate immune responses is pivotal to immunological outcomes. Not surprisingly, many intracellular pathogens have evolved mechanisms to overcome macrophage defenses, using these immune cells as residences and dissemination strategies. With pathogenic infections causing increasing detriments to both aquacultural and wild fish populations, it is imperative to garner greater understanding of fish phagocyte antimicrobial responses and the mechanisms by which aquatic pathogens are able to overcome these teleost macrophage barriers. Insights into the regulation of macrophage immunity of bony fish species will lend to the development of more effective aquacultural prophylaxis as well as broadening our understanding of the evolution of these immune processes. Accordingly, this review focuses on recent advances in the understanding of teleost macrophage antimicrobial responses and the strategies by which intracellular fish pathogens are able to avoid being killed by phagocytes, with a focus on Mycobacterium marinum. PMID:23954721

  10. Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses.

    PubMed

    Begun, Jakob; Gaiani, Jessica M; Rohde, Holger; Mack, Dietrich; Calderwood, Stephen B; Ausubel, Frederick M; Sifri, Costi D

    2007-04-01

    Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms. The ability of staphylococci to produce biofilm is an important virulence mechanism that allows bacteria both to adhere to living and artificial surfaces and to resist host immune factors and antibiotics. Here, we show that the icaADBC locus, which synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA) in staphylococci, is required for the formation of a lethal S. epidermidis infection in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38 mitogen-activated protein (MAP) kinase or DAF-2 insulin-signaling pathways. Loss of PIA production abrogates nematocidal activity and leads to reduced bacterial accumulation in the C. elegans intestine, while overexpression of the icaADBC locus in S. aureus augments virulence towards nematodes. PIA-producing S. epidermidis has a significant survival advantage over ica-deficient S. epidermidis within the intestinal tract of wild-type C. elegans, but not in immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally sensitive to wild-type and icaADBC-deficient S. epidermidis. These results suggest that biofilm exopolysaccharide enhances virulence by playing an immunoprotective role during colonization of the C. elegans intestine. These studies demonstrate that C. elegans can serve as a simple animal model for studying host-pathogen interactions involving staphylococcal biofilm exopolysaccharide and suggest that the protective activity of biofilm matrix represents an ancient conserved function for resisting predation. PMID:17447841

  11. Self/nonself perception in plants in innate immunity and defense

    PubMed Central

    Sanabria, Natasha M; Huang, Ju-Chi

    2010-01-01

    The ability to distinguish self from nonself is the most fundamental aspect of any immune system. The evolutionary solution in plants to the problems of perceiving and responding to pathogens involves surveillance of nonself, damaged-self and altered-self as danger signals. This is reflected in basal resistance or non-host resistance, which is the innate immune response that protects plants against the majority of pathogens. In the case of surveillance of nonself, plants utilize receptor-like proteins or -kinases (RLP/Ks) as pattern recognition receptors (PRRs), which can detect conserved pathogen/microbe-associated molecular pattern (P/MAMP) molecules. P/MAMP detection serves as an early warning system for the presence of a wide range of potential pathogens and the timely activation of plant defense mechanisms. However, adapted microbes express a suite of effector proteins that often interfere or act as suppressors of these defenses. In response, plants have evolved a second line of defense that includes intracellular nucleotide binding leucine-rich repeat (NB-LRR)-containing resistance proteins, which recognize isolate-specific pathogen effectors once the cell wall has been compromised. This host-immunity acts within the species level and is controlled by polymorphic host genes, where resistance protein-mediated activation of defense is based on an altered-self recognition mechanism. PMID:21559176

  12. Silencing and Innate Immunity in Plant Defense Against Viral and Non-Viral Pathogens

    PubMed Central

    Zvereva, Anna S.; Pooggin, Mikhail M.

    2012-01-01

    The frontline of plant defense against non-viral pathogens such as bacteria, fungi and oomycetes is provided by transmembrane pattern recognition receptors that detect conserved pathogen-associated molecular patterns (PAMPs), leading to pattern-triggered immunity (PTI). To counteract this innate defense, pathogens deploy effector proteins with a primary function to suppress PTI. In specific cases, plants have evolved intracellular resistance (R) proteins detecting isolate-specific pathogen effectors, leading to effector-triggered immunity (ETI), an amplified version of PTI, often associated with hypersensitive response (HR) and programmed cell death (PCD). In the case of plant viruses, no conserved PAMP was identified so far and the primary plant defense is thought to be based mainly on RNA silencing, an evolutionary conserved, sequence-specific mechanism that regulates gene expression and chromatin states and represses invasive nucleic acids such as transposons. Endogenous silencing pathways generate 21-24 nt small (s)RNAs, miRNAs and short interfering (si)RNAs, that repress genes post-transcriptionally and/or transcriptionally. Four distinct Dicer-like (DCL) proteins, which normally produce endogenous miRNAs and siRNAs, all contribute to the biogenesis of viral siRNAs in infected plants. Growing evidence indicates that RNA silencing also contributes to plant defense against non-viral pathogens. Conversely, PTI-based innate responses may contribute to antiviral defense. Intracellular R proteins of the same NB-LRR family are able to recognize both non-viral effectors and avirulence (Avr) proteins of RNA viruses, and, as a result, trigger HR and PCD in virus-resistant hosts. In some cases, viral Avr proteins also function as silencing suppressors. We hypothesize that RNA silencing and innate immunity (PTI and ETI) function in concert to fight plant viruses. Viruses counteract this dual defense by effectors that suppress both PTI-/ETI-based innate responses and RNA silencing to establish successful infection. PMID:23202495

  13. Immunization strategy based on the critical node in percolation transition

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Wei, Bo; Wang, Zhen; Deng, Yong

    2015-11-01

    The problem of finding a better immunization strategy for controlling the spreading of the epidemic with limited resources has attracted much attention since its great theoretical significance and wide application. In this letter, we propose a novel and successful targeted immunization strategy based on percolation transition. Our strategy repeatedly looks for the critical nodes for immunizing. The critical node, which leads to the emergence of the giant connected component as the degree threshold increases, is determined when the maximal second-largest connected component disappears. To test the effectiveness of the proposed method, we conduct the experiments on several artificial networks and real-world networks. The results show that the proposed method outperforms the degree centrality strategy, the betweenness centrality strategy and the adaptive degree centrality strategy with 18% to 50% fewer immunized nodes for same amount of immunization.

  14. Control Systems Cyber Security: Defense-in-Depth Strategies

    SciTech Connect

    Mark Fabro

    2007-10-01

    Information infrastructures across many public and private domains share several common attributes regarding IT deployments and data communications. This is particularly true in the control systems domain. A majority of the systems use robust architectures to enhance business and reduce costs by increasing the integration of external, business, and control system networks. However, multi-network integration strategies often lead to vulnerabilities that greatly reduce the security of an organization, and can expose mission-critical control systems to cyber threats. This document provides guidance and direction for developing ‘defense-in-depth’ strategies for organizations that use control system networks while maintaining a multi-tier information architecture that requires: • Maintenance of various field devices, telemetry collection, and/or industrial-level process systems • Access to facilities via remote data link or modem • Public facing services for customer or corporate operations • A robust business environment that requires connections among the control system domain, the external Internet, and other peer organizations.

  15. Harnessing the Prokaryotic Adaptive Immune System as a Eukaryotic Antiviral Defense.

    PubMed

    Price, Aryn A; Grakoui, Arash; Weiss, David S

    2016-04-01

    Clustered, regularly interspaced, short palindromic repeats - CRISPR-associated (CRISPR-Cas) systems - are sequence-specific RNA-directed endonuclease complexes that bind and cleave nucleic acids. These systems evolved within prokaryotes as adaptive immune defenses to target and degrade nucleic acids derived from bacteriophages and other foreign genetic elements. The antiviral function of these systems has now been exploited to combat eukaryotic viruses throughout the viral life cycle. Here we discuss current advances in CRISPR-Cas9 technology as a eukaryotic antiviral defense. PMID:26852268

  16. Local immunization strategy based on the scores of nodes.

    PubMed

    Liu, Yang; Deng, Yong; Wei, Bo

    2016-01-01

    The problem of finding a better immunization strategy for controlling the spreading of the epidemic with limited resources has attracted much attention because of its great theoretical significance and wide application. In this paper, we propose a successful immunization strategy only depending on local information. Our strategy initializes the scores of nodes with the values of their degree and recalculates the score of a certain immunized node based on its local information, and then replaces the certain immunized node with its nonimmunized higher-score neighbor. To test the effectiveness of the proposed strategy, we conduct the experiments on several synthetic networks and real-world networks. The results show that the proposed strategy outperforms the existing well-known local strategies, even the degree centrality targeted strategy. PMID:26826858

  17. Local immunization strategy based on the scores of nodes

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Deng, Yong; Wei, Bo

    2016-01-01

    The problem of finding a better immunization strategy for controlling the spreading of the epidemic with limited resources has attracted much attention because of its great theoretical significance and wide application. In this paper, we propose a successful immunization strategy only depending on local information. Our strategy initializes the scores of nodes with the values of their degree and recalculates the score of a certain immunized node based on its local information, and then replaces the certain immunized node with its nonimmunized higher-score neighbor. To test the effectiveness of the proposed strategy, we conduct the experiments on several synthetic networks and real-world networks. The results show that the proposed strategy outperforms the existing well-known local strategies, even the degree centrality targeted strategy.

  18. Larval Environment Alters Amphibian Immune Defenses Differentially across Life Stages and Populations.

    PubMed

    Krynak, Katherine L; Burke, David J; Benard, Michael F

    2015-01-01

    Recent global declines, extirpations and extinctions of wildlife caused by newly emergent diseases highlight the need to improve our knowledge of common environmental factors that affect the strength of immune defense traits. To achieve this goal, we examined the influence of acidification and shading of the larval environment on amphibian skin-associated innate immune defense traits, pre and post-metamorphosis, across two populations of American Bullfrogs (Rana catesbeiana), a species known for its wide-ranging environmental tolerance and introduced global distribution. We assessed treatment effects on 1) skin-associated microbial communities and 2) post-metamorphic antimicrobial peptide (AMP) production and 3) AMP bioactivity against the fungal pathogen Batrachochytrium dendrobatidis (Bd). While habitat acidification did not affect survival, time to metamorphosis or juvenile mass, we found that a change in average pH from 7 to 6 caused a significant shift in the larval skin microbial community, an effect which disappeared after metamorphosis. Additionally, we found shifts in skin-associated microbial communities across life stages suggesting they are affected by the physiological or ecological changes associated with amphibian metamorphosis. Moreover, we found that post-metamorphic AMP production and bioactivity were significantly affected by the interactions between pH and shade treatments and interactive effects differed across populations. In contrast, there were no significant interactions between treatments on post-metamorphic microbial community structure suggesting that variation in AMPs did not affect microbial community structure within our study. Our findings indicate that commonly encountered variation in the larval environment (i.e. pond pH and degree of shading) can have both immediate and long-term effects on the amphibian innate immune defense traits. Our work suggests that the susceptibility of amphibians to emerging diseases could be related to variability in the larval environment and calls for research into the relative influence of potentially less benign anthropogenic environmental changes on innate immune defense traits. PMID:26107644

  19. Larval Environment Alters Amphibian Immune Defenses Differentially across Life Stages and Populations

    PubMed Central

    2015-01-01

    Recent global declines, extirpations and extinctions of wildlife caused by newly emergent diseases highlight the need to improve our knowledge of common environmental factors that affect the strength of immune defense traits. To achieve this goal, we examined the influence of acidification and shading of the larval environment on amphibian skin-associated innate immune defense traits, pre and post-metamorphosis, across two populations of American Bullfrogs (Rana catesbeiana), a species known for its wide-ranging environmental tolerance and introduced global distribution. We assessed treatment effects on 1) skin-associated microbial communities and 2) post-metamorphic antimicrobial peptide (AMP) production and 3) AMP bioactivity against the fungal pathogen Batrachochytrium dendrobatidis (Bd). While habitat acidification did not affect survival, time to metamorphosis or juvenile mass, we found that a change in average pH from 7 to 6 caused a significant shift in the larval skin microbial community, an effect which disappeared after metamorphosis. Additionally, we found shifts in skin-associated microbial communities across life stages suggesting they are affected by the physiological or ecological changes associated with amphibian metamorphosis. Moreover, we found that post-metamorphic AMP production and bioactivity were significantly affected by the interactions between pH and shade treatments and interactive effects differed across populations. In contrast, there were no significant interactions between treatments on post-metamorphic microbial community structure suggesting that variation in AMPs did not affect microbial community structure within our study. Our findings indicate that commonly encountered variation in the larval environment (i.e. pond pH and degree of shading) can have both immediate and long-term effects on the amphibian innate immune defense traits. Our work suggests that the susceptibility of amphibians to emerging diseases could be related to variability in the larval environment and calls for research into the relative influence of potentially less benign anthropogenic environmental changes on innate immune defense traits. PMID:26107644

  20. Kelps feature systemic defense responses: insights into the evolution of innate immunity in multicellular eukaryotes.

    PubMed

    Thomas, Franois; Cosse, Audrey; Le Panse, Sophie; Kloareg, Bernard; Potin, Philippe; Leblanc, Catherine

    2014-11-01

    Brown algae are one of the few eukaryotic lineages that have evolved complex multicellularity, together with Opisthokonts (animals, fungi) and Plantae (land plants, green and red algae). In these three lineages, biotic stresses induce similar local defense reactions. Animals and land plants also feature a systemic immune response, protecting the whole organism after an attack on one of its parts. However, the occurrence of systemic defenses has never been investigated in brown algae. We elicited selected parts of the kelp Laminaria digitata and monitored distant, nonchallenged areas of the same individual for subsequent defense reactions. A systemic reaction was detected following elicitation on a distant area, including an oxidative response, an increase in haloperoxidase activities and a stronger resistance against herbivory. Based on experiments with pharmacological inhibitors, the liberation of free fatty acids is proposed to play a key role in systemic signaling, reminiscent of what is known in land plants. This study is the first report, outside the phyla of Opisthokonts and Plantae, of an intraorganism communication leading to defense reactions. These findings indicate that systemic immunity emerged independently at least three times, as a consequence of convergent evolution in multicellular eukaryotic lineages. PMID:25041157

  1. Protein Poly(ADP-ribosyl)ation Regulates Arabidopsis Immune Gene Expression and Defense Responses

    PubMed Central

    Feng, Baomin; Liu, Chenglong; de Oliveira, Marcos V. V.; Intorne, Aline C.; Li, Bo; Babilonia, Kevin; de Souza Filho, Gonçalo A.; Shan, Libo; He, Ping

    2015-01-01

    Perception of microbe-associated molecular patterns (MAMPs) elicits transcriptional reprogramming in hosts and activates defense to pathogen attacks. The molecular mechanisms underlying plant pattern-triggered immunity remain elusive. A genetic screen identified Arabidopsis poly(ADP-ribose) glycohydrolase 1 (atparg1) mutant with elevated immune gene expression upon multiple MAMP and pathogen treatments. Poly(ADP-ribose) glycohydrolase (PARG) is predicted to remove poly(ADP-ribose) polymers on acceptor proteins modified by poly(ADP-ribose) polymerases (PARPs) with three PARPs and two PARGs in Arabidopsis genome. AtPARP1 and AtPARP2 possess poly(ADP-ribose) polymerase activity, and the activity of AtPARP2 was enhanced by MAMP treatment. AtPARG1, but not AtPARG2, carries glycohydrolase activity in vivo and in vitro. Importantly, mutation (G450R) in atparg1 blocks its activity and the corresponding residue is highly conserved and essential for human HsPARG activity. Consistently, mutant atparp1atparp2 plants exhibited compromised immune gene activation and enhanced susceptibility to pathogen infections. Our study indicates that protein poly(ADP-ribosyl)ation plays critical roles in plant immune gene expression and defense to pathogen attacks. PMID:25569773

  2. Roles of small RNAs in the immune defense mechanisms of crustaceans.

    PubMed

    He, Yaodong; Ju, Chenyu; Zhang, Xiaobo

    2015-12-01

    Small RNAs, 21-24 nucleotides in length, are non-coding RNAs found in most multicellular organisms, as well as in some viruses. There are three main types of small RNAs including microRNA (miRNA), small-interfering RNA (siRNA), and piwi-interacting RNA (piRNA). Small RNAs play key roles in the genetic regulation of eukaryotes; at least 50% of all eukaryote genes are the targets of small RNAs. In recent years, studies have shown that some unique small RNAs are involved in the immune response of crustaceans, leading to lower or higher immune responses to infections and diseases. SiRNAs could be used as therapy for virus infection. In this review, we provide an overview of the diverse roles of small RNAs in the immune defense mechanisms of crustaceans. PMID:26210184

  3. Interim Strategic Defense Initiative arms negotiation strategy. Research report

    SciTech Connect

    Marshall, H.A.

    1986-05-01

    Comments are presented on some of the pros and cons of the Strategic Defense Initative (SDI). Key issues discussed relate to the projected cost of SDI and the potential violation of the 1972 Anti-ballistic Missile Treaty. A solution is proposed that has the potential to significantly reduce the total cost and circumvents the treaty resulting in the deployment of a more-effective ballistic missile defense system.

  4. Isonitrosoacetophenone Drives Transcriptional Reprogramming in Nicotiana tabacum Cells in Support of Innate Immunity and Defense

    PubMed Central

    Djami-Tchatchou, Arnaud T.; Maake, Mmapula P.; Piater, Lizelle A.; Dubery, Ian A.

    2015-01-01

    Plants respond to various stress stimuli by activating broad-spectrum defense responses both locally as well as systemically. As such, identification of expressed genes represents an important step towards understanding inducible defense responses and assists in designing appropriate intervention strategies for disease management. Genes differentially expressed in tobacco cell suspensions following elicitation with isonitrosoacetophenone (INAP) were identified using mRNA differential display and pyro-sequencing. Sequencing data produced 14579 reads, which resulted in 198 contigs and 1758 singletons. Following BLAST analyses, several inducible plant defense genes of interest were identified and classified into functional categories including signal transduction, transcription activation, transcription and protein synthesis, protein degradation and ubiquitination, stress-responsive, defense-related, metabolism and energy, regulation, transportation, cytoskeleton and cell wall-related. Quantitative PCR was used to investigate the expression of 17 selected target genes within these categories. Results indicate that INAP has a sensitising or priming effect through activation of salicylic acid-, jasmonic acid- and ethylene pathways that result in an altered transcriptome, with the expression of genes involved in perception of pathogens and associated cellular re-programming in support of defense. Furthermore, infection assays with the pathogen Pseudomonas syringae pv. tabaci confirmed the establishment of a functional anti-microbial environment in planta. PMID:25658943

  5. Prime-Boost Immunization Strategies against Chikungunya Virus

    PubMed Central

    Lum, Fok-Moon; Kümmerer, Beate M.; Lulla, Aleksei; Lulla, Valeria; García-Arriaza, Juan; Fazakerley, John K.; Roques, Pierre; Le Grand, Roger; Merits, Andres; Ng, Lisa F. P.; Esteban, Mariano

    2014-01-01

    ABSTRACT Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that causes debilitating arthralgia in humans. Here we describe the development and testing of novel DNA replicon and protein CHIKV vaccine candidates and evaluate their abilities to induce antigen-specific immune responses against CHIKV. We also describe homologous and heterologous prime-boost immunization strategies using novel and previously developed CHIKV vaccine candidates. Immunogenicity and efficacy were studied in a mouse model of CHIKV infection and showed that the DNA replicon and protein antigen were potent vaccine candidates, particularly when used for priming and boosting, respectively. Several prime-boost immunization strategies eliciting unmatched humoral and cellular immune responses were identified. Further characterization by antibody epitope mapping revealed differences in the qualitative immune responses induced by the different vaccine candidates and immunization strategies. Most vaccine modalities resulted in complete protection against wild-type CHIKV infection; however, we did identify circumstances under which certain immunization regimens may lead to enhancement of inflammation upon challenge. These results should help guide the design of CHIKV vaccine studies and will form the basis for further preclinical and clinical evaluation of these vaccine candidates. IMPORTANCE As of today, there is no licensed vaccine to prevent CHIKV infection. In considering potential new vaccine candidates, a vaccine that could raise long-term protective immunity after a single immunization would be preferable. While humoral immunity seems to be central for protection against CHIKV infection, we do not yet fully understand the correlates of protection. Therefore, in the absence of a functional vaccine, there is a need to evaluate a number of different candidates, assessing their merits when they are used either in a single immunization or in a homologous or heterologous prime-boost modality. Here we show that while single immunization with various vaccine candidates results in potent responses, combined approaches significantly enhance responses, suggesting that such approaches need to be considered in the further development of an efficacious CHIKV vaccine. PMID:25210177

  6. Adolescent Humor and Its Relationship to Coping, Defense Strategies, Psychological Distress, and Well-Being

    ERIC Educational Resources Information Center

    Erickson, Sarah J.; Feldstein, Sarah W.

    2007-01-01

    Objective: This study investigated the psychometric properties of the Humor Styles Questionnaire (HSQ) in measuring adolescent humor, including the relationship between humor and coping style, defense style, depressive symptoms, and adjustment in a non-clinical sample of adolescents. Method: Humor, coping, defense strategies, depressive symptoms,

  7. Role of transglutaminase in immune defense against bacterial pathogens via regulation of antimicrobial peptides.

    PubMed

    Zhu, You-Ting; Li, Dan; Zhang, Xing; Li, Xue-Jie; Li, Wei-Wei; Wang, Qun

    2016-02-01

    Transglutaminase (TGase) is critical for blood coagulation, a conserved immunological defense mechanism among invertebrates. Here, a 3248-bp (full-length) TGase cDNA in Eriocheir sinensis (EsTGase) was cloned, with a 2274-bp open reading frame (ORF) encoding a 757 amino acid protein containing two transglut domains, one TGase/protease-like homolog domain and a KGD (Lys-Gly-Asp) motif. Phylogenetic analysis demonstrated that EsTGase appeared earlier in evolution compared with TGases of other crustaceans and mammals. EsTGase mRNA was mainly detected in hemocytes and up-regulated post-challenge with bacteria (Vibrio parahaemolyticus and Staphylococcus aureus), suggesting an immune function for this gene. Moreover, the EsTGase activity in hemocytes challenged with V.parahaemolyticus and S.aureus was decreased significantly. RNA interference of EsTGase down-regulated expression of immune-related genes CrusEs2, EsLecG and Es-DWD1 with or without bacteria stimulation invitro. Furthermore, absence of EsTGase led to higher bacterial counts in the hemocyte culture medium. Thus, EsTGase is an important component of the crab immune response and is involved in the regulation of certain immune-related genes, particularly those encoding anti-microbial peptides. PMID:26464201

  8. Immune defenses of healthy, bleached and diseased Montastraea faveolata during a natural bleaching event.

    PubMed

    Mydlarz, Laura D; Couch, Courtney S; Weil, Ernesto; Smith, Garriet; Harvell, C Drew

    2009-11-16

    One prominent hypothesis regarding climate change and scleractinian corals is that thermal stress compromises immune competence. To test this hypothesis we tracked how the immune defenses of bleached, apparently healthy and yellow band disease (YBD) diseased Montastraea faveolata colonies varied with natural thermal stress in southwestern Puerto Rico. Colonies were monitored for 21 mo from the peak of the bleaching event in October 2005 to August 2007. Since sea surface temperature was significantly higher in summer and fall 2005 than 2006, year of collection was used as a proxy for temperature stress, and colony fragments collected in 2005 were compared with those collected in 2006. Mortality rate was high (43% overall) and all colonies (except one) either died or became infected with YBD by August 2007. YBD-infected tissue did not bleach (i.e. expel zooxanthellae) during the 2005 bleaching event, even when healthy tissue of these colonies bleached. Immune activity was assayed by measuring prophenoloxidase (PPO), peroxidase (POX), lysozyme-like (LYS) and antibacterial (AB) activity. Immune activity was variable between all coral samples, but there was a significant elevation of PPO activity in bleached colonies collected in 2005 relative to apparently healthy and YBD-diseased corals in 2006. In YBD-diseased colonies, LYS and AB activity were elevated in both healthy and infected tissue, indicating a systemic response; activity levels in these colonies were higher compared to those that appeared healthy. In both these immune parameters, there was a trend for suppression of activity in corals that were bleached in 2005. These data, while complicated by between-genet variability, illustrate the complex interaction between disease and temperature stress on immune function. PMID:20095242

  9. Plant Lectins: Wheat Defense Strategy Against Hessian Fly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants produce a variety of defense proteins, including lectins in response to attack by phytophagous insects. Ultrastructural studies reveal that binding to insect gut structures and resistance to proteolytic degradation by insect digestive enzymes are the two main prerequisites for the lectins to...

  10. HIV-1 Strategies of Immune Evasion

    NASA Astrophysics Data System (ADS)

    Castiglione, F.; Bernaschi, M.

    We simulate the progression of the HIV-1 infection in untreated host organisms. The phenotype features of the virus are represented by the replication rate, the probability of activating the transcription, the mutation rate and the capacity to stimulate an immune response (the so-called immunogenicity). It is very difficult to study in-vivo or in-vitro how these characteristics of the virus influence the evolution of the disease. Therefore we resorted to simulations based on a computer model validated in previous studies. We observe, by means of computer experiments, that the virus continuously evolves under the selective pressure of an immune response whose effectiveness downgrades along with the disease progression. The results of the simulations show that immunogenicity is the most important factor in determining the rate of disease progression but, by itself, it is not sufficient to drive the disease to a conclusion in all cases.

  11. Innate immunity in Arabidopsis thaliana: Lipopolysaccharides activate nitric oxide synthase (NOS) and induce defense genes

    PubMed Central

    Zeidler, Dana; Zhringer, Ulrich; Gerber, Isak; Dubery, Ian; Hartung, Thomas; Bors, Wolf; Hutzler, Peter; Durner, Jrg

    2004-01-01

    Lipopolysaccharides (LPS) are cell-surface components of Gram-negative bacteria and are microbe-/pathogen-associated molecular patterns in animal pathosystems. As for plants, the molecular mechanisms of signal transduction in response to LPS are not known. Here, we show that Arabidopsis thaliana reacts to LPS with a rapid burst of NO, a hallmark of innate immunity in animals. Fifteen LPS preparations (among them Burkholderia cepacia, Pseudomonas aeruginosa, and Erwinia carotovora) as well as lipoteichoic acid from Gram-positive Staphylococcus aureus were found to trigger NO production in suspension-cultured Arabidopsis cells as well as in leaves. NO was detected by confocal laser-scanning microscopy in conjunction with the fluorophore 4-amino-5-methylamino-2?,7?-difluorofluorescein diacetate, by electron paramagnetic resonance, and by a NO synthase (NOS) assay. The source of NO was addressed by using T-DNA insertion lines. Interestingly, LPS did not activate the pathogen-inducible varP NOS, but AtNOS1, a distinct NOS previously associated with hormonal signaling in plants. A prominent feature of LPS treatment was activation of defense genes, which proved to be mediated by NO. Northern analyses and transcription profiling by using DNA microarrays revealed induction of defense-associated genes both locally and systemically. Finally, AtNOS1 mutants showed dramatic susceptibility to the pathogen Pseudomonas syringae pv. tomato DC3000. In sum, perception of LPS and induction of NOS contribute toward the activation of plant defense responses. PMID:15498873

  12. Maritime strategy and coalition defense: a synthesis for NATO (North Atlantic Treaty Organization) success

    SciTech Connect

    Glazier, D.W.

    1987-01-01

    Maritime strategy is an essential element underpinning the credibility of the NATO alliance. Far from hampering continental defense, the strategy enhances the deterrent posture and, should deterrence fail, increases the prospects for both preserving NATO allies and for ending hostilities on favorable terms. Execution of the global-war portion of the maritime strategy would almost certainly occur as part of a NATO defensive effort against Warsaw Pact aggression. Also, discussions about the feasibility of executing the maritime strategy have attempted to compare the us national force structure and capabilities to that of the Soviets.

  13. Vaccine strategies to enhance immune responses in the aged

    PubMed Central

    Lefebvre, Julie S.; Haynes, Laura

    2013-01-01

    The elderly population is more susceptible to infections with higher risks of morbidity and mortality. This is caused by the accumulation of immune defects with aging. The best way to protect people against infections is vaccination. Unfortunately, the same immune defects that render the elderly susceptible to infectious diseases also prevent the development of protective immunity following immunization. A good example of this is the influenza vaccine that only protects between 4060% of the vaccinees over 65 years. In the past decade, tremendous efforts have been put toward improving the influenza vaccine for the elderly. We therefore use this example to present various strategies employed to overcome these age-associated immune defects and hence make vaccines more efficacious for the aged. PMID:23764092

  14. Vaccine strategies to enhance immune responses in the aged.

    PubMed

    Lefebvre, Julie S; Haynes, Laura

    2013-08-01

    The elderly population is more susceptible to infections with higher risks of morbidity and mortality. This is caused by the accumulation of immune defects with aging. The best way to protect people against infections is vaccination. Unfortunately, the same immune defects that render the elderly susceptible to infectious diseases also prevent the development of protective immunity following immunization. A good example of this is the influenza vaccine that only protects between 40 and 60% of the vaccinees over 65 years. In the past decade, tremendous efforts have been put toward improving the influenza vaccine for the elderly. We therefore use this example to present various strategies employed to overcome these age-associated immune defects and hence make vaccines more efficacious for the aged. PMID:23764092

  15. Immunization strategy for epidemic spreading on multilayer networks

    NASA Astrophysics Data System (ADS)

    Buono, C.; Braunstein, L. A.

    2015-01-01

    In many real-world complex systems, individuals have many kinds of interactions among them, suggesting that it is necessary to consider a layered-structure framework to model systems such as social interactions. This structure can be captured by multilayer networks and can have major effects on the spreading of process that occurs over them, such as epidemics. In this letter we study a targeted immunization strategy for epidemic spreading over a multilayer network. We apply the strategy in one of the layers and study its effect in all layers of the network disregarding degree-degree correlation among layers. We found that the targeted strategy is not as efficient as in isolated networks, due to the fact that in order to stop the spreading of the disease it is necessary to immunize more than 80% of the individuals. However, the size of the epidemic is drastically reduced in the layer where the immunization strategy is applied compared to the case with no mitigation strategy. Thus, the immunization strategy has a major effect on the layer were it is applied, but does not efficiently protect the individuals of other layers.

  16. Strategies to increase vitamin C in plants: from plant defense perspective to food biofortification

    PubMed Central

    Locato, Vittoria; Cimini, Sara; Gara, Laura De

    2013-01-01

    Vitamin C participates in several physiological processes, among others, immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption. Severe deficiency leads to scurvy, whereas a limited vitamin C intake causes general symptoms, such as increased susceptibility to infections, fatigue, insomnia, and weight loss. Surprisingly vitamin C deficiencies are spread in both developing and developed countries, with the latter actually trying to overcome this lack through dietary supplements and food fortification. Therefore new strategies aimed to increase vitamin C in food plants would be of interest to improve human health. Interestingly, plants are not only living bioreactors for vitamin C production in optimal growing conditions, but also they can increase their vitamin C content as consequence of stress conditions. An overview of the different approaches aimed at increasing vitamin C level in plant food is given. They include genotype selection by “classical” breeding, bio-engineering and changes of the agronomic conditions, on the basis of the emerging concepts that plant can enhance vitamin C synthesis as part of defense responses. PMID:23734160

  17. Strategies to increase vitamin C in plants: from plant defense perspective to food biofortification.

    PubMed

    Locato, Vittoria; Cimini, Sara; Gara, Laura De

    2013-01-01

    Vitamin C participates in several physiological processes, among others, immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption. Severe deficiency leads to scurvy, whereas a limited vitamin C intake causes general symptoms, such as increased susceptibility to infections, fatigue, insomnia, and weight loss. Surprisingly vitamin C deficiencies are spread in both developing and developed countries, with the latter actually trying to overcome this lack through dietary supplements and food fortification. Therefore new strategies aimed to increase vitamin C in food plants would be of interest to improve human health. Interestingly, plants are not only living bioreactors for vitamin C production in optimal growing conditions, but also they can increase their vitamin C content as consequence of stress conditions. An overview of the different approaches aimed at increasing vitamin C level in plant food is given. They include genotype selection by "classical" breeding, bio-engineering and changes of the agronomic conditions, on the basis of the emerging concepts that plant can enhance vitamin C synthesis as part of defense responses. PMID:23734160

  18. Role of Analytical Chemistry in Defense Strategies Against Chemical and Biological Attack

    NASA Astrophysics Data System (ADS)

    Janata, Jiri

    2009-07-01

    Analytical chemistry plays a role in the two strategies of defense against chemical or biological weapons that are discussed in this review: the detect-to-protect and the prevent-and-detect strategies. The detect-to-protect method, which is based on detection of a known chemical agent with a specific chemical sensor designed for said agent, has serious flaws. I argue that this approach should be replaced with the prevent-and-detect strategy. Such a change in the defense paradigm would require reallocation of resources, but it is necessary for effective protection of enclosed civilians from chemical and/or biological attack.

  19. Reentrant phase transitions and defensive alliances in social dilemmas with informed strategies

    NASA Astrophysics Data System (ADS)

    Szolnoki, Attila; Perc, Matja

    2015-05-01

    Knowing the strategy of an opponent in a competitive environment conveys obvious evolutionary advantages. But this information is costly, and the benefit of being informed may not necessarily offset the additional cost. Here we introduce social dilemmas with informed strategies, and we show that this gives rise to two cyclically dominant triplets that form defensive alliances. The stability of these two alliances is determined by the rotation velocity of the strategies within each triplet. A weaker strategy in a faster rotating triplet can thus overcome an individually stronger competitor. Fascinating spatial patterns favor the dominance of a single defensive alliance, but enable also the stable coexistence of both defensive alliances in very narrow regions of the parameter space. A continuous reentrant phase transition reveals before unseen complexity behind the stability of strategic alliances in evolutionary social dilemmas.

  20. Quantitative proteomics of the human skin secretome reveal a reduction in immune defense mediators in ectodermal dysplasia patients.

    PubMed

    Burian, Marc; Velic, Ana; Matic, Katarina; Gnther, Stephanie; Kraft, Beatrice; Gonser, Lena; Forchhammer, Stephan; Tiffert, Yvonne; Naumer, Christian; Krohn, Michael; Berneburg, Mark; Yazdi, Amir S; Ma?ek, Boris; Schittek, Birgit

    2015-03-01

    In healthy human skin host defense molecules such as antimicrobial peptides (AMPs) contribute to skin immune homeostasis. In patients with the congenital disease ectodermal dysplasia (ED) skin integrity is disturbed and as a result patients have recurrent skin infections. The disease is characterized by developmental abnormalities of ectodermal derivatives and absent or reduced sweating. We hypothesized that ED patients have a reduced skin immune defense because of the reduced ability to sweat. Therefore, we performed a label-free quantitative proteome analysis of wash solution of human skin from ED patients or healthy individuals. A clear-cut difference between both cohorts could be observed in cellular processes related to immunity and host defense. In line with the extensive underrepresentation of proteins of the immune system, dermcidin, a sweat-derived AMP, was reduced in its abundance in the skin secretome of ED patients. In contrast, proteins involved in metabolic/catabolic and biosynthetic processes were enriched in the skin secretome of ED patients. In summary, our proteome profiling provides insights into the actual situation of healthy versus diseased skin. The systematic reduction in immune system and defense-related proteins may contribute to the high susceptibility of ED patients to skin infections and altered skin colonization. PMID:25347115

  1. NOD2, an intracellular innate immune sensor involved in host defense and Crohn's disease.

    PubMed

    Strober, W; Watanabe, T

    2011-09-01

    Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular sensor for small peptides derived from the bacterial cell wall component, peptidoglycan. Recent studies have uncovered unexpected functions of NOD2 in innate immune responses such as induction of type I interferon and facilitation of autophagy; moreover, they have disclosed extensive cross-talk between NOD2 and Toll-like receptors, which has an indispensable role both in host defense against microbial infection and in the development of autoimmunity. Of particular interest, polymorphisms of CARD15 encoding NOD2 are associated with Crohn's disease and other autoimmune states such as graft vs. host disease. In this review, we summarize recent findings regarding normal functions of NOD2 and discuss the mechanisms by which NOD2 polymorphisms associated with Crohn's disease lead to intestinal inflammation. PMID:21750585

  2. The long and short of antiviral defense: small RNA-based immunity in insects.

    PubMed

    Bronkhorst, Alfred W; van Rij, Ronald P

    2014-08-01

    The host RNA interference (RNAi) pathway of insects senses virus infection and induces an antiviral response to restrict virus replication. Dicer-2 detects viral double-stranded RNA, produced by RNA and DNA viruses, and generates viral small interfering RNAs (vsiRNAs). Recent small RNA profiling studies provided new insights into the viral RNA substrates that trigger vsiRNA biogenesis. The importance of the antiviral RNAi pathway is underscored by the observation that viruses have evolved sophisticated mechanisms to counteract this small RNA-based immune response. More recently, it was proposed that another small RNA silencing mechanism, the piRNA pathway, also processes viral RNAs in Drosophila and mosquitoes. Here, we review recent insights into the mechanism of antiviral RNAi, viral small RNA profiles, and viral counter-defense mechanisms in insects. PMID:24732439

  3. Involvement of the Lectin Pathway of Complement Activation in Antimicrobial Immune Defense during Experimental Septic Peritonitis

    PubMed Central

    Windbichler, Michaela; Echtenacher, Bernd; Hehlgans, Thomas; Jensenius, Jens C.; Schwaeble, Wilhelm; Mnnel, Daniela N.

    2004-01-01

    A critical first line of defense against infection is constituted by the binding of natural antibodies to microbial surfaces, activating the complement system via the classical complement activation pathway. In this function, the classical activation pathway is supported and amplified by two antibody-independent complement activation routes, i.e., the lectin pathway and the alternative pathway. We studied the contribution of the different complement activation pathways in the host defense against experimental polymicrobial peritonitis induced by cecal ligation and puncture by using mice deficient in either C1q or factors B and C2. The C1q-deficient mice lack the classical complement activation pathway. While infection-induced mortality of wild-type mice was 27%, mortality of C1q-deficient mice was increased to 60%. Mice with a deficiency of both factors B and C2 lack complement activation via the classical, the alternative, and the lectin pathways and exhibit a mortality of 92%, indicating a significant contribution of the lectin and alternative pathways of complement activation to survival. For 14 days after infection, mannan-binding lectin (MBL)-dependent activation of C4 was compromised. Serum MBL-A and MBL-C levels were significantly reduced for 1 week, possibly due to consumption. mRNA expression profiles did not lend support for either of the two MBL genes to respond as typical acute-phase genes. Our results demonstrate a long-lasting depletion of MBL-A and MBL-C from serum during microbial infection and underline the importance of both the lectin and the alternative pathways for antimicrobial immune defense. PMID:15322019

  4. Immune-Related Transcriptome of Coptotermes formosanus Shiraki Workers: The Defense Mechanism

    PubMed Central

    Hussain, Abid; Li, Yi-Feng; Cheng, Yu; Liu, Yang; Chen, Chuan-Cheng; Wen, Shuo-Yang

    2013-01-01

    Formosan subterranean termites, Coptotermes formosanus Shiraki, live socially in microbial-rich habitats. To understand the molecular mechanism by which termites combat pathogenic microbes, a full-length normalized cDNA library and four Suppression Subtractive Hybridization (SSH) libraries were constructed from termite workers infected with entomopathogenic fungi (Metarhizium anisopliae and Beauveria bassiana), Gram-positive Bacillus thuringiensis and Gram-negative Escherichia coli, and the libraries were analyzed. From the high quality normalized cDNA library, 439 immune-related sequences were identified. These sequences were categorized as pattern recognition receptors (47 sequences), signal modulators (52 sequences), signal transducers (137 sequences), effectors (39 sequences) and others (164 sequences). From the SSH libraries, 27, 17, 22 and 15 immune-related genes were identified from each SSH library treated with M. anisopliae, B. bassiana, B. thuringiensis and E. coli, respectively. When the normalized cDNA library was compared with the SSH libraries, 37 immune-related clusters were found in common; 56 clusters were identified in the SSH libraries, and 259 were identified in the normalized cDNA library. The immune-related gene expression pattern was further investigated using quantitative real time PCR (qPCR). Important immune-related genes were characterized, and their potential functions were discussed based on the integrated analysis of the results. We suggest that normalized cDNA and SSH libraries enable us to discover functional genes transcriptome. The results remarkably expand our knowledge about immune-inducible genes in C. formosanus Shiraki and enable the future development of novel control strategies for the management of Formosan subterranean termites. PMID:23874972

  5. Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

    PubMed

    Vinay, Dass S; Ryan, Elizabeth P; Pawelec, Graham; Talib, Wamidh H; Stagg, John; Elkord, Eyad; Lichtor, Terry; Decker, William K; Whelan, Richard L; Kumara, H M C Shantha; Signori, Emanuela; Honoki, Kanya; Georgakilas, Alexandros G; Amin, Amr; Helferich, William G; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Keith, W Nicol; Bilsland, Alan; Bhakta, Dipita; Halicka, Dorota; Fujii, Hiromasa; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan; Choi, Beom K; Kwon, Byoung S

    2015-12-01

    Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection. PMID:25818339

  6. Strategies for Enhancing Vaccine-Induced CTL Antitumor Immune Responses

    PubMed Central

    Yong, Xin; Xiao, Yü-Feng; Luo, Gang; He, Bin; Lü, Mu-Han; Hu, Chang-Jiang; Guo, Hong; Yang, Shi-Ming

    2012-01-01

    Vaccine-induced cytotoxic T lymphocytes (CTLs) play a critical role in adaptive immunity against cancers. An important goal of current vaccine research is to induce durable and long-lasting functional CTLs that can mediate cytotoxic effects on tumor cells. To attain this goal, there are four distinct steps that must be achieved. To initiate a vaccine-induced CTL antitumor immune response, dendritic cells (DCs) must capture antigens derived from exogenous tumor vaccines in vivo or autologous DCs directly loaded in vitro with tumor antigens must be injected. Next, tumor-antigen-loaded DCs must activate CTLs in lymphoid organs. Subsequently, activated CTLs must enter the tumor microenvironment to perform their functions, at which point a variety of negative regulatory signals suppress the immune response. Finally, CTL-mediated cytotoxic effects must overcome the tolerance induced by tumor cells. Each step is a complex process that may be impeded in many ways. However, if these steps happen under appropriate regulation, the vaccine-induced CTL antitumor immune response will be more successful. For this reason, we should gain a better understanding of the basic mechanisms that govern the immune response. This paper, based on the steps necessary to induce an immune response, discusses current strategies for enhancing vaccine-induced CTL antitumor immune responses. PMID:23093850

  7. An abscisic acid-independent oxylipin pathway controls stomatal closure and immune defense in Arabidopsis.

    PubMed

    Montillet, Jean-Luc; Leonhardt, Nathalie; Mondy, Samuel; Tranchimand, Sylvain; Rumeau, Dominique; Boudsocq, Marie; Garcia, Ana Victoria; Douki, Thierry; Bigeard, Jean; Laurire, Christiane; Chevalier, Anne; Castresana, Carmen; Hirt, Heribert

    2013-01-01

    Plant stomata function in innate immunity against bacterial invasion and abscisic acid (ABA) has been suggested to regulate this process. Using genetic, biochemical, and pharmacological approaches, we demonstrate that (i) the Arabidopsis thaliana nine-specific-lipoxygenase encoding gene, LOX1, which is expressed in guard cells, is required to trigger stomatal closure in response to both bacteria and the pathogen-associated molecular pattern flagellin peptide flg22; (ii) LOX1 participates in stomatal defense; (iii) polyunsaturated fatty acids, the LOX substrates, trigger stomatal closure; (iv) the LOX products, fatty acid hydroperoxides, or reactive electrophile oxylipins induce stomatal closure; and (v) the flg22-mediated stomatal closure is conveyed by both LOX1 and the mitogen-activated protein kinases MPK3 and MPK6 and involves salicylic acid whereas the ABA-induced process depends on the protein kinases OST1, MPK9, or MPK12. Finally, we show that the oxylipin and the ABA pathways converge at the level of the anion channel SLAC1 to regulate stomatal closure. Collectively, our results demonstrate that early biotic signaling in guard cells is an ABA-independent process revealing a novel function of LOX1-dependent stomatal pathway in plant immunity. PMID:23526882

  8. An Abscisic Acid-Independent Oxylipin Pathway Controls Stomatal Closure and Immune Defense in Arabidopsis

    PubMed Central

    Mondy, Samuel; Tranchimand, Sylvain; Rumeau, Dominique; Boudsocq, Marie; Garcia, Ana Victoria; Douki, Thierry; Bigeard, Jean; Laurire, Christiane; Chevalier, Anne; Castresana, Carmen; Hirt, Heribert

    2013-01-01

    Plant stomata function in innate immunity against bacterial invasion and abscisic acid (ABA) has been suggested to regulate this process. Using genetic, biochemical, and pharmacological approaches, we demonstrate that (i) the Arabidopsis thaliana nine-specific-lipoxygenase encoding gene, LOX1, which is expressed in guard cells, is required to trigger stomatal closure in response to both bacteria and the pathogen-associated molecular pattern flagellin peptide flg22; (ii) LOX1 participates in stomatal defense; (iii) polyunsaturated fatty acids, the LOX substrates, trigger stomatal closure; (iv) the LOX products, fatty acid hydroperoxides, or reactive electrophile oxylipins induce stomatal closure; and (v) the flg22-mediated stomatal closure is conveyed by both LOX1 and the mitogen-activated protein kinases MPK3 and MPK6 and involves salicylic acid whereas the ABA-induced process depends on the protein kinases OST1, MPK9, or MPK12. Finally, we show that the oxylipin and the ABA pathways converge at the level of the anion channel SLAC1 to regulate stomatal closure. Collectively, our results demonstrate that early biotic signaling in guard cells is an ABA-independent process revealing a novel function of LOX1-dependent stomatal pathway in plant immunity. PMID:23526882

  9. Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense*

    PubMed Central

    Jones, Alexis; Kainz, Danielle; Khan, Faatima; Lee, Cara; Carrithers, Michael D.

    2014-01-01

    Pattern recognition receptors contain a binding domain for pathogen-associated molecular patterns coupled to a signaling domain that regulates transcription of host immune response genes. Here, a novel mechanism that links pathogen recognition to channel activation and downstream signaling is proposed. We demonstrate that an intracellular sodium channel variant, human macrophage SCN5A, initiates signaling and transcription through a calcium-dependent isoform of adenylate cyclase, ADCY8, and the transcription factor, ATF2. Pharmacological stimulation with a channel agonist or treatment with cytoplasmic poly(I:C), a mimic of viral dsRNA, activates this pathway to regulate expression of SP100-related genes and interferon ?. Electrophysiological analysis reveals that the SCN5A variant mediates nonselective outward currents and a small, but detectable, inward current. Intracellular poly(I:C) markedly augments an inward voltage-sensitive sodium current and inhibits the outward nonselective current. These results suggest human macrophage SCN5A initiates signaling in an innate immune pathway relevant to antiviral host defense. It is postulated that SCN5A is a novel pathogen sensor and that this pathway represents a channel activation-dependent mechanism of transcriptional regulation. PMID:25368329

  10. Toxin Production as a Wheat Defense Strategy against Hessian fly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hessian fly (Mayetiola destructor) is one of the major insect pests of wheat (Triticum spp.), with severe infestations leading to complete loss of seed set. Currently, the most effective control of this pest is deployment of host-plant resistance (R) genes in wheat. However, this strategy is challen...

  11. Social marketing as a strategy to increase immunization rates.

    PubMed

    Opel, Douglas J; Diekema, Douglas S; Lee, Nancy R; Marcuse, Edgar K

    2009-05-01

    Today in the United States, outbreaks of vaccine-preventable disease are often traced to susceptible children whose parents have claimed an exemption from school or child care immunization regulations. The origins of this immunization hesitancy and resistance have roots in the decline of the threat of vaccine-preventable disease coupled with an increase in concerns about the adverse effects of vaccines, the emergence of mass media and the Internet, and the intrinsic limitations of modern medicine. Appeals to emotion have drowned out thoughtful discussion in public forums, and overall, public trust in immunizations has declined. We present an often overlooked behavior change strategy-social marketing-as a way to improve immunization rates by addressing the important roots of immunization hesitancy and effectively engaging emotions. As an example, we provide a synopsis of a social marketing campaign that is currently in development in Washington state and that is aimed at increasing timely immunizations in children from birth to age 24 months. PMID:19414689

  12. The impact of high-fat diet on metabolism and immune defense in small intestine mucosa.

    PubMed

    Wiśniewski, Jacek R; Friedrich, Alexandra; Keller, Thorsten; Mann, Matthias; Koepsell, Hermann

    2015-01-01

    Improved procedures for sample preparation and proteomic data analysis allowed us to identify 7700 different proteins in mouse small intestinal mucosa and calculate the concentrations of >5000 proteins. We compared protein concentrations of small intestinal mucosa from mice that were fed for two months with normal diet (ND) containing 34.4% carbohydrates, 19.6% protein, and 3.3% fat or high-fat diet (HFD) containing 25.3% carbohydrates, 24.1% protein, and 34.6% fat. Eleven percent of the quantified proteins were significantly different between ND and HFD. After HFD, we observed an elevation of proteins involved in protein synthesis, protein N-glycosylation, and vesicle trafficking. Proteins engaged in fatty acid absorption, fatty acid β-oxidation, and steroid metabolism were also increased. Enzymes of glycolysis and pentose phosphate cycle were decreased, whereas proteins of the respiratory chain and of ATP synthase were increased. The protein concentrations of various nutrient transporters located in the enterocyte plasma membrane including the Na(+)-d-glucose cotransporter SGLT1, the passive glucose transporter GLUT2, and the H(+)-peptide cotransporter PEPT1 were decreased. The concentration of the Na(+),K(+)-ATPase, which turned out to be the most strongly expressed enterocyte transporter, was also decreased. HFD also induced concentration changes of drug transporters and of enzymes involved in drug metabolism, which suggests effects of HFD on pharmacokinetics and toxicities. Finally, we observed down-regulation of antibody subunits and of components of the major histocompatibility complex II that may reflect impaired immune defense and immune tolerance in HFD. Our work shows dramatic changes in functional proteins of small intestine mucosa upon excessive fat consumption. PMID:25285821

  13. Defensive strategy of twoHypselodoris nudibranchs from Italian and Spanish coasts.

    PubMed

    Avila, C; Cimino, G; Fontana, A; Gavagnin, M; Ortea, J; Trivellone, E

    1991-03-01

    Hypselodoris nudibranchs from different geographic areas (Spain and Italy) have been studied in order to investigate their general defensive strategy. Longifolin (1) and nakafuran-9 (2) are the main ichthyodeterrent allomones used by the mollusks to avoid predation. Evidence of their dietary origin is presented and the very effective strategy against predators, which includes secretion of allomones into the mucus and their storage into specific mantle dermal formations (MDFs), is also discussed. PMID:24258811

  14. Hybrid advantage in skin peptide immune defenses of water frogs (Pelophylax esculentus) at risk from emerging pathogens.

    PubMed

    Daum, Janine M; Davis, Leyla R; Bigler, Laurent; Woodhams, Douglas C

    2012-12-01

    Heterogeneity in immune defense effectors can benefit hosts encountering a variety of parasites and pathogens. Antimicrobial peptides (AMPs) are a diverse set of immune defense effectors in many amphibians, and are secreted from dermal granular glands to protect the skin from infection. Over 50 different skin peptides have been reported from the European water frog hybridogenic complex (Pelophylax esculentus complex), consisting of the hybrid P. esculentus, and the parent species Pelophylax lessonae and Pelophylax ridibundus. In central Europe the hybrid is sympatric with only P. lessonae, while in other areas all three species can co-occur. Amphibian immune defenses are likely under selective pressure from emerging pathogens such as the chytrid fungus Batrachochytrium dendrobatidis (Bd). To assess if hybridization affects immune defenses against Bd, we compared skin peptides of the three species in terms of (i) quantity, (ii) activity against Bd, (iii) repertoire, and (iv) stability. Hybrids secreted AMPs at higher quantities and with greater fungicidal activity compared to cohabiting P. lessonae. Compared to P. ridibundus, AMPs from hybrids were of similar quantity but slightly greater antifungal activity. Mass spectrometric analyses (MALDI-TOF) revealed that of all three species P. esculentus has the greatest peptide diversity, a repertoire inclusive of peptides occurring in either one or the other parent species. Measurements of degradation dynamics indicate that peptides remain relatively stable on the skin of all species for over an hour after induction of skin gland secretions. Our data demonstrate that the hybrid has more effective peptide defenses against Bd and a richer peptide repertoire than either parent species. Hybrid advantage in environments hosting virulent pathogens may contribute to disassortative mating preferences, and we suggest that AMP diversity may be analogous to major histocompatibility complex (MHC) heterozygosity by benefiting hosts encountering multiple parasites. PMID:22940461

  15. Defensive applications of gene transfer technology in the face of bioterrorism: DNA-based vaccines and immune targeting.

    PubMed

    Ackley, Catherine J; Greene, Michael R; Lowrey, Christopher H

    2003-12-01

    Gene transfer involves the introduction of an engineered gene into a person's cells with the expectation that the protein expressed from the gene will produce a therapeutic benefit. Strategies based on this principle have led to the approval of > 600 clinical trials and enrollment of approximately 3500 subjects worldwide in attempts to treat diseases ranging from cancer to AIDS to cystic fibrosis. While gene therapy has met with limited success and still has many hurdles to overcome before it sees wide application, it may be useful as a defensive strategy against bioterrorism agents including infectious microbes and toxins. Although many defensive strategies are possible, immunological strategies are currently the most developed and are being actively applied to the development of strategies against several of the most virulent potential bio-weapons. While most of these strategies are not yet ready for human application, DNA-based vaccines appear to be among the most promising in the fight against bioterrorism. PMID:14640954

  16. Molecular characterization and expressional affirmation of the beta proteasome subunit cluster in rock bream immune defense.

    PubMed

    Kasthuri, Saranya Revathy; Umasuthan, Navaneethaiyer; Whang, Ilson; Lim, Bong-Soo; Jung, Hyung-Bok; Oh, Myung-Joo; Jung, Sung-Ju; Yeo, Sang-Yeob; Kim, Sung Yeon; Lee, Jehee

    2014-08-01

    Immunoproteasomes are primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation. In this study, we report the molecular characterization and expression analysis of the inducible immunosubunits PSMB8, PSMB9, PSMB9-L, and PSMB10 from rock bream, Oplegnathus fasciatus. The three subunits shared common active site residues and were placed in close proximity to fish homologues in the reconstructed phylogenetic tree, in which the mammalian homologues formed separate clades, indicating a common ancestral origin. The rock bream immunosubunits possessed higher identity and similarity with the fish homologues. RbPSMB8, RbPSMB9, RbPSMB9-L, and RbPSMB10 were multi-exonic genes with 6, 6, 7 and 8 exons, respectively. These four genes were constitutively expressed in all the examined tissues. Immunostimulants such as lipopolysaccharide and poly I:C induced RbPSMB8, RbPSMB9, RbPSMB9-L, and RbPSMB10 in liver and head kidney, suggesting their possible involvement in immune defense in rock bream. PMID:24867079

  17. The full-of-bacteria gene is required for phagosome maturation during immune defense in Drosophila

    PubMed Central

    Akbar, Mohammed Ali; Tracy, Charles; Kahr, Walter H.A.

    2011-01-01

    Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a fatal recessive disorder caused by mutations in the VPS33B or VPS16B genes. Both encode homologues of the Vps33p and Vps16p subunits of the HOPS complex necessary for fusions of vacuoles in yeast. Here, we describe a mutation in the full-of-bacteria (fob) gene, which encodes Drosophila Vps16B. Flies null for fob are homozygous viable and fertile. They exhibit, however, a defect in their immune defense that renders them hypersensitive to infections with nonpathogenic bacteria. fob hemocytes (fly macrophages) engulf bacteria but fail to digest them. Phagosomes undergo early steps of maturation and transition to a Rab7-positive stage, but do not mature to fully acidified phagolysosomes. This reflects a specific requirement of fob in the fusion of phagosomes with late endosomes/lysosomes. In contrast, cargo of autophagosomes as well as endosomes exhibit normal lysosomal delivery in fob cells. These findings suggest that defects in phagosome maturation may contribute to symptoms of ARC patients including recurring infections. PMID:21282466

  18. Evolution of mixed strategies of plant defense allocation against natural enemies.

    PubMed

    Fornoni, Juan; Núñez-Farfán, Juan; Valverde, Pedro Luis; Rausher, Mark D

    2004-08-01

    In this study we present a simple optimization model for the evolution of defensive strategies (tolerance and resistance) of plants against their natural enemies. The model specifically evaluates the consequences of introducing variable costs and benefits of tolerance and resistance and nonlinear cost-and-benefit functions for tolerance and resistance. Incorporating these assumptions, the present model of plant defense predicts different evolutionary scenarios, not expected by previous work. Basically, the presence of an adaptive peak corresponding to intermediate levels of allocation to tolerance and resistance can arise when the shape parameter of the cost function is higher than the corresponding of the benefit function. The presence of two alternatives peaks of maximum tolerance and maximum resistance occurs only when benefits of tolerance and resistance interact less than additive. Finally, the presence of one peak of maximum resistance or maximum tolerance depends on the relative values of the magnitude of costs for tolerance and resistance. An important outcome of our model is that under a plausible set of conditions, variable costs of tolerance and resistance can represent an important aspect involved in the maintenance of intermediate levels of tolerance and resistance, and in favoring adaptive divergence in plant defensive strategies among populations. The model offers a framework for future theoretical and empirical work toward understanding spatial variation in levels of allocation to different defensive strategies. PMID:15446423

  19. Innate Immune Defenses in Human Tuberculosis: An Overview of the Interactions between Mycobacterium tuberculosis and Innate Immune Cells.

    PubMed

    Sia, Jonathan Kevin; Georgieva, Maria; Rengarajan, Jyothi

    2015-01-01

    Tuberculosis (TB) remains a serious global public health problem that results in up to 2 million deaths each year. TB is caused by the human pathogen, Mycobacterium tuberculosis (Mtb), which infects primarily innate immune cells patrolling the lung. Innate immune cells serve as barometers of the immune response against Mtb infection by determining the inflammatory milieu in the lungs and promoting the generation of adaptive immune responses. However, innate immune cells are also potential niches for bacterial replication and are readily manipulated by Mtb. Our understanding of the early interactions between Mtb and innate immune cells is limited, especially in the context of human infection. This review will focus on Mtb interactions with human macrophages, dendritic cells, neutrophils, and NK cells and detail evidence that Mtb modulation of these cells negatively impacts Mtb-specific immune responses. Furthermore, this review will emphasize important innate immune pathways uncovered through human immunogenetic studies. Insights into the human innate immune response to Mtb infection are necessary for providing a rational basis for the augmentation of immune responses against Mtb infection, especially with respect to the generation of effective anti-TB immunotherapeutics and vaccines. PMID:26258152

  20. Innate Immune Defenses in Human Tuberculosis: An Overview of the Interactions between Mycobacterium tuberculosis and Innate Immune Cells

    PubMed Central

    Sia, Jonathan Kevin; Georgieva, Maria; Rengarajan, Jyothi

    2015-01-01

    Tuberculosis (TB) remains a serious global public health problem that results in up to 2 million deaths each year. TB is caused by the human pathogen, Mycobacterium tuberculosis (Mtb), which infects primarily innate immune cells patrolling the lung. Innate immune cells serve as barometers of the immune response against Mtb infection by determining the inflammatory milieu in the lungs and promoting the generation of adaptive immune responses. However, innate immune cells are also potential niches for bacterial replication and are readily manipulated by Mtb. Our understanding of the early interactions between Mtb and innate immune cells is limited, especially in the context of human infection. This review will focus on Mtb interactions with human macrophages, dendritic cells, neutrophils, and NK cells and detail evidence that Mtb modulation of these cells negatively impacts Mtb-specific immune responses. Furthermore, this review will emphasize important innate immune pathways uncovered through human immunogenetic studies. Insights into the human innate immune response to Mtb infection are necessary for providing a rational basis for the augmentation of immune responses against Mtb infection, especially with respect to the generation of effective anti-TB immunotherapeutics and vaccines. PMID:26258152

  1. Optimization strategies with resource scarcity: From immunization of networks to the traveling salesman problem

    NASA Astrophysics Data System (ADS)

    Bellingeri, Michele; Agliari, Elena; Cassi, Davide

    2015-10-01

    The best strategy to immunize a complex network is usually evaluated in terms of the percolation threshold, i.e. the number of vaccine doses which make the largest connected cluster (LCC) vanish. The strategy inducing the minimum percolation threshold represents the optimal way to immunize the network. Here we show that the efficacy of the immunization strategies can change during the immunization process. This means that, if the number of doses is limited, the best strategy is not necessarily the one leading to the smallest percolation threshold. This outcome should warn about the adoption of global measures in order to evaluate the best immunization strategy.

  2. Influence of diet on fecundity, immune defense and content of 2-isopropyl-3-methoxypyrazine in Harmonia axyridis Pallas.

    PubMed

    Kgel, Susanne; Eben, Astrid; Hoffmann, Christoph; Gross, Jrgen

    2012-07-01

    Food type can affect all functional aspects of an insect's life. We investigated the effects of different diet regimes on life history parameters of the ladybird beetle Harmonia axyridis. Furthermore, we tested the importance of elytral color, sex, and diet on chemical and immune defense in this species. We also compared hemolymph from cohorts of H. axyridis and Coccinella septempunctata (Coleoptera: Coccinellidae) fed different diets to examine effects on the 2-isopropyl-3-methoxypyrazine (IPMP) content in these beetles. No effects of diet on the duration of larval development and on adult weight were found. We detected, however, significantly higher fecundity and oviposition rates when female H. axyridis were reared on pea aphids than when reared on eggs of Ephestia kuehniella. Males and females did not differ in their immune response. Elytral color affected both immune defense and chemical defense. The antimicrobial activity of the hemolymph differed only when morphotypes were tested against E. coli. Moreover, we observed an effect of elytral pigmentation on IPMP content. The succinea 2 type (orange without dots) had the lowest IPMP content in two out of three feeding regimes compared to the succinea 1 (orange with dots) type. Depending on diet, IPMP contents differed in both species leading to higher contents either in H. axyridis or C. septempunctata. Furthermore, aphid species ingested during larval development significantly affected IPMP content in adult beetles. These results implicate new aspects for risk assessment of H. axyridis in viticulture. PMID:22648506

  3. Innate Immune Defense Defines Susceptibility of Sarcoma Cells to Measles Vaccine Virus-Based Oncolysis

    PubMed Central

    Berchtold, Susanne; Lampe, Johanna; Weiland, Timo; Smirnow, Irina; Schleicher, Sabine; Handgretinger, Rupert; Kopp, Hans-Georg; Reiser, Jeanette; Stubenrauch, Frank; Mayer, Nora; Malek, Nisar P.; Bitzer, Michael

    2013-01-01

    The oncolytic potential of measles vaccine virus (MeV) has been demonstrated in several tumor entities. Here, we investigated the susceptibility of eight sarcoma cell lines to MeV-mediated oncolysis and found five to be susceptible, whereas three proved to be resistant. In the MeV-resistant cell lines, we often observed an inhibition of viral replication along with a strong upregulation of the intracellular virus-sensing molecule RIG-I and of the interferon (IFN)-stimulated gene IFIT1. Not only expression of IFIT1 but also phosphorylation of IFN-stimulated Stat1 took place rapidly and were found to be persistent over time. In contrast, susceptible cell lines showed a much weaker, delayed, or completely missing expression of IFIT1 as well as a delayed or only transient phosphorylation of Stat1, whereas exogenic stimulation with beta interferon (IFN-?) resulted in a comparable profound activation of Stat1 and expression of IFIT1 in all cell lines. Pretreatment with IFN-? rendered three of the susceptible cell lines more resistant to MeV-mediated oncolysis. These data suggest that differences in the innate immune defense often account for different degrees of susceptibility of sarcoma cell lines to MeV-mediated oncolysis. From a therapeutic perspective, we were able to overcome resistance to MeV by increasing the multiplicity of infection (MOI) and by addition of the prodrug 5-fluorocytosine (FC), thereby exploiting the suicide gene function of virotherapeutic vector MeV-SCD armed with the SCD fusion protein, which consists of yeast cytosine deaminase and yeast uracil phosphoribosyltransferase. PMID:23302892

  4. Innate immune defense defines susceptibility of sarcoma cells to measles vaccine virus-based oncolysis.

    PubMed

    Berchtold, Susanne; Lampe, Johanna; Weiland, Timo; Smirnow, Irina; Schleicher, Sabine; Handgretinger, Rupert; Kopp, Hans-Georg; Reiser, Jeanette; Stubenrauch, Frank; Mayer, Nora; Malek, Nisar P; Bitzer, Michael; Lauer, Ulrich M

    2013-03-01

    The oncolytic potential of measles vaccine virus (MeV) has been demonstrated in several tumor entities. Here, we investigated the susceptibility of eight sarcoma cell lines to MeV-mediated oncolysis and found five to be susceptible, whereas three proved to be resistant. In the MeV-resistant cell lines, we often observed an inhibition of viral replication along with a strong upregulation of the intracellular virus-sensing molecule RIG-I and of the interferon (IFN)-stimulated gene IFIT1. Not only expression of IFIT1 but also phosphorylation of IFN-stimulated Stat1 took place rapidly and were found to be persistent over time. In contrast, susceptible cell lines showed a much weaker, delayed, or completely missing expression of IFIT1 as well as a delayed or only transient phosphorylation of Stat1, whereas exogenic stimulation with beta interferon (IFN-?) resulted in a comparable profound activation of Stat1 and expression of IFIT1 in all cell lines. Pretreatment with IFN-? rendered three of the susceptible cell lines more resistant to MeV-mediated oncolysis. These data suggest that differences in the innate immune defense often account for different degrees of susceptibility of sarcoma cell lines to MeV-mediated oncolysis. From a therapeutic perspective, we were able to overcome resistance to MeV by increasing the multiplicity of infection (MOI) and by addition of the prodrug 5-fluorocytosine (FC), thereby exploiting the suicide gene function of virotherapeutic vector MeV-SCD armed with the SCD fusion protein, which consists of yeast cytosine deaminase and yeast uracil phosphoribosyltransferase. PMID:23302892

  5. Epidemic spreading and immunization strategy in multiplex networks

    NASA Astrophysics Data System (ADS)

    Alvarez Zuzek, Lucila G.; Buono, Camila; Braunstein, Lidia A.

    2015-09-01

    A more connected world has brought major consequences such as facilitate the spread of diseases all over the world to quickly become epidemics, reason why researchers are concentrated in modeling the propagation of epidemics and outbreaks in multilayer networks. In this networks all nodes interact in different layers with different type of links. However, in many scenarios such as in the society, a multiplex network framework is not completely suitable since not all individuals participate in all layers. In this paper, we use a partially overlapped, multiplex network where only a fraction of the individuals are shared by the layers. We develop a mitigation strategy for stopping a disease propagation, considering the Susceptible-Infected- Recover model, in a system consisted by two layers. We consider a random immunization in one of the layers and study the effect of the overlapping fraction in both, the propagation of the disease and the immunization strategy. Using branching theory, we study this scenario theoretically and via simulations and find a lower epidemic threshold than in the case without strategy.

  6. Pipecolic Acid, an Endogenous Mediator of Defense Amplification and Priming, Is a Critical Regulator of Inducible Plant Immunity[W

    PubMed Central

    Návarová, Hana; Bernsdorff, Friederike; Döring, Anne-Christin; Zeier, Jürgen

    2012-01-01

    Metabolic signals orchestrate plant defenses against microbial pathogen invasion. Here, we report the identification of the non-protein amino acid pipecolic acid (Pip), a common Lys catabolite in plants and animals, as a critical regulator of inducible plant immunity. Following pathogen recognition, Pip accumulates in inoculated Arabidopsis thaliana leaves, in leaves distal from the site of inoculation, and, most specifically, in petiole exudates from inoculated leaves. Defects of mutants in AGD2-LIKE DEFENSE RESPONSE PROTEIN1 (ALD1) in systemic acquired resistance (SAR) and in basal, specific, and β-aminobutyric acid–induced resistance to bacterial infection are associated with a lack of Pip production. Exogenous Pip complements these resistance defects and increases pathogen resistance of wild-type plants. We conclude that Pip accumulation is critical for SAR and local resistance to bacterial pathogens. Our data indicate that biologically induced SAR conditions plants to more effectively synthesize the phytoalexin camalexin, Pip, and salicylic acid and primes plants for early defense gene expression. Biological priming is absent in the pipecolate-deficient ald1 mutants. Exogenous pipecolate induces SAR-related defense priming and partly restores priming responses in ald1. We conclude that Pip orchestrates defense amplification, positive regulation of salicylic acid biosynthesis, and priming to guarantee effective local resistance induction and the establishment of SAR. PMID:23221596

  7. Modulation of host immune defenses by Aeromonas and Yersinia species: convergence on toxins secreted by various secretion systems

    PubMed Central

    Rosenzweig, Jason A.; Chopra, Ashok K.

    2013-01-01

    Like other pathogenic bacteria, Yersinia and Aeromonas species have been continuously co-evolving with their respective hosts. Although the former is a bonafide human pathogen, the latter has gained notararity as an emerging disease-causing agent. In response to immune cell challenges, bacterial pathogens have developed diverse mechanism(s) enabling their survival, and, at times, dominance over various host immune defense systems. The bacterial type three secretion system (T3SS) is evolutionarily derived from flagellar subunits and serves as a vehicle by which microbes can directly inject/translocate anti-host factors/effector proteins into targeted host immune cells. A large number of Gram-negative bacterial pathogens possess a T3SS empowering them to disrupt host cell signaling, actin cytoskeleton re-arrangements, and even to induce host-cell apoptotic and pyroptotic pathways. All pathogenic yersiniae and most Aeromonas species possess a T3SS, but they also possess T2- and T6-secreted toxins/effector proteins. This review will focus on the mechanisms by which the T3SS effectors Yersinia outer membrane protein J (YopJ) and an Aeromonas hydrophila AexU protein, isolated from the diarrheal isolate SSU, mollify host immune system defenses. Additionally, the mechanisms that are associated with host cell apoptosis/pyroptosis by Aeromonas T2SS secreted Act, a cytotoxic enterotoxin, and Hemolysin co-regulated protein (Hcp), an A. hydrophila T6SS effector, will also be discussed. PMID:24199174

  8. Invertebrate and avian predators as drivers of chemical defensive strategies in tenthredinid sawflies

    PubMed Central

    2013-01-01

    Background Many insects are chemically defended against predatory vertebrates and invertebrates. Nevertheless, our understanding of the evolution and diversity of insect defenses remains limited, since most studies have focused on visual signaling of defenses against birds, thereby implicitly underestimating the impact of insectivorous insects. In the larvae of sawflies in the family Tenthredinidae (Hymenoptera), which feed on various plants and show diverse lifestyles, two distinct defensive strategies are found: easy bleeding of deterrent hemolymph, and emission of volatiles by ventral glands. Here, we used phylogenetic information to identify phylogenetic correlations among various ecological and defensive traits in order to estimate the relative importance of avian versus invertebrate predation. Results The mapping of 12 ecological and defensive traits on phylogenetic trees inferred from DNA sequences reveals the discrete distribution of easy bleeding that occurs, among others, in the genus Athalia and the tribe Phymatocerini. By contrast, occurrence of ventral glands is restricted to the monophyletic subfamily Nematinae, which are never easy bleeders. Both strategies are especially effective towards insectivorous insects such as ants, while only Nematinae species are frequently brightly colored and truly gregarious. Among ten tests of phylogenetic correlation between traits, only a few are significant. None of these involves morphological traits enhancing visual signals, but easy bleeding is associated with the absence of defensive body movements and with toxins occurring in the host plant. Easy bleeding functions through a combination of attributes, which is corroborated by an independent contrasts test indicating a statistically significant negative correlation between species-level integument mechanical resistance and hemolymph feeding deterrence against ants. Conclusions Our analyses evidence a repeated occurrence of easy bleeding, and no phylogenetic correlation including specific visual signals is significant. We conclude that the evolution of chemically-based defenses in tenthredinids may have been driven by invertebrate as much as by avian predation. The clear-cut visual signaling often encountered in the Nematinae would be linked to differential trends of habitat use by prey and predators. Further studies on (prey) insect groups should include visual signals and other traits, as well as several groups of natural enemies, to better interpret their relative significance and to refine our understanding of insect chemical defenses. PMID:24041372

  9. Common gamma chain cytokines in combinatorial immune strategies against cancer.

    PubMed

    Pulliam, Stephanie R; Uzhachenko, Roman V; Adunyah, Samuel E; Shanker, Anil

    2016-01-01

    Common ? chain (?C) cytokines, namely IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 are important for the proliferation, differentiation, and survival of lymphocytes that display antitumor activity, thus stimulating considerable interest for the use of cytokines in cancer immunotherapy. In this review, we will focus on the ?C cytokines that demonstrate the greatest potential for immunotherapy, IL-2, IL-7, IL-15, and IL-21. We will briefly cover their biological function, potential applications in cancer therapy, and update on their use in combinatorial immune strategies for eradicating tumors and hematopoietic malignancies. PMID:26597610

  10. Does investment in leaf defenses drive changes in leaf economic strategy? A focus on whole-plant ontogeny.

    PubMed

    Mason, Chase M; Donovan, Lisa A

    2015-04-01

    Leaf defenses have long been studied in the context of plant growth rate, resource availability, and optimal investment theory. Likewise, one of the central modern paradigms of plant ecophysiology, the leaf economics spectrum (LES), has been extensively studied in the context of these factors across ecological scales ranging from global species data sets to temporal shifts within individuals. Despite strong physiological links between LES strategy and leaf defenses in structure, function, and resource investment, the relationship between these trait classes has not been well explored. This study investigates the relationship between leaf defenses and LES strategy across whole-plant ontogeny in three diverse Helianthus species known to exhibit dramatic ontogenetic shifts in LES strategy, focusing primarily on physical and quantitative chemical defenses. Plants were grown under controlled environmental conditions and sampled for LES and defense traits at four ontogenetic stages. Defenses were found to shift strongly with ontogeny, and to correlate strongly with LES strategy. More advanced ontogenetic stages with more conservative LES strategy leaves had higher tannin activity and toughness in all species, and higher leaf dry matter content in two of three species. Modeling results in two species support the conclusion that changes in defenses drive changes in LES strategy through ontogeny, and in one species that changes in defenses and LES strategy are likely independently driven by ontogeny. Results of this study support the hypothesis that leaf-level allocation to defenses might be an important determinant of leaf economic traits, where high investment in defenses drives a conservative LES strategy. PMID:25480481

  11. The Role of Innate Immunity in Osteoarthritis: When Our First Line of Defense Goes on the Offensive

    PubMed Central

    Orlowsky, Eric W.; Kraus, Virginia Byers

    2015-01-01

    Although mankind has been suffering from osteoarthritis (OA) dating to the dawn of humankind, its pathogenesis remains poorly understood. OA is no longer considered a “wear and tear” condition but rather one driven by proteases where chronic low-grade inflammation may play a role in perpetuating proteolytic activity. While multiple factors are likely active in this process, recent evidence has implicated the importance of the innate immune system, the older or more primitive part of our body’s immune defense mechanisms. The role of some of the components of the innate immune system have been tested in OA models in vivo including the role of synovial macrophages and the complement system. This review is a selective overview of a large and evolving field. Insights into these mechanisms might inform our ability to phenotype patient subsets and give hope for the advent of novel OA therapies. PMID:25593231

  12. Alpha 2 macroglobulin is a maternally-derived immune factor in amphioxus embryos: New evidence for defense roles of maternal immune components in invertebrate chordate.

    PubMed

    Pathirana, Anjalika; Diao, Mingyue; Huang, Shibo; Zuo, Lingling; Liang, Yujun

    2016-03-01

    In fish, a series of maternal derived immune components have been identified in their eggs or embryos at very early stages, which are proposed to provide protections to themselves against pathogenic attacks from hostile environment. The phenomenon of maternal immunity has been also recorded in several invertebrate species, however, so far, very limited information about the maternal immune molecules are available. In this study, it was demonstrated maternal alpha2 macroglobulin (A2m) protein, an important innate immune factor, exists in the fertilized eggs of amphioxus Branchiostoma japonicum, an invertebrate chordate. Maternal mRNA of A2m was also detected in amphioxus embryos at very early developing stages. In addition, it was recorded that the egg lysate prepared from the newly fertilized eggs can inhibit the growth of both Gram-negative bacterium Escherichia coli and Gram-positive bacterium Staphylococcus aureus in a concentration dependent manner. The bacteriostatic activity can be reduced notably after precipitated A2m with anti-A2m antibody. Thus maternal A2m is partly attributed to the bacteriostatic activity. It was further demonstrated that recombinant A2m can bind to E. coli cells directly. All these points come to a result that A2m is a maternal immune factor existing in eggs of invertebrate chordate, which may be involved in defense their embryos against harmful microbes' attacks. PMID:26796816

  13. Strategies to use immune modulators in therapeutic vaccines against cancer

    PubMed Central

    Berzofsky, Jay A.; Terabe, Masaki; Wood, Lauren V.

    2012-01-01

    Cancers so much resemble self that they prove difficult for the immune system to eliminate, and those that have already escaped natural immunosurveillance have gotten past the natural immune barriers to malignancy. A successful therapeutic cancer vaccine must overcome these escape mechanisms. Our laboratory has focused on a multistep “push-pull” approach in which we combine strategies to overcome each of the mechanisms of escape. If tumor epitopes are insufficiently immunogenic, we increase their immunogenicity by epitope enhancement, improving their binding affinity to major histocompatibility complex (MHC) molecules. If the anti-tumor response is too weak or of the wrong phenotype, we use cytokines, costimulatory molecules, Toll-like receptor ligands, and other molecular adjuvants to increase not only the quantity of the response, but also its quality, to push the response in the right direction. Finally, the tumor invokes multiple immunosuppressive mechanisms to defend itself, so we need to overcome those as well, including blocking or depleting regulatory cells or inhibiting regulatory molecules, to pull the response by removing the brakes. Some of these strategies individually have now been translated into human clinical trials in cancer patients. Combinations of these in a push-pull approach are promising for the successful immunotherapy of cancer. PMID:22595057

  14. The Nuclear Immune Receptor RPS4 Is Required for RRS1SLH1-Dependent Constitutive Defense Activation in Arabidopsis thaliana

    PubMed Central

    Sarris, Panagiotis F.; Woo, Joo Yong; Williams, Simon J.; Newman, Toby E.; Paek, Kyung Hee; Kobe, Bostjan; Jones, Jonathan D. G.

    2014-01-01

    Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific avirulent pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4) and RRS1 (resistance to Ralstonia solanacearum 1), function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NB-LRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1) mutant encodes an RRS1 allele (RRS1SLH1) with a single amino acid (leucine) insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi) mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed new light on mechanisms by which NB-LRR protein pairs activate defense signaling, or are held inactive in the absence of a pathogen effector. PMID:25340333

  15. The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana.

    PubMed

    Sohn, Kee Hoon; Segonzac, Ccile; Rallapalli, Ghanasyam; Sarris, Panagiotis F; Woo, Joo Yong; Williams, Simon J; Newman, Toby E; Paek, Kyung Hee; Kobe, Bostjan; Jones, Jonathan D G

    2014-10-01

    Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific "avirulent" pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4) and RRS1 (resistance to Ralstonia solanacearum 1), function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NB-LRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1) mutant encodes an RRS1 allele (RRS1SLH1) with a single amino acid (leucine) insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi) mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed new light on mechanisms by which NB-LRR protein pairs activate defense signaling, or are held inactive in the absence of a pathogen effector. PMID:25340333

  16. Plant defense response against Fusarium oxysporum and strategies to develop tolerant genotypes in banana.

    PubMed

    Swarupa, V; Ravishankar, K V; Rekha, A

    2014-04-01

    Soil-borne fungal pathogen, Fusarium oxysporum causes major economic losses by inducing necrosis and wilting symptoms in many crop plants. Management of fusarium wilt is achieved mainly by the use of chemical fungicides which affect the soil health and their efficiency is often limited by pathogenic variability. Hence understanding the nature of interaction between pathogen and host may help to select and improve better cultivars. Current research evidences highlight the role of oxidative burst and antioxidant enzymes indicating that ROS act as an important signaling molecule in banana defense response against Fusarium oxysporum f.sp. cubense. The role of jasmonic acid signaling in plant defense against necrotrophic pathogens is well recognized. But recent studies show that the role of salicylic acid is complex and ambiguous against necrotrophic pathogens like Fusarium oxysporum, leading to many intriguing questions about its relationship between other signaling compounds. In case of banana, a major challenge is to identify specific receptors for effector proteins like SIX proteins and also the components of various signal transduction pathways. Significant progress has been made to uncover the role of defense genes but is limited to only model plants such as Arabidopsis and tomato. Keeping this in view, we review the host response, pathogen diversity, current understanding of biochemical and molecular changes that occur during host and pathogen interaction. Developing resistant cultivars through mutation, breeding, transgenic and cisgenic approaches have been discussed. This would help us to understand host defenses against Fusarium oxysporum and to formulate strategies to develop tolerant cultivars. PMID:24420701

  17. Transcriptomic insight into the immune defenses in the ghost moth, Hepialus xiaojinensis, during an Ophiocordyceps sinensis fungal infection.

    PubMed

    Meng, Qian; Yu, Hai-Ying; Zhang, Huan; Zhu, Wei; Wang, Meng-Long; Zhang, Ji-Hong; Zhou, Gui-Ling; Li, Xuan; Qin, Qi-Lian; Hu, Song-Nian; Zou, Zhen

    2015-09-01

    Hepialus xiaojinensis is an economically important species of Lepidopteran insect. The fungus Ophiocordyceps sinensis can infect its larvae, which leads to mummification after 5-12 months, providing a valuable system with which to study interactions between the insect hosts and pathogenic fungi. However, little sequence information is available for this insect. A time-course analysis of the fat body transcriptome was performed to explore the host immune response to O. sinensis infection. In total, 50,164 unigenes were obtained by assembling the reads from two high-throughput approaches: 454 pyrosequencing and Illumina Hiseq2000. Hierarchical clustering and functional examination revealed four major gene clusters. Clusters 1-3 included transcripts markedly induced by the fungal infection within 72h. Cluster 4, with a lower number of transcripts, was suppressed during the early phase of infection but returned to normal expression levels sometime before 1 year. Based on sequence similarity to orthologs known to participate in immune defenses, 258 candidate immunity-related transcripts were identified, and their functions were hypothesized. The genes were more primitive than those in other Lepidopteran insects. In addition, lineage-specific family expansion of the clip-domain serine proteases and C-type lectins were apparent and likely caused by selection pressures. Global expression profiles of immunity-related genes indicated that H. xiaojinensis was capable of a rapid response to an O. sinensis challenge; however, the larvae developed tolerance to the fungus after prolonged infection, probably due to immune suppression. Specifically, antimicrobial peptide mRNAs could not be detected after chronic infection, because key components of the Toll pathway (MyD88, Pelle and Cactus) were downregulated. Taken together, this study provides insights into the defense system of H. xiaojinensis, and a basis for understanding the molecular aspects of the interaction between the host and the entomopathogen. PMID:26165779

  18. Production and Release of Antimicrobial and Immune Defense Proteins by Mammary Epithelial Cells following Streptococcus uberis Infection of Sheep

    PubMed Central

    Pisanu, Salvatore; Marogna, Gavino; Cubeddu, Tiziana; Pagnozzi, Daniela; Cacciotto, Carla; Campesi, Franca; Schianchi, Giuseppe; Rocca, Stefano

    2013-01-01

    Investigating the innate immune response mediators released in milk has manifold implications, spanning from elucidation of the role played by mammary epithelial cells (MECs) in fighting microbial infections to the discovery of novel diagnostic markers for monitoring udder health in dairy animals. Here, we investigated the mammary gland response following a two-step experimental infection of lactating sheep with the mastitis-associated bacterium Streptococcus uberis. The establishment of infection was confirmed both clinically and by molecular methods, including PCR and fluorescent in situ hybridization of mammary tissues. Proteomic investigation of the milk fat globule (MFG), a complex vesicle released by lactating MECs, enabled detection of enrichment of several proteins involved in inflammation, chemotaxis of immune cells, and antimicrobial defense, including cathelicidins and calprotectin (S100A8/S100A9), in infected animals, suggesting the consistent involvement of MECs in the innate immune response to pathogens. The ability of MECs to produce and release antimicrobial and immune defense proteins was then demonstrated by immunohistochemistry and confocal immunomicroscopy of cathelicidin and the calprotectin subunit S100A9 on mammary tissues. The time course of their release in milk was also assessed by Western immunoblotting along the course of the experimental infection, revealing the rapid increase of these proteins in the MFG fraction in response to the presence of bacteria. Our results support an active role of MECs in the innate immune response of the mammary gland and provide new potential for the development of novel and more sensitive tools for monitoring mastitis in dairy animals. PMID:23774600

  19. Inter-organ defense networking: Leaf whitefly sucking elicits plant immunity to crown gall disease caused by Agrobacterium tumefaciens.

    PubMed

    Park, Yong-Soon; Ryu, Choong-Min

    2015-01-01

    Plants have elaborate defensive machinery to protect against numerous pathogens and insects. Plant hormones function as modulators of defensive mechanisms to maintain plant resistance to natural enemies. Our recent study suggests that salicylic acid (SA) is the primary phytohormone regulating plant responses to Agrobacterium tumefaciens infection. Tobacco (Nicotiana benthamiana Domin.) immune responses against Agrobacterium-mediated crown gall disease were activated by exposure to the sucking insect whitefly, which stimulated SA biosynthesis in aerial tissues; in turn, SA synthesized in aboveground tissues systemically modulated SA secretion in root tissues. Further investigation revealed that endogenous SA biosynthesis negatively modulated Agrobacterium-mediated plant genetic transformation. Our study provides novel evidence that activation of the SA-signaling pathway mediated by a sucking insect infestation has a pivotal role in subsequently attenuating Agrobacterium infection. These results demonstrate new insights into interspecies cross-talking among insects, plants, and soil bacteria. PMID:26357873

  20. Tolerance of fungal infection in European water frogs exposed to Batrachochytrium dendrobatidis after experimental reduction of innate immune defenses

    PubMed Central

    2012-01-01

    Background While emerging diseases are affecting many populations of amphibians, some populations are resistant. Determining the relative contributions of factors influencing disease resistance is critical for effective conservation management. Innate immune defenses in amphibian skin are vital host factors against a number of emerging pathogens such as ranaviruses and the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). Adult water frogs from Switzerland (Pelophylax esculentus and P. lessonae) collected in the field with their natural microbiota intact were exposed to Bd after experimental reduction of microbiota, skin peptides, both, or neither to determine the relative contributions of these defenses. Results Naturally-acquired Bd infections were detected in 10/51 P. lessonae and 4/19 P. esculentus, but no disease outbreaks or population declines have been detected at this site. Thus, this population was immunologically primed, and disease resistant. No mortality occurred during the 64 day experiment. Forty percent of initially uninfected frogs became sub-clinically infected upon experimental exposure to Bd. Reduction of both skin peptide and microbiota immune defenses caused frogs to gain less mass when exposed to Bd than frogs in other treatments. Microbiota-reduced frogs increased peptide production upon Bd infection. Ranavirus was undetectable in all but two frogs that appeared healthy in the field, but died within a week under laboratory conditions. Virus was detectable in both toe-clips and internal organs. Conclusion Intact skin microbiota reduced immune activation and can minimize subclinical costs of infection. Tolerance of Bd or ranavirus infection may differ with ecological conditions. PMID:23088169

  1. Targeting an antimicrobial effector function in insect immunity as a pest control strategy

    PubMed Central

    Bulmer, Mark S.; Bachelet, Ido; Raman, Rahul; Rosengaus, Rebeca B.; Sasisekharan, Ram

    2009-01-01

    Insect pests such as termites cause damages to crops and man-made structures estimated at over $30 billion per year, imposing a global challenge for the human economy. Here, we report a strategy for compromising insect immunity that might lead to the development of nontoxic, sustainable pest control methods. Gram-negative bacteria binding proteins (GNBPs) are critical for sensing pathogenic infection and triggering effector responses. We report that termite GNBP-2 (tGNBP-2) shows ?(1,3)-glucanase effector activity previously unknown in animal immunity and is a pleiotropic pattern recognition receptor and an antimicrobial effector protein. Termites incorporate this protein into the nest building material, where it functions as a nest-embedded sensor that cleaves and releases pathogenic components, priming termites for improved antimicrobial defense. By means of rational design, we present an inexpensive, nontoxic small molecule glycomimetic that blocks tGNBP-2, thus exposing termites in vivo to accelerated infection and death from specific and opportunistic pathogens. Such a molecule, introduced into building materials and agricultural methods, could protect valuable assets from insect pests. PMID:19506247

  2. Central immune alterations in passive strategy following chronic defeat stress.

    PubMed

    Joana, Perez-Tejada; Amaia, Arregi; Arantza, Azpiroz; Garikoitz, Beitia; Eneritz, Gomez-Lazaro; Larraitz, Garmendia

    2016-02-01

    The relationship between stress, mood disorders and immune disorders is known, but what remains to be resolved is why certain individuals are more susceptible than others to suffer different disorders, along with the biological mechanisms that underlie these differences. The objective of this study was to analyze the changes in the expression patterns of proinflammatory cytokines in the hypothalamus, hippocampus, amygdala and prefrontal cortex after chronic defeat, depending on the coping strategy used. The expression levels of α1b and α2a adrenergic receptors and cytokine-inducible nitric oxide synthase (iNOS) in the prefrontal cortex were also measured. The results indicated that subjects with a passive coping strategy showed high levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) expression in several cerebral structures in resting conditions after 21 days of chronic stress and increases in these cytokine levels in the hippocampus following an additional stress. Low expression levels of tumour necrosis factor-alpha (TNF-α) in the prefrontal cortex in active subjects at rest and in passive subjects after an additional defeat were detected. The iNOS expression levels were lower in the prefrontal cortex of the active group at rest. With respect to adrenergic receptor expression, there were no changes as a function of stress, but there were changes as a function of coping strategy. These results indicate differences in the variables studied in terms of the coping strategy adopted, with passive subjects having a biological profile that could be considered more vulnerable to the development of stress-related disorders. PMID:26602284

  3. IFN-?-producing PDCA-1+ Siglec-H- B cells mediate innate immune defense by activating NK cells.

    PubMed

    Bao, Yan; Han, Yanmei; Chen, Zhubo; Xu, Sheng; Cao, Xuetao

    2011-03-01

    B cells have multiple functions in adaptive immunity, including antibody production, antigen presentation and regulation of T-cell responses. Recent evidences indicate that B cells have more subsets than previously thought and may have non-classical functions, such as involvement in innate immunity and immune regulation; however, how B cells respond to microbial infection and elicit innate defense remain unclear. In this study, we identified a new subset of PDCA-1(+) Siglec-H(-) CD19(+) B cells in mice during the early period of bacterial infection with Listeria monocytogenes. PDCA-1(+) Siglec-H(-) CD19(+) B cells secreted large amounts of IFN-? and thus facilitated IFN-? production and cytotoxicity function of natural killer (NK) cells via IFN-?. B-cell-deficient Btk(-/-) mice were incapable of producing PDCA-1(+) CD19(+) B cells, and were more sensitive to L. monocytogenes infection. Adoptive transfer of PDCA-1(+) CD19(+) B cells to Btk(-/-) mice normalized their resistance to L. monocytogenes infection. Furthermore, we found that macrophages were essential for the inducible generation of PDCA-1(+) Siglec-H(-) CD19(+) B cells via CD40-CD40L ligation. Therefore, we have identified a new subset of PDCA-1(+) Siglec-H(-) CD19(+) B cells, which enhances innate immune responses against bacterial infection by activating NK cells via secretion of IFN-?. PMID:21287550

  4. Immune defense is the primary function associated with the differentially expressed genes in the cochlea following acoustic trauma.

    PubMed

    Yang, Shuzhi; Cai, Qunfeng; Vethanayagam, R Robert; Wang, Jianmin; Yang, Weiping; Hu, Bo Hua

    2016-03-01

    Our previous RNA-sequencing analysis of the rat cochlear genes identified multiple biological processes and molecular pathways in the cochlear response to acoustic overstimulation. However, the biological processes and molecular pathways that are common to other species have not been documented. The identification of these common stress processes is pivotal for a better understanding of the essential response of the cochlea to acoustic injury. Here, we compared the RNA-sequencing data collected from mice and rats that sustained a similar, but not identical, acoustic injury. The transcriptome analysis of cochlear genes identified the differentially expressed genes in the mouse and rat samples. Bioinformatics analysis revealed a marked similarity in the changes in the biological processes between the two species, although the differentially expressed genes did not overlap well. The common processes associated with the differentially expressed genes are primarily associated with immunity and inflammation, which include the immune response, response to wounding, the defense response, chemotaxis and inflammatory responses. Moreover, analysis of the molecular pathways showed considerable overlap between the two species. The common pathways include cytokine-cytokine receptor interactions, the chemokine signaling pathway, the Toll-like receptor signaling pathway, and the NOD-like receptor signaling pathway. Further analysis of the transcriptional regulators revealed common upstream regulators of the differentially expressed genes, and these upstream regulators are also functionally related to the immune and inflammatory responses. These results suggest that the immune and inflammatory responses are the essential responses to acoustic overstimulation in the cochlea. PMID:26520584

  5. Final Report for Bio-Inspired Approaches to Moving-Target Defense Strategies

    SciTech Connect

    Fink, Glenn A.; Oehmen, Christopher S.

    2012-09-01

    This report records the work and contributions of the NITRD-funded Bio-Inspired Approaches to Moving-Target Defense Strategies project performed by Pacific Northwest National Laboratory under the technical guidance of the National Security Agency’s R6 division. The project has incorporated a number of bio-inspired cyber defensive technologies within an elastic framework provided by the Digital Ants. This project has created the first scalable, real-world prototype of the Digital Ants Framework (DAF)[11] and integrated five technologies into this flexible, decentralized framework: (1) Ant-Based Cyber Defense (ABCD), (2) Behavioral Indicators, (3) Bioinformatic Clas- sification, (4) Moving-Target Reconfiguration, and (5) Ambient Collaboration. The DAF can be used operationally to decentralize many such data intensive applications that normally rely on collection of large amounts of data in a central repository. In this work, we have shown how these component applications may be decentralized and may perform analysis at the edge. Operationally, this will enable analytics to scale far beyond current limitations while not suffering from the bandwidth or computational limitations of centralized analysis. This effort has advanced the R6 Cyber Security research program to secure digital infrastructures by developing a dynamic means to adaptively defend complex cyber systems. We hope that this work will benefit both our client’s efforts in system behavior modeling and cyber security to the overall benefit of the nation.

  6. The Anopheles innate immune system in the defense against malaria infection

    PubMed Central

    Clayton, April M.; Dong, Yuemei; Dimopoulos, George

    2014-01-01

    The multifaceted innate immune system of insects is capable of fighting infection by a variety of pathogens including those causing human malaria. Malaria transmission by the Anopheles mosquito depends on the Plasmodium parasites successful completion of its lifecycle in the insect vector, a process that involves interactions with several tissues and cell types as well as with the mosquitos innate immune system. This review will discuss our current understanding of the Anopheles mosquitos innate immune responses against the malaria parasite Plasmodium and the influence of the insects intestinal microbiota on parasite infection. PMID:23988482

  7. The evolutionary strategies of plant defenses have a dynamic impact on the adaptations and interactions of vectors and pathogens.

    PubMed

    Huot, Ordom Brian; Nachappa, Punya; Tamborindeguy, Cecilia

    2013-06-01

    Plants have evolved and diversified to reduce the damages imposed by infectious pathogens and herbivorous insects. Living in a sedentary lifestyle, plants are constantly adapting to their environment. They employ various strategies to increase performance and fitness. Thus, plants developed cost-effective strategies to defend against specific insects and pathogens. Plant defense, however, imposes selective pressure on insects and pathogens. This selective pressure provides incentives for pathogens and insects to diversify and develop strategies to counter plant defense. This results in an evolutionary arms race among plants, pathogens and insects. The ever-changing adaptations and physiological alterations among these organisms make studying plant-vector-pathogen interactions a challenging and fascinating field. Studying plant defense and plant protection requires knowledge of the relationship among organisms and the adaptive strategies each organism utilize. Therefore, this review focuses on the integral parts of plant-vector-pathogen interactions in order to understand the factors that affect plant defense and disease development. The review addresses plant-vector-pathogen co-evolution, plant defense strategies, specificity of plant defenses and plant-vector-pathogen interactions. Improving the comprehension of these factors will provide a multi-dimensional perspective for the future research in pest and disease management. PMID:23955882

  8. Interferon-γ Is a Crucial Activator of Early Host Immune Defense against Mycobacterium ulcerans Infection in Mice

    PubMed Central

    Bieri, Raphael; Bolz, Miriam; Ruf, Marie-Thérèse; Pluschke, Gerd

    2016-01-01

    Buruli ulcer (BU), caused by infection with Mycobacterium ulcerans, is a chronic necrotizing human skin disease associated with the production of the cytotoxic macrolide exotoxin mycolactone. Despite extensive research, the type of immune responses elicited against this pathogen and the effector functions conferring protection against BU are not yet fully understood. While histopathological analyses of advanced BU lesions have demonstrated a mainly extracellular localization of the toxin producing acid fast bacilli, there is growing evidence for an early intra-macrophage growth phase of M. ulcerans. This has led us to investigate whether interferon-γ might play an important role in containing M. ulcerans infections. In an experimental Buruli ulcer mouse model we found that interferon-γ is indeed a critical regulator of early host immune defense against M. ulcerans infections. Interferon-γ knockout mice displayed a faster progression of the infection compared to wild-type mice. This accelerated progression was reflected in faster and more extensive tissue necrosis and oedema formation, as well as in a significantly higher bacterial burden after five weeks of infection, indicating that mice lacking interferon-γ have a reduced capacity to kill intracellular bacilli during the early intra-macrophage growth phase of M. ulcerans. This data demonstrates a prominent role of interferon-γ in early defense against M. ulcerans infection and supports the view that concepts for vaccine development against tuberculosis may also be valid for BU. PMID:26863011

  9. Immune Defense Varies within an Instar in the Tobacco Hornworm, Manduca sexta*.

    PubMed

    Booth, Kimberly; Cambron, Lizzette; Fisher, Nathan; Greenlee, Kendra J

    2015-01-01

    Research on how insect immunity changes with age as insects develop within an instar, or larval developmental stage, is limited and contradictory. Insects within an instar are preparing for the next developmental stage, which may involve changes in morphology or habitat. Immunity may also vary accordingly. To determine how immunity varies in the fifth instar, we tested humoral immune responses, antimicrobial peptide activity, and phenoloxidase activity using the tobacco hornworm, Manduca sexta. We determined that while M. sexta have more robust antimicrobial peptide and phenoloxidase responses at the beginning of their fifth instar, this did not translate into better survival of bacterial infection or lower bacterial load in the hemolymph. We also determined that M. sexta injected with bacteria early in the fifth instar experience lower growth rates and longer development times than caterpillars of the same age injected with sham. This could indicate a shift in energy allocation from growth and development to metabolically costly immune responses. Because of the importance of insects as pests and pollinators, understanding how immunity varies throughout development is critical. PMID:25730277

  10. Visual search strategies of soccer players in one-on-one defensive situations on the field.

    PubMed

    Nagano, Tomohisa; Kato, Takaaki; Fukuda, Tadahiko

    2004-12-01

    This study analyzed visual search strategies of soccer players in one-on-one defensive situations on the field. The 8 subjects were 4 experts and 4 novices. While subjects tackled an offensive player for possession of the ball, their eye movements were measured and analyzed. Statistically significant differences between the visual search strategies of experts and novices showed experts fixated more often on both the knee and the hip regions of opponents than novices did. This suggests that information gained from the movements of these areas was important in anticipating an opponent's next move. Findings suggest the importance in soccer for players not to focus too closely on the ball, but on an opponent's knee and hip. PMID:15648495

  11. Microbiota regulates immune defense against respiratory tract influenza A virus infection

    PubMed Central

    Ichinohe, Takeshi; Pang, Iris K.; Kumamoto, Yosuke; Peaper, David R.; Murray, Thomas S.; Iwasaki, Akiko

    2011-01-01

    Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. By using various antibiotic treatments, we found that neomycin-sensitive bacteria are associated with the induction of productive immune responses in the lung. Local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in the antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for pro–IL-1β and pro–IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes. PMID:21402903

  12. [Surfactant protein D--endogenous regulator of inflammation and immune defense].

    PubMed

    Liamina, S V; Shimshelashvili, Sh L; Malyshev, I Iu

    2012-01-01

    Surfactant protein D (SP-D) is a component of lung surfactant, the representative of collagen-like lectines (collectines) family. It plays one of the significant roles in innate antibody-independent immune response. Structural features of SP-D, the possibility of its influence on pathogenetic componentes of inflammatory reaction, expression of inflammatory mediators and attainment of necessary balance between control of inflammatory reaction intensity and formation of the proper response to pathogens allow to consider SP-D as a part of innate immune system of the lung and endogenous regulator of inflammatory reactions in the organism. PMID:22629864

  13. A new role for PGRP-S (Tag7) in immune defense: lymphocyte migration is induced by a chemoattractant complex of Tag7 with Mts1.

    PubMed

    Dukhanina, E A; Lukyanova, T I; Romanova, E A; Guerriero, V; Gnuchev, N V; Georgiev, G P; Yashin, D V; Sashchenko, L P

    2015-11-17

    PGRP-S (Tag7) is an innate immunity protein involved in the antimicrobial defense systems, both in insects and in mammals. We have previously shown that Tag7 specifically interacts with several proteins, including Hsp70 and the calcium binding protein S100A4 (Mts1), providing a number of novel cellular functions. Here we show that Tag7-Mts1 complex causes chemotactic migration of lymphocytes, with NK cells being a preferred target. Cells of either innate immunity (neutrophils and monocytes) or acquired immunity (CD4(+) and CD8(+) lymphocytes) can produce this complex, which confirms the close connection between components of the 2 branches of immune response. PMID:26654597

  14. Genetic and phenotypic relationships between immune defense, melanism and life-history traits at different temperatures and sexes in Tenebrio molitor

    PubMed Central

    Prokkola, J; Roff, D; Krkkinen, T; Krams, I; Rantala, M J

    2013-01-01

    Insect cuticle melanism is linked to a number of life-history traits, and a positive relationship is hypothesized between melanism and the strength of immune defense. In this study, the phenotypic and genetic relationships between cuticular melanization, innate immune defense, individual development time and body size were studied in the mealworm beetle (Tenebrio molitor) using three different temperatures with a half-sib breeding design. Both innate immune defense and cuticle darkness were higher in females than males, and a positive correlation between the traits was found at the lowest temperature. The effect of temperature on all the measured traits was strong, with encapsulation ability and development time decreasing and cuticle darkness increasing with a rise in temperature, and body size showing a curved response. The analysis showed a highly integrated system sensitive to environmental change involving physiological, morphological and life-history traits. PMID:23572120

  15. Genetic and phenotypic relationships between immune defense, melanism and life-history traits at different temperatures and sexes in Tenebrio molitor.

    PubMed

    Prokkola, J; Roff, D; Kärkkäinen, T; Krams, I; Rantala, M J

    2013-08-01

    Insect cuticle melanism is linked to a number of life-history traits, and a positive relationship is hypothesized between melanism and the strength of immune defense. In this study, the phenotypic and genetic relationships between cuticular melanization, innate immune defense, individual development time and body size were studied in the mealworm beetle (Tenebrio molitor) using three different temperatures with a half-sib breeding design. Both innate immune defense and cuticle darkness were higher in females than males, and a positive correlation between the traits was found at the lowest temperature. The effect of temperature on all the measured traits was strong, with encapsulation ability and development time decreasing and cuticle darkness increasing with a rise in temperature, and body size showing a curved response. The analysis showed a highly integrated system sensitive to environmental change involving physiological, morphological and life-history traits. PMID:23572120

  16. A Multipopulation Coevolutionary Strategy for Multiobjective Immune Algorithm

    PubMed Central

    Shi, Jiao; Gong, Maoguo; Ma, Wenping; Jiao, Licheng

    2014-01-01

    How to maintain the population diversity is an important issue in designing a multiobjective evolutionary algorithm. This paper presents an enhanced nondominated neighbor-based immune algorithm in which a multipopulation coevolutionary strategy is introduced for improving the population diversity. In the proposed algorithm, subpopulations evolve independently; thus the unique characteristics of each subpopulation can be effectively maintained, and the diversity of the entire population is effectively increased. Besides, the dynamic information of multiple subpopulations is obtained with the help of the designed cooperation operator which reflects a mutually beneficial relationship among subpopulations. Subpopulations gain the opportunity to exchange information, thereby expanding the search range of the entire population. Subpopulations make use of the reference experience from each other, thereby improving the efficiency of evolutionary search. Compared with several state-of-the-art multiobjective evolutionary algorithms on well-known and frequently used multiobjective and many-objective problems, the proposed algorithm achieves comparable results in terms of convergence, diversity metrics, and running time on most test problems. PMID:24672330

  17. Quorum Sensing Determines the Choice of Antiphage Defense Strategy in Vibrio anguillarum

    PubMed Central

    Tan, Demeng; Svenningsen, Sine Lo

    2015-01-01

    ABSTRACT Selection for phage resistance is a key driver of bacterial diversity and evolution, and phage-host interactions may therefore have strong influence on the genetic and functional dynamics of bacterial communities. In this study, we found that an important, but so far largely overlooked, determinant of the outcome of phage-bacterial encounters in the fish pathogen Vibrio anguillarum is bacterial cell-cell communication, known as quorum sensing. Specifically, V.anguillarum PF430-3 cells locked in the low-cell-density state (?vanT mutant) express high levels of the phage receptor OmpK, resulting in a high susceptibility to phage KVP40, but achieve protection from infection by enhanced biofilm formation. By contrast, cells locked in the high-cell-density state (?van? mutant) are almost completely unsusceptible due to quorum-sensing-mediated downregulation of OmpK expression. The phenotypes of the two quorum-sensing mutant strains are accurately reflected in the behavior of wild-type V.anguillarum, which (i) displays increased OmpK expression in aggregated cells compared to free-living variants in the same culture, (ii) displays a clear inverse correlation between ompK mRNA levels and the concentration of N-acylhomoserine lactone quorum-sensing signals in the culture medium, and (iii) survives mainly by one of these two defense mechanisms, rather than by genetic mutation to phage resistance. Taken together, our results demonstrate that V.anguillarum employs quorum-sensing information to choose between two complementary antiphage defense strategies. Further, the prevalence of nonmutational defense mechanisms in strain PF430-3 suggests highly flexible adaptations to KVP40 phage infection pressure, possibly allowing the long-term coexistence of phage and host. PMID:26081633

  18. Poplar Extrafloral Nectaries: Two Types, Two Strategies of Indirect Defenses against Herbivores1[C][W

    PubMed Central

    Escalante-Prez, Mara; Jaborsky, Mario; Lautner, Silke; Fromm, Jrg; Mller, Tobias; Dittrich, Marcus; Kunert, Maritta; Boland, Wilhelm; Hedrich, Rainer; Ache, Peter

    2012-01-01

    Many plant species grow extrafloral nectaries and produce nectar to attract carnivore arthropods as defenders against herbivores. Two nectary types that evolved with Populus trichocarpa (Ptr) and Populus tremula Populus tremuloides (Ptt) were studied from their ecology down to the genes and molecules. Both nectary types strongly differ in morphology, nectar composition and mode of secretion, and defense strategy. In Ptt, nectaries represent constitutive organs with continuous merocrine nectar flow, nectary appearance, nectar production, and flow. In contrast, Ptr nectaries were found to be holocrine and inducible. Neither mechanical wounding nor the application of jasmonic acid, but infestation by sucking insects, induced Ptr nectar secretion. Thus, nectaries of Ptr and Ptt seem to answer the same threat by the use of different mechanisms. PMID:22573802

  19. Prion-like Polymerization Underlies Signal Transduction in Antiviral Immune Defense and Inflammasome Activation

    PubMed Central

    Cai, Xin; Chen, Jueqi; Xu, Hui; Liu, Siqi; Jiang, Qiu-Xing; Halfmann, Randal; Chen, Zhijian J.

    2014-01-01

    SUMMARY Pathogens and cellular danger signals activate sensors such as RIG-I and NLRP3 to produce robust immune and inflammatory responses through respective adaptor proteins MAVS and ASC, which harbor essential N-terminal CARD and PYRIN domains, respectively. Here, we show that CARD and PYRIN function as bona fide prions in yeast and their prion forms are inducible by their respective upstream activators. Likewise, a yeast prion domain can functionally replace CARD and PYRIN in mammalian cell signaling. Mutations in MAVS and ASC that disrupt their prion activities in yeast also abrogate their ability to signal in mammalian cells. Furthermore, fibers of recombinant PYRIN can convert ASC into functional polymers capable of activating caspase-1. Remarkably, a conserved fungal NOD-like receptor and prion pair can functionally reconstitute signaling of NLRP3 and ASC PYRINs in mammalian cells. These results indicate that prion-like polymerization is a conserved signal transduction mechanism in innate immunity and inflammation. PMID:24630723

  20. IRAK-M regulation and function in host defense and immune homeostasis.

    PubMed

    Hubbard, Leah L N; Moore, Bethany B

    2010-01-01

    Antigen presenting cells (APCs) of the innate immune system sense a wide range of pathogens via pattern recognition receptors (PRRs). Engagement of certain PRRs can induce production of pro-inflammatory mediators that facilitate effective clearance of pathogen. Toll-like receptors (TLRs) are a well described group of PRRs that belong to the TLR/Interleukin-1 receptor (IL-1R) superfamily. However, TLR/IL-1R induction of pro-inflammatory mediators must be regulated to prevent excessive inflammation and tissue damage. One molecule of recent interest that is known to inhibit TLR/IL-1R signaling is interleukin-1 receptor associated kinase (IRAK)-M, also known as IRAK-3. IRAK-M is expressed in a number of immune and epithelial cells types, and through its inhibition of pro-inflammatory cytokine production, IRAK-M can regulate immune homeostasis and tolerance in a number of infectious and non-infectious diseases. Furthermore, use of IRAK-M deficient animals has increased our understanding of the importance of IRAK-M in regulating immune responsiveness to a variety of pathogens. Although IRAK-M expression is typically induced through TLR signaling, IRAK-M can also be expressed in response to various endogenous and exogenous soluble factors as well as cell surface and intracellular signaling molecules.This review will focus on clinical scenarios in which expression of IRAK-M is beneficial (as in early sepsis) and those situations where IRAK-M expression is harmful to the host (as in cancer and following bone marrow transplant). There is strong rationale for therapeutic targeting of IRAK-M for clinical benefit. However, effective targeting will require a greater understanding of the transcriptional regulation of this gene. PMID:21390243

  1. Infection of goats with goatpox virus triggers host antiviral defense through activation of innate immune signaling.

    PubMed

    Zeng, Xiancheng; Wang, Song; Chi, Xiaojuan; Chen, Shi-Long; Huang, Shile; Lin, Qunqun; Xie, Baogui; Chen, Ji-Long

    2016-02-01

    Goatpox, caused by goatpox virus (GTPV), is one of the most serious infectious diseases associated with high morbidity and mortality in goats. However, little is known about involvement of host innate immunity during the GTPV infection. For this, goats were experimentally infected with GTPV. The results showed that GTPV infection significantly induced mRNA expression of type I interferon (IFN)-? and IFN-? in peripheral blood lymphocytes, spleen and lung. In addition, GTPV infection enhanced expression of several inflammatory cytokines, including interleukin (IL)-1?, IL-6, IL-18; and tumor necrosis factor-? (TNF-?). Strikingly, infection with GTPV activated signal transducers and activators of transcription 3 (STAT3), a critical cytokine signaling molecule. Interestingly, the virus infection induced expression of suppressor of cytokine signaling (SOCS)-1. Importantly, the infection resulted in an increased expression of some critical interferon-stimulated genes, such as interferon-induced transmembrane protein (IFITM) 1, IFITM3, interferon stimulated gene (ISG) 15 and ISG20. Furthermore, we found that infection with GTPV up-regulated expression of Toll-like receptor (TLR) 2 and TLR9. These results revealed that GTPV infection activated host innate immune signaling and thereby triggered antiviral innate immunity. The findings provide novel insights into complex mechanisms underlying GTPV-host interaction and pathogenesis of GTPV. PMID:26850535

  2. EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes.

    PubMed

    Miyazaki, T; Ikeda, K; Horie-Inoue, K; Kondo, T; Takahashi, S; Inoue, S

    2014-01-01

    Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) is a primary estrogen-responsive gene that we previously identified in MCF-7 breast cancer cells using the CpG genomic binding-site cloning technique. The expression of EBAG9 protein is often upregulated in malignant tumors, suggesting that this protein is involved in cancer pathophysiology. In the present study, we investigated the role of EBAG9 in host defense against implanted tumors in Ebag9-knockout (Ebag9KO) mice. MB-49 mouse bladder cancer cells were subcutaneously implanted into Ebag9KO and control mice. We found that tumor formation and metastasis to the lung by MB-49 cells were substantially reduced in Ebag9KO mice compared with control mice. The infiltration of CD8(+), CD3(+) and CD4(+) T cells into the generated tumors was enhanced in Ebag9KO mice compared with controls. Notably, CD8(+) T cells isolated from tumors in Ebag9KO mice exhibited substantial upregulation of immunity- and chemoattraction-related genes, including interleukin-10 receptor, interferon gamma, granzyme A, granzyme B and chemokine (C-X-C motif) receptor 3 compared with CD8(+) T cells from tumors in control mice. The CD8(+) T cells isolated from tumors in Ebag9KO mice also exhibited enhanced degranulation and increased cytolytic activity. Furthermore, the adoptive transfer of CD8(+) T cells isolated from tumors in Ebag9KO host could repress tumor growth by MB-49 cells implanted in wild-type host. These results suggest that EBAG9 modulates tumor growth and metastasis by negatively regulating the adaptive immune response in host defense. EBAG9 could be a potential target for tumor immunotherapy. PMID:25365482

  3. Novel vaccine development strategies for inducing mucosal immunity.

    PubMed

    Fujkuyama, Yoshiko; Tokuhara, Daisuke; Kataoka, Kosuke; Gilbert, Rebekah S; McGhee, Jerry R; Yuki, Yoshikazu; Kiyono, Hiroshi; Fujihashi, Kohtaro

    2012-03-01

    To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed. PMID:22380827

  4. Novel vaccine development strategies for inducing mucosal immunity

    PubMed Central

    Fujkuyama, Yoshiko; Tokuhara, Daisuke; Kataoka, Kosuke; Gilbert, Rebekah S; McGhee, Jerry R; Yuki, Yoshikazu; Kiyono, Hiroshi; Fujihashi, Kohtaro

    2012-01-01

    To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed. PMID:22380827

  5. Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy.

    PubMed

    Morrone, Seamus R; Wang, Tao; Constantoulakis, Leeza M; Hooy, Richard M; Delannoy, Michael J; Sohn, Jungsan

    2014-01-01

    Whether host DNA receptors have any capacity to distinguish self from nonself at the molecular level is an outstanding question in the innate immunity of mammals. Here, by using quantitative assays and electron microscopy, we show that cooperatively assembling into filaments on dsDNA may serve as an integral mechanism by which human IFN-inducible protein-16 (IFI16) engages foreign DNA. IFI16 is essential for defense against a number of different pathogens, and its aberrant activity is also implicated in several autoimmune disorders, such as Sjgren syndrome. IFI16 cooperatively binds dsDNA in a length-dependent manner and clusters into distinct protein filaments even in the presence of excess dsDNA. Consequently, the assembled IFI16?dsDNA oligomers are clearly different from the conventional noninteracting entities resembling beads on a string. The isolated DNA-binding domains of IFI16 engage dsDNA without forming filaments and with weak affinity, and it is the non-DNA-binding pyrin domain of IFI16 that drives the cooperative filament assembly. The surface residues on the pyrin domain that mediate the cooperative DNA binding are conserved, suggesting that related receptors use a common mechanism. These results suggest that IFI16 clusters into signaling foci in a switch-like manner and that it is capable of using the size of naked dsDNA as a molecular ruler to distinguish self from nonself. PMID:24367117

  6. Temperature effect on the immune defense functions of Arctic charr Salvelinus alpinus.

    PubMed

    Pylkk, P; Lyytikinen, T; Ritola, O; Pelkonen, S; Valtonen, E T

    2002-11-01

    The Arctic charr Salvelinus alpinus is an endangered fish species in Finland, and thus farming is carried out mainly for stocking purposes. Farmed charr are susceptible to infection with atypical Aeromonas salmonicida (aAS). Losses of valuable brood stock will severely reduce the genetic diversity of stocked charr. No commercial vaccines are available to prevent aAS infection, and vaccines against furunculosis (caused by typical A. salmonicida, tAS) do not protect the charr against aAS infection. The effects of a metabolizable oil-adjuvanted, bivalent vaccine (containing killed aAS and A. salmonicida salmonicida bacteria) on the immune system of 1 yr old hatchery-reared charr originating from Lake Inari in Northern Finland were examined. Fish vaccination in Finland generally takes place either from October to November or from February to April, when the water temperature is low (1 to 3degrees C). The water temperature starts to increase in mid-May. Therefore, we also investigated whether post-vaccination (p.v.) temperature had an influence on the immune system of this cold-water fish species. The fish were immunized intraperitoneally at 2.9 degrees C at the end of April. After 52 d, during which the water temperature increased from 2.9 to 10.0 degrees C, the charr were exposed to 1 of 3 test temperatures: 10.3, 14.1 or 18.1 degrees C. Prior to vaccination, and 49, 75 and 103 d p.v., several immune parameters were measured in both unvaccinated and vaccinated charr. Vaccination induced a significant anti-aAS-specific antibody response, and increased plasma lysozyme activity at all p.v. temperatures. The haemolytic activity of the complement system was unaffected either by vaccination or p.v. temperatures. There was a slight positive correlation between p.v. temperature and lysozyme activity of the charr. The significant increase in lysozyme activity took place in vaccinated charr in the first 49 d p.v. as water temperatures increased from 2.9 to 10 degrees C. Furthermore, the highest activity of lysozyme in the plasma was observed 49 d p.v. Our results indicate that a rise in water temperature above 10 degrees C does not significantly enhance the vaccination response of charr. This could be one reason why farmed Arctic charr, which are well adapted to a cold climate, are highly susceptible to aAS infection in the summer. PMID:12517005

  7. Actions for damages against medical examiners and the defense of sovereign immunity.

    PubMed

    Bierig, J R

    1998-03-01

    The doctrine of sovereign or official immunity has protected medical examiners in cases alleging negligent performance of the autopsy and in cases involving negligent harvesting of organs. It has not protected examiners in cases alleging performance of autopsy without authorization. The medical examiner, therefore, is well advised to determine whether there may be any objection by the next-of-kin to an autopsy and particularly any religious objection-and if there is such an objection, to proceed only after making contemporaneous and documented decision that there is a compelling need for the autopsy. PMID:9523069

  8. Biomphalysin, a New ? Pore-forming Toxin Involved in Biomphalaria glabrata Immune Defense against Schistosoma mansoni

    PubMed Central

    Mon, Yves; Allienne, Jean Franois; Henri, Hlne; Delbecq, Stphane; Mitta, Guillaume; Gourbal, Benjamin; Duval, David

    2013-01-01

    Aerolysins are virulence factors belonging to the ? pore-forming toxin (?-PFT) superfamily that are abundantly distributed in bacteria. More rarely, ?-PFTs have been described in eukaryotic organisms. Recently, we identified a putative cytolytic protein in the snail, Biomphalaria glabrata, whose primary structural features suggest that it could belong to this ?-PFT superfamily. In the present paper, we report the molecular cloning and functional characterization of this protein, which we call Biomphalysin, and demonstrate that it is indeed a new eukaryotic ?-PFT. We show that, despite weak sequence similarities with aerolysins, Biomphalysin shares a common architecture with proteins belonging to this superfamily. A phylogenetic approach revealed that the gene encoding Biomphalysin could have resulted from horizontal transfer. Its expression is restricted to immune-competent cells and is not induced by parasite challenge. Recombinant Biomphalysin showed hemolytic activity that was greatly enhanced by the plasma compartment of B. glabrata. We further demonstrated that Biomphalysin with plasma is highly toxic toward Schistosoma mansoni sporocysts. Using in vitro binding assays in conjunction with Western blot and immunocytochemistry analyses, we also showed that Biomphalysin binds to parasite membranes. Finally, we showed that, in contrast to what has been reported for most other members of the family, lytic activity of Biomphalysin is not dependent on proteolytic processing. These results provide the first functional description of a mollusk immune effector protein involved in killing S. mansoni. PMID:23555242

  9. Short Toxin-like Proteins Attack the Defense Line of Innate Immunity

    PubMed Central

    Tirosh, Yitshak; Ofer, Dan; Eliyahu, Tsiona; Linial, Michal

    2013-01-01

    ClanTox (classifier of animal toxins) was developed for identifying toxin-like candidates from complete proteomes. Searching mammalian proteomes for short toxin-like proteins (coined TOLIPs) revealed a number of overlooked secreted short proteins with an abundance of cysteines throughout their sequences. We applied bioinformatics and data-mining methods to infer the function of several top predicted candidates. We focused on cysteine-rich peptides that adopt the fold of the three-finger proteins (TFPs). We identified a cluster of duplicated genes that share a structural similarity with elapid neurotoxins, such as ?-bungarotoxin. In the murine proteome, there are about 60 such proteins that belong to the Ly6/uPAR family. These proteins are secreted or anchored to the cell membrane. Ly6/uPAR proteins are associated with a rich repertoire of functions, including binding to receptors and adhesion. Ly6/uPAR proteins modulate cell signaling in the context of brain functions and cells of the innate immune system. We postulate that TOLIPs, as modulators of cell signaling, may be associated with pathologies and cellular imbalance. We show that proteins of the Ly6/uPAR family are associated with cancer diagnosis and malfunction of the immune system. PMID:23881252

  10. Identification of a serine proteinase homolog (Sp-SPH) involved in immune defense in the mud crab Scylla paramamosain.

    PubMed

    Zhang, Qiu-xia; Liu, Hai-peng; Chen, Rong-yuan; Shen, Kai-li; Wang, Ke-jian

    2013-01-01

    Clip domain serine proteinase homologs are involved in many biological processes including immune response. To identify the immune function of a serine proteinase homolog (Sp-SPH), originally isolated from hemocytes of the mud crab, Scylla paramamosain, the Sp-SPH was expressed recombinantly and purified for further studies. It was found that the Sp-SPH protein could bind to a number of bacteria (including Aeromonas hydrophila, Escherichia coli, Staphylococcus aureus, Vibrio fluvialis, Vibrio harveyi and Vibrio parahemolyticus), bacterial cell wall components such as lipopolysaccharide or peptidoglycan (PGN), and ?-1, 3-glucan of fungus. But no direct antibacterial activity of Sp-SPH protein was shown by using minimum inhibitory concentration or minimum bactericidal concentration assays. Nevertheless, the Sp-SPH protein was found to significantly enhance the crab hemocyte adhesion activity (paired t-test, P<0.05), and increase phenoloxidase activity if triggered by PGN in vitro (paired t-test, P<0.05). Importantly, the Sp-SPH protein was demonstrated to promote the survival rate of the animals after challenge with A. hydrophila or V. parahemolyticus which were both recognized by Sp-SPH protein, if pre-incubated with Sp-SPH protein, respectively. Whereas, the crabs died much faster when challenged with Vibrio alginolyiicus, a pathogenic bacterium not recognized by Sp-SPH protein, compared to those of crabs challenged with A. hydrophila or V. parahemolyticus when pre-coated with Sp-SPH protein. Taken together, these data suggested that Sp-SPH molecule might play an important role in immune defense against bacterial infection in the mud crab S. paramamosain. PMID:23724001

  11. Identification of a Serine Proteinase Homolog (Sp-SPH) Involved in Immune Defense in the Mud Crab Scylla paramamosain

    PubMed Central

    Zhang, Qiu-xia; Liu, Hai-peng; Chen, Rong-yuan; Shen, Kai-li; Wang, Ke-jian

    2013-01-01

    Clip domain serine proteinase homologs are involved in many biological processes including immune response. To identify the immune function of a serine proteinase homolog (Sp-SPH), originally isolated from hemocytes of the mud crab, Scylla paramamosain, the Sp-SPH was expressed recombinantly and purified for further studies. It was found that the Sp-SPH protein could bind to a number of bacteria (including Aeromonas hydrophila, Escherichia coli, Staphylococcus aureus, Vibrio fluvialis, Vibrio harveyi and Vibrio parahemolyticus), bacterial cell wall components such as lipopolysaccharide or peptidoglycan (PGN), and ?-1, 3-glucan of fungus. But no direct antibacterial activity of Sp-SPH protein was shown by using minimum inhibitory concentration or minimum bactericidal concentration assays. Nevertheless, the Sp-SPH protein was found to significantly enhance the crab hemocyte adhesion activity (paired t-test, P<0.05), and increase phenoloxidase activity if triggered by PGN in vitro (paired t-test, P<0.05). Importantly, the Sp-SPH protein was demonstrated to promote the survival rate of the animals after challenge with A. hydrophila or V. parahemolyticus which were both recognized by Sp-SPH protein, if pre-incubated with Sp-SPH protein, respectively. Whereas, the crabs died much faster when challenged with Vibrio alginolyiicus, a pathogenic bacterium not recognized by Sp-SPH protein, compared to those of crabs challenged with A. hydrophila or V. parahemolyticus when pre-coated with Sp-SPH protein. Taken together, these data suggested that Sp-SPH molecule might play an important role in immune defense against bacterial infection in the mud crab S. paramamosain. PMID:23724001

  12. A bacterial sensory system that activates resistance to innate immune defenses: potential targets for antimicrobial therapeutics.

    PubMed

    Brodsky, Igor E; Gunn, John S

    2005-12-01

    Bacteria posses multiple two component regulatory systems consisting typically of a kinase and a transcription factor that, in concert, monitor the concentrations of particular extracellular factors and regulate specific gene expression accordingly. Salmonella possess PhoP-PhoQ, which are activated under conditions of suboptimal [Mg(2+)] and result in gene expression leading to greater stability of the outer membrane. New research identifies PhoQ as a receptor for sublethal concentrations of antimicrobial peptides (AMPs), adapting bacteria for survival. The development of AMPs that do not activate Phop-PhoQ, however, should proceed with great caution: AMPs are part of the host innate immune response and bacterial resistance to newly developed AMPs could possibly lead to intractable infection in immunocompetent hosts. PMID:16394247

  13. An effective immunization strategy for airborne epidemics in modular and hierarchical social contact network

    NASA Astrophysics Data System (ADS)

    Song, Zhichao; Ge, Yuanzheng; Luo, Lei; Duan, Hong; Qiu, Xiaogang

    2015-12-01

    Social contact between individuals is the chief factor for airborne epidemic transmission among the crowd. Social contact networks, which describe the contact relationships among individuals, always exhibit overlapping qualities of communities, hierarchical structure and spatial-correlated. We find that traditional global targeted immunization strategy would lose its superiority in controlling the epidemic propagation in the social contact networks with modular and hierarchical structure. Therefore, we propose a hierarchical targeted immunization strategy to settle this problem. In this novel strategy, importance of the hierarchical structure is considered. Transmission control experiments of influenza H1N1 are carried out based on a modular and hierarchical network model. Results obtained indicate that hierarchical structure of the network is more critical than the degrees of the immunized targets and the modular network layer is the most important for the epidemic propagation control. Finally, the efficacy and stability of this novel immunization strategy have been validated as well.

  14. HDAC2 deregulation in tumorigenesis is causally connected to repression of immune modulation and defense escape

    PubMed Central

    Conte, Mariarosaria; Dell'Aversana, Carmela; Benedetti, Rosaria; Petraglia, Francesca; Carissimo, Annamaria; Petrizzi, Valeria Belsito; D'Arco, Alfonso Maria; Abbondanza, Ciro; Nebbioso, Angela; Altucci, Lucia

    2015-01-01

    Histone deacetylase 2 (HDAC2) is overexpressed or mutated in several disorders such as hematological cancers, and plays a critical role in transcriptional regulation, cell cycle progression and developmental processes. Here, we performed comparative transcriptome analyses in acute myeloid leukemia to investigate the biological implications of HDAC2 silencing versus its enzymatic inhibition using epigenetic-based drug(s). By gene expression analysis of HDAC2-silenced vs wild-type cells, we found that HDAC2 has a specific role in leukemogenesis. Gene expression profiling of U937 cell line with or without treatment of the well-known HDAC inhibitor vorinostat (SAHA) identifies and characterizes several gene clusters where inhibition of HDAC2 ‘mimics’ its silencing, as well as those where HDAC2 is selectively and exclusively regulated by HDAC2 protein expression levels. These findings may represent an important tool for better understanding the mechanisms underpinning immune regulation, particularly in the study of major histocompatibility complex class II genes. PMID:25473896

  15. Beyond TLR SignalingThe Role of SARM in Antiviral Immune Defense, Apoptosis & Development.

    PubMed

    Panneerselvam, Porkodi; Ding, Jeak Ling

    2015-01-01

    SARM (Sterile alpha and armadillo motif-containing protein) is the recently identified TIR domain-containing cytosolic protein. Classified as a member of the TLR adaptor family, the multiple locations and functions of SARM (sometimes playing opposing roles), provoke an enigma on its biology. Although originally assumed to be a member of the TLR adaptor family (functioning as a negative regulator of TLR signaling pathway), latest findings indicate that SARM regulates signaling differently from other TLR adaptor proteins. Recent studies have highlighted the significant functional role of SARM in mediating apoptosis and antiviral innate immune response. In this review, we provide an update on the evolutionary conservation, spatial distribution, and regulated expression of SARM to highlight its diverse functional roles. The review will summarize findings on the known interacting partners of SARM and provide analogy on how they add new dimensions to the current understanding on the multifaceted roles of SARM in antiviral activities and apoptotic functions. In addition, we provide a future perspective on the roles of SARM in differentiation and development, with substantial emphasis on the molecular insights to its mechanisms of action. PMID:26268046

  16. HDAC2 deregulation in tumorigenesis is causally connected to repression of immune modulation and defense escape.

    PubMed

    Conte, Mariarosaria; Dell'Aversana, Carmela; Benedetti, Rosaria; Petraglia, Francesca; Carissimo, Annamaria; Petrizzi, Valeria Belsito; D'Arco, Alfonso Maria; Abbondanza, Ciro; Nebbioso, Angela; Altucci, Lucia

    2015-01-20

    Histone deacetylase 2 (HDAC2) is overexpressed or mutated in several disorders such as hematological cancers, and plays a critical role in transcriptional regulation, cell cycle progression and developmental processes. Here, we performed comparative transcriptome analyses in acute myeloid leukemia to investigate the biological implications of HDAC2 silencing versus its enzymatic inhibition using epigenetic-based drug(s). By gene expression analysis of HDAC2-silenced vs wild-type cells, we found that HDAC2 has a specific role in leukemogenesis. Gene expression profiling of U937 cell line with or without treatment of the well-known HDAC inhibitor vorinostat (SAHA) identifies and characterizes several gene clusters where inhibition of HDAC2 'mimics' its silencing, as well as those where HDAC2 is selectively and exclusively regulated by HDAC2 protein expression levels. These findings may represent an important tool for better understanding the mechanisms underpinning immune regulation, particularly in the study of major histocompatibility complex class II genes. PMID:25473896

  17. Immune defence strategies of generalist and specialist insect herbivores.

    PubMed

    Barthel, Andrea; Kopka, Isabell; Vogel, Heiko; Zipfel, Peter; Heckel, David G; Groot, Astrid T

    2014-08-01

    Ecological immunology examines the adaptive responses of animals to pathogens in relation to other environmental factors and explores the consequences of trade-offs between investment in immune function and other life-history traits. Among species of herbivorous insects, diet breadth may vary greatly, with generalists consuming a wide variety of plant families and specialists restricted to a few species. Generalists may thus be exposed to a wider range of pathogens exerting stronger selection on the innate immune system. To examine whether this produces an increase in the robustness of the immune response, we compared larvae of the generalist herbivore Heliothis virescens and the specialist Heliothis subflexa challenged by entomopathogenic and non-pathogenic bacteria. Heliothis virescens larvae showed lower mortality, a lower number of recoverable bacteria, lower proliferation of haemocytes and higher phagocytic activity. These results indicate a higher tolerance to entomopathogenic bacteria by the generalist, which is associated with a more efficient cell-mediated immune response by mechanisms that differ between these closely related species. Our findings provide novel insights into the consequences of diet breadth and related environmental factors, which may be significant in further studies to understand the ecological forces and investment trade-offs that shape the evolution of innate immunity. PMID:24943370

  18. Comparative analysis of the effectiveness of three immunization strategies in controlling disease outbreaks in realistic social networks.

    PubMed

    Xu, Zhijing; Zu, Zhenghu; Zheng, Tao; Zhang, Wendou; Xu, Qing; Liu, Jinjie

    2014-01-01

    The high incidence of emerging infectious diseases has highlighted the importance of effective immunization strategies, especially the stochastic algorithms based on local available network information. Present stochastic strategies are mainly evaluated based on classical network models, such as scale-free networks and small-world networks, and thus are insufficient. Three frequently referred stochastic immunization strategies-acquaintance immunization, community-bridge immunization, and ring vaccination-were analyzed in this work. The optimal immunization ratios for acquaintance immunization and community-bridge immunization strategies were investigated, and the effectiveness of these three strategies in controlling the spreading of epidemics were analyzed based on realistic social contact networks. The results show all the strategies have decreased the coverage of the epidemics compared to baseline scenario (no control measures). However the effectiveness of acquaintance immunization and community-bridge immunization are very limited, with acquaintance immunization slightly outperforming community-bridge immunization. Ring vaccination significantly outperforms acquaintance immunization and community-bridge immunization, and the sensitivity analysis shows it could be applied to controlling the epidemics with a wide infectivity spectrum. The effectiveness of several classical stochastic immunization strategies was evaluated based on realistic contact networks for the first time in this study. These results could have important significance for epidemic control research and practice. PMID:24787718

  19. A novel ortholog of serum response factor (SRF) with immune defense function identified in Crassostrea hongkongensis.

    PubMed

    Xiang, Zhiming; Qu, Fufa; Qi, Lin; Zhang, Yang; Xiao, Shu; Yu, Ziniu

    2014-01-01

    Serum response factor (SRF) function is essential for transcriptional regulation of numerous growth-factor-inducible genes and triggers proliferation, differentiation and apoptosis of the cells. In this report, the first mollusk serum response factor like homolog gene (designated ChSRF) was identified and characterized from the Hong Kong oyster, Crassostrea hongkongensis. The full-length cDNA of ChSRF was 1716bp in length and encodes a putative protein of 434 amino acids respectively, and shares the MADS domain at the N-terminal. ChSRF is ubiquitously expressed in various tissues, with the highest expression level observed in muscle. Temporal expression of ChSRF following microbe infection shows that the expression of ChSRF in hemocytes increases from 3 to 24h post-challenge. As a target gene of SRF, ?-actin demonstrates a similar gene expression mode in constitutive tissue and pathogen infection. Furthermore, some protein profiles of ChSRF was revealed, fluorescence microscopy results show that ChSRF located in the nuclei of HeLa cells and over-expression of ChSRF activated the transcriptional activities of MAPK signal pathway in HEK293T cells. These results indicate that ChSRF maybe play an important role in signal transduction in the immunity and development response of oysters. Furthermore, we found that ChSRF could regulate the expression of ?-actin gene, which indicate that ChSRF is a muscle differentiation regulator in the oyster and it will help us to improve aquaculture production. PMID:24161761

  20. The identification of the first molluscan Akirin2 with immune defense function in the Hong Kong oyster Crassostrea hongkongensis.

    PubMed

    Qu, Fufa; Xiang, Zhiming; Zhang, Yang; Li, Jun; Zhang, Yuehuan; Yu, Ziniu

    2014-12-01

    The Akirin protein is a nuclear factor in the innate immune system that is highly conserved from insects to mammals and plays key roles in diverse biological processes, including immunity, myogenesis, development and the cellular stress response. However, the function of Akirins in mollusk, the second most diverse group of animals, is still poorly understood. In this study, we report the discovery of an Akirin2 gene homolog (ChAkirin2) and its biological functions in the Hong Kong oyster Crassostrea hongkongensis. ChAkirin2 is 189 amino acids in length and shares significant homology with invertebrate homologs. Phylogenetic analysis results revealed that ChAkirin2 is clustered with invertebrate Akirin2s. A sequence analysis of the 5' flanking regions of ChAkirin2 indicated that it harbors several potential PAMP-activated transcription factor binding sites (TFB), including sites for NF-?B, C/EBP?, AP-1, SRF, Oct-1 and GATA-1. An RT-PCR analysis showed that ChAkirin2 mRNA was ubiquitously expressed in various tissues and at different embryonic and larval stages. Additionally, upon infection by pathogens (Vibrio alginolyticus, Staphylococcus haemolyticus and Saccharomyces cerevisiae) and pathogen-associated molecular patterns (PAMPs: LPS, PGN and polyI:C), the expression of ChAkirin2 was significantly up-regulated. Moreover, fluorescence microscopy observations show that ChAkirin2 is located in the nuclei of HeLa cells, and the overexpression of ChAkirin2 activated the transcriptional activities of the NF-?B reporter gene in HEK293T cells. Altogether, this report provided the first experimental demonstration that mollusks possess a functional Akirin2 that is involved in the innate defense and embryogenesis processes of the oyster. PMID:25284180

  1. A thymosin beta-4 is involved in production of hemocytes and immune defense of Hong Kong oyster, Crassostrea hongkongensis.

    PubMed

    Li, Jun; Zhang, Yuehuan; Liu, Ying; Zhang, Yang; Xiang, Zhiming; Qu, Fufa; Yu, Ziniu

    2016-04-01

    Thymosin beta-4 (Tβ4) is a ubiquitous protein with multiple and diverse intracellular and extracellular functions in vertebrates. In this study, the full-length cDNA of Tβ4 was cloned and identified in Crassostrea hongkongensis, designated as ChTβ4. The full-length cDNA of ChTβ4 consists of 530 bp with an open reading frame of 126 bp encoding a 41 amino acid polypeptide. SMART analysis indicated that there is one thymosin domain and a highly conserved actin-binding motif (18LKKTET23) in ChTβ4. In vivo injection of recombinant ChTβ4 protein could significantly increase total hemocytes count in oysters, and knockdown of the expression of ChTβ4 resulted in a significant decrease in the circulating hemocytes. Tissue distribution analysis revealed a ubiquitous presence of ChTβ4, with the highest expression in hemocytes. The upregulated transcripts of ChTβ4 in response to bacterial challenge and tissue injury suggest that ChTβ4 is involved in both innate immunity against pathogen infection and wound healing. Moreover, bacteria-clearance experiment showed ChTβ4 could facilitate the clearance of injected bacteria in oysters. In vivo injection with ChTβ4 resulted in reduction of the intracellular ROS in hemocytes, which was associated with increased expression of antioxidant enzymes Cu/Zn superoxide dismutase (SOD), Catalase, and Glutathione Peroxidase (GPX) by pre-treatment with ChTβ4. These results suggest that ChTβ4 is a thymosin beta-4 homolog and plays a vital role in the immune defense of C. hongkongensis. PMID:26695126

  2. The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypes

    PubMed Central

    Ramirez, Jose L.; Dimopoulos, George

    2010-01-01

    Dengue virus has become one of the most important arboviral pathogens affecting the world today. The virus is transmitted among humans by the mosquitoes Aedes aegypti and Ae. albopictus. Like other vector-borne pathogens, this virus encounters innate immune defenses within the mosquito vector that limit infection. We have previously demonstrated the involvement of the Toll pathway in the anti-dengue defense at 7 days after infection. In the present study, we have investigated the activity of this immune signaling pathway against different dengue virus serotypes at the early stages of infection in laboratory and field-derived mosquito strains. Our studies corroborate the importance of the Toll pathway in the anti-dengue defense repertoire at 3 days after an infectious blood meal, when new virions are released from the midgut for dissemination and infection of other mosquito tissues. These immune defenses are furthermore conserved among different Ae. aegypti strains and can act against a broad range of dengue virus serotypes. PMID:20079370

  3. Strategies to potentiate immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.

    2015-03-01

    Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not yet advanced to a mainstream cancer treatment. Although PDT has been shown to be an efficient photochemical way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT a great potential to become more widely used. Although the stimulation of tumorspecific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. Some of these combination approaches use immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen associated molecular patterns. Other approaches use cytokines and growth factors whether directly administered or genetically encoded. Other promising approaches involve depleting regulatory T-cells and epigenetic reversal agents. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised.

  4. The Cnes2 locus on mouse chromosome 17 regulates host defense against cryptococcal infection through pleiotropic effects on host immunity.

    PubMed

    Shourian, Mitra; Flaczyk, Adam; Angers, Isabelle; Mindt, Barbara C; Fritz, Jrg H; Qureshi, Salman T

    2015-12-01

    The genetic basis of natural susceptibility to progressive Cryptococcus neoformans infection is not well understood. Using C57BL/6 and CBA/J inbred mice, we previously identified three chromosomal regions associated with C. neoformans susceptibility (Cnes1, Cnes2, and Cnes3). To validate and characterize the role of Cnes2 during the host response, we constructed a congenic strain on the C57BL/6 background (B6.CBA-Cnes2). Phenotypic analysis of B6.CBA-Cnes2 mice 35 days after C. neoformans infection showed a significant reduction of fungal burden in the lungs and spleen with higher pulmonary expression of gamma interferon (IFN-?) and interleukin-12 (IL-12), lower expression of IL-4, IL-5, and IL-13, and an absence of airway epithelial mucus production compared to that in C57BL/6 mice. Multiparameter flow cytometry of infected lungs also showed a significantly higher number of neutrophils, exudate macrophages, CD11b(+) dendritic cells, and CD4(+) cells in B6.CBA-Cnes2 than in C57BL/6 mice. The activation state of recruited macrophages and dendritic cells was also significantly increased in B6.CBA-Cnes2 mice. Taken together, these findings demonstrate that the Cnes2 interval is a potent regulator of host defense, immune responsiveness, and differential Th1/Th2 polarization following C. neoformans infection. PMID:26371125

  5. The First Line of Defense: The Effects of Alcohol on Post-Burn Intestinal Barrier, Immune Cells, and Microbiome.

    PubMed

    Hammer, Adam M; Morris, Niya L; Earley, Zachary M; Choudhry, Mashkoor A

    2015-01-01

    Alcohol (ethanol) is one of the most globally abused substances, and is one of the leading causes of premature death in the world. As a result of its complexity and direct contact with ingested alcohol, the intestine represents the primary source from which alcohol-associated pathologies stem. The gut is the largest reservoir of bacteria in the body, and under healthy conditions, it maintains a barrier preventing bacteria from translocating out of the intestinal lumen. The intestinal barrier is compromised following alcohol exposure, which can lead to life-threatening systemic complications including sepsis and multiple organ failure. Furthermore, alcohol is a major confounding factor in pathology associated with trauma. Experimental data from both human and animal studies suggest that alcohol perturbs the intestinal barrier and its function, which is exacerbated by a "second hit" from traumatic injury. This article highlights the role of alcohol-mediated alterations of the intestinal epithelia and its defense against bacteria within the gut, and the impact of alcohol on intestinal immunity, specifically on T cells and neutrophils. Finally, it discusses how the gut microbiome both contributes to and protects the intestines from dysbiosis after alcohol exposure and trauma. PMID:26695746

  6. Death Concerns in Differential Levels of Consciousness as Functions of Defense Strategy and Religious Belief.

    ERIC Educational Resources Information Center

    Rosenheim, Eliyahu; Muchnik, Benjamin

    1985-01-01

    Explores the relationships between defensive style (repression-sensitization) and Jewish religiosity and death concerns in the context of differential levels of awareness of 64 Israeli students. Found that the personality attribute of defensive style was linked systematically to death concern at all levels of consciousness. Religiosity was less

  7. AtNUDT7, a negative regulator of basal immunity in Arabidopsis, modulates two distinct defense response pathways and is involved in maintaining redox homeostasis.

    PubMed

    Ge, Xiaochun; Li, Guo-Jing; Wang, Sheng-Bing; Zhu, Huifen; Zhu, Tong; Wang, Xun; Xia, Yiji

    2007-09-01

    Plants have evolved complicated regulatory systems to control immune responses. Both positive and negative signaling pathways interplay to coordinate development of a resistance response with the appropriate amplitude and duration. AtNUDT7, a Nudix domain-containing protein in Arabidopsis (Arabidopsis thaliana) that hydrolyzes nucleotide derivatives, was found to be a negative regulator of the basal defense response, and its loss-of-function mutation results in enhanced resistance to infection by Pseudomonas syringae. The nudt7 mutation does not cause a strong constitutive disease resistance phenotype, but it leads to a heightened defense response, including accelerated activation of defense-related genes that can be triggered by pathogenic and nonpathogenic microorganisms. The nudt7 mutation enhances two distinct defense response pathways: one independent of and the other dependent on NPR1 and salicylic acid accumulation. In vitro enzymatic assays revealed that ADP-ribose and NADH are preferred substrates of NUDT7, and the hydrolysis activity of NUDT7 is essential for its biological function and is sensitive to inhibition by Ca(2+). Further analyses indicate that ADP-ribose is not likely the physiological substrate of NUDT7. However, the nudt7 mutation leads to perturbation of cellular redox homeostasis and a higher level of NADH in pathogen-challenged leaves. The study suggests that the alteration in cellular antioxidant status caused by the nudt7 mutation primes the cells for the amplified defense response and NUDT7 functions to modulate the defense response to prevent excessive stimulation. PMID:17660350

  8. Sebum free fatty acids enhance the innate immune defense of human sebocytes by upregulating beta-defensin-2 expression.

    PubMed

    Nakatsuji, Teruaki; Kao, Mandy C; Zhang, Liangfang; Zouboulis, Christos C; Gallo, Richard L; Huang, Chun-Ming

    2010-04-01

    Various sebum free fatty acids (FFAs) have shown antibacterial activity against a broad range of gram-positive bacteria, resulting in the suggestion that they are accountable, at least partially, for the direct antimicrobial activity of the skin surface. In this study, we examined the effects of sebum FFAs on the antimicrobial peptide (AMP)-mediated innate immune defense of human sebocytes. Incubation of lauric acid, palmitic acid, or oleic acid (OA) with human sebocytes dramatically enhanced their expression of human beta-defensin (hBD)-2, one of the predominant AMPs found in the skin, whereas remarkable increases in hBD-1, hBD-3, and human cathelicidin LL-37 were not observed. Secreted hBD-2 was detectable by western blotting in the supernatant of sebocyte culture incubated with each FFA, but not with a vehicle control. The supernatant of FFA-incubated sebocyte culture showed antimicrobial activity against Propionibacterium acnes, whereas the enhanced antimicrobial activity of human sebocytes was neutralized by anti-hBD-2 IgG. In addition, the FFA-induced hBD-2 expression was suppressed by blocking the cluster of differentiation (CD)36 fatty acid translocase on the surface of sebocytes with anti-human CD36 IgG or blocking the NF-kappaB signaling pathway with BMS-345541, a highly selective inhibitor of inhibitory kappaB kinase. These data suggest that sebum FFAs upregulate the expression of hBD-2 in human sebocytes, which may enhance the disinfecting activity of the human sebaceous gland. The FFA-induced upregulation of hBD-2 is facilitated by CD36-mediated FFA uptake and NF-kappaB-mediated transactivation. The upregulation of mouse beta-defensin 4, a mouse ortholog for hBD-2, was also observed in the hair follicle sebaceous glands of mouse ear skin after an epicutaneous application of OA, the most hBD-2-inducible FFA tested. This report highlights the potential of using FFAs as a multifunctional antimicrobial therapy agent for acne vulgaris treatment; FFAs may provide direct antibacterial activities against P. acnes and enhance the skin's innate antibacterial defense by inducing the expression of hBD-2 in sebocytes as well. PMID:20032992

  9. Shell colour polymorphism, injuries and immune defense in three helicid snail species, Cepaea hortensis, Theba pisana and Cornu aspersummaximum?

    PubMed Central

    Scheil, Alexandra E.; Hilsmann, Stefanie; Triebskorn, Rita; Khler, Heinz-R.

    2013-01-01

    Shell colour polymorphism is a widespread feature of various land snail species. In our study we aimed at elucidating the question whether there is a correlation between shell colouration and immune defense in three land snail species by comparing phenoloxidase (PO) activity levels of different morphs after immunostimulation via Zymosan A-injection. Since phenoloxidase is involved both in immune defense as well as in melanin production, the PO activity level is particularly interesting when trying to resolve this question. Even though Zymosan A failed to induce PO activity rendering a comparison of inducible PO activity impossible, an interesting difference between pale and dark morphs of all tested species could be observed: dark snails were less affected by hemolymph withdrawal and were able to maintain or regenerate a significantly higher PO activity level after hemolymph withdrawal than pale snails. Possible implications of this observation are discussed. PMID:24600561

  10. A Scallop Nitric Oxide Synthase (NOS) with Structure Similar to Neuronal NOS and Its Involvement in the Immune Defense

    PubMed Central

    Jiang, Qiufen; Zhou, Zhi; Wang, Leilei; Wang, Lingling; Yue, Feng; Wang, Jingjing; Song, Linsheng

    2013-01-01

    Background Nitric oxide synthase (NOS) is responsible for synthesizing nitric oxide (NO) from L-arginine, and involved in multiple physiological functions. However, its immunological role in mollusc was seldom reported. Methodology In the present study, an NOS (CfNOS) gene was identified from the scallop Chlamys farreri encoding a polypeptide of 1486 amino acids. Its amino acid sequence shared 50.0~54.7, 40.7~47.0 and 42.5~44.5% similarities with vertebrate neuronal (n), endothelial (e) and inducible (i) NOSs, respectively. CfNOS contained PDZ, oxygenase and reductase domains, which resembled those in nNOS. The CfNOS mRNA transcripts expressed in all embryos and larvae after the 2-cell embryo stage, and were detectable in all tested tissues with the highest level in the gonad, and with the immune tissues hepatopancreas and haemocytes included. Moreover, the immunoreactive area of CfNOS distributed over the haemocyte cytoplasm and cell membrane. After LPS, ?-glucan and PGN stimulation, the expression level of CfNOS mRNA in haemocytes increased significantly at 3 h (4.0-, 4.8- and 2.7-fold, respectively, P < 0.01), and reached the peak at 12 h (15.3- and 27.6-fold for LPS and ?-glucan respectively, P < 0.01) and 24 h (17.3-fold for PGN, P < 0.01). In addition, TNF-? also induced the expression of CfNOS, which started to increase at 1 h (5.2-fold, P < 0.05) and peaked at 6 h (19.9-fold, P < 0.01). The catalytic activity of the native CfNOS protein was 30.3 0.3 U mgprot-1, and it decreased significantly after the addition of the selective inhibitors of nNOS and iNOS (26.9 0.4 and 29.3 0.1 U mgprot-1, respectively, P < 0.01). Conclusions These results suggested that CfNOS, with identical structure with nNOS and similar enzymatic characteristics to nNOS and iNOS, played the immunological role of iNOS to be involved in the scallop immune defense against PAMPs and TNF-?. PMID:23922688

  11. Strategies and challenges in eliciting immunity to melanoma

    PubMed Central

    Ferguson, Andrew R.; Nichols, Lisa A.; Zarling, Angela L.; Thompson, Elizabeth D.; Brinkman, Colin C.; Hargadon, Kristian M.; Bullock, Timothy N.; Engelhard, Victor H.

    2010-01-01

    Summary The ability of CD8 T cells to recognize melanoma tumors has led to the development of immunotherapeutic approaches that use the antigens CD8 T cells recognize. However, clinical responses rates have been disappointing. Here we summarize our work to understand the mechanisms of self-tolerance that limit responses to currently utilized antigens, and our approach to identify new antigens directly tied to malignancy. We also explore several aspects of the anti-tumor immune response induced by peptide-pulsed dendritic cells. Dendritic cells differentially augment the low avidity of recall T cells specific for self-antigens, and overcome a process of aberrant CD8 T cell differentiation that occurs in tumor-draining lymph nodes. Dendritic cell migration is constrained by injection route, resulting in immune responses in localized lymphoid tissue, and differential control of tumors depending on their location in the body. We demonstrate that CD8 T cell differentiation in different lymphoid compartments alters the expression of homing receptor molecules and the presence of systemic central memory cells. Our studies highlight several issues that must be addressed to improve the efficacy of tumor immunotherapy. PMID:18363993

  12. Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

    PubMed

    Botelho, Danielle J; Leo, Bey Fen; Massa, Christopher B; Sarkar, Srijata; Tetley, Terry D; Chung, Kian Fan; Chen, Shu; Ryan, Mary P; Porter, Alexandra E; Zhang, Junfeng; Schwander, Stephan K; Gow, Andrew J

    2016-02-01

    Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered. PMID:26152688

  13. Bacterial evasion of host immune defense: Yersinia enterocolitica encodes a suppressor for tumor necrosis factor alpha expression.

    PubMed Central

    Beuscher, H U; Rödel, F; Forsberg, A; Röllinghoff, M

    1995-01-01

    The ability of the enteropathogenic Yersinia enterocolitica to survive and proliferate in host tissue depends on a 70-kb plasmid known to encode a number of released Yersinia outer proteins that act as virulence factors by inducing cytotoxicity and inhibiting phagocytosis. This study demonstrates that one of the Yersinia outer proteins, the 41-kDa YopB, suppresses the production of tumor necrosis factor alpha (TNF-alpha), a macrophage-derived cytokine with central roles in the regulation of immune and inflammatory responses to infection. This conclusion is based on several lines of evidence. First, in macrophage cultures, suppression of TNF-alpha mRNA expression was induced by culture supernatant (CS+) of plasmid-bearing yersiniae, the effect which was blocked by anti-YopB antiserum. Second, suppression of TNF-alpha production, but not of interleukin-1 (IL-1) and IL-6, was induced by purified YopB. Third, in Yersinia-infected mice, no increase in TNF-alpha mRNA expression was observed in Peyer's patches, the primary site of bacterial invasion, compared with IL-1 (alpha and beta) mRNA. Finally, administration of anti-YopB antiserum to mice prior to infection with Y. enterocolitica increased TNF activity levels in Peyer's patches and coincided with a reduction in bacterial growth. The results thus provide direct evidence for a secreted eubacterial virulence factor that mediates selective suppression of TNF-alpha production. Although suppression of this single cytokine response is probably not sufficient to facilitate survival of the infecting organisms, the results suggest that suppression of TNF-alpha production by YopB significantly contributes to the evasion of Y. enterocolitica from antibacterial host defense. PMID:7890384

  14. Nanovectorized radiotherapy: a new strategy to induce anti-tumor immunity

    PubMed Central

    Vanpouille-Box, Claire; Hindré, François

    2012-01-01

    Recent experimental findings show that activation of the host immune system is required for the success of chemo- and radiotherapy. However, clinically apparent tumors have already developed multiple mechanisms to escape anti-tumor immunity. The fact that tumors are able to induce a state of tolerance and immunosuppression is a major obstacle in immunotherapy. Hence, there is an overwhelming need to develop new strategies that overcome this state of immune tolerance and induce an anti-tumor immune response both at primary and metastatic sites. Nanovectorized radiotherapy that combines ionizing radiation and nanodevices, is one strategy that could boost the quality and magnitude of an immune response in a predictable and designable fashion. The potential benefits of this emerging treatment may be based on the unique combination of immunostimulatory properties of nanoparticles with the ability of ionizing radiation to induce immunogenic tumor cell death. In this review, we will discuss available data and propose that the nanovectorized radiotherapy could be a powerful new strategy to induce anti-tumor immunity required for positive patient outcome. PMID:23087900

  15. Adeno-associated virus (AAV) vectors in gene therapy: immune challenges and strategies to circumvent them.

    PubMed

    Hareendran, Sangeetha; Balakrishnan, Balaji; Sen, Dwaipayan; Kumar, Sanjay; Srivastava, Alok; Jayandharan, Giridhara R

    2013-11-01

    AAV-based gene transfer protocols have shown remarkable success when directed to immune-privileged sites such as for retinal disorders like Lebers congenital amaurosis. In contrast, AAV-mediated gene transfer into liver or muscle tissue for diseases such as hemophilia B, ?1 anti-trypsin deficiency and muscular dystrophy has demonstrated a decline in gene transfer efficacy over time. It is now known that in humans, AAV triggers specific pathways that recruit immune sensors. These factors initiate an immediate reaction against either the viral capsid or the vector encoded protein as part of innate immune response or to produce a more specific adaptive response that generates immunological memory. The vector-transduced cells are then rapidly destroyed due to this immune activation. However, unlike other viral vectors, AAV is not immunogenic in murine models. Its immunogenicity becomes apparent only in large animal models and human subjects. Moreover, humans are natural hosts to AAV and exhibit a high seroprevalence against AAV vectors. This limits the widespread application of AAV vectors into patients with pre-existing neutralising antibodies or memory T cells. To address these issues, various strategies are being tested. Alternate serotype vectors (AAV1-10), efficient expression cassettes, specific tissue targeting, immune-suppression and engineered capsid variants are some approaches proposed to minimise this immune stimulation. In this review, we have summarised the nature of the immune response documented against AAV in various pre-clinical and clinical settings and have further discussed the strategies to evade them. PMID:24023004

  16. Immune mechanisms of new therapeutic strategies in MS: teriflunomide.

    PubMed

    Claussen, Malte C; Korn, Thomas

    2012-01-01

    At present, a series of oral disease-modifying agents is being introduced for the treatment of multiple sclerosis. With the exception of laquinimod, the "new" oral compounds have already been approved for other indications such as organ transplantation (FTY720), psoriasis (dimethylfumarate), hairy cell leukemia (cladribine), and rheumatoid arthritis (leflunomide). Leflunomide is the prodrug of teriflunomide which is the latest compound that has successfully been tested in a large phase III clinical trial in relapsing MS. Due to its favorable safety profile and its efficacy in rheumatoid arthritis where the aberrant immune response is in various aspects similar to the autoimmune reaction in MS patients, teriflunomide is a promising treatment option for MS patients. Here, we review the most important cell biological and immunological modes of action of teriflunomide, report on the available data on its pharmacokinetics in humans, and summarize the recent clinical trials of teriflunomide in relapsing MS. PMID:21367665

  17. Dissemination strategy for immunizing scale-free networks

    NASA Astrophysics Data System (ADS)

    Stauffer, Alexandre O.; Barbosa, Valmir C.

    2006-11-01

    We consider the problem of distributing a vaccine for immunizing a scale-free network against a given virus or worm. We introduce a method, based on vaccine dissemination, that seems to reflect more accurately what is expected to occur in real-world networks. Also, since the dissemination is performed using only local information, the method can be easily employed in practice. Using a random-graph framework, we analyze our method both mathematically and by means of simulations. We demonstrate its efficacy regarding the trade-off between the expected number of nodes that receive the vaccine and the network’s resulting vulnerability to develop an epidemic as the virus or worm attempts to infect one of its nodes. For some scenarios, the method is seen to render the network practically invulnerable to attacks while requiring only a small fraction of the nodes to receive the vaccine.

  18. Interceptor-to-target allocation strategies for Strategic Defense I: adaptive strategies based upon system and threat characteristics. Final report, January-September 1987

    SciTech Connect

    Smith, M.E.; Paterson, T.S.

    1988-07-01

    This paper examines the topic of interceptor-to-target assignment algorithms and compares the system performance of a strategic defense system (SDS) as a function of the algorithm used. The algorithms used in this study range from being similar to some of those being developed under the SDIO's advanced-algorithm programs to those used in some of the more-popular engagement models. It is shown that the use of less-sophisticated algorithms can often lead to RV leakages twice as large compared to cases in which sophisticated algorithms are used. The primary conclusion from this paper is that as the defense becomes interceptor-rich and/or the Pk of the interceptor becomes low, the popular one-interceptor-per-target approaches to interceptor allocation, which are typically found in the community-wide engagement models, can perform poorly. When the defense is in either, or both, of these regimes, it can perform significantly better by adopting an approach in which the salvo becomes a credible strategy. Because the salvo strategies have not been implemented in the popular engagement models, the past analyses which have studied these types of architectures have been biased toward providing a lower level of performance. Interceptor allocation strategies for the midcourse and terminal phase are not analyzed in this paper.

  19. Mucosal Immune System and M Cell-targeting Strategies for Oral Mucosal Vaccination

    PubMed Central

    Kim, Sae-Hae; Lee, Kyung-Yeol

    2012-01-01

    Vaccination is one of the most effective methods available to prevent infectious diseases. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganisms, are one of the first areas where infections are established, and therefore have frontline status in immunity, making mucosa ideal sites for vaccine application. Moreover, vaccination through the mucosal immune system could induce effective systemic immune responses together with mucosal immunity in contrast to parenteral vaccination, which is a poor inducer of effective immunity at mucosal surfaces. Among mucosal vaccines, oral mucosal vaccines have the advantages of ease and low cost of vaccine administration. The oral mucosal immune system, however, is generally recognized as poorly immunogenic due to the frequent induction of tolerance against orally-introduced antigens. Consequently, a prerequisite for successful mucosal vaccination is that the orally introduced antigen should be transported across the mucosal surface into the mucosa-associated lymphoid tissue (MALT). In particular, M cells are responsible for antigen uptake into MALT, and the rapid and effective transcytotic activity of M cells makes them an attractive target for mucosal vaccine delivery, although simple transport of the antigen into M cells does not guarantee the induction of specific immune responses. Consequently, development of mucosal vaccine adjuvants based on an understanding of the biology of M cells has attracted much research interest. Here, we review the characteristics of the oral mucosal immune system and delineate strategies to design effective oral mucosal vaccines with an emphasis on mucosal vaccine adjuvants. PMID:23213309

  20. Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-κB and MAPK signaling.

    PubMed

    Philip, Naomi H; Dillon, Christopher P; Snyder, Annelise G; Fitzgerald, Patrick; Wynosky-Dolfi, Meghan A; Zwack, Erin E; Hu, Baofeng; Fitzgerald, Louise; Mauldin, Elizabeth A; Copenhaver, Alan M; Shin, Sunny; Wei, Lei; Parker, Matthew; Zhang, Jinghui; Oberst, Andrew; Green, Douglas R; Brodsky, Igor E

    2014-05-20

    Toll-like receptor signaling and subsequent activation of NF-κB- and MAPK-dependent genes during infection play an important role in antimicrobial host defense. The YopJ protein of pathogenic Yersinia species inhibits NF-κB and MAPK signaling, resulting in blockade of NF-κB-dependent cytokine production and target cell death. Nevertheless, Yersinia infection induces inflammatory responses in vivo. Moreover, increasing the extent of YopJ-dependent cytotoxicity induced by Yersinia pestis and Yersinia pseudotuberculosis paradoxically leads to decreased virulence in vivo, suggesting that cell death promotes anti-Yersinia host defense. However, the specific pathways responsible for YopJ-induced cell death and how this cell death mediates immune defense against Yersinia remain poorly defined. YopJ activity induces processing of multiple caspases, including caspase-1, independently of inflammasome components or the adaptor protein ASC. Unexpectedly, caspase-1 activation in response to the activity of YopJ required caspase-8, receptor-interacting serine/threonine kinase 1 (RIPK1), and Fas-associated death domain (FADD), but not RIPK3. Furthermore, whereas RIPK3 deficiency did not affect YopJ-induced cell death or caspase-1 activation, deficiency of both RIPK3 and caspase-8 or FADD completely abrogated Yersinia-induced cell death and caspase-1 activation. Mice lacking RIPK3 and caspase-8 in their hematopoietic compartment showed extreme susceptibility to Yersinia and were deficient in monocyte and neutrophil-derived production of proinflammatory cytokines. Our data demonstrate for the first time to our knowledge that RIPK1, FADD, and caspase-8 are required for YopJ-induced cell death and caspase-1 activation and suggest that caspase-8-mediated cell death overrides blockade of immune signaling by YopJ to promote anti-Yersinia immune defense. PMID:24799700

  1. A VACCINE STRATEGY THAT INDUCES PROTECTIVE IMMUNITY AGAINST HEROIN

    PubMed Central

    Stowe, G. Neil; Vendruscolo, Leandro F.; Edwards, Scott; Schlosburg, Joel E.; Misra, Kaushik K.; Schulteis, Gery; Mayorov, Alexander V.; Zakhari, Joseph S.; Koob, George F.; Janda, Kim D.

    2011-01-01

    Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target as it is metabolized to multiple psychoactive molecules. To reconcile this dilemma we examined the idea of a singular vaccine with the potential to display multiple drug-like antigens; thus two haptens were synthesized, one heroin-like and another morphine-like in chemical structure. A key feature in this approach is that immunopresentation with the heroin-like hapten is thought to be immunochemically dynamic such that multiple haptens are simultaneously presented to the immune system. We demonstrate the significance of this approach though the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity. Importantly, both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten. PMID:21692508

  2. Charting Immune Signaling Proteomes En Route to New Therapeutic Strategies.

    PubMed

    Haura, Eric B; Beg, Amer A; Rix, Uwe; Antonia, Scott

    2015-07-01

    The activation state of an antitumor effector T cell in a tumor depends on the sum of all stimulatory signals and inhibitory signals that it receives in the tumor microenvironment. Accumulating data address the increasing complexity of these signals produced by a myriad of immune checkpoint molecules, cytokines, and metabolites. While reductionist experiments have identified key molecules and their importance in signaling, less clear is the integration of all these signals that allows T cells to guide their responses in health and in disease. Mass spectrometry-based proteomics is well poised to offer such insights, including monitoring emergence of resistance mechanisms to immunotherapeutics during treatments. A major application of this technology is in the discovery and characterization of small-molecule agents capable of enhancing the response to immunotherapeutic agents. Such an approach would reinvigorate small-molecule drug development aimed not at tumor cells but rather at tumor-resident T cells capable of producing dramatic and durable antitumor responses. PMID:26081226

  3. Strategies To Boost Maternal Immunization To Achieve Further Gains In Improved Maternal And Newborn Health.

    PubMed

    Steedman, Mark R; Kampmann, Beate; Schillings, Egbert; Al Kuwari, Hanan; Darzi, Ara

    2016-02-01

    Despite the indisputable successes of the United Nations Millennium Development Goals, which include goals on improving maternal health and reducing child mortality, millions of mothers and newborns still die tragically and unnecessarily each year. Many of these deaths result from vaccine-preventable diseases, since obstacles such as cost and accessibility have hampered efforts to deliver efficacious vaccines to those most in need. Additionally, many vaccines given to mothers and children under age five are not suitable for newborns, since their maturing immune systems do not respond optimally during the first few months of life. Maternal immunization-the process by which a pregnant woman's immune system is fortified against a particular disease and the protection is then transferred to her unborn child-has emerged as a strategy to prevent many unnecessary maternal and newborn deaths. We review vaccines that are already used for maternal immunization, analyze vaccines under development that could be used for maternal immunization strategies in the future, and recommend that policy makers use maternal immunization for improved maternal and newborn health. PMID:26858385

  4. Comparative study of out-reach immunization strategies in rural area.

    PubMed

    Kumar, R; Khosla, R K; Kumar, V

    1990-11-01

    Efficiency of out-reach immunization strategies operationalised in a rural area of district Ambala (Haryana) was evaluated. Till year 1984-85 immunization delivery was 'sporadic'. Annual cluster immunization campaigns were conducted during 1985-86 and 1986-87. This comprised of delivery of oral polio vaccine (OPV) and/or measles once in a year to all eligible children, other vaccine continued to be delivered by health workers during routine beats. Regular immunization sessions were undertaken in 1987-88 and 1988-89. All the vaccines were delivered on 4 fixed days (one day per week) of each month, covering village at least once a month. Significant increase in immunization coverage was observed after cluster campaigns. OPV increased from 46.5 to 73.6%, DPT from 49.1 to 75.5%, BCG from 48.7 to 72.2%, measles from 8.6 to 45.8% and tetanus toxoid (TT) for pregnant women (PW) from 41.8 to 65.3%. Under regular programme the coverage levels were maintained at OPV 79.4%, DPT 78.2%, BCG 70.6%, measles 48% and TT (PW) 76.2%. Regular out-reach immunization strategy was found to be better than cluster campaigns as it was 'regular' and high coverage level could be maintained. PMID:2081638

  5. Controlled release strategies for modulating immune responses to promote tissue regeneration.

    PubMed

    Dumont, Courtney M; Park, Jonghyuck; Shea, Lonnie D

    2015-12-10

    Advances in the field of tissue engineering have enhanced the potential of regenerative medicine, yet the efficacy of these strategies remains incomplete, and is limited by the innate and adaptive immune responses. The immune response associated with injury or disease combined with that mounted to biomaterials, transplanted cells, proteins, and gene therapies vectors can contribute to the inability to fully restore tissue function. Blocking immune responses such as with anti-inflammatory or immunosuppressive agents are either ineffective, as the immune response contributes significantly to regeneration, or have significant side effects. This review describes targeted strategies to modulate the immune response in order to limit tissue damage following injury, promote an anti-inflammatory environment that leads to regeneration, and induce antigen (Ag)-specific tolerance that can target degenerative diseases that destroy tissues and promote engraftment of transplanted cells. Focusing on targeted immuno-modulation, we describe local delivery techniques to sites of inflammation as well as systemic approaches that preferentially target subsets of immune populations. PMID:26264833

  6. Seasonality influences cuticle melanization and immune defense in a cricket: support for a temperature-dependent immune investment hypothesis in insects

    SciTech Connect

    Fedorka, K. M.; Copeland, E. K.; Winterhalter, W. E.

    2013-07-18

    To improve thermoregulation in colder environments, insects are expected to darken their cuticles with melanin via the phenoloxidase cascade, a phenomenon predicted by the thermal melanin hypothesis. However, the phenoloxidase cascade also plays a significant role in insect immunity, leading to the additional hypothesis that the thermal environment indirectly shapes immune function via direct selection on cuticle color. Support for the latter hypothesis comes from the cricket Allonemobius socius, where cuticle darkness and immune-related phenoloxidase activity increase with latitude. However, thermal environments vary seasonally as well as geographically, suggesting that seasonal plasticity in immunity may also exist. Although seasonal fluctuations in vertebrate immune function are common (because of flux in breeding or resource abundance), seasonality in invertebrate immunity has not been widely explored. We addressed this possibility by rearing crickets in simulated summer and fall environments and assayed their cuticle color and immune function. Prior to estimating immunity, crickets were placed in a common environment to minimize metabolic rate differences. Individuals reared under fall-like conditions exhibited darker cuticles, greater phenoloxidase activity and greater resistance to the bacteria Serratia marcescens. These data support the hypothesis that changes in the thermal environment modify cuticle color, which indirectly shapes immune investment through pleiotropy. This hypothesis may represent a widespread mechanism governing immunity in numerous systems, considering that most insects operate in seasonally and geographically variable thermal environments.

  7. Mucosal and systemic immune responses induced by a single time vaccination strategy in mice.

    PubMed

    Gonzlez Aznar, Elizabeth; Romeu, Belkis; Lastre, Miriam; Zayas, Caridad; Cuello, Maribel; Cabrera, Osmir; Valdez, Yolanda; Farias, Mildrey; Prez, Oliver

    2015-08-01

    Vaccination is considered by the World Health Organization as the most cost-effective strategy for controlling infectious diseases. In spite of great successes with vaccines, many infectious diseases are still leading killers, because of the inadequate coverage of many vaccines. Several factors have been responsible: number of doses, high vaccine reactogenicity, vaccine costs, vaccination policy, among others. Contradictorily, few vaccines are of single dose and even less of mucosal administration. However, more common infections occur via mucosa, where secretory immunoglobulin A plays an essential role. As an alternative, we proposed a novel protocol of vaccination called Single Time Vaccination Strategy (SinTimVaS) by immunizing 2 priming doses at the same time: one by mucosal route and the other by parenteral route. Here, the mucosal and systemic responses induced by Finlay adjuvants (AF Proteoliposome 1 and AF Cochleate 1) implementing SinTimVaS in BALB/c mice were evaluated. One intranasal dose of AF Cochleate 1 and an intramuscular dose of AF Proteoliposome 1 adsorbed onto aluminum hydroxide, with bovine serum albumin or tetanus toxoid as model antigens, administrated at the same time, induced potent specific mucosal and systemic immune responses. Also, we demonstrated that SinTimVaS using other mucosal routes like oral and sublingual, in combination with the subcutaneous route elicits immune responses. SinTimVaS, as a new immunization strategy, could increase vaccination coverage and reduce time-cost vaccines campaigns, adding the benefits of immune response in mucosa. PMID:26140382

  8. 75 FR 8272 - Defense Federal Acquisition Regulation Supplement; Acquisition Strategies To Ensure Competition...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... Defense Federal Acquisition Regulation Supplement (DFARS) to implement the Weapon Systems Acquisition..., 2009, The Weapon Systems Acquisition Reform Act (Pub. L. 111-23) was enacted to improve the organization and procedures of DoD for the acquisition of major weapon systems. This law establishes...

  9. Strategies to accelerate immune recovery after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Lucarelli, Barbarella; Merli, Pietro; Bertaina, Valentina; Locatelli, Franco

    2016-03-01

    The interplay existing between immune reconstitution and patient outcome has been extensively demonstrated in allogeneic hematopoietic stem cell transplantation. One of the leading causes of infection-related mortality is the slow recovery of T-cell immunity due to the conditioning regimen and/or age-related thymus damage, poor nave T-cell output, and restricted T-cell receptor (TCR) repertoires. With the aim of improving posttransplantation immune reconstitution, several immunotherapy approaches have been explored. Donor leukocyte infusions are widely used to accelerate immune recovery, but they carry the risk of provoking graft-versus-host disease. This review will focus on sophisticated strategies of thymus function-recovery, adoptive infusion of donor-derived, allodepleted T cells, T-cell lines/clones specific for life-threatening pathogens, regulatory T cells, and of T cells transduced with suicide genes. PMID:26588325

  10. Replicating viral vectors for cancer therapy: strategies to synergize with host immune responses

    PubMed Central

    Altomonte, Jennifer; Ebert, Oliver

    2012-01-01

    Summary Tumour‐specific replicating (oncolytic) viruses are novel anticancer agents, currently under intense investigation in preclinical studies and phase I–III clinical trials. Until recently, most studies have focused on the direct antitumour properties of these viruses. There is now an increasing body of evidence indicating that host immune responses may be critical to the efficacy of oncolytic virotherapy. Although the immune response to oncolytic viruses can rapidly restrict viral replication, thereby limiting the efficacy of therapy, oncolytic virotherapy also has the potential to induce potent antitumoural immune effectors that destroy those cancer cells, which are not directly lysed by virus. In this review, we discuss the role of the immune system in terms of antiviral and antitumoural responses, as well as strategies to evade or promote these responses in favour of improved therapeutic potentials. PMID:21923638

  11. Progresses in DNA-based heterologous prime-boost immunization strategies.

    PubMed

    Jackson, Ronald J; Boyle, David B; Ranasinghe, Charani

    2014-01-01

    Although recombinant DNA and recombinant viral vectors expressing HIV antigens have yielded positive outcomes in animal models, these vaccines have not been effectively translated to humans. Despite this, there is still a high level of optimism that poxviral-based vaccine strategies could offer the best hope for developing an effective vaccine against not only HIV-1 but also other chronic diseases where good-quality T and B cell immunity is needed for protection. In this chapter we discuss step by step (1) how recombinant poxviral vectors co-expressing HIV antigens and promising mucosal/systemic adjuvants (e.g., IL-13Rα2) are constructed, (2) how these vectors can be used in alternative heterologous prime-boost immunization strategies, (3) how systemic and mucosal samples are prepared for analysis, followed by (4) two immunological assays: multicolor intracellular cytokine staining and tetramer/homing maker analysis that are used to evaluate effective systemic and mucosal T cell immunity. PMID:24715282

  12. Multi-granularity immunization strategy based on SIRS model in scale-free network

    NASA Astrophysics Data System (ADS)

    Nian, Fuzhong; Wang, Ke

    2015-04-01

    In this paper, a new immunization strategy was established to prevent the epidemic spreading based on the principle of "Multi-granularity" and "Pre-warning Mechanism", which send different pre-warning signal with the risk rank of the susceptible node to be infected. The pre-warning means there is a higher risk that the susceptible node is more likely to be infected. The multi-granularity means the susceptible node is linked with multi-infected nodes. In our model, the effect of the different situation of the multi-granularity immunizations is compared and different spreading rates are adopted to describe the epidemic behavior of nodes. In addition the threshold value of epidemic outbreak is investigated, which makes the result more convincing. The theoretical analysis and the simulations indicate that the proposed immunization strategy is effective and it is also economic and feasible.

  13. Sympathetic Modulation of Immunity: Relevance to Disease

    PubMed Central

    Bellinger, Denise L.; Millar, Brooke A.; Perez, Sam; Carter, Jeff; Wood, Carlo; ThyagaRajan, Srinivasan; Molinaro, Christine; Lubahn, Cheri; Lorton, Dianne

    2008-01-01

    Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far as focused on neural-immune modulation in secondary lymphoid organs, and have revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS-immune interaction may enhance immune readiness during disease- or injury-induced ‘fight’ responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks. PMID:18308299

  14. TNF? and IFN? contribute to F1/LcrV-targeted immune defense in mouse models of fully virulent pneumonic plague.

    PubMed

    Lin, Jr-Shiuan; Park, Steven; Adamovicz, Jeffrey J; Hill, Jim; Bliska, James B; Cote, Christopher K; Perlin, David S; Amemiya, Kei; Smiley, Stephen T

    2010-12-16

    Immunization with the Yersinia pestis F1 and LcrV proteins improves survival in mouse and non-human primate models of pneumonic plague. F1- and LcrV-specific antibodies contribute to protection, however, the mechanisms of antibody-mediated defense are incompletely understood and serum antibody titers do not suffice as quantitative correlates of protection. Previously we demonstrated roles for tumor necrosis factor-alpha (TNF?) and gamma-interferon (IFN?) during defense against conditionally attenuated pigmentation (pgm) locus-negative Y. pestis. Here, using intranasal challenge with fully virulent pgm-positive Y. pestis strain CO92, we demonstrate that neutralizing TNF? and IFN? interferes with the capacity of therapeutically administered F1- or LcrV-specific antibody to reduce bacterial burden and increase survival. Moreover, using Y. pestis strain CO92 in an aerosol challenge model, we demonstrate that neutralizing TNF? and IFN? interferes with protection conferred by immunization with recombinant F1-LcrV fusion protein vaccine (p<0.0005). These findings establish that TNF? and IFN? contribute to protection mediated by pneumonic plague countermeasures targeting F1 and LcrV, and suggest that an individual's capacity to produce these cytokines in response to Y. pestis challenge will be an important co-determinant of antibody-mediated defense against pneumonic plague. PMID:20840834

  15. TNF? and IFN? contribute to F1/LcrV-targeted immune defense in mouse models of fully virulent pneumonic plague

    PubMed Central

    Lin, Jr-Shiuan; Park, Steven; Adamovicz, Jeffrey J.; Hill, Jim; Bliska, James B.; Cote, Christopher K.; Perlin, David S.; Amemiya, Kei; Smiley, Stephen T.

    2010-01-01

    Immunization with the Yersinia pestis F1 and LcrV proteins improves survival in mouse and non-human primate models of pneumonic plague. F1- and LcrV-specific antibodies contribute to protection, however, the mechanisms of antibody-mediated defense are incompletely understood and serum antibody titers do not suffice as quantitative correlates of protection. Previously we demonstrated roles for tumor necrosis factor-alpha (TNF?) and gamma-interferon (IFN?) during defense against conditionally attenuated pigmentation (pgm) locus-negative Y. pestis. Here, using intranasal challenge with fully virulent pgm-positive Y. pestis strain CO92, we demonstrate that neutralizing TNF? and IFN? interferes with the capacity of therapeutically administered F1- or LcrV-specific antibody to reduce bacterial burden and increase survival. Moreover, using Y. pestis strain CO92 in an aerosol challenge model, we demonstrate that neutralizing TNF? and IFN? interferes with protection conferred by immunization with recombinant F1-LcrV fusion protein vaccine (p<0.0005). These findings establish that TNF? and IFN? contribute to protection mediated by pneumonic plague countermeasures targeting F1 and LcrV, and suggest that an individuals capacity to produce these cytokines in response to Y. pestis challenge will be an important co-determinant of antibody-mediated defense against pneumonic plague. PMID:20840834

  16. Immunizations

    MedlinePLUS

    ... How Can I Help a Friend Who Cuts? Immunizations KidsHealth > For Teens > Immunizations Print A A A ... That Shot? en español Las vacunas Why Are Vaccinations Important? Measles, mumps, and whooping cough may seem ...

  17. Immunization

    MedlinePLUS

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against things like measles, ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  18. Immunizations

    MedlinePLUS

    ... How Can I Help a Friend Who Cuts? Immunizations KidsHealth > For Teens > Immunizations Print A A A ... That Shot? en espaol Las vacunas Why Are Vaccinations Important? Measles, mumps, and whooping cough may seem ...

  19. A tale of two tumours: comparison of the immune escape strategies of contagious cancers.

    PubMed

    Siddle, Hannah V; Kaufman, Jim

    2013-09-01

    The adaptive immune system should prevent cancer cells passing from one individual to another, in much the same way that it protects against pathogens. However, in rare cases cancer cells do not die within a single individual, but successfully pass between individuals, escaping the adaptive immune response and becoming a contagious cancer. There are two naturally occurring contagious cancers, Devil Facial Tumour Disease (DFTD), found in Tasmanian devils, and Canine Transmissible Venereal Tumour (CTVT), found in dogs. Despite sharing an ability to pass as allografts, these cancers have a very different impact on their hosts. While DFTD causes 100% mortality among infected devils and has had a devastating impact on the devil population, CTVT co-exists with its host in a manner that does not usually cause death of the dog. Although immune evasion strategies for CTVT have been defined, why DFTD is not rejected as an allograft is not understood. We have made progress in revealing mechanisms of immune evasion for DFTD both in vitro and in vivo, and here we compare how DFTD and CTVT interact with their respective hosts and avoid rejection. Our findings highlight factors that may be important for the evolution of contagious cancers and cancer more generally. Perhaps most importantly, this work has opened up important areas for future research, including the effect of epigenetic factors on immune escape mechanisms and the basis of a vaccine strategy that may protect Tasmanian devils against DFTD. PMID:23200636

  20. Simultaneous transcriptome analysis of Colletotrichum gloeosporioides and tomato fruit pathosystem reveals novel fungal pathogenicity and fruit defense strategies.

    PubMed

    Alkan, Noam; Friedlander, Gilgi; Ment, Dana; Prusky, Dov; Fluhr, Robert

    2015-01-01

    The fungus Colletotrichum gloeosporioides breaches the fruit cuticle but remains quiescent until fruit ripening signals a switch to necrotrophy, culminating in devastating anthracnose disease. There is a need to understand the distinct fungal arms strategy and the simultaneous fruit response. Transcriptome analysis of fungal-fruit interactions was carried out concurrently in the appressoria, quiescent and necrotrophic stages. Conidia germinating on unripe fruit cuticle showed stage-specific transcription that was accompanied by massive fruit defense responses. The subsequent quiescent stage showed the development of dendritic-like structures and swollen hyphae within the fruit epidermis. The quiescent fungal transcriptome was characterized by activation of chromatin remodeling genes and unsuspected environmental alkalization. Fruit response was portrayed by continued highly integrated massive up-regulation of defense genes. During cuticle infection of green or ripe fruit, fungi recapitulate the same developmental stages but with differing quiescent time spans. The necrotrophic stage showed a dramatic shift in fungal metabolism and up-regulation of pathogenicity factors. Fruit response to necrotrophy showed activation of the salicylic acid pathway, climaxing in cell death. Transcriptome analysis of C.gloeosporioides infection of fruit reveals its distinct stage-specific lifestyle and the concurrent changing fruit response, deepening our perception of the unfolding fungal-fruit arms and defenses race. PMID:25377514

  1. Global Immunization Vision and Strategy (GIVS): a mid-term analysis of progress in 50 countries.

    PubMed

    Kamara, Lidija; Lydon, Patrick; Bilous, Julian; Vandelaer, Jos; Eggers, Rudi; Gacic-Dobo, Marta; Meaney, William; Okwo-Bele, Jean-Marie

    2013-01-01

    Within the overall framework set out in the Global Immunization Vision and Strategy (GIVS) for the period 2006-2015, over 70 countries had developed comprehensive Multi-Year Plans (cMYPs) by 2008, outlining their plans for implementing the GIVS strategies and for attaining the GIVS Goals at the midpoint in 2010 or earlier. These goals are to: (1) reach ?90% and ?80% vaccination coverage at national and district level, respectively; and (2) reduce measles-related mortality by 90% compared with the 2000 level. Fifty cMYPs were analysed along the four strategic areas of the GIVS: (1) protecting more people in a changing world; (2) introducing new vaccines and technologies; (3) integrating immunization, other health interventions and surveillance in the health system context; and (4) immunizing in the context of global interdependence. By 2010, all 50 countries planned to have introduced hepatitis B (HepB) vaccine, 48 the Haemophilus influenzae type B (Hib) vaccine and only a few countries had firm plans to introduce pneumococcal or rotavirus vaccines. Countries seem to be inadequately prepared in terms of cold-chain requirements to deal with the expected increases in storage that will be required for vaccines, and in making provisions to establish a corresponding surveillance system for planned new vaccine introductions. Immunization contacts are used to deliver other health interventions, especially in the countries in the World Health Organization (WHO) Africa Region. The cost for the planned immunization activities will double to U$27 per infant, of which U$5 per infant is the expected shortfall. Global Alliance for Vaccines and Immunization (GAVI) funding is becoming the largest contributor to immunization programmes. PMID:22411879

  2. The immune system is limited by oxidative stress: Dietary selenium promotes optimal antioxidative status and greatest immune defense in pacu Piaractus mesopotamicus.

    PubMed

    Biller-Takahashi, Jaqueline D; Takahashi, Leonardo S; Mingatto, Fbio E; Urbinati, Elisabeth C

    2015-11-01

    Reactive oxygen species (ROS) are reactive molecules containing oxygen, that form as byproducts of aerobic metabolism, including immune system processes. Too much ROS may cause oxidative stress. In this study, we examined whether it can also limit the production of immune system compounds. To assess the relationship between antioxidant status and immunity we evaluated the effect of dietary supplementation with organic selenium, given at various levels for 10 days, on the antioxidant and immune system of the pacu fish (Piaractus mesopotamicus). Fish fed a diet containing 0.6 mg Se-yeast kg(-1) showed significant improvement in antioxidant status, as well as in hematological and immunological profiles. Specifically, they had the highest counts for catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), red blood cells, and thrombocytes; the highest leukocyte count (particularly for monocytes); and the highest serum lysozyme activity. There was also a positive correlation between GPx and lysozyme in this group of fish. These findings indicate that short-term supplementation with 0.6 mg Se-yeast kg(-1) reestablished the antioxidative status, allowing the production of innate components which can boost immunity without the risk of oxidative stress. This study shows a relationship between oxidative stress and immunity, and, from a practical perspective, shows that improving immunity and health in pacu through the administration of selenium could improve their growth performance. PMID:26370542

  3. Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11

    PubMed Central

    Santos, Diego M; Carneiro, Marcia W; de Moura, Tatiana R; Fukutani, Kiyoshi; Clarencio, Jorge; Soto, Manuel; Espuelas, Socorro; Brodskyn, Claudia; Barral, Aldina; Barral-Netto, Manoel; de Oliveira, Camila I

    2012-01-01

    Background Vaccine development has been a priority in the fight against leishmaniases, which are vector-borne diseases caused by Leishmania protozoa. Among the different immunization strategies employed to date is inoculation of plasmid DNA coding for parasite antigens, which has a demonstrated ability to induce humoral and cellular immune responses. In this sense, inoculation of plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was able to confer protection against visceral leishmaniasis. However, recently the use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles has also proven effective for eliciting protective immune responses. Methods In the present work, we tested two immunization strategies with the goal of obtaining protection, in terms of lesion development and parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP-11. Alternatively, mice were primed with PLGA nanoparticles loaded with the recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with recombinant KMP-11. Results Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti-inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development was not inhibited following either immunization strategy. However, immunization with PLGA nanoparticles resulted in a more prominent reduction in parasite load at the infection site when compared with immunization using plasmid DNA alone. This effect was associated with a local increase in interferon-gamma and in tumor necrosis factor-alpha. Both immunization strategies also resulted in a lower parasite load in the draining lymph nodes, albeit not significantly. Conclusion Our results encourage the pursuit of immunization strategies employing nanobased delivery systems for vaccine development against cutaneous leishmaniasis caused by L. braziliensis infection. PMID:22619548

  4. Innate Immune Defenses Induced by CpG do not Promote Vaccine-Induced Protection Against Foot-and-Mouth Disease in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Emergency vaccination as part of the control strategies against Foot-and-Mouth Disease (FMD) epidemics has the potential not only to limit the spread of the virus but also to reduce large-scale culling of affected herds. With the aim to reduce the time between vaccination and the onset of immunity, ...

  5. Immune System (For Parents)

    MedlinePLUS

    ... Allergy Emergency Cerebral Palsy: Caring for Your Child Immune System KidsHealth > For Parents > Immune System Print A A ... can lead to illness and infection. About the Immune System The immune system is the body's defense against ...

  6. Construction of a full-length cDNA library of Solen grandis dunker and identification of defense- and immune-related genes

    NASA Astrophysics Data System (ADS)

    Sun, Guohua; Liu, Xiangquan; Ren, Lihua; Yang, Jianmin; Wei, Xiumei; Yang, Jialong

    2013-11-01

    The basic genetic characteristics, important functional genes, and entire transcriptome of Solen grandis Dunker were investigated by constructing a full-length cDNA library with the `switching mechanism at the 5'-end of the RNA transcript' (SMART) technique. Total RNA was isolated from the immune-relevant tissues, gills and hemocytes, using the Trizol reagent, and cDNA fragments were digested with Sfi I before being ligated to the pBluescript II SK* vector. The cDNA library had a titer of 1048 cfu ?L-1 and a storage capacity of 1.05106 cfu. Approximately 98% of the clones in the library were recombinants, and the fragment lengths of insert cDNA ranged from 0.8 kb to 3.0 kb. A total of 2038 expressed sequence tags were successfully sequenced and clustered into 965 unigenes. BLASTN analysis showed that 240 sequences were highly similar to the known genes (E-value < 1e -5; percent identity >80%), accounting for 25% of the total unigenes. According to the Gene Ontology, these unigenes were related to several biological processes, including cell structure, signal transport, protein synthesis, transcription, energy metabolism, and immunity. Fifteen of the identified sequences were related to defense and immunity. The full-length cDNA sequence of HSC70 was obtained. The cDNA library of S. grandis provided a useful resource for future researches of functional genomics related to stress tolerance, immunity, and other physiological activities.

  7. Interaction of Candida albicans with host cells: virulence factors, host defense, escape strategies, and the microbiota.

    PubMed

    Höfs, Sarah; Mogavero, Selene; Hube, Bernhard

    2016-03-01

    The interaction between Candida albicans and its host cells is characterized by a complex interplay between the expression of fungal virulence factors, which results in adherence, invasion and cell damage, and the host immune system, which responds by secreting proinflammatory cytokines, activating antimicrobial activities and killing the fungal pathogen. In this review we describe this interplay by taking a closer look at how C. albicans pathogenicity is induced and executed, how the host responds in order to prevent and clear an infection, and which mechanisms C. albicans has evolved to bypass these immune responses to avoid clearance. Furthermore, we review studies that show how the presence of other microorganisms affects this interplay. PMID:26920876

  8. Regulated CRISPR Modules Exploit a Dual Defense Strategy of Restriction and Abortive Infection in a Model of Prokaryote-Phage Coevolution

    PubMed Central

    Kumar, M. Senthil; Plotkin, Joshua B.; Hannenhalli, Sridhar

    2015-01-01

    CRISPRs offer adaptive immunity in prokaryotes by acquiring genomic fragments from infecting phage and subsequently exploiting them for phage restriction via an RNAi-like mechanism. Here, we develop and analyze a dynamical model of CRISPR-mediated prokaryote-phage coevolution that incorporates classical CRISPR kinetics along with the recently discovered infection-induced activation and autoimmunity side effects. Our analyses reveal two striking characteristics of the CRISPR defense strategy: that both restriction and abortive infections operate during coevolution with phages, driving phages to much lower densities than possible with restriction alone, and that CRISPR maintenance is determined by a key dimensionless combination of parameters, which upper bounds the activation level of CRISPRs in uninfected populations. We contrast these qualitative observations with experimental data on CRISPR kinetics, which offer insight into the spacer deletion mechanism and the observed low CRISPR prevalence in clinical isolates. More generally, we exploit numerical simulations to delineate four regimes of CRISPR dynamics in terms of its host, kinetic, and regulatory parameters. PMID:26544847

  9. Regulated CRISPR Modules Exploit a Dual Defense Strategy of Restriction and Abortive Infection in a Model of Prokaryote-Phage Coevolution.

    PubMed

    Kumar, M Senthil; Plotkin, Joshua B; Hannenhalli, Sridhar

    2015-11-01

    CRISPRs offer adaptive immunity in prokaryotes by acquiring genomic fragments from infecting phage and subsequently exploiting them for phage restriction via an RNAi-like mechanism. Here, we develop and analyze a dynamical model of CRISPR-mediated prokaryote-phage coevolution that incorporates classical CRISPR kinetics along with the recently discovered infection-induced activation and autoimmunity side effects. Our analyses reveal two striking characteristics of the CRISPR defense strategy: that both restriction and abortive infections operate during coevolution with phages, driving phages to much lower densities than possible with restriction alone, and that CRISPR maintenance is determined by a key dimensionless combination of parameters, which upper bounds the activation level of CRISPRs in uninfected populations. We contrast these qualitative observations with experimental data on CRISPR kinetics, which offer insight into the spacer deletion mechanism and the observed low CRISPR prevalence in clinical isolates. More generally, we exploit numerical simulations to delineate four regimes of CRISPR dynamics in terms of its host, kinetic, and regulatory parameters. PMID:26544847

  10. Development of oral vaccines to stimulate mucosal and systemic immunity: barriers and novel strategies.

    PubMed

    Shalaby, W S

    1995-02-01

    Many questions regarding the induction of mucosal and humoral immunity through oral vaccination exist. Efficacy is dependent on the physicochemical properties of the antigen, the gastrointestinal environment, the presence of adjuvants, and the mode of delivery. Understanding how these factors interrelate will be critical to the development of new oral vaccines. A number of approaches are currently being studied to enhance the immune response. These include chemical conjugation, immunization with recombinant bacteria and viruses, and mucosal adjuvants. Vaccine delivery systems prepared from natural or synthetic polymers is a particularly promising area because many of the current methods to induce mucosal stimulation can be incorporated within these systems. Thus, the polymeric delivery system functions as a platform to facilitate uptake by M-cells and prolong antigen presentation and stimulation of the Peyer's patches. This Review examines some of the physiological and immunological barriers associated with oral vaccination and discusses novel strategies to overcome such barriers. PMID:7828366

  11. Antimicrobial Mechanisms of Macrophages and the Immune Evasion Strategies of Staphylococcus aureus

    PubMed Central

    Flannagan, Ronald S.; Heit, Bryan; Heinrichs, David E.

    2015-01-01

    Habitually professional phagocytes, including macrophages, eradicate microbial invaders from the human body without overt signs of infection. Despite this, there exist select bacteria that are professional pathogens, causing significant morbidity and mortality across the globe and Staphylococcus aureus is no exception. S. aureus is a highly successful pathogen that can infect virtually every tissue that comprises the human body causing a broad spectrum of diseases. The profound pathogenic capacity of S. aureus can be attributed, in part, to its ability to elaborate a profusion of bacterial effectors that circumvent host immunity. Macrophages are important professional phagocytes that contribute to both the innate and adaptive immune response, however from in vitro and in vivo studies, it is evident that they fail to eradicate S. aureus. This review provides an overview of the antimicrobial mechanisms employed by macrophages to combat bacteria and describes the immune evasion strategies and some representative effectors that enable S. aureus to evade macrophage-mediated killing. PMID:26633519

  12. Passive and active immunization strategies against Clostridium difficile infections: state of the art.

    PubMed

    Mizrahi, Assaf; Collignon, Anne; Pchin, Sverine

    2014-12-01

    The pathophysiology of Clostridium difficile infections (CDI) could be considered as a three-step process that takes place after disruption of the digestive microbiota by antibiotics: 1) germination of spores; 2) multiplication and persistence of C.difficile in the colonic niche thanks to colonization factors; 3) production of the two toxins TcdA and TcdB and for some strains an additional toxin, the binary toxin CDT. Different immunization strategies against C.difficile have been developed, first regarding the toxins. Immunization assays with colonization factors have followed, and allowed accumulation of new data concerning theirs functions and immunogenicity. Here, we present the toxins, the colonization factors and their use in passive and active immunizations to treat and/or to prevent C.difficile infections. The various experiments performed in animal models and the first clinical trials in humans are reported. PMID:25079668

  13. Drosophila immune response: From systemic antimicrobial peptide production in fat body cells to local defense in the intestinal tract.

    PubMed

    Charroux, Bernard; Royet, Julien

    2010-01-01

    The innate immune response was once considered to be a limited set of responses that aims to contain an infection by primitive "ingest and kill" mechanisms, thus giving the host time to mount a more specific humoral and cellular immune response. It is now known that the innate immune response is a complex integrated response involving multiple players that work together to eliminate the pathogen. The fruit fly has been a great model to decipher various aspects of the immune response of invertebrates, including the transcriptional regulation of the antimicrobial genes during systemic response. Various reports have recently shown that Drosophila can also be used as a model system to study the mechanisms that control epithelial immune responses and more specifically gut immunity. We will present here our current knowledge on the genetic control of antimicrobial peptides production and recent progress made in our comprehension of the mechanisms through which Drosophila gut epithelium tolerates commensal microbiota yet remains able to mount an efficient immune response to food-borne pathogens. PMID:20383054

  14. Understanding the main barriers to immunization in Colombia to better tailor communication strategies

    PubMed Central

    2014-01-01

    Background The Expanded Program on Immunization (EPI) in Colombia has made great advances since its inception in 1979; however, by 2010 vaccination coverage rates had been declining. In 2010, the EPI commissioned a nationwide study on practices on immunization, attitudes and knowledge, perceived service quality, and barriers to childhood immunization in order to tailor EPI communication strategies. Methods Colombias 32 geographical departments were divided into 10 regions. Interviewers from an independent polling company administered a survey to 4802 parents and guardians of children aged <5years in these regions. To better assess barriers to vaccination, the study was designed to have 70% of participants who had children with incomplete vaccination schedules. Explanatory factorial, principal component, and cluster analyses were performed to place participants into a group (segment) representing the primary category of reasons respondents offered for not vaccinating their children. Types of barriers were then compared to other variables, such as service quality, communication preferences, and parental attitudes on vaccination. Results Although all respondents indicated that vaccines have health benefits, and 4738 (98.7%) possessed vaccination cards for their children, attitudes and knowledge were not always favorable to immunization. Six groups of immunization barriers were identified: 1) factors related to caregivers (24.4%), 2) vaccinators (19.7%), 3) health centers (18.0%), 4) the health system (13.4%), 5) concerns about adverse events (13.1%), and 6) cultural and religious beliefs (11.4%); groups 1, 5 and 6 together represented almost half (48.9%) of users, indicating problems related to the demand for vaccines as the primary barriers to immunization. Differences in demographics, communication preferences, and reported service quality were found among participants in the six groups and among participants in the 10 regions. Additionally, differences between how participants reported receiving information on vaccination and how they believed such information should be communicated were observed. Conclusions Better understanding immunization barriers and the users of the EPI can help tailor communication strategies to increase demand for immunization services. Results of the study have been used by Colombias EPI to inform the design of new communication strategies. PMID:24981729

  15. Lipid Body–Phagosome Interaction in Macrophages during Infectious Diseases: Host Defense or Pathogen Survival Strategy?

    PubMed Central

    Melo, Rossana C. N.; Dvorak, Ann M.

    2012-01-01

    Phagocytosis of invading microorganisms by specialized cells such as macrophages and neutrophils is a key component of the innate immune response. These cells capture and engulf pathogens and subsequently destroy them in intracellular vacuoles—the phagosomes. Pathogen phagocytosis and progression and maturation of pathogen-containing phagosomes, a crucial event to acquire microbicidal features, occurs in parallel with accentuated formation of lipid-rich organelles, termed lipid bodies (LBs), or lipid droplets. Experimental and clinical infections with different pathogens such as bacteria, parasites, and viruses induce LB accumulation in cells from the immune system. Within these cells, LBs synthesize and store inflammatory mediators and are considered structural markers of inflammation. In addition to LB accumulation, interaction of these organelles with pathogen-containing phagosomes has increasingly been recognized in response to infections and may have implications in the outcome or survival of the microorganism within host cells. In this review, we summarize our current knowledge on the LB-phagosome interaction within cells from the immune system, with emphasis on macrophages, and discuss the functional meaning of this event during infectious diseases. PMID:22792061

  16. A novel "priming-boosting" strategy for immune interventions in cervical cancer.

    PubMed

    Liao, Shujie; Zhang, Weina; Hu, Xiaoji; Wang, Wei; Deng, Dongrui; Wang, Hui; Wang, Changyu; Zhou, Jianfeng; Wang, Shixuan; Zhang, Hanwang; Ma, Ding

    2015-04-01

    Despite the encouraging development of a preventive vaccine for human papillomavirus (HPV), it cannot improve ongoing infections. Therefore, a new vaccine is urgently needed that can prevent and treat cervical cancer, and cure pre-cancerous lesions. In this study, we constructed two peptide-based vaccines. The first was a short-term, long-peptide (ST-LP) vaccine that simultaneously targeted three key carcinogenic epitopes (E5-E6-E7) on HPV16. We tested this vaccine in murine TC-1 cells infected with a recombinant adeno-associated virus (rAAV) fused with HPV16E5 DNA (rTC-1 cells), which served as a cell model; we also tested it in immune-competent mice loaded with rTC-1 cells, which served as an ectopic tumor model. The ST-LP injections resulted in strong, cell-mediated immunity, capable of attacking and eliminating abnormal antigen-bearing cells. Furthermore, to prolong immunogenic capability, we designed a unique rAAV that encoded the three predicted epitopes for a second, long-term, long-peptide (LT-LP) vaccine. Moreover, we used a new immune strategy of continuous re-injections, where three ST-LP injections were performed at one-week intervals (days 0, 7, 14), then one LT-LP injection was performed on day 120. Our in vitro and in vivo studies revealed that this strategy could boost the immune response to produce longer and stronger protection against target cells, and mice were thoroughly protected from tumor growth. Our results showed that priming the immune system with the ST-LP vaccine, followed by boosting the immune system with the LT-LP vaccine could generate a rapid, robust, durable cytotoxic T-lymphocyte response to HPV16-positive tumors. PMID:25575128

  17. A heterologous DNA prime/protein boost immunization strategy for rhesus cytomegalovirus

    PubMed Central

    Abel, Kristina; Strelow, Lisa; Yue, Yujuan; Eberhardt, Meghan K.; Schmidt, Kimberli A.; Barry, Peter A.

    2008-01-01

    A previous study in nonhuman primates demonstrated that genetic immunization against the rhesus cytomegalovirus phosphoprotein 65-2 (pp65-2) and glycoprotein B (gB) antigens both stimulated antigen-specific antibodies and CD8 T cell responses, and significantly reduced plasma viral loads following intravenous challenge with RhCMV. It was also noted in this study that weak CD4 T cell and neutralizing antibody responses were generated by DNA alone. To broaden the type of immune responses, a DNA prime/protein boost strategy was used in seronegative macaques, consisting of four DNA immunizations against pp65-2, gB, and immediate-early 1 (IE1), followed by two boosts with formalin-inactivated RhCMV virions. This heterologous prime/boost strategy elicited robust antigen-specific CD4 and CD8 T cell responses in addition to biologically relevant neutralizing antibody titers. Animals were challenged with RhCMV delivered into four sites via a subcutaneous route. Skin biopsies of one of the inoculation sites 7 days post challenge revealed marked differences in the level of RhCMV replication between the vaccinated and control monkeys. Whereas the inoculation site in the controls was noted for a prominent inflammatory response and numerous cytomegalic, antigen-positive (IE1) cells, the inoculation site in the vaccinees was characterized by an absence of inflammation and antigen-positive cells. All five vaccinees developed robust recall responses to viral antigens, and four of them exhibited long-term viral immune responses consistent with effective control of viral expression and replication. These results demonstrate that a heterologous DNA prime/protein boost strategy greatly expands the breadth of antiviral immune responses and greatly reduces the level of viral replication at the primary site of challenge infection. PMID:18760319

  18. Strategies to overcome host immunity to adenovirus vectors in vaccine development

    PubMed Central

    Thacker, Erin E; Timares, Laura; Matthews, Qiana L

    2013-01-01

    The first clinical evaluations of adenovirus (Ad)-based vectors for gene therapy were initiated in the mid-1990s and led to great anticipation for future utility. However, excitement surrounding gene therapy, particularly Ad-based therapy, was diminished upon the death of Jesse Gelsinger, and recent discouraging results from the HIV vaccine STEP trial have brought efficacy and safety issues to the forefront again. Even so, Ad vectors are still considered among the safest and most effective vaccine vectors. Innate and pre-existing immunity to Ad mediate much of the acute toxicities and reduced therapeutic efficacies observed following vaccination with this vector. Thus, innovative strategies must continue to be developed to reduce Ad-specific antigenicity and immune recognition. This review provides an overview and critique of the most promising strategies, including results from preclinical trials in mice and nonhuman primates, which aim to revive the future of Ad-based vaccines. PMID:19485756

  19. Defensive reaper - Induction of mx and Apoptosis in mosquito midgut cells as an innate immune response to baculovirus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many vertebrate and insect viruses posses anti-apoptotic genes that are required for their infectivity. This has led to the hypothesis that apoptosis is an innate immunoresponse important for limiting virus infections. The role of apoptosis may be especially important in insect anti-viral defense ...

  20. A cognitive and economic decision theory for examining cyber defense strategies.

    SciTech Connect

    Bier, Asmeret Brooke

    2014-01-01

    Cyber attacks pose a major threat to modern organizations. Little is known about the social aspects of decision making among organizations that face cyber threats, nor do we have empirically-grounded models of the dynamics of cooperative behavior among vulnerable organizations. The effectiveness of cyber defense can likely be enhanced if information and resources are shared among organizations that face similar threats. Three models were created to begin to understand the cognitive and social aspects of cyber cooperation. The first simulated a cooperative cyber security program between two organizations. The second focused on a cyber security training program in which participants interact (and potentially cooperate) to solve problems. The third built upon the first two models and simulates cooperation between organizations in an information-sharing program.

  1. Synthetic innate defense regulator peptide combination using CpG ODN as a novel adjuvant induces long‑lasting and balanced immune responses.

    PubMed

    Yu, Chao-Heng; Luo, Zi-Chao; Li, Meng; Lu, Lian; Li, Zhan; Wu, Xiao-Zhe; Fan, Ying-Zi; Zhang, Hai-Long; Zhou, Bai-Ling; Wan, Yang; Men, Ke; Tian, Yao-Mei; Chen, Shuang; Yuan, Feng-Jiao; Xiang, Rong; Yang, Li

    2016-01-01

    Vaccines are critical tools for the prevention and treatment of several diseases. Adjuvants have been traditionally used to enhance immunity to vaccines and experimental antigens. In the present study, the adjuvant combination of CpG oligodeoxynucleotides (CpG ODN) and the innate defense regulator (IDR) peptide, IDR‑HH2, was evaluated for its ability to enhance and modulate the immune response when formulated with alum and the recombinant hepatitis B surface antigen (HBsAg). The CpG‑HH2 complex enhanced the secretions of tumor necrosis factor‑α, monocyte chemotactic protein 1 and interferon‑γ by human peripheral blood mononuclear cells and promoted murine bone marrow dentritic cell maturation. In addition, the present study demonstrated that IDR‑HH2 was chemotactic for human neutrophils, THP‑1 cells and RAW264.7 cells at concentrations between 2.5 and 40 µg/ml. The present study also observed that significantly higher anti‑HBs antibody titers, which were sustained at high levels for as long as 35 weeks following the boost immunization, were induced by the combination adjuvant, even when co‑administered with a commercial hepatitis B vaccine at a low antigen dose (0.1 µg HBsAg). Notably, the level of IgG2a was almost equal to the level of IgG1, indicating that a balanced T helper (Th)1/Th2 immune response was elicited by the novel vaccine, which was consistent with the ELISpot results. These data suggest that the CpG‑HH2 complex may be a potential effective adjuvant, which facilitates a reduction in the dose of antigen and induces long‑lasting, balanced immune responses. PMID:26647852

  2. Identification and expression of antioxidant and immune defense genes in the surf clam Mesodesma donacium challenged with Vibrio anguillarum.

    PubMed

    Maldonado-Aguayo, W; Lafarga-De la Cruz, F; Gallardo-Escrate, C

    2015-02-01

    The immune system in marine invertebrates is mediated through cellular and humoral components, which act together to address the action of potential pathogenic microorganisms. In bivalve mollusks biomolecules implicated in oxidative stress and recognition of pathogens have been involved in the innate immune response. To better understand the molecular basis of the immune response of surf clam Mesodesma donacium, qPCR approaches were used to identify genes related to its immune response against Vibrio anguillarum infection. Genes related to oxidative stress response and recognition of pathogens like superoxide dismutase (MdSOD), catalase (MdCAT), ferritin (MdFER) and filamin (MdFLMN) were identified from 454-pyrosequencing cDNA library of M. donacium and were evaluated in mantle, adductor muscle and gills. The results for transcripts expression indicated that MdSOD, MdFLMN and MdFER were primarily expressed in the muscle, while MdCAT was more expressed in gills. Challenge experiments with the pathogen V. anguillarum had showed that levels of transcript expression for MdSOD, MdCAT, MdFER, and MdFLMN were positively regulated by pathogen, following a time-dependent expression pattern with significant statistical differences between control and challenge group responses (p<0.05). These results suggest that superoxide dismutase, catalase, ferritin and filamin, could be contributing to the innate immune response of M. donacium against the pathogen V. anguillarum. PMID:25481276

  3. Autophagy as a defense strategy against stress: focus on Paracentrotus lividus sea urchin embryos exposed to cadmium.

    PubMed

    Chiarelli, Roberto; Martino, Chiara; Agnello, Maria; Bosco, Liana; Roccheri, Maria Carmela

    2016-01-01

    Autophagy is used by organisms as a defense strategy to face environmental stress. This mechanism has been described as one of the most important intracellular pathways responsible for the degradation and recycling of proteins and organelles. It can act as a cell survival mechanism if the cellular damage is not too extensive or as a cell death mechanism if the damage/stress is irreversible; in the latter case, it can operate as an independent pathway or together with the apoptotic one. In this review, we discuss the autophagic process activated in several aquatic organisms exposed to different types of environmental stressors, focusing on the sea urchin embryo, a suitable system recently included into the guidelines for the use and interpretation of assays to monitor autophagy. After cadmium (Cd) exposure, a heavy metal recognized as an environmental toxicant, the sea urchin embryo is able to adopt different defense mechanisms, in a hierarchical way. Among these, autophagy is one of the main responses activated to preserve the developmental program. Finally, we discuss the interplay between autophagy and apoptosis in the sea urchin embryo, a temporal and functional choice that depends on the intensity of stress conditions. PMID:26362931

  4. Effects of interaction between temperature conditions and copper exposure on immune defense and other life-history traits of the blow fly Protophormia terraenovae.

    PubMed

    Pölkki, Mari; Kangassalo, Katariina; Rantala, Markus J

    2014-01-01

    Environmental pollution is considered one of the major threats to organisms. Direct effects of heavy metal pollution on various life-history traits are well recognized, while the effects of potential interactions between two distinct environmental conditions on different traits are poorly understood. Here, we have tested the effects of interactions between temperature conditions and heavy metal exposure on innate immunity and other life-history traits. Maggots of the blow fly Protophormia terraenovae were reared on either copper-contaminated or uncontaminated food, under three different temperature environments. Encapsulation response, body mass, and development time were measured for adult flies that were not directly exposed to copper. We found that the effects of copper exposure on immunity and other traits are temperature-dependent, suggesting that the ability to regulate toxic compounds in body tissues might depend on temperature conditions. Furthermore, we found that temperature has an effect on sex differences in immune defense. Males had an encapsulation response at higher temperatures stronger than that of females. Our results indicate that the effects of environmental conditions on different traits are much more intricate than what can be predicted. This is something that should be considered when conducting immunological experiments or comparing results of previous studies. PMID:24926809

  5. Neutrophils and keratinocytes in innate immunity--cooperative actions to provide antimicrobial defense at the right time and place.

    PubMed

    Borregaard, Niels; Theilgaard-Mnch, Kim; Cowland, Jack B; Sthle, Mona; Srensen, Ole E

    2005-04-01

    The human neutrophil is a professional phagocyte of fundamental importance for defense against microorganisms, as witnessed by the life-threatening infections occurring in patients with neutropenia or with defects that result in decreased microbicidal activity of the neutrophil. Likewise, the skin and mucosal surfaces provide important barriers against infections. Traditionally, these major defense systems, the epithelial cells and the neutrophils, have been viewed as limited in their armory: The epithelial cells provide defense by constituting a physical barrier, and the neutrophils provide instant delivery of preformed antimicrobial substances or on-the-spot assembly of the multicomponent reduced nicotinamide adenine dinucleotide phosphate oxidase from stored components for the generation of reactive oxygen metabolites. Recent research has shown that epithelial cells are highly dynamic and able to generate antimicrobial peptides in response not only to microbial infection itself but more importantly, to the growth factors that are called into play when the physical barrier is broken, and the risk of microbial infection is imminent. Likewise, the neutrophil changes its profile of actively transcribed genes when it diapedeses into wounded skin. This results in generation of signaling molecules, some of which support the growth and antimicrobial potential of keratinocytes and epithelial cells. This paper will highlight some recent advances in this field. PMID:15582983

  6. Spectroelectrochemistry as a Strategy for Improving Selectivity of Sensors for Security and Defense Applications

    SciTech Connect

    Heineman, William R.; Seliskar, Carl J.; Morris, Laura K.; Bryan, Samuel A.

    2012-12-19

    Spectroelectrochemistry provides improved selectivity for sensors by electrochemically modulating the optical signal associated with the analyte. The sensor consists of an optically transparent electrode (OTE) coated with a film that preconcentrates the target analyte. The OTE functions as an optical waveguide for attenuated total reflectance (ATR) spectroscopy, which detects the analyte by absorption. Alternatively, the OTE can serve as the excitation light for fluorescence detection, which is generally more sensitive than absorption. The analyte partitions into the film, undergoes an electrochemical redox reaction at the OTE surface, and absorbs or emits light in its oxidized or reduced state. The change in the optical response associated with electrochemical oxidation or reduction at the OTE is used to quantify the analyte. Absorption sensors for metal ion complexes such as [Fe(CN)6]4- and [Ru(bpy)3]2+ and fluorescence sensors for [Ru(bpy)3]2+ and the polycyclic aromatic hydrocarbon 1-hydroxypyrene have been developed. The sensor concept has been extended to binding assays for a protein using avidinbiotin and 17?-estradiolanti-estradiol antibodies. The sensor has been demonstrated to measure metal complexes in complex samples such as nuclear waste and natural water. This sensor has qualities needed for security and defense applications that require a high level of selectivity and good detection limits for target analytes in complex samples. Quickly monitoring and designating intent of a nuclear program by measuring the Ru/Tc fission product ratio is such an application.

  7. Spectroelectrochemistry as a strategy for improving selectivity of sensors for security and defense applications

    NASA Astrophysics Data System (ADS)

    Heineman, William R.; Seliskar, Carl J.; Morris, Laura K.; Bryan, Samuel A.

    2012-09-01

    Spectroelectrochemistry provides improved selectivity for sensors by electrochemically modulating the optical signal associated with the analyte. The sensor consists of an optically transparent electrode (OTE) coated with a film that preconcentrates the target analyte. The OTE functions as an optical waveguide for attenuated total reflectance (ATR) spectroscopy, which detects the analyte by absorption. Alternatively, the OTE can serve as the excitation light for fluorescence detection, which is generally more sensitive than absorption. The analyte partitions into the film, undergoes an electrochemical redox reaction at the OTE surface, and absorbs or emits light in its oxidized or reduced state. The change in the optical response associated with electrochemical oxidation or reduction at the OTE is used to quantify the analyte. Absorption sensors for metal ion complexes such as [Fe(CN)6]4- and [Ru(bpy)3]2+ and fluorescence sensors for [Ru(bpy)3]2+ and the polycyclic aromatic hydrocarbon 1-hydroxypyrene have been developed. The sensor concept has been extended to binding assays for a protein using avidin-biotin and 17?-estradiol-anti-estradiol antibodies. The sensor has been demonstrated to measure metal complexes in complex samples such as nuclear waste and natural water. This sensor has qualities needed for security and defense applications that require a high level of selectivity and good detection limits for target analytes in complex samples. Quickly monitoring and designating intent of a nuclear program by measuring the Ru/Tc fission product ratio is such an application.

  8. Dynamic Patterns of Parasitism and Immunity across Host Development Influence Optimal Strategies of Resource Allocation.

    PubMed

    Tate, Ann T; Graham, Andrea L

    2015-10-01

    The integration of physiological mechanisms into life-history theory is an emerging frontier in our understanding of the constraints and drivers of life-history evolution. Dynamic patterns of antagonism between developmental and immunological pathways in juvenile insects illustrate the importance of mechanisms for determining life-history strategy optima in the face of trade-offs. For example, developmental interference occurs when developmental processes transiently take priority over resources or pathway architecture, preventing allocation to immunity or other traits. We designed a within-host model of infected larval development to explore the impact of developmental dynamics on optimal resource mobilization and allocation strategies as well as on larval resistance and tolerance phenotypes. The model incorporates mechanism-inspired functional forms of developmental interference with immunity against parasites that attack specific larval stages. We find that developmental interference generally increases optimal investment in constitutive immunity and decreases optimal resource mobilization rates, but the results are sensitive to the developmental stage at first infection. Moreover, developmental interference reduces resistance but generally increases tolerance of infection. We demonstrate the potential impact of these dynamics on empirical estimates of host susceptibility and discuss the general implications of incorporating realistic physiological mechanisms and developmental dynamics for life-history theory in insects and other organisms. PMID:26655573

  9. Comparative transcriptomics of Central Asian Vitis vinifera accessions reveals distinct defense strategies against powdery mildew

    PubMed Central

    Amrine, Katherine C H; Blanco-Ulate, Barbara; Riaz, Summaira; Pap, Dániel; Jones, Laura; Figueroa-Balderas, Rosa; Walker, M Andrew; Cantu, Dario

    2015-01-01

    Grape powdery mildew (PM), caused by the biotrophic ascomycete Erysiphe necator, is a devastating fungal disease that affects most Vitis vinifera cultivars. We have previously identified a panel of V. vinifera accessions from Central Asia with partial resistance to PM that possess a Ren1-like local haplotype. In this study, we show that in addition to the typical Ren1-associated late post-penetration resistance, these accessions display a range of different levels of disease development suggesting that alternative alleles or additional genes contribute to determining the outcome of the interaction with the pathogen. To identify potential Ren1-dependent transcriptional responses and functions associated with the different levels of resistance, we sequenced and analyzed the transcriptomes of these Central Asian accessions at two time points of PM infection. Transcriptomes were compared to identify constitutive differences and PM-inducible responses that may underlie their disease resistant phenotype. Responses to E. necator in all resistant accessions were characterized by an early up-regulation of 13 genes, most encoding putative defense functions, and a late down-regulation of 32 genes, enriched in transcriptional regulators and protein kinases. Potential Ren1-dependent responses included a hotspot of co-regulated genes on chromosome 18. We also identified 81 genes whose expression levels and dynamics correlated with the phenotypic differences between the most resistant accessions ‘Karadzhandahal’, DVIT3351.27, and O34-16 and the other genotypes. This study provides a first exploration of the functions associated with varying levels of partial resistance to PM in V. vinifera accessions that can be exploited as sources of genetic resistance in grape breeding programs. PMID:26504579

  10. Comparative transcriptomics of Central Asian Vitis vinifera accessions reveals distinct defense strategies against powdery mildew.

    PubMed

    Amrine, Katherine C H; Blanco-Ulate, Barbara; Riaz, Summaira; Pap, Dniel; Jones, Laura; Figueroa-Balderas, Rosa; Walker, M Andrew; Cantu, Dario

    2015-01-01

    Grape powdery mildew (PM), caused by the biotrophic ascomycete Erysiphe necator, is a devastating fungal disease that affects most Vitis vinifera cultivars. We have previously identified a panel of V. vinifera accessions from Central Asia with partial resistance to PM that possess a Ren1-like local haplotype. In this study, we show that in addition to the typical Ren1-associated late post-penetration resistance, these accessions display a range of different levels of disease development suggesting that alternative alleles or additional genes contribute to determining the outcome of the interaction with the pathogen. To identify potential Ren1-dependent transcriptional responses and functions associated with the different levels of resistance, we sequenced and analyzed the transcriptomes of these Central Asian accessions at two time points of PM infection. Transcriptomes were compared to identify constitutive differences and PM-inducible responses that may underlie their disease resistant phenotype. Responses to E. necator in all resistant accessions were characterized by an early up-regulation of 13 genes, most encoding putative defense functions, and a late down-regulation of 32 genes, enriched in transcriptional regulators and protein kinases. Potential Ren1-dependent responses included a hotspot of co-regulated genes on chromosome 18. We also identified 81 genes whose expression levels and dynamics correlated with the phenotypic differences between the most resistant accessions 'Karadzhandahal', DVIT3351.27, and O34-16 and the other genotypes. This study provides a first exploration of the functions associated with varying levels of partial resistance to PM in V. vinifera accessions that can be exploited as sources of genetic resistance in grape breeding programs. PMID:26504579

  11. Lead toxicity, defense strategies and associated indicative biomarkers in Talinum triangulare grown hydroponically.

    PubMed

    Kumar, Abhay; Prasad, M N V; Sytar, Oksana

    2012-11-01

    Talinum species have been used to investigate a variety of environmental problems for e.g. determination of metal pollution index and total petroleum hydrocarbons in roadside soils, stabilization and reclamation of heavy metals (HMs) in dump sites, removal of HMs from storm water-runoff and green roof leachates. Species of Talinum are popular leaf vegetables having nutrient antinutrient properties. In this study, Talinum triangulare (Jacq.) Willd (Ceylon spinach) grown hydroponically were exposed to different concentrations of lead (Pb) (0, 0.25, 0.5, 0.75, 1.0 and 1.25 mM) to investigate the biomarkers of toxicity and tolerance mechanisms. Relative water content, cell death, photosynthetic pigments, sulphoquinovosyldiacylglycerol (SQDG), anthocyanins, ?-tocopherol, malondialdehyde (MDA), reactive oxygen species (ROS) glutathione (GSH and GSSG) and elemental analysis have been investigated. The results showed that Pb in roots and shoots gradually increased as the function of Pb exposure; however Pb concentration in leaves was below detectable level. Chlorophylls and SQDG contents increased at 0.25 mM of Pb treatment in comparison to control at all treated durations, thereafter decreased. Levels of carotenoid, anthocyanins, ?-tocopherol, and lipid peroxidation increased in Pb treated plants compared to control. Water content, cells death and elemental analysis suggested the damage of transport system interfering with nutrient transport causing cell death. The present study also explained that Pb imposed indirect oxidative stress in leaves is characterized by decreases in GSH/GSSG ratio with increased doses of Pb treatment. Lead-induced oxidative stress was alleviated by carotenoids, anthocyanins, ?-tocopherol and glutathione suggesting that these defense responses as potential biomarkers for detecting Pb toxicity. PMID:22722003

  12. Resistance and Susceptibility to Malarial Infection: A Host Defense Strategy against Malaria

    PubMed Central

    BAKIR, Hanaa; YONES, Doaa; GALAL, Lamia; HUSEEIN, Enas

    2015-01-01

    Background: In an effort to understand what limits the virulence of malaria parasites in relation to the host genetic and immunogenic background, we investigated the possibility that the parasite and host genotype crossover interactions constrain virulence. Methods: Two groups of mice from different genotypes were used (C57BL/6 (B6) and DBA/2 mice). The mice were infected with a virulent parasite line Plasmodium yoelii 17XL (P. yoelii 17XL). Parasitemia, hematocrit value and lymphocytes yielded by livers and spleens were evaluated. Fluorescence Activated Cell Sorting (FACS) analysis illustrated phenotypic characterization of lymphocytes. Results: Infection with P. yoelii 17XL did not result in the death of DBA/2 mice. In contrast, B6 mice developed significantly high parasitemia and succumbed to death. Using (FACS) analysis, DBA/2 mice were found to experience a marked expansion of interleukin (IL)-2R?+ CD3int cells and ?? T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220+ T cells) was also marked in DBA/2 mice. Conclusion: The outcome of murine malaria infections depends on the dynamic interplay between the immune-mediator and the genotype of the host.

  13. Strategies to circumvent humoral immunity to adeno-associated viral vectors

    PubMed Central

    Tse, Longping V; Moller-Tank, Sven; Asokan, Aravind

    2015-01-01

    Introduction Recent success in gene therapy of certain monogenic diseases in the clinic has infused enthusiasm into the continued development of recombinant adeno-associated viral (AAV) vectors as next-generation biologics. However, progress in clinical trials has also highlighted the challenges posed by the host humoral immune response to AAV vectors. Specifically, while pre-existing neutralizing antibodies (NAbs) limit the cohort of eligible patients, NAb generation following treatment prevents vector re-dosing. Areas covered In this review, we discuss a spectrum of complementary strategies that can help circumvent the host humoral immune response to AAV. Expert opinion Specifically, we present a dual perspective, that is, vector versus host, and highlight the clinical attributes, potential caveats and limitations as well as complementarity associated with the various approaches. PMID:25985812

  14. Host–pathogen interactions and immune evasion strategies in Francisella tularensis pathogenicity

    PubMed Central

    Steiner, Don J; Furuya, Yoichi; Metzger, Dennis W

    2014-01-01

    Francisella tularensis is an intracellular Gram-negative bacterium that causes life-threatening tularemia. Although the prevalence of natural infection is low, F. tularensis remains a tier I priority pathogen due to its extreme virulence and ease of aerosol dissemination. F. tularensis can infect a host through multiple routes, including the intradermal and respiratory routes. Respiratory infection can result from a very small inoculum (ten organisms or fewer) and is the most lethal form of infection. Following infection, F. tularensis employs strategies for immune evasion that delay the immune response, permitting systemic distribution and induction of sepsis. In this review we summarize the current knowledge of F. tularensis in an immunological context, with emphasis on the host response and bacterial evasion of that response. PMID:25258544

  15. Nutritional strategies to boost immunity and prevent infection in elderly individuals.

    PubMed

    High, K P

    2001-12-01

    Older adults are at risk for malnutrition, which may contribute to their increased risk of infection. Nutritional supplementation strategies can reduce this risk and reverse some of the immune dysfunction associated with advanced age. This review discusses nutritional interventions that have been examined in clinical trials of older adults. The data support use of a daily multivitamin or trace-mineral supplement that includes zinc (elemental zinc, >20 mg/day) and selenium (100 microg/day), with additional vitamin E, to achieve a daily dosage of 200 mg/day. Specific syndromes may also be addressed by nutritional interventions (for example, cranberry juice consumption to reduce urinary tract infections) and may reduce antibiotic use in older adults, particularly those living in long-term care facilities. Drug-nutrient interactions are common in elderly individuals, and care providers should be aware of these interactions. Future research should evaluate important clinical end points rather than merely surrogate markers of immunity. PMID:11692301

  16. Effects of temperature on hard clam (Mercenaria mercenaria) immunity and QPX (Quahog Parasite Unknown) disease development: II. Defense parameters.

    PubMed

    Perrigault, Mickael; Dahl, Soren F; Espinosa, Emmanuelle Pales; Gambino, Laura; Allam, Bassem

    2011-02-01

    Quahog Parasite Unknown (QPX) is a protistan parasite affecting hard clams Mercenaria mercenaria along the Northeastern coast of the United States. The geographic distribution and occurrence of disease epizootics suggests a primary role of temperature in disease development. This study was designed to investigate the effect of temperature on constitutive and QPX-induced defense factors in M. mercenaria. Control and QPX-challenged (both experimentally and naturally) clams were maintained at 13, 21 and 27C for 4 months. Control and experimentally-infected clams originated from a southern broodstock (Florida, no prior reports of disease outbreak) while naturally-infected clams originated from a northern broodstock (Massachusetts, enzootic area). Standard and QPX-specific cellular and humoral defense parameters were assessed after 2 and 4 months. Measured parameters included total and differential hemocyte counts, reactive oxygen species production, phagocytic activity of hemocytes, lysozyme concentration in plasma, anti-QPX activity in plasma and resistance of hemocytes to cytotoxic QPX extracellular products. Results demonstrated a strong influence of temperature on constitutive clam defense factors with significant modulation of cellular and humoral parameters of control clams maintained at 13C compared to 21 and 27C. Similarly, clam response to QPX challenge was also affected by temperature. Challenged clams exhibited no difference from controls at 27C whereas different responses were observed at 21C and 13C compared to controls. Despite differences in infection mode (experimentally or naturally infected) and clam origin (northern and southern broodstocks), similarities were observed at 13C and 21C between QPX infected clams from Florida and Massachusetts. Clam response to temperature and to QPX exhibited interesting relationship with QPX disease development highlighting major influence of temperature on disease development. PMID:21115017

  17. Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infection.

    PubMed

    Cunningham-Rundles, Susanna; Ahrné, Siv; Johann-Liang, Rosemary; Abuav, Rachel; Dunn-Navarra, Ann-Margaret; Grassey, Claudia; Bengmark, Stig; Cervia, Joseph S

    2011-12-01

    The hypothesis that probiotic administration protects the gut surface and could delay progression of Human Immunodeficiency Virus type1 (HIV-1) infection to the Acquired Immunodeficiency Syndrome (AIDS) was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT) for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg) cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria which upregulate Treg activation have shown promise in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections, and immune activation contributes to nutritional deficiencies that have lasting consequences especially in the HIV-1 infected child. While effective anti-retroviral therapy (ART) has enhanced survival, wasting is still an independent predictor of survival and a major presenting symptom. Congenital exposure to HIV-1 is a risk factor for growth delay in both infected and non-infected infants. Nutritional intervention after 6 months of age appears to be largely ineffective. A meta analysis of randomized, controlled clinical trials of infant formulae supplemented with Bifidobacterium lactis showed that weight gain was significantly greater in infants who received B. lactis compared to formula alone. Pilot studies have shown that probiotic bacteria given as a supplement have improved growth and protected against loss of CD4+ T cells. The recognition that normal bacterial flora prime neonatal immune response and that abnormal flora have a profound impact on metabolism has generated insight into potential mechanisms of gut dysfunction in many settings including HIV-1 infection. As discussed here, current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection. Probiotic bacteria have proven active against bacterial vaginosis in HIV-1 positive women and have enhanced growth in infants with congenital HIV-1 infection. Probiotic bacteria may stabilize CD4+ T cell numbers in HIV-1 infected children and are likely to have protective effects against inflammation and chronic immune activation of the gastrointestinal immune system. PMID:22292110

  18. Maternal uptake of pertussis cocooning strategy and other pregnancy related recommended immunizations.

    PubMed

    Wong, C Y; Thomas, N J; Clarke, M; Boros, C; Tuckerman, J; Marshall, H S

    2015-01-01

    Maternal immunization is an important strategy to prevent severe morbidity and mortality in mothers and their offspring. This study aimed to identify whether new parents were following immunization recommendations prior to pregnancy, during pregnancy, and postnatally. A cross-sectional survey was conducted by a questionnaire administered antenatally to pregnant women attending a maternity hospital with a follow-up telephone interview at 8-10 weeks post-delivery. Factors associated with uptake of pertussis vaccination within the previous 5 y or postnatally and influenza vaccination during pregnancy were explored using log binomial regression models. A total of 297 pregnant women completed the questionnaire. For influenza vaccine, 20.3% were immunized during pregnancy and 3.0% postnatally. For pertussis vaccine, 13.1% were vaccinated within 5 y prior to pregnancy and 31 women received the vaccine postnatally, 16 (51.6%) received the vaccine >4 weeks after delivery. Receiving a recommendation from a healthcare provider (HCP) was an independent predictor for receipt of both pertussis (RR 2.07, p < 0.001) and influenza vaccine (RR 2.26, p = 0.001). Non-English speaking mothers were significantly less likely to have received pertussis vaccination prior to pregnancy or postnatally (RR 0.24, p = 0.011). Multiparous pregnant women were less likely to have received an influenza vaccine during their current pregnancy (p = 0.015). Uptake of pregnancy related immunization is low and likely due to poor knowledge of availability, language barriers and lack of recommendations from HCPs. Strategies to improve maternal vaccine uptake should include education about recommended vaccines for both HCPs and parents and written information in a variety of languages. PMID:25874807

  19. Protective immunity enhanced by chimeric DNA prime-protein booster strategy against Eimeria tenella challenge.

    PubMed

    Xu, Shou-Zhen; Chen, Tong; Wang, Ming

    2006-12-01

    In an attempt to investigate the immune efficacy ofa DNA prime-protein booster strategy against avian coccidiosis with a chimeric construct, the Eimeria tenella antigen gene (3-1E) and chicken interferon gamma gene (ChIFN-gamma) were subcloned into the mammalian expression vector proVAX forming the plasmids proE and prol, and then linked by splicing overlap extension by polymerase chain reaction to construct the chimeric plasmid prolE; the chimeric protein (rlE) was expressed in Escherichia coli harboring the constructed plasmid pGEX/IE. Broilers were administered two intramuscular injections with the constructed DNA vaccines (50 microg); in the protein booster groups 100 microg of the rlE were given following the proIE prime. After challenge the proIE-vaccinated chickens showed the protective immunity as demonstrated by significantly reduced oocyst shedding compared with chickens immunized with proE, but the prolE vaccine did not have an additive effect of increasing antibody titer and body weight gain. The chickens in the rlE booster groups had significantly higher specific antibody responses than those immunized with prolE, and displayed further decreased oocyst shedding and increased body weight gain. Taken together, these results indicate that ChIFN-gamma exerts an adjuvant effect coexpressed with 3-1E and provide the first evidence that the DNA prime-protein booster strategy is able to augment the protective efficacy of chimeric DNA vaccine against challenge with Eimeria tenella. PMID:17274297

  20. Maternal Antibodies: Clinical Significance, Mechanism of Interference with Immune Responses, and Possible Vaccination Strategies

    PubMed Central

    Niewiesk, Stefan

    2014-01-01

    Neonates have an immature immune system, which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is exemplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B cell receptor (BCR) with the Fcγ-receptor IIB by a vaccine–antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2) signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant, the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing this concept. PMID:25278941

  1. Innate immune response during herpes simplex virus encephalitis and development of immunomodulatory strategies.

    PubMed

    Piret, Jocelyne; Boivin, Guy

    2015-09-01

    Herpes simplex viruses are large double-stranded DNA viruses. These viruses have the ability to establish a lifelong latency in sensory ganglia and to invade and replicate in the CNS. Apart from relatively benign mucosal infections, HSV is responsible for severe illnesses including HSV encephalitis (HSE). HSE is the most common cause of sporadic, potentially fatal viral encephalitis in Western countries. If left untreated, the mortality rate associated with HSE is approximately 70%. Despite antiviral therapy, the mortality is still higher than 30%, and almost 60% of surviving individuals develop neurological sequelae. It is suggested that direct virus-related and indirect immune-mediated mechanisms contribute to the damages occurring in the CNS during HSE. In this manuscript, we describe the innate immune response to HSV, the development of HSE in mice knock-out for proteins of the innate immune system as well as inherited deficiencies in key components of the signaling pathways involved in the production of type I interferon that could predispose individuals to develop HSE. Finally, we review several immunomodulatory strategies aimed at modulating the innate immune response at a critical time after infection that were evaluated in mouse models and could be combined with antiviral therapy to improve the prognosis of HSE. In conclusion, the cerebral innate immune response that develops during HSE is a "double-edged sword" as it is critical to control viral replication in the brain early after infection, but, if left uncontrolled, may also result in an exaggerated inflammatory response that could be detrimental to the host. PMID:26205506

  2. Sexual self-defense versus the liaison dangereuse: a strategy for AIDS prevention in the '90s.

    PubMed

    Nelson, E W

    1991-01-01

    The present public health strategy to encourage the adoption of "safe sex" practices to contain the AIDS epidemic in America is incomplete. Current policy is responsive to and appropriate for control of homosexual, but not heterosexual transmission. Powerful societal forces restrict a woman's perception of risk. Consequently, the adoption of safe sex (condom use/insistence on use) by women at risk has not matched safe sex practice by homosexual men. Predictably, pattern two (heterosexual, maternal-fetal) HIV transmission is now rapidly increasing in the United States, particularly among minority women. In anticipation of an intensified pattern two subepidemic, AIDS containment policy should be reoriented to develop the role of women in AIDS prevention. An initiative, termed "sexual self-defense" (SSD), combines the technology of double-barrier (female irrespective of male) protection with a "universal precautions" approach to long-term sexual risk management. The initiative addresses both per-contact infectiousness and new partner acquisition, the principal determinants of HIV spread. As a female-targeted strategy, SSD is a timely supplement to existing programs, consistent with the direction of contemporary women's movements in the United States. A "street smart" approach, SSD bridges ethnic and socioeconomic individual differences. As a unifying philosophy of risk management in health promotion, SSD may avert the threatened fragmentation of AIDS control from existing programs of sexually transmitted disease control and teenage pregnancy prevention. PMID:1931142

  3. Immunizations.

    PubMed

    Sanford, Christopher A; Jong, Elaine C

    2016-03-01

    Vaccinations are a cornerstone of the pretravel consultation. The pretravel provider should assess a traveler's past medical history, planned itinerary, activities, mode of travel, and duration of stay and make appropriate vaccine recommendations. Given that domestic vaccine-preventable illnesses are more common in international travelers than are exotic or low-income nation-associated vaccine-preventable illnesses, clinicians should first ensure that travelers are current regarding routine immunizations. Additional immunizations may be indicated in some travelers. Familiarity with geographic distribution and seasonality of infectious diseases is essential. Clinicians should be cognizant of which vaccines are live, as there exist contraindications for live vaccines. PMID:26900111

  4. Innate immune recognition of microbial cell wall components and microbial strategies to evade such recognitions.

    PubMed

    Sukhithasri, V; Nisha, N; Biswas, Lalitha; Anil Kumar, V; Biswas, Raja

    2013-08-25

    The innate immune system constitutes the first line of defence against invading microbes. The basis of this defence resides in the recognition of defined structural motifs of the microbes called "Microbial associated molecular patterns" that are absent in the host. Cell wall, the outer layer of both bacterial and fungal cells, a unique structure that is absent in the host and is recognized by the germ line encoded host receptors. Nucleotide oligomerization domain proteins, peptidoglycan recognition proteins and C-type lectins are host receptors that are involved in the recognition of bacterial cell wall (usually called peptidoglycan), whereas fungal cell wall components (N- and O-linked mannans, β-glucans etc.) are recognized by host receptors like C-type lectins (Dectin-1, Dectin-2, mannose receptor, DC-SIGN), Toll like receptors-2 and -4 (TLR-2 and TLR-4). These recognitions lead to activation of a variety of host signaling cascades and ultimate production of anti-microbial compounds including phospholipase A2, antimicrobial peptides, lysozyme, reactive oxygen and nitrogen species. These molecules act in cohort against the invading microbes to eradicate infections. Additionally pathogen recognition leads to the production of cytokines, which further activate the adaptive immune system. Both pathogenic and commensal bacteria and fungus use numerous strategies to subvert the host defence. These strategies include bacterial peptidoglycan glycan backbone modifications by O-acetylation, N-deacetylation, N-glycolylation and stem peptide modifications by amidation of meso-Diaminopimelic acid; fungal cell wall modifications by shielding the β-glucan layer with mannoproteins and α-1,3 glucan. This review focuses on the recent advances in understanding the role of bacterial and fungal cell wall in their innate immune recognition and evasion strategies. PMID:23578963

  5. Comparative proteomic analysis of oil palm leaves infected with Ganoderma boninense revealed changes in proteins involved in photosynthesis, carbohydrate metabolism, and immunity and defense.

    PubMed

    Jeffery Daim, Leona Daniela; Ooi, Tony Eng Keong; Ithnin, Nalisha; Mohd Yusof, Hirzun; Kulaveerasingam, Harikrishna; Abdul Majid, Nazia; Karsani, Saiful Anuar

    2015-08-01

    The basidiomycete fungal pathogen Ganoderma boninense is the causative agent for the incurable basal stem rot (BSR) disease in oil palm. This disease causes significant annual crop losses in the oil palm industry. Currently, there is no effective method for disease control and elimination, nor is any molecular marker for early detection of the disease available. An understanding of how BSR affects protein expression in plants may help identify and/or assist in the development of an early detection protocol. Although the mode of infection of BSR disease is primarily via the root system, defense-related genes have been shown to be expressed in both the root and leafs. Thus, to provide an insight into the changes in the global protein expression profile in infected plants, comparative 2DE was performed on leaf tissues sampled from palms with and without artificial inoculation of the Ganoderma fungus. Comparative 2DE revealed that 54 protein spots changed in abundance. A total of 51 protein spots were successfully identified by LC-QTOF MS/MS. The majority of these proteins were those involved in photosynthesis, carbohydrate metabolism as well as immunity and defense. PMID:25930948

  6. Differences in acquired immune deficiency syndrome treatment and evaluation strategies between Chinese and Western Medicine.

    PubMed

    Liu, Zhibin; Li, Xia; Yang, Jiping; Xu, Liran; Guo, Huijun

    2015-12-01

    Complementary and alternative medicine, including Chinese medicine (CM), has been used to treat acquired immune deficiency syndrome (AIDS) foralmost 30 years. We aimed to compare the main differences between AIDS treatment and evaluation strategies between CM and Western Medicine (WM), and analyze advantages and disadvantages. The characteristics of integrative medicine (IM), based on CM and WM, include a patient-centered mode of medicine based on evidence. IM focuses on complex intervention and management with systemic and individual treatment. The evaluation indexes of IM might consist of objective indicators and subjective indexes. IM might be a more valuable method for treating AIDS in the future instead of WM or CM alone. PMID:26742320

  7. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

    Contents of this double journal issue concern immunization and primary health care of children. The issue decribes vaccine storage and sterilization techniques, giving particular emphasis to the role of the cold chain, i.e., the maintenance of a specific temperature range to assure potency of vaccines as they are moved from a national storage…

  8. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

    Contents of this double journal issue concern immunization and primary health care of children. The issue decribes vaccine storage and sterilization techniques, giving particular emphasis to the role of the cold chain, i.e., the maintenance of a specific temperature range to assure potency of vaccines as they are moved from a national storage

  9. A Metabolic Profiling Strategy for the Dissection of Plant Defense against Fungal Pathogens

    PubMed Central

    Aliferis, Konstantinos A.; Faubert, Denis; Jabaji, Suha

    2014-01-01

    Here we present a metabolic profiling strategy employing direct infusion Orbitrap mass spectrometry (MS) and gas chromatography-mass spectrometry (GC/MS) for the monitoring of soybean's (Glycine max L.) global metabolism regulation in response to Rhizoctonia solani infection in a time-course. Key elements in the approach are the construction of a comprehensive metabolite library for soybean, which accelerates the steps of metabolite identification and biological interpretation of results, and bioinformatics tools for the visualization and analysis of its metabolome. The study of metabolic networks revealed that infection results in the mobilization of carbohydrates, disturbance of the amino acid pool, and activation of isoflavonoid, α-linolenate, and phenylpropanoid biosynthetic pathways of the plant. Components of these pathways include phytoalexins, coumarins, flavonoids, signaling molecules, and hormones, many of which exhibit antioxidant properties and bioactivity helping the plant to counterattack the pathogen's invasion. Unraveling the biochemical mechanism operating during soybean-Rhizoctonia interaction, in addition to its significance towards the understanding of the plant's metabolism regulation under biotic stress, provides valuable insights with potential for applications in biotechnology, crop breeding, and agrochemical and food industries. PMID:25369450

  10. Simulations of defense strategies for Bennu: Material characterization and impulse delivery

    DOE PAGESBeta

    Herbold, E. B.; Owen, J. M.; Swift, D. C.; Miller, P. L.

    2015-05-19

    Assessments of asteroid deflection strategies depend on material characterization to reduce the uncertainty in predictions of the deflection velocity resulting from impulsive loading. In addition to strength, equation of state, the initial state of the material including its competency (i.e. fractured or monolithic) and the amount of micro- or macroscopic porosity are important considerations to predict the thermomechanical response. There is recent interest in observing near-Earth asteroid (101955) Bennu due to its classification of being potentially hazardous with close approaches occurring every 6 years. Bennu is relatively large with a nominal diameter of 492 m, density estimates ranging from 0.9-1.26more » g/cm³ and is composed mainly of carbonaceous chondrite. There is a lack of data for highly porous carbonaceous chondrite at very large pressures and temperatures. In the absence of the specific material composition and state (e.g. layering, porosity as a function of depth) on Bennu we introduce a continuum constitutive model based on the response of granular materials and provide impact and standoff explosion simulations to investigate the response of highly porous materials to these types of impulsive loading scenarios. Simulations with impact speeds of 5 km/s show that the shock wave emanating from the impact site is highly dispersive and that a 10% porous material has a larger compacted volume compared with a 40% porous material with the same bulk density due to differences in compaction response.« less

  11. Simulations of defense strategies for Bennu: Material characterization and impulse delivery

    SciTech Connect

    Herbold, E. B.; Owen, J. M.; Swift, D. C.; Miller, P. L.

    2015-05-19

    Assessments of asteroid deflection strategies depend on material characterization to reduce the uncertainty in predictions of the deflection velocity resulting from impulsive loading. In addition to strength, equation of state, the initial state of the material including its competency (i.e. fractured or monolithic) and the amount of micro- or macroscopic porosity are important considerations to predict the thermomechanical response. There is recent interest in observing near-Earth asteroid (101955) Bennu due to its classification of being potentially hazardous with close approaches occurring every 6 years. Bennu is relatively large with a nominal diameter of 492 m, density estimates ranging from 0.9-1.26 g/cm³ and is composed mainly of carbonaceous chondrite. There is a lack of data for highly porous carbonaceous chondrite at very large pressures and temperatures. In the absence of the specific material composition and state (e.g. layering, porosity as a function of depth) on Bennu we introduce a continuum constitutive model based on the response of granular materials and provide impact and standoff explosion simulations to investigate the response of highly porous materials to these types of impulsive loading scenarios. Simulations with impact speeds of 5 km/s show that the shock wave emanating from the impact site is highly dispersive and that a 10% porous material has a larger compacted volume compared with a 40% porous material with the same bulk density due to differences in compaction response.

  12. The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes

    PubMed Central

    Witte, Katrin; Koch, Egon; Volk, Hans-Dieter; Wolk, Kerstin; Sabat, Robert

    2015-01-01

    Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-?, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-?, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-?, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-? staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-? production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-? and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. PMID:26406906

  13. Tribolium castaneum immune defense genes are differentially expressed in response to Bacillus thuringiensis toxins sharing common receptor molecules and exhibiting disparate toxicity.

    PubMed

    Contreras, Estefanía; Benito-Jardón, María; López-Galiano, M José; Real, M Dolores; Rausell, Carolina

    2015-06-01

    In Tribolium castaneum larvae we have demonstrated by RNA interference knockdown that the Bacillus thuringiensis Cry3Ba toxin receptors Cadherin-like and Sodium solute symporter proteins are also functional receptors of the less active Cry3Aa toxin. Differences in susceptibility to B. thuringiensis infection might not only rely on toxin-receptor interaction but also on host defense mechanisms. We compared the expression of the immune related genes encoding Apolipophorin-III and two antimicrobial peptides, Defensin3 and Defensin2 after B. thuringiensis challenge. All three genes were up-regulated following Cry3Ba spore-crystal intoxication whereas only Defensins gene expression was induced upon Cry3Aa spore-crystal treatment, evidencing a possible association between host immune response and larval susceptibility to B. thuringiensis. We assessed the antimicrobial activity spectra of T. castaneum defensins peptide fragments and found that a peptide fragment of Defensin3 was effective against the human microbial pathogens, Escherichia coli, Staphylococcus aureus and Candida albicans, being S. aureus the most susceptible one. PMID:25684675

  14. An Active Immune Defense with a Minimal CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) RNA and without the Cas6 Protein*

    PubMed Central

    Maier, Lisa-Katharina; Stachler, Aris-Edda; Saunders, Sita J.; Backofen, Rolf; Marchfelder, Anita

    2015-01-01

    The prokaryotic immune system CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) is a defense system that protects prokaryotes against foreign DNA. The short CRISPR RNAs (crRNAs) are central components of this immune system. In CRISPR-Cas systems type I and III, crRNAs are generated by the endonuclease Cas6. We developed a Cas6b-independent crRNA maturation pathway for the Haloferax type I-B system in vivo that expresses a functional crRNA, which we termed independently generated crRNA (icrRNA). The icrRNA is effective in triggering degradation of an invader plasmid carrying the matching protospacer sequence. The Cas6b-independent maturation of the icrRNA allowed mutation of the repeat sequence without interfering with signals important for Cas6b processing. We generated 23 variants of the icrRNA and analyzed them for activity in the interference reaction. icrRNAs with deletions or mutations of the 3? handle are still active in triggering an interference reaction. The complete 3? handle could be removed without loss of activity. However, manipulations of the 5? handle mostly led to loss of interference activity. Furthermore, we could show that in the presence of an icrRNA a strain without Cas6b (?cas6b) is still active in interference. PMID:25512373

  15. Cloak and Dagger: Alternative Immune Evasion and Modulation Strategies of Poxviruses.

    PubMed

    Bidgood, Susanna R; Mercer, Jason

    2015-08-01

    As all viruses rely on cellular factors throughout their replication cycle, to be successful they must evolve strategies to evade and/or manipulate the defence mechanisms employed by the host cell. In addition to their expression of a wide array of host modulatory factors, several recent studies have suggested that poxviruses may have evolved unique mechanisms to shunt or evade host detection. These potential mechanisms include mimicry of apoptotic bodies by mature virions (MVs), the use of viral sub-structures termed lateral bodies for the packaging and delivery of host modulators, and the formation of a second, "cloaked" form of infectious extracellular virus (EVs). Here we discuss these various strategies and how they may facilitate poxvirus immune evasion. Finally we propose a model for the exploitation of the cellular exosome pathway for the formation of EVs. PMID:26308043

  16. Cloak and Dagger: Alternative Immune Evasion and Modulation Strategies of Poxviruses

    PubMed Central

    Bidgood, Susanna R.; Mercer, Jason

    2015-01-01

    As all viruses rely on cellular factors throughout their replication cycle, to be successful they must evolve strategies to evade and/or manipulate the defence mechanisms employed by the host cell. In addition to their expression of a wide array of host modulatory factors, several recent studies have suggested that poxviruses may have evolved unique mechanisms to shunt or evade host detection. These potential mechanisms include mimicry of apoptotic bodies by mature virions (MVs), the use of viral sub-structures termed lateral bodies for the packaging and delivery of host modulators, and the formation of a second, cloaked form of infectious extracellular virus (EVs). Here we discuss these various strategies and how they may facilitate poxvirus immune evasion. Finally we propose a model for the exploitation of the cellular exosome pathway for the formation of EVs. PMID:26308043

  17. Unraveling the Evolution of the Atlantic Cods (Gadus morhua L.) Alternative Immune Strategy

    PubMed Central

    Malmstrm, Martin; Jentoft, Sissel; Gregers, Tone F.; Jakobsen, Kjetill S.

    2013-01-01

    Genes encoding the major histocompatibility complex (MHC) have been thought to play a vital role in the adaptive immune system in all vertebrates. The discovery that Atlantic cod (Gadus morhua) has lost important components of the MHC II pathway, accompanied by an unusually high number of MHC I genes, shed new light on the evolution and plasticity of the immune system of teleosts as well as in higher vertebrates. The overall aim of this study was to further investigate the highly expanded repertoire of MHC I genes using a cDNA approach to obtain sequence information of both the binding domains and the sorting signaling potential in the cytoplasmic tail. Here we report a novel combination of two endosomal sorting motifs, one tyrosine-based associated with exogenous peptide presentation by cross-presenting MHCI molecules, and one dileucine-based associated with normal MHC II functionality. The two signal motifs were identified in the cytoplasmic tail in a subset of the genes. This indicates that these genes have evolved MHC II-like functionality, allowing a more versatile use of MHC I through cross-presentation. Such an alternative immune strategy may have arisen through adaptive radiation and acquisition of new gene function as a response to changes in the habitat of its ancestral lineage. PMID:24019946

  18. Unraveling the evolution of the Atlantic cod's (Gadus morhua L.) alternative immune strategy.

    PubMed

    Malmstrøm, Martin; Jentoft, Sissel; Gregers, Tone F; Jakobsen, Kjetill S

    2013-01-01

    Genes encoding the major histocompatibility complex (MHC) have been thought to play a vital role in the adaptive immune system in all vertebrates. The discovery that Atlantic cod (Gadus morhua) has lost important components of the MHC II pathway, accompanied by an unusually high number of MHC I genes, shed new light on the evolution and plasticity of the immune system of teleosts as well as in higher vertebrates. The overall aim of this study was to further investigate the highly expanded repertoire of MHC I genes using a cDNA approach to obtain sequence information of both the binding domains and the sorting signaling potential in the cytoplasmic tail. Here we report a novel combination of two endosomal sorting motifs, one tyrosine-based associated with exogenous peptide presentation by cross-presenting MHCI molecules, and one dileucine-based associated with normal MHC II functionality. The two signal motifs were identified in the cytoplasmic tail in a subset of the genes. This indicates that these genes have evolved MHC II-like functionality, allowing a more versatile use of MHC I through cross-presentation. Such an alternative immune strategy may have arisen through adaptive radiation and acquisition of new gene function as a response to changes in the habitat of its ancestral lineage. PMID:24019946

  19. A novel molluscan Fos gene with immune defense function identified in the Hong Kong oyster, Crassostrea hongkongensis.

    PubMed

    Qu, Fufa; Xiang, Zhiming; Wang, Fuxuan; Zhang, Yang; Tong, Ying; Li, Jun; Zhang, Yuehuan; Yu, Ziniu

    2015-07-01

    The transcription factor Fos is a member of one of the best-studied AP-1 sub-families and has been implicated in a wide variety of biological processes, including the regulation of apoptosis, immune responses and cytokine production. In this report, a novel mollusk Fos (referred to as ChFos) gene was cloned and characterized from the Hong Kong oyster, Crassostrea hongkongensis. The deduced ChFos protein sequence comprised 333 amino acids and shared significant homology with invertebrate homologs. Phylogenetic analysis revealed that ChFos clusters with Fos from Crassostrea gigas and Crassostrea ariakensis. Quantitative real-time PCR analysis revealed that ChFos mRNA was broadly expressed in all tested tissues and during different stages of the oyster's embryonic and larval development. In addition, the expression of ChFos mRNA was significantly up-regulated under challenge with microorganisms (Vibrio alginolyticus, Staphylococcus haemolyticus and Saccharomyces cerevisiae) and pathogen-associated molecular patterns (PAMPs: LPS, PGN and polyI:C). Moreover, fluorescence microscopy showed that ChFos protein is localized in the nucleus in HEK293T cells. Reporter assays suggested that ChFos may act as an efficient transcription activator in the regulation of AP-1-responsive gene expression through interaction with ChJun. Overall, this study presents the first experimental evidence of the presence and functional characteristics of Fos in mollusks, which reveals its involvement in host protection against immune challenge in the oyster. PMID:25841657

  20. Co-immunization with DNA and protein mixture: A safe and efficacious immunotherapeutic strategy for Alzheimer's disease in PDAPP mice

    PubMed Central

    Liu, Si; Shi, DanYang; Wang, Hai-Chao; Yu, Yun-Zhou; Xu, Qing; Sun, Zhi-Wei

    2015-01-01

    Active immunotherapy targeting β-amyloid (Aβ) is the most promising strategy to prevent or treat Alzheimer's disease (AD). Based on pre-clinical studies and clinical trials, a safe and effective AD vaccine requires a delicate balance between providing therapeutically adequate anti-Aβ antibodies and eliminating or suppressing unwanted adverse T cell-mediated inflammatory reactions. We describe here the immunological characterization and protective efficacy of co-immunization with a 6Aβ15-T DNA and protein mixture without adjuvant as an AD immunotherapeutic strategy. Impressively, this co-immunization induced robust Th2-polarized Aβ-specific antibodies while simultaneously suppressed unwanted inflammatory T cell reactions and avoiding Aβ42-specific T cell-mediated autoimmune responses in immunized mice. Co-immunization with the DNA + protein vaccine could overcome Aβ42-associated hypo-responsiveness and elicit long-term Aβ-specific antibody responses, which helped to maintain antibody-mediated clearance of amyloid and accordingly alleviated AD symptoms in co-immunized PDAPP mice. Our DNA and protein combined vaccine, which could induce an anti-inflammatory Th2 immune response with high level Aβ-specific antibodies and low level IFN-γ production, also demonstrated the capacity to inhibit amyloid accumulation and prevent cognitive dysfunction. Hence, co-immunization with antigen-matched DNA and protein may represent a novel and efficacious strategy for AD immunotherapy to eliminate T cell inflammatory reactions while retaining high level antibody responses. PMID:25586780

  1. [Enhancement of endogenous antioxidant defenses: a promising strategy for prevention of skin cancers].

    PubMed

    Béani, J C

    2001-01-01

    There is considerable evidence that ultraviolet radiation (UV) from sunlight is implicated in skin carcinogenesis. So the risks of cutaneous cancer have increased during the last decade due to increase of sun exposure. For a long time, ultraviolet B radiation (UVB: 290-320 nm) have been considered to be the more efficient wavelength in eliciting carcinogenesis in human skin. It is today clear that UVA (320-400 nm), especially UVA1 (340-400 nm) also participate to photo carcinogenesis. One of molecular mechanisms in the biological effects of UV is the induction of reactive oxygen species (ROS) directly or through endogenous photosensitization reactions. UVA radiation mainly acts via this production of ROS and the subsequent oxidative stress seems to play a crucial role in the deleterious effects of UVA. Fortunately, the skin possesses a wide range of interlinked antioxidant defence mechanism to protect itself from damage by UV-induced ROS. However, the capacity of these systems is not unlimited; they can be overwhelmed by excessive exposure to UV and then ROS can reach damaging levels. An interesting strategy to provide photoprotection would be to support or enhance one or more of these endogenous systems. In our experiments, we have evaluated the protective effect of glutathion, selenium and zinc, three compounds playing a pivotal role in the cellular defence against oxidative damage. We have irradiated both by UVA1 and UVB culture of human normal skin fibroblasts or of spontaneously immortalised human keratinocyte cell line Hacat. Before irradiation, treated cells were submitted to zinc deprivation by a diffusible zinc chelator, NNN' N'-tetrakis (2-pyridylmethyl) ethylene diamine (TPEN) or supplied with zinc chloride, thiols (N-acetyl-cysteine; N-acetyl-homocysteine-thiolactone, L2oxothiozolidine-4 carboxylate) selenium as sodium selenite. The cell viability was measured using the adhesion-proliferation method or a tetrazolium colorimetric assay. The damages induced to cellular membrane were appreciated by determination of thiobarbituric reactants (Tbars) by a fluorometric micromethod. Cellular DNA damage was examined by strand break determination carried out using the method described by Birnboim and Jevcak and by the Comet assay. Our results show that: UVA1 have a main part in cytotoxic effect of UVA and this effect is linked to ROS; thiols and selenium protect cells against UVA radiation with a synergic interaction and this protection acts though an increase in glutathion peroxidase activity; zinc protects against cytotoxicity of UVA and UVB and against UVB induced DNA damages; above all, DNA damages induced by UVA or UVB are significantly prevented by thiol molecules, selenium and zinc. As DNA damages have a main place in photocarcinogenesis, our results point out the potential interest of a photoprotection based on the support of endogenous antioxidant system. The research of new ways for photoprotection is indeed a necessity because sunscreens did not give convincing evidences of efficacy in preventing skin cancers. PMID:11974970

  2. Influence of OM-85 BV on different humoral and cellular immune defense mechanisms of the respiratory tract.

    PubMed

    Emmerich, B; Pachmann, K; Milatovic, D; Emslander, H P

    1992-01-01

    To clarify the mode of action of an oral bacterial extract (OM-85 BV) on local airway immunity pre- and posttherapeutic washings from bronchoalveolar lavage (BAL) fluid of 28 adult patients with nonobstructive chronic bronchitis were analysed. In comparison to healthy controls, an elevation of total cell count due to an increased number of PMN leukocytes, and an impaired activity of the alveolar macrophages measured by the chemiluminescence response to opsonized zymosan was observed in patients with chronic bronchitis. After treatment with OM-85 BV, the BAL CD4+/CD8+ lymphocyte ratio and BAL interferon-gamma levels were increased. The alveolar macrophage activity was normalized and the BAL IgA was regulated from a reduced or hyperelevated to a moderately increased level. PMID:1439235

  3. Human and animal isolates of Yersinia enterocolitica show significant serotype-specific colonization and host-specific immune defense properties.

    PubMed

    Schaake, Julia; Kronshage, Malte; Uliczka, Frank; Rohde, Manfred; Knuuti, Tobias; Strauch, Eckhard; Fruth, Angelika; Wos-Oxley, Melissa; Dersch, Petra

    2013-11-01

    Yersinia enterocolitica is a human pathogen that is ubiquitous in livestock, especially pigs. The bacteria are able to colonize the intestinal tract of a variety of mammalian hosts, but the severity of induced gut-associated diseases (yersiniosis) differs significantly between hosts. To gain more information about the individual virulence determinants that contribute to colonization and induction of immune responses in different hosts, we analyzed and compared the interactions of different human- and animal-derived isolates of serotypes O:3, O:5,27, O:8, and O:9 with murine, porcine, and human intestinal cells and macrophages. The examined strains exhibited significant serotype-specific cell binding and entry characteristics, but adhesion and uptake into different host cells were not host specific and were independent of the source of the isolate. In contrast, survival and replication within macrophages and the induced proinflammatory response differed between murine, porcine, and human macrophages, suggesting a host-specific immune response. In fact, similar levels of the proinflammatory cytokine macrophage inflammatory protein 2 (MIP-2) were secreted by murine bone marrow-derived macrophages with all tested isolates, but the equivalent interleukin-8 (IL-8) response of porcine bone marrow-derived macrophages was strongly serotype specific and considerably lower in O:3 than in O:8 strains. In addition, all tested Y. enterocolitica strains caused a considerably higher level of secretion of the anti-inflammatory cytokine IL-10 by porcine than by murine macrophages. This could contribute to limiting the severity of the infection (in particular of serotype O:3 strains) in pigs, which are the primary reservoir of Y. enterocolitica strains pathogenic to humans. PMID:23959720

  4. RabGAP22 Is Required for Defense to the Vascular Pathogen Verticillium longisporum and Contributes to Stomata Immunity

    PubMed Central

    Roos, Jonas; Bejai, Sarosh; Oide, Shinichi; Dixelius, Christina

    2014-01-01

    Verticillium longisporum is a soil-borne pathogen with a preference for plants within the family Brassicaceae. Following invasion of the roots, the fungus proliferates in the plant vascular system leading to stunted plant growth, chlorosis and premature senescence. RabGTPases have been demonstrated to play a crucial role in regulating multiple responses in plants. Here, we report on the identification and characterization of the Rab GTPase-activating protein RabGAP22 gene from Arabidopsis, as an activator of multiple components in the immune responses to V. longisporum. RabGAP22Pro:GUS transgenic lines showed GUS expression predominantly in root meristems, vascular tissues and stomata, whereas the RabGAP22 protein localized in the nucleus. Reduced RabGAP22 transcript levels in mutants of the brassinolide (BL) signaling gene BRI1-ASSOCIATED RECEPTOR KINASE 1, together with a reduction of fungal proliferation following BL pretreatment, suggested RabGAP22 to be involved in BL-mediated responses. Pull-down assays revealed SERINE:GLYOXYLATE AMINOTRANSFERASE (AGT1) as an interacting partner during V. longisporum infection and bimolecular fluorescence complementation (BiFC) showed the RabGAP22-AGT1 protein complex to be localized in the peroxisomes. Further, fungal-induced RabGAP22 expression was found to be associated with elevated endogenous levels of the plant hormones jasmonic acid (JA) and abscisic acid (ABA). An inadequate ABA response in rabgap22-1 mutants, coupled with a stomata-localized expression of RabGAP22 and impairment of guard cell closure in response to V. longisporum and Pseudomonas syringae, suggest that RabGAP22 has multiple roles in innate immunity. PMID:24505423

  5. Salmonella enterica serovar enteritidis antimicrobial peptide resistance genes aid in defense against chicken innate immunity, fecal shedding, and egg deposition.

    PubMed

    McKelvey, Jessica A; Yang, Ming; Jiang, Yanhua; Zhang, Shuping

    2014-12-01

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is a major etiologic agent of nontyphoid salmonellosis in the United States. S. Enteritidis persistently and silently colonizes the intestinal and reproductive tract of laying hens, resulting in contaminated poultry products. The consumption of contaminated poultry products has been identified as a significant risk factor for human salmonellosis. To understand the mechanisms S. Enteritidis utilizes to colonize and persist in laying hens, we used selective capture of transcribed sequences to identify genes overexpressed in the HD11 chicken macrophage cell line and in primary chicken oviduct epithelial cells. From the 15 genes found to be overexpressed in both cell types, we characterized the antimicrobial peptide resistance (AMPR) genes, virK and ybjX, in vitro and in vivo. In vitro, AMPR genes were required for natural morphology, motility, secretion, defense against detergents such as EDTA and bile salts, and resistance to antimicrobial peptides polymyxin B and avian β-defensins. From this, we inferred the AMPR genes play a role in outer membrane stability and/or modulation. In the intestinal tract, AMPR genes were involved in early intestinal colonization and fecal shedding. In the reproductive tract, virK was required in early colonization whereas a deletion of ybjX caused prolonged ovary colonization and egg deposition. Data from the present study indicate that AMPR genes are differentially utilized in various host environments, which may ultimately assist S. Enteritidis in persistent and silent colonization of chickens. PMID:25267840

  6. Salmonella enterica Serovar Enteritidis Antimicrobial Peptide Resistance Genes Aid in Defense against Chicken Innate Immunity, Fecal Shedding, and Egg Deposition

    PubMed Central

    McKelvey, Jessica A.; Yang, Ming; Jiang, Yanhua

    2014-01-01

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is a major etiologic agent of nontyphoid salmonellosis in the United States. S. Enteritidis persistently and silently colonizes the intestinal and reproductive tract of laying hens, resulting in contaminated poultry products. The consumption of contaminated poultry products has been identified as a significant risk factor for human salmonellosis. To understand the mechanisms S. Enteritidis utilizes to colonize and persist in laying hens, we used selective capture of transcribed sequences to identify genes overexpressed in the HD11 chicken macrophage cell line and in primary chicken oviduct epithelial cells. From the 15 genes found to be overexpressed in both cell types, we characterized the antimicrobial peptide resistance (AMPR) genes, virK and ybjX, in vitro and in vivo. In vitro, AMPR genes were required for natural morphology, motility, secretion, defense against detergents such as EDTA and bile salts, and resistance to antimicrobial peptides polymyxin B and avian β-defensins. From this, we inferred the AMPR genes play a role in outer membrane stability and/or modulation. In the intestinal tract, AMPR genes were involved in early intestinal colonization and fecal shedding. In the reproductive tract, virK was required in early colonization whereas a deletion of ybjX caused prolonged ovary colonization and egg deposition. Data from the present study indicate that AMPR genes are differentially utilized in various host environments, which may ultimately assist S. Enteritidis in persistent and silent colonization of chickens. PMID:25267840

  7. A multifunctional peptide based on the neutrophil immune defense molecule, CAP37, has antibacterial and wound-healing properties

    PubMed Central

    Kasus-Jacobi, Anne; Noor-Mohammadi, Samaneh; Griffith, Gina L.; Hinsley, Heather; Mathias, Lauren; Pereira, H. Anne

    2015-01-01

    CAP37, a protein constitutively expressed in human neutrophils and induced in response to infection in corneal epithelial cells, plays a significant role in host defense against infection. Initially identified through its potent bactericidal activity for Gram-negative bacteria, it is now known that CAP37 regulates numerous host cell functions, including corneal epithelial cell chemotaxis. Our long-term goal is to delineate the domains of CAP37 that define these functions and synthesize bioactive peptides for therapeutic use. We report the novel finding of a multifunctional domain between aa 120 and 146. Peptide analogs 120–146 QR, 120–146 QH, 120–146 WR, and 120–146 WH were synthesized and screened for induction of corneal epithelial cell migration by use of the modified Boyden chamber assay, antibacterial activity, and LPS-binding activity. In vivo activity was demonstrated by use of mouse models of sterile and infected corneal wounds. The identity of the amino acid at position 132 (H vs. R) was important for cell migration and in vivo corneal wound healing. All analogs demonstrated antimicrobial activity. However, analogs containing a W at position 131 showed significantly greater antibacterial activity against the Gram-negative pathogen Pseudomonas aeruginosa. All analogs bound P. aeruginosa LPS. Topical administration of analog 120–146 WH, in addition to accelerating corneal wound healing, effectively cleared a corneal infection as a result of P. aeruginosa. In conclusion, we have identified a multifunctional bioactive peptide, based on CAP37, that induces cell migration, possesses antibacterial and LPS-binding activity, and is effective at healing infected and noninfected corneal wounds in vivo. PMID:25412625

  8. Spray-dried plasma promotes growth, modulates the activity of antioxidant defenses, and enhances the immune status of gilthead sea bream (Sparus aurata) fingerlings.

    PubMed

    Gisbert, E; Skalli, A; Campbell, J; Solovyev, M M; Rodríguez, C; Dias, J; Polo, J

    2015-01-01

    Terrestrial animal byproduct meals, including nonruminant blood meal and blood products, represent the largest and largely untapped safe source of animal protein available within the international market for the aquafeed industry. Spray-dried blood and spray-dried plasma (SDP) proteins have long been recognized as high-quality feed ingredients for farmed animals. In this study, we evaluated the inclusion of SDP from porcine blood (SDPP) in growing diets for gilthead sea bream. Three isonitrogenous (CP = 51.2%) and isolipidic (fat = 12.4%) diets manufactured by cold extrusion (0.8 to 1.5 mm pellet size) were prepared by substituting high-quality fish meal with 0, 3, and 6% SDPP. The diets were tested for a period of 60 d at 22°C with 4 replicates each (400-L cylindroconical tanks, 150 fish per tank, and initial density = 0.5 kg/m(3)). The SDPP inclusion in diets for gilthead sea bream fingerlings were evaluated in terms of growth performance, feed utilization, histological organization of the intestinal mucosa, activity of oxidative stress enzymes (catalase, glutathione S-transferase, glutathione peroxidase, and glutathione reductase) in the intestine, and nonspecific serum immune parameters (lysozyme and bactericidal activity). Results from this study indicated that dietary SDPP promoted fish growth in terms of BW and length; fish fed 3% SDPP were 10.5% heavier (P < 0.05) than those fed the control diet. Spray-dried plasma from porcine blood modulated the activity of the antioxidative defenses in the intestine (P < 0.05) and increased the density of goblet cells in the intestine (P < 0.05) and benefited the host by providing an effective immune barrier against gut pathogenic microbiota. The nonspecific serum immune response in fish fed diets with SDPP was greater (P < 0.05) than in fish fed the control diet. These results indicated that the inclusion of SDPP in gilthead sea bream feed could be beneficial for the fish by enhancing intestinal and serum innate immune function and the activity of antioxidative stress enzymes of the intestine and promoting growth performance. PMID:25568376

  9. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection.

    PubMed

    Fujimura, Kei E; Demoor, Tine; Rauch, Marcus; Faruqi, Ali A; Jang, Sihyug; Johnson, Christine C; Boushey, Homer A; Zoratti, Edward; Ownby, Dennis; Lukacs, Nicholas W; Lynch, Susan V

    2014-01-14

    Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c(+)/CD11b(+) and CD11c(+)/CD8(+) cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults. PMID:24344318

  10. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection

    PubMed Central

    Fujimura, Kei E.; Demoor, Tine; Rauch, Marcus; Faruqi, Ali A.; Jang, Sihyug; Johnson, Christine C.; Boushey, Homer A.; Zoratti, Edward; Ownby, Dennis; Lukacs, Nicholas W.; Lynch, Susan V.

    2014-01-01

    Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults. PMID:24344318

  11. How Biofilms Evade Host Defenses.

    PubMed

    Roilides, Emmanuel; Simitsopoulou, Maria; Katragkou, Aspasia; Walsh, Thomas J

    2015-06-01

    The steps involved during the biofilm growth cycle include attachment to a substrate followed by more permanent adherence of the microorganisms, microcolony arrangement, and cell detachment required for the dissemination of single or clustered cells to other organ systems. Various methods have been developed for biofilm detection and quantitation. Biofilm-producing microorganisms can be detected in tissue culture plates, using silicone tubes and staining methods, and by visual assessment using scanning electron microscopy or confocal scanning laser microscopy. Quantitative measurement of biofilm growth is determined by using methods that include dry cell weight assays, colony-forming-unit counting, DNA quantification, or XTT 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide reduction assay. Upon infection, innate immune defense strategies are able to establish an immediate response through effector mechanisms mediated by immune cells, receptors, and several humoral factors. We present an overview of the life cycle of biofilms and their diversity, detection methods for biofilm development, and host immune responses to pathogens. We then focus on current concepts in bacterial and fungal biofilm immune evasion mechanisms. This appears to be of particular importance because the use of host immune responses may represent a novel therapeutic approach against biofilms. PMID:26185085

  12. Modeling the Impact of Alternative Immunization Strategies: Using Matrices as Memory Lanes.

    PubMed

    Alonso, Wladimir J; Rabaa, Maia A; Giglio, Ricardo; Miller, Mark A; Schuck-Paim, Cynthia

    2015-01-01

    Existing modeling approaches are divided between a focus on the constitutive (micro) elements of systems or on higher (macro) organization levels. Micro-level models enable consideration of individual histories and interactions, but can be unstable and subject to cumulative errors. Macro-level models focus on average population properties, but may hide relevant heterogeneity at the micro-scale. We present a framework that integrates both approaches through the use of temporally structured matrices that can take large numbers of variables into account. Matrices are composed of several bidimensional (timeage) grids, each representing a state (e.g. physiological, immunological, socio-demographic). Time and age are primary indices linking grids. These matrices preserve the entire history of all population strata and enable the use of historical events, parameters and states dynamically in the modeling process. This framework is applicable across fields, but particularly suitable to simulate the impact of alternative immunization policies. We demonstrate the framework by examining alternative strategies to accelerate measles elimination in 15 developing countries. The model recaptured long-endorsed policies in measles control, showing that where a single routine measles-containing vaccine is employed with low coverage, any improvement in coverage is more effective than a second dose. It also identified an opportunity to save thousands of lives in India at attractively low costs through the implementation of supplementary immunization campaigns. The flexibility of the approach presented enables estimating the effectiveness of different immunization policies in highly complex contexts involving multiple and historical influences from different hierarchical levels. PMID:26509976

  13. A novel strategy for the rapid preparation and isolation of intact immune complexes from peptide mixtures.

    PubMed

    Al-Majdoub, Mahmoud; Opuni, Kwabena F M; Yefremova, Yelena; Koy, Cornelia; Lorenz, Peter; El-Kased, Reham F; Thiesen, Hans-Jrgen; Glocker, Michael O

    2014-09-01

    The development and application of a miniaturized affinity system for the preparation and release of intact immune complexes are demonstrated. Antibodies were reversibly affinity-adsorbed on pipette tips containing protein G and protein A, respectively. Antigen proteins were digested with proteases and peptide mixtures were exposed to attached antibodies; forming antibody-epitope complexes, that is, immune complexes. Elution with millimolar indole propionic acid (IPA)-containing buffers under neutral pH conditions allowed to effectively isolate the intact immune complexes in purified form. Size exclusion chromatography was performed to determine the integrity of the antibody-epitope complexes. Mass spectrometric analysis identified the epitope peptides in the respective SEC fractions. His-tag-containing recombinant human glucose-6-phosphate isomerase in combination with an anti-His-tag monoclonal antibody was instrumental to develop the method. Application was extended to the isolation of the intact antibody-epitope complex of a recombinant human tripartite motif 21 (rhTRIM21) auto-antigen in combination with a rabbit polyclonal anti-TRIM21 antibody. Peptide chip analysis showed that antibody-epitope binding of rhTRIM21 peptide antibody complexes was not affected by the presence of IPA in the elution buffer. By contrast, protein G showed an ion charge structure by electrospray mass spectrometry that resembled a denatured conformation when exposed to IPA-containing buffers. The advantages of this novel isolation strategy are low sample consumption and short experimental duration in addition to the direct and robust methodology that provides easy access to intact antibody-antigen complexes under neutral pH and low salt conditions for subsequent investigations. PMID:25042711

  14. Modeling the Impact of Alternative Immunization Strategies: Using Matrices as Memory Lanes

    PubMed Central

    Alonso, Wladimir J.; Rabaa, Maia A.; Giglio, Ricardo; Miller, Mark A.; Schuck-Paim, Cynthia

    2015-01-01

    Existing modeling approaches are divided between a focus on the constitutive (micro) elements of systems or on higher (macro) organization levels. Micro-level models enable consideration of individual histories and interactions, but can be unstable and subject to cumulative errors. Macro-level models focus on average population properties, but may hide relevant heterogeneity at the micro-scale. We present a framework that integrates both approaches through the use of temporally structured matrices that can take large numbers of variables into account. Matrices are composed of several bidimensional (timeage) grids, each representing a state (e.g. physiological, immunological, socio-demographic). Time and age are primary indices linking grids. These matrices preserve the entire history of all population strata and enable the use of historical events, parameters and states dynamically in the modeling process. This framework is applicable across fields, but particularly suitable to simulate the impact of alternative immunization policies. We demonstrate the framework by examining alternative strategies to accelerate measles elimination in 15 developing countries. The model recaptured long-endorsed policies in measles control, showing that where a single routine measles-containing vaccine is employed with low coverage, any improvement in coverage is more effective than a second dose. It also identified an opportunity to save thousands of lives in India at attractively low costs through the implementation of supplementary immunization campaigns. The flexibility of the approach presented enables estimating the effectiveness of different immunization policies in highly complex contexts involving multiple and historical influences from different hierarchical levels. PMID:26509976

  15. Message framing strategies to increase influenza immunization uptake among pregnant African American women.

    PubMed

    Marsh, Heather A; Malik, Fauzia; Shapiro, Eve; Omer, Saad B; Frew, Paula M

    2014-09-01

    We explored the attitudes, opinions, and concerns of African American women regarding influenza vaccination during pregnancy. As influenza immunization coverage rates remain suboptimal in the United States among this population, we elicited message framing strategies for multicomponent interventions aimed at decreasing future incident cases of maternal and neonatal influenza. Semi-structured in-depth interviews (N = 21) were conducted with pregnant African American women at urban OB/GYN clinics who had not received an influenza vaccine. Interviews were transcribed, subjected to intercoder reliability assessment, and content analyzed to identify common thematic factors related to acceptance of the influenza vaccine and health communication message preferences. Four major themes were identified. These were communication approaches, normal vaccine behavior, pregnancy vaccination, and positive versus negative framing. Two strong themes emerged: positively-framed messages were preferred over negatively-framed messages and those emphasizing the health of the infant. Additionally, previous immunization, message source, and vaccine misperceptions also played important roles in decision-making. The majority of women indicated that positively framed messages focusing on the infant's health would encourage them to receive an influenza vaccine. Messages emphasizing immunization benefits such as protection against preterm birth and low birth weight outcomes have potential to overcome widespread negative community perceptions and cultural beliefs. Additionally, messages transmitted via interpersonal networks and social media strongly influence motivation to obtain vaccination during pregnancy. The findings of this study will assist in developing tailored messages that change pregnant African American women's influenza vaccination decision-making to achieve improved coverage. PMID:24337776

  16. Peptidoglycan recognition protein of Chlamys farreri (CfPGRP-S1) mediates immune defenses against bacterial infection.

    PubMed

    Yang, Jialong; Wang, Wan; Wei, Xiumei; Qiu, Limei; Wang, Lingling; Zhang, Huan; Song, Linsheng

    2010-12-01

    Peptidoglycan recognition protein (PGRP) is an essential molecule in innate immunity for both invertebrates and vertebrates, owing to its prominent ability in detecting and eliminating the invading bacteria. Several PGRPs have been identified from mollusk, but their functions and the underlined mechanism are still unclear. In the present study, the mRNA expression profiles, location, and possible functions of PGRP-S1 from Zhikong scallop Chlamys farreri (CfPGRP-S1) were analyzed. The CfPGRP-S1 protein located in the mantle, gill, kidney and gonad of the scallops. Its mRNA expression in hemocytes was up-regulated extremely after PGN stimulation (P<0.01), while moderately after the stimulations of LPS (P<0.01) and β-glucan (P<0.05). The recombinant protein of CfPGRP-S1 (designated as rCfPGRP-S1) exhibited high affinity to PGN and moderate affinity to LPS, but it did not bind β-glucan. Meanwhile, rCfPGRP-S1 also exhibited strong agglutination activity to Gram-positive bacteria Micrococcus luteus and Bacillus subtilis and weak activity to Gram-negative bacteria Escherichia coli. More importantly, rCfPGRP-S1 functioned as a bactericidal amidase to degrade PGN and strongly inhibit the growth of E. coli and Staphyloccocus aureus in the presence of Zn(2+). These results indicated that CfPGRP-S1 could not only serve as a pattern recognition receptor recognizing bacterial PGN and LPS, but also function as a scavenger involved in eliminating response against the invaders. PMID:20713083

  17. CsTNF1, a teleost tumor necrosis factor that promotes antibacterial and antiviral immune defense in a manner that depends on the conserved receptor binding site.

    PubMed

    Li, Mo-Fei; Zhang, Jian

    2016-02-01

    Tumor necrosis factor (TNF) is one of the most important cytokines involved in inflammation, apoptosis, cell proliferation, and stimulation of the immune system. The TNF gene has been cloned in teleost fish; however, the invivo function of fish TNF is essentially unknown. In this study, we report the identification of a TNF homologue, CsTNF1, from tongue sole (Cynoglossus semilaevis) and analysis of its expression and biological effect. CsTNF1 is composed of 242 amino acid residues and possesses a TNF domain and conserved receptor binding sites. Expression of CsTNF1 was detected in a wide range of tissues and up-regulated in a time-dependent manner by experimental challenge with bacterial and viral pathogens. Bacterial infection of peripheral blood leukocytes (PBL) caused extracellular secretion of CsTNF1. Purified recombinant CsTNF1 (rCsTNF1) was able to bind to PBL and stimulate the respiratory burst activity of PBL. In contrast, rCsTNF1M1 and rCsTNF1M2, the mutant CsTNF1 bearing substitutions at the receptor binding site, failed to activate PBL. Fish administered with rCsTNF1, but not with rCsTNF1M1 and rCsTNF1M2, exhibited enhanced expression of IL-1, IL-6, IL-8, IL-27, TLR9 and G3BP in a time-dependent manner and augmented resistance against bacterial and viral infection. These results provide the first evidence that the receptor binding sites are essential to a fish TNF, and that CsTNF1 is involved in the innate immune defense of fish against microbial pathogens. PMID:26478190

  18. New strategies for using mucosal vaccination to achieve more effective immunization.

    PubMed

    Walker, R I

    1994-04-01

    Future progress in vaccination will be significantly advanced by application of emerging technologies for immunization of mucosal surfaces. It should now be possible to maximize the antigenicity of many vaccines and facilitate their interaction with appropriate lymphoid tissues to induce protective cellular and humoral responses. Mucosal vaccines requiring no more than two doses are achievable with current technologies. Living vaccines have been among the most promising candidates for mucosal vaccination, but with few exceptions their promise is still to be realized. Development of new microencapsulated delivery systems and adjuvants has made non-living vaccines reasonable options for mucosal immunization. To be practical, such vaccines should be developed as combined agent vaccines, possibly deliverable by multiple mucosal routes. Although strategies to be used for specific mucosal vaccines will depend upon a number of factors pertinent to the disease agent, in concept an adjuvant administered with inactivated but maximally antigenic pathogens or their recombinant adhesive subcomponents could prove to be among the more practical mucosal vaccine options for use globally. PMID:8023545

  19. Virus Counterdefense: Diverse Strategies for Evading the RNA-Silencing Immunity

    PubMed Central

    Li, Feng; Ding, Shou-Wei

    2009-01-01

    Viruses are obligate, intracellular pathogens that must manipulate and exploit host molecular mechanisms to prosper in the hostile cellular environment. Here we review the strategies used by viruses to evade the immunity controlled by 21- to 26-nt small RNAs. Viral suppressors of RNA silencing (VSRs) are encoded by genetically diverse viruses infecting plants, invertebrates, and vertebrates. VSRs target key steps in the small RNA pathways by inhibiting small RNA production,sequestering small RNAs,orpreventing short- and long-distance spread of RNA silencing. However, although VSRs are required for infection, explicit data demonstrating a role of silencing suppression in virus infection are available only for a few VSRs. A subset of VSRs bind double-stranded RNA, but a distinct protein fold is revealed for each of the four VSRs examined. We propose that VSR families are evolved independently as a viral adaptation to immunity. Unresolved issues on the role of RNA silencing in virus-host interactions are highlighted. PMID:16768647

  20. Immune-modulators to combat hepatitis B virus infection: From IFN-? to novel investigational immunotherapeutic strategies.

    PubMed

    Isorce, Nathalie; Lucifora, Julie; Zoulim, Fabien; Durantel, David

    2015-10-01

    Chronic hepatitis B virus (HBV) infection remains a major challenge for clinicians, as there are only two types of approved therapies: interferon-alpha (IFN-?) or its pegylated form, Peg-IFN-? and nucleoside analogs (e.g. tenofovir, entecavir...). The first are used as finite-duration treatments of around 48-52 weeks, while the second must be taken life-long to prevent rebound. Other immune-modulators, including other types of recombinant IFNs and cytokines/chemokines, could be developed for treating chronic hepatitis B. Alternatively, strategies aimed either at restoring or favoring the endogenous production of IFNs, cytokines and/or chemokines, or at alleviating HBV-mediated inhibitory processes could also be envisaged. In this article, we review current investigational, preclinical and clinical efforts to implement immune-modulatory components in the therapy of chronic hepatitis B. This review forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B". PMID:26275801

  1. Immune Defenses of the Invasive Apple Snail Pomacea canaliculata (Caenogastropoda, Ampullariidae): Phagocytic Hemocytes in the Circulation and the Kidney

    PubMed Central

    Vega, Israel A.; Castro-Vazquez, Alfredo

    2015-01-01

    Hemocytes in the circulation and kidney islets, as well as their phagocytic responses to microorganisms and fluorescent beads, have been studied in Pomacea canaliculata, using flow cytometry, light microscopy (including confocal laser scanning microscopy) and transmission electron microscopy (TEM). Three circulating hemocyte types (hyalinocytes, agranulocytes and granulocytes) were distinguished by phase contrast microscopy of living cells and after light and electron microscopy of fixed material. Also, three different populations of circulating hemocytes were separated by flow cytometry, which corresponded to the three hemocyte types. Hyalinocytes showed a low nucleus/cytoplasm ratio, and no apparent granules in stained material, but showed granules of moderate electron density under TEM (L granules) and at least some L granules appear acidic when labeled with LysoTracker Red. Both phagocytic and non-phagocytic hyalinocytes lose most (if not all) L granules when exposed to microorganisms in vitro. The phagosomes formed differed whether hyalinocytes were exposed to yeasts or to Gram positive or Gram negative bacteria. Agranulocytes showed a large nucleus/cytoplasm ratio and few or no granules. Granulocytes showed a low nucleus/cytoplasm ratio and numerous eosinophilic granules after staining. These granules are electron dense and rod-shaped under TEM (R granules). Granulocytes may show merging of R granules into gigantic ones, particularly when exposed to microorganisms. Fluorescent bead exposure of sorted hemocytes showed phagocytic activity in hyalinocytes, agranulocytes and granulocytes, but the phagocytic index was significantly higher in hyalinocytes. Extensive hemocyte aggregates ('islets') occupy most renal hemocoelic spaces and hyalinocyte-like cells are the most frequent component in them. Presumptive glycogen deposits were observed in most hyalinocytes in renal islets (they also occur in the circulation but less frequently) and may mean that hyalinocytes participate in the storage and circulation of this compound. Injection of microorganisms in the foot results in phagocytosis by hemocytes in the islets, and the different phagosomes formed are similar to those in circulating hyalinocytes. Dispersed hemocytes were obtained after kidney collagenase digestion and cell sorting, and they were able to phagocytize fluorescent beads. A role for the kidney as an immune barrier is proposed for this snail. PMID:25893243

  2. Unique IL-13R?2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8(+) T-cell avidity and protective immunity.

    PubMed

    Ranasinghe, C; Trivedi, S; Stambas, J; Jackson, R J

    2013-11-01

    We have established that mucosal immunization can generate high-avidity human immunodeficiency virus (HIV)-specific CD8(+) T cells compared with systemic immunization, and interleukin (IL)-13 is detrimental to the functional avidity of these T cells. We have now constructed two unique recombinant HIV-1 vaccines that co-express soluble or membrane-bound forms of the IL-13 receptor ?2 (IL-13R?2), which can "transiently" block IL-13 activity at the vaccination site causing wild-type animals to behave similar to an IL-13 KO animal. Following intranasal/intramuscular prime-boost immunization, these IL-13R?2-adjuvanted vaccines have shown to induce (i) enhanced HIV-specific CD8(+) T cells with higher functional avidity, with broader cytokine/chemokine profiles and greater protective immunity using a surrogate mucosal HIV-1 challenge, and also (ii) excellent multifunctional mucosal CD8(+) T-cell responses, in the lung, genito-rectal nodes (GN), and Peyer's patch (PP). Data revealed that intranasal delivery of these IL-13R?2-adjuvanted HIV vaccines recruited large numbers of unique antigen-presenting cell subsets to the lung mucosae, ultimately promoting the induction of high-avidity CD8(+) T cells. We believe our novel IL-13R cytokine trap vaccine strategy offers great promise for not only HIV-1, but also as a platform technology against range of chronic infections that require strong sustained high-avidity mucosal/systemic immunity for protection. PMID:23403475

  3. Immune Modulation of Stem Cells and Regeneration

    PubMed Central

    Aurora, Arin B.; Olson, Eric N.

    2014-01-01

    The immune system, best known as the first line of defense against invading pathogens, is integral to tissue development, homeostasis and wound repair. In recent years, there has been a growing appreciation that cellular and humoral components of the immune system also contribute to regeneration of damaged tissues, including limbs, skeletal muscle, heart and the nervous system. Here, we discuss key findings that implicate inflammatory cells and their secreted factors in tissue replacement following injury via stem cells and other reparative mechanisms. We highlight clinical conditions that are amenable to immune-mediated regeneration and suggest immune targeting strategies for tissue regeneration. PMID:24996166

  4. CsCTL1, a teleost C-type lectin that promotes antibacterial and antiviral immune defense in a manner that depends on the conserved EPN motif.

    PubMed

    Zhou, Ze-jun; Sun, Li

    2015-06-01

    Many C-type lectins (CTLs) have been identified in teleost, however, the in vivo function of fish CTLs is essentially unknown. In this study, we examined the function of a CTL (CsCTL1) from tongue sole. CsCTL1 possesses the conserved EPN motif required for mannose binding in mammals but unknown in function in fish. Recombinant CsCTL1 (rCsCTL1), but not the mutant rCsCTL1M bearing substitutions at EPN, interacted with and agglutinated a limited range of bacteria. The agglutinating ability of rCsCTL1 was abolished in the absence of calcium or presence of mannose. Binding of rCsCTL1 to bacteria promoted phagocytosis and antimicrobial activity of head kidney monocytes. Fish administered with rCsCTL1 exhibited enhanced resistance against bacterial and viral infections. These results provide the first evidence that the EPN site is essential to a fish CTL and that, in addition to antibacterial properties, a fish CTL promotes the immune defense against viral infection as well. PMID:25636784

  5. Abnormal immune system development and function in schizophrenia helps reconcile diverse findings and suggests new treatment and prevention strategies.

    PubMed

    Anders, Sherry; Kinney, Dennis K

    2015-08-18

    Extensive research implicates disturbed immune function and development in the etiology and pathology of schizophrenia. In addition to reviewing evidence for immunological factors in schizophrenia, this paper discusses how an emerging model of atypical immune function and development helps explain a wide variety of well-established - but puzzling - findings about schizophrenia. A number of theorists have presented hypotheses that early immune system programming, disrupted by pre- and perinatal adversity, often combines with abnormal brain development to produce schizophrenia. The present paper focuses on the hypothesis that disruption of early immune system development produces a latent immune vulnerability that manifests more fully after puberty, when changes in immune function and the thymus leave individuals more susceptible to infections and immune dysfunctions that contribute to schizophrenia. Complementing neurodevelopmental models, this hypothesis integrates findings on many contributing factors to schizophrenia, including prenatal adversity, genes, climate, migration, infections, and stress, among others. It helps explain, for example, why (a) schizophrenia onset is typically delayed until years after prenatal adversity, (b) individual risk factors alone often do not lead to schizophrenia, and (c) schizophrenia prevalence rates actually tend to be higher in economically advantaged countries. Here we discuss how the hypothesis explains 10 key findings, and suggests new, potentially highly cost-effective, strategies for treatment and prevention of schizophrenia. Moreover, while most human research linking immune factors to schizophrenia has been correlational, these strategies provide ethical ways to experimentally test in humans theories about immune function and schizophrenia. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. PMID:25736181

  6. Macrophage defense mechanisms against intracellular bacteria.

    PubMed

    Weiss, Gnter; Schaible, Ulrich E

    2015-03-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

  7. Macrophage defense mechanisms against intracellular bacteria

    PubMed Central

    Weiss, Günter; Schaible, Ulrich E

    2015-01-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

  8. Coping Strategies of Patients with Haemophilia as a Risk Group for AIDS (Acquired Immune Deficiency Syndrome). Brief Research Report.

    ERIC Educational Resources Information Center

    Naji, Simon; And Others

    1986-01-01

    Plans are described for a 2-year project whose major focus is the identification of ways in which patients with hemophilia and their families assimilate, interpret, and act on information about Acquired Immune Deficiency Syndrome (AIDS). Findings will be related to perceived risk, anxiety levels, and the development of coping strategies.…

  9. Coping Strategies of Patients with Haemophilia as a Risk Group for AIDS (Acquired Immune Deficiency Syndrome). Brief Research Report.

    ERIC Educational Resources Information Center

    Naji, Simon; And Others

    1986-01-01

    Plans are described for a 2-year project whose major focus is the identification of ways in which patients with hemophilia and their families assimilate, interpret, and act on information about Acquired Immune Deficiency Syndrome (AIDS). Findings will be related to perceived risk, anxiety levels, and the development of coping strategies.

  10. Plant defense syndromes.

    PubMed

    Agrawal, Anurag A; Fishbein, Mark

    2006-07-01

    Given that a plant's defensive strategy against herbivory is never likely to be a single trait, we develop the concept of plant defense syndromes, where association with specific ecological interactions can result in convergence on suites of covarying defensive traits. Defense syndromes can be studied within communities of diverse plant species as well as within clades of closely related species. In either case, theory predicts that plant defense traits can consistently covary across species, due to shared evolutionary ancestry or due to adaptive convergence. We examined potential defense syndromes in 24 species of milkweeds (Asclepias spp.) in a field experiment. Employing phylogenetically independent contrasts, we found few correlations between seven defensive traits, no bivariate trade-offs, and notable positive correlations between trichome density and latex production, and between C:N ratio and leaf toughness. We then used a hierarchical cluster analysis to produce a phenogram of defense trait similarity among the 24 species. This analysis revealed three distinct clusters of species. The defense syndromes of these species clusters are associated with either low nutritional quality or a balance of higher nutritional quality coupled with physical or chemical defenses. The phenogram based on defense traits was not congruent, however, with a molecular phylogeny of the group, suggesting convergence on defense syndromes. Finally, we examined the performance of monarch butterfly caterpillars on the 24 milkweed species in the field; monarch growth and survival did not differ on plants in the three syndromes, although multiple regression revealed that leaf trichomes and toughness significantly reduced caterpillar growth. The discovery of convergent plant defense syndromes can be used as a framework to ask questions about how abiotic environments, communities of herbivores, and biogeography are associated with particular defense strategies of plants. PMID:16922309

  11. Quiescent Innate Response to Infective Filariae by Human Langerhans Cells Suggests a Strategy of Immune Evasion

    PubMed Central

    Boyd, Alexis; Bennuru, Sasisekhar; Wang, Yuanyuan; Sanprasert, Vivornpun; Law, Melissa; Chaussabel, Damien; Nutman, Thomas B.

    2013-01-01

    Filarial infection is initiated by mosquito-derived third-stage larvae (L3) deposited on the skin that transit through the epidermis, which contains Langerhans cells (LC) and keratinocytes (KC), among other cells. This earliest interaction between L3 and the LC likely conditions the priming of the immune system to the parasite. To determine the nature of this interaction, human LC (langerin+ E-cadherin+ CD1a+) were generated in vitro and exposed to live L3. LC exposed to live L3 for 48 h showed no alterations in the cell surface markers CD14, CD86, CD83, CD207, E-cadherin, CD80, CD40, and HLA-DR or in mRNA expression of inflammation-associated genes, such as those for interleukin 18 (IL-18), IL-18BP, and caspase 1. In contrast to L3, live tachyzoites of Toxoplasma gondii, an intracellular parasite, induced production of CXCL9, IP-10, and IL-6 in LC. Furthermore, preexposure of LC to L3 did not alter Toll-like receptor 3 (TLR3)- or TLR4-mediated expression of the proinflammatory cytokines IL-1?, gamma interferon (IFN-?), IL-6, or IL-10. Interestingly, cocultures of KC and LC produced significantly more IL-18, IL-1?, and IL-8 than did cultures of LC alone, although exposure of the cocultures to live L3 did not result in altered cytokine production. Microarray examination of ex vivo LC from skin blisters that were exposed to live L3 also showed few significant changes in gene expression compared with unexposed blisters, further underscoring the relatively muted response of LC to L3. Our data suggest that failure by LC to initiate an inflammatory response to the invasive stage of filarial parasites may be a strategy for immune evasion by the filarial parasite. PMID:23429540

  12. Adaptive HIV-Specific B Cell-Derived Humoral Immune Defenses of the Intestinal Mucosa in Children Exposed to HIV via Breast-Feeding

    PubMed Central

    Moussa, Sandrine; Jenabian, Mohammad-Ali; Gody, Jean Chrysostome; Léal, Josiane; Grésenguet, Gérard; Le Faou, Alain; Bélec, Laurent

    2013-01-01

    Background We evaluated whether B cell-derived immune defenses of the gastro-intestinal tract are activated to produce HIV-specific antibodies in children continuously exposed to HIV via breast-feeding. Methods Couples of HIV-1-infected mothers (n = 14) and their breastfed non HIV-infected (n = 8) and HIV-infected (n = 6) babies, and healthy HIV-negative mothers and breastfed babies (n = 10) as controls, were prospectively included at the Complexe Pédiatrique of Bangui, Central African Republic. Immunoglobulins (IgA, IgG and IgM) and anti-gp160 antibodies from mother’s milk and stools of breastfed children were quantified by ELISA. Immunoaffinity purified anti-gp160 antibodies were characterized functionally regarding their capacity to reduce attachment and/or infection of R5- and X4- tropic HIV-1 strains on human colorectal epithelial HT29 cells line or monocyte-derived-macrophages (MDM). Results The levels of total IgA and IgG were increased in milk of HIV-infected mothers and stools of HIV-exposed children, indicating the activation of B cell-derived mucosal immunity. Breast milk samples as well as stool samples from HIV-negative and HIV-infected babies exposed to HIV by breast-feeding, contained high levels of HIV-specific antibodies, mainly IgG antibodies, less frequently IgA antibodies, and rarely IgM antibodies. Relative ratios of excretion by reference to lactoferrin calculated for HIV-specific IgA, IgG and IgM in stools of HIV-exposed children were largely superior to 1, indicating active production of HIV-specific antibodies by the intestinal mucosa. Antibodies to gp160 purified from pooled stools of HIV-exposed breastfed children inhibited the attachment of HIV-1NDK on HT29 cells by 63% and on MDM by 77%, and the attachment of HIV-1JRCSF on MDM by 40%; and the infection of MDM by HIV-1JRCSF by 93%. Conclusions The intestinal mucosa of children exposed to HIV by breast-feeding produces HIV-specific antibodies harbouring in vitro major functional properties against HIV. These observations lay the conceptual basis for the design of a prophylactic vaccine against HIV in exposed children. PMID:23704905

  13. Strategies and Advancements in Harnessing the Immune System for Gastric Cancer Immunotherapy

    PubMed Central

    Subhash, Vinod Vijay; Yeo, Mei Shi; Tan, Woei Loon; Yong, Wei Peng

    2015-01-01

    In cancer biology, cells and molecules that form the fundamental components of the tumor microenvironment play a major role in tumor initiation, and progression as well as responses to therapy. Therapeutic approaches that would enable and harness the immune system to target tumor cells mark the future of anticancer therapy as it could induce an immunological memory specific to the tumor type and further enhance tumor regression and relapse-free survival in cancer patients. Gastric cancer is one of the leading causes of cancer-related mortalities that has a modest survival benefit from existing treatment options. The advent of immunotherapy presents us with new approaches in gastric cancer treatment where adaptive cell therapies, cancer vaccines, and antibody therapies have all been used with promising outcomes. In this paper, we review the current advances and prospects in the gastric cancer immunotherapy. Special focus is laid on new strategies and clinical trials that attempt to enhance the efficacy of various immunotherapeutic modalities in gastric cancer. PMID:26579545

  14. The Immune System in Hepatocellular Carcinoma and Potential New Immunotherapeutic Strategies

    PubMed Central

    Bertino, Gaetano; Demma, Shirin; Ardiri, Annalisa; Proiti, Maria; Mangia, Alessandra; Gruttadauria, Salvatore; Toro, Adriana; Di Carlo, Isidoro; Malaguarnera, Giulia; Bertino, Nicoletta; Malaguarnera, Mariano; Malaguarnera, Michele

    2015-01-01

    Background. Hepatocellular carcinoma is a major health problem worldwide and the third most common cause of cancer-related death. HCC treatment decisions are complex and dependent upon tumor staging. Several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Despite of only modest objective response rates according to the Response Evaluation Criteria in Solid Tumors, several studies showed encouraging results in terms of prolongation of the time to progression, disease stabilization, and survival. Cellular immunotherapy would improve the immune state and has potential in enhancing the therapeutic outcome for HCC patients. Materials and Methods. A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” “molecular immunological targets,” “tumour-associated antigens,” “Tregs,” “MDSCs,” “immunotherapy.” Discussion and Conclusion. Treatment strategies combining blockade of immunoregulatory cell types such as Tregs and MDSCs and of inhibitory receptors, with vaccine-induced activation of TAA-specific T cells, may be necessary to achieve the most effective therapeutic antitumour activity in HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways. PMID:25893197

  15. Through the Immune Looking Glass: A Model for Brain Memory Strategies

    PubMed Central

    Sánchez-Ramón, Silvia; Faure, Florence

    2016-01-01

    The immune system (IS) and the central nervous system (CNS) are complex cognitive networks involved in defining the identity (self) of the individual through recognition and memory processes that enable one to anticipate responses to stimuli. Brain memory has traditionally been classified as either implicit or explicit on psychological and anatomical grounds, with reminiscences of the evolutionarily-based innate-adaptive IS responses. Beyond the multineuronal networks of the CNS, we propose a theoretical model of brain memory integrating the CNS as a whole. This is achieved by analogical reasoning between the operational rules of recognition and memory processes in both systems, coupled to an evolutionary analysis. In this new model, the hippocampus is no longer specifically ascribed to explicit memory but rather it both becomes part of the innate (implicit) memory system and tightly controls the explicit memory system. Alike the antigen presenting cells for the IS, the hippocampus would integrate transient and pseudo-specific (i.e., danger-fear) memories and would drive the formation of long-term and highly specific or explicit memories (i.e., the taste of the Proust’s madeleine cake) by the more complex and recent, evolutionarily speaking, neocortex. Experimental and clinical evidence is provided to support the model. We believe that the singularity of this model’s approximation could help to gain a better understanding of the mechanisms operating in brain memory strategies from a large-scale network perspective. PMID:26869886

  16. Through the Immune Looking Glass: A Model for Brain Memory Strategies.

    PubMed

    Sánchez-Ramón, Silvia; Faure, Florence

    2016-01-01

    The immune system (IS) and the central nervous system (CNS) are complex cognitive networks involved in defining the identity (self) of the individual through recognition and memory processes that enable one to anticipate responses to stimuli. Brain memory has traditionally been classified as either implicit or explicit on psychological and anatomical grounds, with reminiscences of the evolutionarily-based innate-adaptive IS responses. Beyond the multineuronal networks of the CNS, we propose a theoretical model of brain memory integrating the CNS as a whole. This is achieved by analogical reasoning between the operational rules of recognition and memory processes in both systems, coupled to an evolutionary analysis. In this new model, the hippocampus is no longer specifically ascribed to explicit memory but rather it both becomes part of the innate (implicit) memory system and tightly controls the explicit memory system. Alike the antigen presenting cells for the IS, the hippocampus would integrate transient and pseudo-specific (i.e., danger-fear) memories and would drive the formation of long-term and highly specific or explicit memories (i.e., the taste of the Proust's madeleine cake) by the more complex and recent, evolutionarily speaking, neocortex. Experimental and clinical evidence is provided to support the model. We believe that the singularity of this model's approximation could help to gain a better understanding of the mechanisms operating in brain memory strategies from a large-scale network perspective. PMID:26869886

  17. Interference with the Autophagic Process as a Viral Strategy to Escape from the Immune Control: Lesson from Gamma Herpesviruses

    PubMed Central

    Santarelli, Roberta; Granato, Marisa; Faggioni, Alberto; Cirone, Mara

    2015-01-01

    We summarized the most recent findings on the role of autophagy in antiviral immune response. We described how viruses have developed strategies to subvert the autophagic process. A particular attention has been given to Epstein-Barr and Kaposi's sarcoma associated Herpesvirus, viruses studied for many years in our laboratory. These two viruses belong to ?-Herpesvirus subfamily and are associated with several human cancers. Besides the effects on the immune response, we have described how autophagy subversion by viruses may also concur to the enhancement of their replication and to viral tumorigenesis. PMID:26090494

  18. Interference with the Autophagic Process as a Viral Strategy to Escape from the Immune Control: Lesson from Gamma Herpesviruses.

    PubMed

    Santarelli, Roberta; Granato, Marisa; Faggioni, Alberto; Cirone, Mara

    2015-01-01

    We summarized the most recent findings on the role of autophagy in antiviral immune response. We described how viruses have developed strategies to subvert the autophagic process. A particular attention has been given to Epstein-Barr and Kaposi's sarcoma associated Herpesvirus, viruses studied for many years in our laboratory. These two viruses belong to ?-Herpesvirus subfamily and are associated with several human cancers. Besides the effects on the immune response, we have described how autophagy subversion by viruses may also concur to the enhancement of their replication and to viral tumorigenesis. PMID:26090494

  19. Integrated Immune

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarnece

    2010-01-01

    This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  20. Pakistan's expanded programme on immunization: an overview in the context of polio eradication and strategies for improving coverage.

    PubMed

    Owais, Aatekah; Khowaja, Asif Raza; Ali, Syed Asad; Zaidi, Anita K M

    2013-07-18

    Since its inception in 1978, Pakistan's Expanded Programme on Immunization (EPI) has contributed significantly towards child health and survival in Pakistan. However, the WHO-estimated immunization coverage of 88% for 3 doses of Diptheria-Tetanus-Pertussis vaccine in Pakistan is likely an over-estimate. Many goals, such as polio, measles and neonatal tetanus elimination have not been met. Pakistan reported more cases of poliomyelits in 2011 than any other country globally, threatening the Global Polio Eradication Initiative. Although the number of polio cases decreased to 58 in 2012 through better organized supplementary immunization campaigns, country-wide measles outbreaks with over 15,000 cases and several hundred deaths in 2012-13 underscore sub-optimal EPI performance in delivering routine immunizations. There are striking inequities in immunization coverage between different parts of the country. Barriers to universal immunization coverage include programmatic dysfunction at lower tiers of the program, socioeconomic inequities in access to services, low population demand, poor security, and social resistance to vaccines among population sub-groups. Recent conflicts and large-scale natural disasters have severely stressed the already constrained resources of the national EPI. Immunization programs remain low priority for provincial and many district governments in the country. The recent decision to devolve the national health ministry to the provinces has had immediate adverse consequences. Mitigation strategies aimed at rapidly improving routine immunization coverage should include improving the infrastructure and management capacity for vaccine delivery at district levels and increasing the demand for vaccines at the population level. Accurate vaccine coverage estimates at district/sub-district level and local accountability of district government officials are critical to improving performance and eradicating polio in Pakistan. PMID:23707167

  1. Microbial pathogenesis and host defense in the nematode C. elegans.

    PubMed

    Cohen, Lianne B; Troemel, Emily R

    2015-02-01

    Epithelial cells line the surfaces of the body, and are on the front lines of defense against microbial infection. Like many other metazoans, the nematode Caenorhabditis elegans lacks known professional immune cells and relies heavily on defense mediated by epithelial cells. New results indicate that epithelial defense in C. elegans can be triggered through detection of pathogen-induced perturbation of core physiology within host cells and through autophagic defense against intracellular and extracellular pathogens. Recent studies have also illuminated a diverse array of pathogenic attack strategies used against C. elegans. These findings are providing insight into the underpinnings of host/pathogen interactions in a simple animal host that can inform studies of infectious diseases in humans. PMID:25461579

  2. Microbial pathogenesis and host defense in the nematode C. elegans

    PubMed Central

    Cohen, Lianne B.; Troemel, Emily R.

    2014-01-01

    Epithelial cells line the surfaces of the body, and are on the front lines of defense against microbial infection. Like many other metazoans, the nematode C. elegans lacks known professional immune cells and relies heavily on defense mediated by epithelial cells. New results indicate that epithelial defense in C. elegans can be triggered through detection of pathogen-induced perturbation of core physiology within host cells and through autophagic defense against intracellular and extracellular pathogens. Recent studies have also illuminated a diverse array of pathogenic attack strategies used against C. elegans. These findings are providing insight into the underpinnings of host/pathogen interactions in a simple animal host that can inform studies of infectious diseases in humans. PMID:25461579

  3. Allergic Host Defenses

    PubMed Central

    Palm, Noah W.; Rosenstein, Rachel K.

    2012-01-01

    Allergies are generally thought to be a detrimental outcome of a mistargeted immune response that evolved to provide immunity to macro-parasites. Here we present arguments to suggest that allergic immunity plays an important role in host defense against noxious environmental substances, including venoms, hematophagous fluids, environmental xenobiotics and irritants. We argue that appropriately targeted allergic reactions are beneficial, although they can become detrimental when excessive. Furthermore, we suggest that allergic hypersensitivity evolved to elicit anticipatory responses and to promote avoidance of suboptimal environments. PMID:22538607

  4. Child Immunization Status among a Sample of Adolescent Mothers: Comparing the Validity of Measurement Strategies

    ERIC Educational Resources Information Center

    Phillips, Clarissa; Cota-Robles, Sonia; Knight, Margaret; Francis, Judith; Phillips, Elizabeth; Mazerbo, Laurie

    2011-01-01

    This study of adolescent mothers sought to identify whether a single general question asked by phone or a detailed, vaccine-specific question asked in a self-report questionnaire best captured infant immunization status at 6 months postpartum, by comparing them with immunization record books. Responses to a global question about whether infants

  5. Child Immunization Status among a Sample of Adolescent Mothers: Comparing the Validity of Measurement Strategies

    ERIC Educational Resources Information Center

    Phillips, Clarissa; Cota-Robles, Sonia; Knight, Margaret; Francis, Judith; Phillips, Elizabeth; Mazerbo, Laurie

    2011-01-01

    This study of adolescent mothers sought to identify whether a single general question asked by phone or a detailed, vaccine-specific question asked in a self-report questionnaire best captured infant immunization status at 6 months postpartum, by comparing them with immunization record books. Responses to a global question about whether infants…

  6. 78 FR 79469 - Strategies To Address Hemolytic Complications of Immune Globulin Infusions; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ... Globulin Infusions; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public... Address Hemolytic Complications of Immune Globulin Infusions.'' The purpose of the public workshop is to... complication of Immune Globulin Intravenous (IGIV) (Human) infusion. Complications of hemolysis include...

  7. A Starter Culture Rotation Strategy Incorporating Paired Restriction/ Modification and Abortive Infection Bacteriophage Defenses in a Single Lactococcus lactis Strain

    PubMed Central

    Durmaz, E.; Klaenhammer, T. R.

    1995-01-01

    Three derivatives of Lactococcus lactis subsp. lactis NCK203, each with a different pair of restriction/ modification (R/M) and abortive infection (Abi) phage defense systems, were constructed and then rotated in repeated cycles of a milk starter culture activity test (SAT). The rotation proceeded successfully through nine successive SATs in the presence of phage and whey containing phage from previous cycles. Lactococcus cultures were challenged with 2 small isometric-headed phages, (phi)31 and ul36, in one rotation series and with a composite of 10 industrial phages in another series. Two native lactococcal R(sup+)/M(sup+) plasmids, pTRK68 and pTRK11, and one recombinant plasmid, pTRK308, harboring a third distinct R/M system were incorporated into three NCK203 derivatives constructed separately for the rotation. The R(sup+)/M(sup+) NCK203 derivatives were transformed with high-copy-number plasmids encoding four Abi genes, abiA, abiC, per31, and per50. Various Abi and R/M combinations constructed in NCK203 were evaluated for their effects on cell growth, level of phage resistance, and retardation of phage development during repeated cycles of the SAT. The three NCK203 derivatives chosen for use in the SAT exhibited additive effects of the R/M and Abi phenotypes against sensitive phages. In such combinations, phage escaping restriction are prevented from completing their infective cycle by an abortive response that kills the host cell. The rotation series successfully controlled modified, recombinant, and mutant phages which were resistant to any one of the individual defense systems by presenting a different set of R/M and Abi defenses in the next test of the rotation. PMID:16534987

  8. Biomimetic strategies based on viruses and bacteria for the development of immune evasive biomaterials

    PubMed Central

    Novak, Matthew T.; Bryers, James D.; Reichert, William M.

    2009-01-01

    The field of biomaterial design has begun to focus upon methods by which materials can modulate immune response. While certain approaches appear promising, they are limited to isolated facets of inflammation. It is well documented that both bacteria and viruses have highly developed methods for evading the immune system, providing impetus for a more biomimetic approach to material design. This review presents the immune evasive tactics employed by viruses and bacteria and offers suggestions for future directions in applying these principles to biomaterial design. PMID:19185345

  9. Maternal immune transfer in mollusc.

    PubMed

    Wang, Lingling; Yue, Feng; Song, Xiaorui; Song, Linsheng

    2015-02-01

    Maternal immunity refers to the immunity transferred from mother to offspring via egg, playing an important role in protecting the offspring at early life stages and contributing a trans-generational effect on offspring's phenotype. Because fertilization is external in most of the molluscs, oocytes and early embryos are directly exposed to pathogens in the seawater, and thus maternal immunity could provide a better protection before full maturation of their immunological systems. Several innate immune factors including pattern recognition receptors (PRRs) like lectins, and immune effectors like lysozyme, lipopolysaccharide binding protein/bacterial permeability-increasing proteins (LBP/BPI) and antioxidant enzymes have been identified as maternally derived immune factors in mollusc eggs. Among these immune factors, some maternally derived lectins and antibacterial factors have been proved to endue mollusc eggs with effective defense ability against pathogen infection, while the roles of other factors still remain untested. The physiological condition of mollusc broodstock has a profound effect on their offspring fitness. Many other factors such as nutrients, pathogens, environment conditions and pollutants could exert considerable influence on the maternal transfer of immunity. The parent molluscs which have encountered an immune stimulation endow their offspring with a trans-generational immune capability to protect them against infections effectively. The knowledge on maternal transfer of immunity and the trans-generational immune effect could provide us with an ideal management strategy of mollusc broodstock to improve the immunity of offspring and to establish a disease-resistant family for a long-term improvement of cultured stocks. PMID:24858027

  10. Innate immune cell networking in hepatitis C virus infection.

    PubMed

    Saha, Banishree; Szabo, Gyongyi

    2014-11-01

    Persistent viral infection, such as HCV infection, is the result of the inability of the host immune system to mount a successful antiviral response, as well as the escape strategies devised by the virus. Although each individual component of the host immune system plays important roles in antiviral immunity, the interactive network of immune cells as a whole acts against the virus. The innate immune system forms the first line of host defense against viral infection, and thus, virus elimination or chronic HCV infection is linked to the direct outcome of the interactions between the various innate immune cells and HCV. By understanding how the distinct components of the innate immune system function both individually and collectively during HCV infection, potential therapeutic targets can be identified to overcome immune dysfunction and control chronic viral infection. PMID:25001860

  11. The Immune Strategy and Stress Response of the Mediterranean Species of the Bemisia tabaci Complex to an Orally Delivered Bacterial Pathogen

    PubMed Central

    Xia, Jun; Li, Fang-Fang; Xia, Wen-Qiang; Liu, Shu-Sheng; Wang, Xiao-Wei

    2014-01-01

    Background The whitefly, Bemisia tabaci, a notorious agricultural pest, has complex relationships with diverse microbes. The interactions of the whitefly with entomopathogens as well as its endosymbionts have received great attention, because of their potential importance in developing novel whitefly control technologies. To this end, a comprehensive understanding on the whitefly defense system is needed to further decipher those interactions. Methodology/Principal Findings We conducted a comprehensive investigation of the whitefly's defense responses to infection, via oral ingestion, of the pathogen, Pseudomonas aeruginosa, using RNA-seq technology. Compared to uninfected whiteflies, 6 and 24 hours post-infected whiteflies showed 1,348 and 1,888 differentially expressed genes, respectively. Functional analysis of the differentially expressed genes revealed that the mitogen associated protein kinase (MAPK) pathway was activated after P. aeruginosa infection. Three knottin-like antimicrobial peptide genes and several components of the humoral and cellular immune responses were also activated, indicating that key immune elements recognized in other insect species are also important for the response of B. tabaci to pathogens. Our data also suggest that intestinal stem cell mediated epithelium renewal might be an important component of the whitefly's defense against oral bacterial infection. In addition, we show stress responses to be an essential component of the defense system. Conclusions/Significance We identified for the first time the key immune-response elements utilized by B. tabaci against bacterial infection. This study provides a framework for future research into the complex interactions between whiteflies and microbes. PMID:24722540

  12. Mosquito Immunity against Arboviruses

    PubMed Central

    Sim, Shuzhen; Jupatanakul, Natapong; Dimopoulos, George

    2014-01-01

    Arthropod-borne viruses (arboviruses) pose a significant threat to global health, causing human disease with increasing geographic range and severity. The recent availability of the genome sequences of medically important mosquito species has kick-started investigations into the molecular basis of how mosquito vectors control arbovirus infection. Here, we discuss recent findings concerning the role of the mosquito immune system in antiviral defense, interactions between arboviruses and fundamental cellular processes such as apoptosis and autophagy, and arboviral suppression of mosquito defense mechanisms. This knowledge provides insights into co-evolutionary processes between vector and virus and also lays the groundwork for the development of novel arbovirus control strategies that target the mosquito vector. PMID:25415198

  13. Mosquito immunity against arboviruses.

    PubMed

    Sim, Shuzhen; Jupatanakul, Natapong; Dimopoulos, George

    2014-11-01

    Arthropod-borne viruses (arboviruses) pose a significant threat to global health, causing human disease with increasing geographic range and severity. The recent availability of the genome sequences of medically important mosquito species has kick-started investigations into the molecular basis of how mosquito vectors control arbovirus infection. Here, we discuss recent findings concerning the role of the mosquito immune system in antiviral defense, interactions between arboviruses and fundamental cellular processes such as apoptosis and autophagy, and arboviral suppression of mosquito defense mechanisms. This knowledge provides insights into co-evolutionary processes between vector and virus and also lays the groundwork for the development of novel arbovirus control strategies that target the mosquito vector. PMID:25415198

  14. Strategies for Coordination of a Serosurvey in Parallel with an Immunization Coverage Survey

    PubMed Central

    Travassos, Mark A.; Beyene, Berhane; Adam, Zenaw; Campbell, James D.; Mulholland, Nigisti; Diarra, Seydou S.; Kassa, Tassew; Oot, Lisa; Sequeira, Jenny; Reymann, Mardi; Blackwelder, William C.; Pasetti, Marcela F.; Sow, Samba O.; Steinglass, Robert; Kebede, Amha; Levine, Myron M.

    2015-01-01

    A community-based immunization coverage survey is the standard way to estimate effective vaccination delivery to a target population in a region. Accompanying serosurveys can provide objective measures of protective immunity against vaccine-preventable diseases but pose considerable challenges with respect to specimen collection and preservation and community compliance. We performed serosurveys coupled to immunization coverage surveys in three administrative districts (woredas) in rural Ethiopia. Critical to the success of this effort were serosurvey equipment and supplies, team composition, and tight coordination with the coverage survey. Application of these techniques to future studies may foster more widespread use of serosurveys to derive more objective assessments of vaccine-derived seroprotection and monitor and compare the performance of immunization services in different districts of a country. PMID:26055737

  15. Effects of ozone on the defense to a respiratory Listeria monocytogenes infection in the rat. Suppression of macrophage function and cellular immunity and aggravation of histopathology in lung and liver during infection

    SciTech Connect

    Van Loveren, H.; Rombout, P.J.; Wagenaar, S.S.; Walvoort, H.C.; Vos, J.G.

    1988-07-01

    We have investigated the effect of exposure to ozone on defense mechanisms to a respiratory infection with Listeria monocytogenes in the rat. For this purpose rats were continuously exposed to O/sub 3/ concentrations ranging from 0.25 to 2.0 mg/m3 for a period of 1 week. In this model defense to a respiratory infection with Listeria depends on acquired specific cellular immune responses, as well as on natural nonspecific defense mechanisms. The results confirm earlier findings that show that ozone exposure can suppress the capacity of macrophages to ingest and kill Listeria. Moreover, the results show that ozone can also have a suppressive effect on the development of cellular immune responses to a respiratory Listeria infection, i.e., on T/B ratios in lung draining lymph nodes, delayed-type hypersensitivity responses to Listeria antigen, and lymphoproliferative responses in spleen and lung draining lymph nodes to Listeria antigen. The effects on the specific immune responses are especially overt if exposure to the oxidant gas occurs during an ongoing primary infection. The pathological lesions induced by a pulmonary Listeria monocytogenes infection were characterized by multifocal infiltrates of histiocytic and lymphoid cells. The foci sometimes had a granulomatous appearance. Moreover, the cellularity of the interstitial tissues was increased. In the lung many diffuse alveolar macrophages could be seen in the alveoli. Ozone exposure greatly increased the severity of the lung lesions and also of liver lesions resulting from the pulmonary infection. A prominent finding was the formation of granulomas in ozone-exposed and Listeria-infected rats.

  16. Defense management

    SciTech Connect

    Not Available

    1988-12-01

    This report discusses how some action has been taken on most of the recommendations made by the President's Blue Ribbon Commission of Defense Management (Packard Commission), although little or no action has been taken on others. Specifically, the National Security Council provided a single budget level, instead of provisional budget levels, in the presidential guidance to the Secretary of Defense; no charges have been made to reduce the redundancy among congressional committees reviewing the defense budget or the number of reports Congress requests from the Department of Defense; and the 5-year defense guidance did not include budgets with an operationally oriented structure.

  17. DNA priming E and NS1 constructs--homologous proteins boosting immunization strategy to improve immune response against dengue in mice.

    PubMed

    Mellado-Sánchez, Gabriela; García-Cordero, Julio; Luria-Pérez, Rosendo; Lázaro-Olan, Lucero; Santos-Argumedo, Leopoldo; Gutiérrez-Castañeda, Benito; Estrada-García, Iris; Cedillo-Barrón, Leticia

    2005-01-01

    DNA priming-protein boosting is a strategy used to establish strong immunity to a specific pathogen by the use of two different antigens through sequential delivery systems. In this work, two recombinant plasmids were used, one encoding for the dengue virus E protein, which is know to induce neutralizing antibodies (pcDNA 3.1/E), and the other encoding for the Dengue virus nonstructural protein 1 (pcDNA 3.1/NS1), as a source of B- and T-cell epitopes possibly involved in protective immunity. We showed that immunization of BALB/c mice with three priming doses of both plasmids pcDNA 3.1/E and/or pcDNA 3.1/NS1 were able to induce antibody responses to E protein with a single plasmid; in contrast to the antibody response to NS1 protein we observed an additive effect in terms of antibody response. Moreover, using a prime-boost protocol in which both plasmid constructs were co-administrated followed by a boost of homologous GST-E and GST-NS1 recombinant proteins, we observed an increased antibody response to NS1 and to E protein compared to animals vaccinated with the proteins or with dengue constructs alone. If neutralizing antibodies play an important role in dengue infection, antibodies generated with this regimen was also significantly better than the administration of the mix of proteins alone. These results suggest that NS1 and E proteins together could be considered in a design of subunit recombinant vaccines. PMID:16359237

  18. Strategies to Improve Child Immunization via Antenatal Care Visits in India: A Propensity Score Matching Analysis.

    PubMed

    Dixit, Priyanka; Dwivedi, Laxmi Kant; Ram, Faujdar

    2013-01-01

    Numerous studies have examined the empirical evidence concerning the influence of demographic and socio-economic factors influencing child immunization, but no documentation is available which shows the actual impact of antenatal care (ANC) visits on subsequent child immunization. Therefore, this paper aims to examine the net impact of ANC visits on subsequent utilization of child immunization after removing the presence of selection bias. Nationwide data from India's latest National Family Health Survey conducted during 2005-06 is used for the present study. The analysis has been carried out in the two separate models, in the first model 1-2 ANC visit and in the second model three or more ANC visits has been compared with no visit. We have used propensity score matching method with a counterfactual model that assesses the actual ANC visits effect on treated (ANC visits) and untreated groups (no ANC visit), and have employed Mantel-Haenszel bounds to examine whether result would be free from hidden bias or not. Using matched sample analysis result shows that child immunization among the groups of women who have completed 1-2 ANC visits and those who had more than two visits was about 13 percent and 19 percent respectively, higher than the group of women who have not made any ANC visit. Findings of nearest neighbor matching with replacement method, which completely eliminated the bias, indicate that selection bias present in data set leads to overestimates the positive effects of ANC visits on child immunization. Result based on Mantel-Haenszel bounds method suggest that if around 19 percent bias would be involved in the result then also we could observe the true positive effect of 1-2 ANC visits on child immunization. This also indicates that antenatal clinics are the conventional platforms for educating pregnant women on the benefits of child immunization. PMID:23824555

  19. Estimating the costs of achieving the WHOUNICEF Global Immunization Vision and Strategy, 20062015

    PubMed Central

    Gasse, Franois; Lee-Martin, Shook-Pui; Lydon, Patrick; Magan, Ahmed; Tibouti, Abdelmajid; Johns, Benjamin; Hutubessy, Raymond; Salama, Peter; Okwo-Bele, Jean-Marie

    2008-01-01

    Abstract Objective To estimate the cost of scaling up childhood immunization services required to reach the WHOUNICEF Global Immunization Vision and Strategy (GIVS) goal of reducing mortality due to vaccine-preventable diseases by two-thirds by 2015. Methods A model was developed to estimate the total cost of reaching GIVS goals by 2015 in 117 low- and lower-middle-income countries. Current spending was estimated by analysing data from country planning documents, and scale-up costs were estimated using a bottom-up, ingredients-based approach. Financial costs were estimated by country and year for reaching 90% coverage with all existing vaccines; introducing a discrete set of new vaccines (rotavirus, conjugate pneumococcal, conjugate meningococcal A and Japanese encephalitis); and conducting immunization campaigns to protect at-risk populations against polio, tetanus, measles, yellow fever and meningococcal meningitis. Findings The 72 poorest countries of the world spent US$ 2.5 (range: US$ 1.84.2) billion on immunization in 2005, an increase from US$ 1.1 (range: US$ 0.91.6) billion in 2000. By 2015 annual immunization costs will on average increase to about US$ 4.0 (range US$ 2.96.7) billion. Total immunization costs for 20062015 are estimated at US$ 35 (range US$ 1340) billion; of this, US$ 16.2 billion are incremental costs, comprised of US$ 5.6 billion for system scale-up and US$ 8.7 billion for vaccines; US$ 19.3 billion is required to maintain immunization programmes at 2005 levels. In all 117 low- and lower-middle-income countries, total costs for 20062015 are estimated at US$ 76 (range: US$ 23110) billion, with US$ 49 billion for maintaining current systems and $27 billion for scaling-up. Conclusion In the 72 poorest countries, US$ 1115 billion (30%40%) of the overall resource needs are unmet if the GIVS goals are to be reached. The methods developed in this paper are approximate estimates with limitations, but provide a roadmap of financing gaps that need to be filled to scale up immunization by 2015. PMID:18235887

  20. Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses.

    PubMed

    Khan, Shahneaz Ali; Waugh, Courtney; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

    2014-10-01

    Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime. PMID:25196393

  1. Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site.

    PubMed

    Kiefer, Jonathan D; Neri, Dario

    2016-03-01

    The activation of the immune system for a selective removal of tumor cells represents an attractive strategy for the treatment of metastatic malignancies, which cannot be cured by existing methodologies. In this review, we examine the design and therapeutic potential of immunocytokines and bispecific antibodies, two classes of bifunctional products which can selectively activate the immune system at the tumor site. Certain protein engineering aspects, such as the choice of the antibody format, are common to both classes of therapeutic agents and can have a profound impact on tumor homing performance invivo of individual products. However, immunocytokines and bispecific antibodies display different mechanisms of action. Future research activities will reveal whether an additive of even synergistic benefit can be obtained from the judicious combination of these two types of biopharmaceutical agents. PMID:26864112

  2. Immune defence, parasite evasion strategies and their relevance for ‘macroscopic phenomena’ such as virulence

    PubMed Central

    Schmid-Hempel, Paul

    2008-01-01

    The discussion of host–parasite interactions, and of parasite virulence more specifically, has so far, with a few exceptions, not focused much attention on the accumulating evidence that immune evasion by parasites is not only almost universal but also often linked to pathogenesis, i.e. the appearance of virulence. Now, the immune evasion hypothesis offers a deeper insight into the evolution of virulence than previous hypotheses. Sensitivity analysis for parasite fitness and life-history theory shows promise to generate a more general evolutionary theory of virulence by including a major element, immune evasion to prevent parasite clearance from the host. Also, the study of dose–response relationships and multiple infections should be particularly illuminating to understand the evolution of virulence. Taking into account immune evasion brings immunological processes to the core of understanding the evolution of parasite virulence and for a range of related issues such as dose, host specificity or immunopathology. The aim of this review is to highlight the mechanism underlying immune evasion and to discuss possible consequences for the evolutionary ecology analysis of host–parasite interactions. PMID:18930879

  3. Sialic acids siglec interaction: A unique strategy to circumvent innate immune response by pathogens

    PubMed Central

    Khatua, Biswajit; Roy, Saptarshi; Mandal, Chitra

    2013-01-01

    Sialic acids (Sias) are nine-carbon keto sugars primarily present on the terminal residue of cell surface glycans. Sialic acid binding immunoglobulins (Ig)-like lectins (siglecs) are generally expressed on various immune cells. They selectively recognize different linkage-specific sialic acids and undertake a variety of cellular functions. Many pathogens either synthesize or acquire sialic acids from the host. Sialylated pathogens generally use siglecs to manipulate the host immune response. The present review mainly deals with the newly developed information regarding mechanism of acquisition of sialic acids by pathogens and their biological relevance especially in the establishment of successful infection by impairing host innate immunity. The pathogens which are unable to synthesize sialic acids might adsorb these from the host as a way to engage the inhibitory siglecs. They promote association with the immune cells through sialic acids-siglec dependent manner. Such an association plays an important role to subvert host's immunity. Detailed investigation of these pathways has been discussed in this review. Particular attention has been focused on Pseudomonas aeruginosa (PA) and Leishmania donovani. PMID:24434319

  4. Does the devil facial tumour produce immunosuppressive cytokines as an immune evasion strategy?

    PubMed

    Morris, Katrina; Belov, Katherine

    2013-05-15

    A unique transmissible cancer known as the Devil Facial Tumour Disease (DFTD) is threatening the Tasmanian devil (Sarcophilus harrisii) with extinction. This disease is highly unusual as it is one of only two naturally occurring contagious cancers. The tumour is transmitted by biting and is able to spread between genetically diverse hosts. Why the tumours are not recognised as foreign and rejected by the host immune system in unknown. One mechanism that allows human cancers to avoid immune suppression is by producing cytokines which down-regulate the hosts immune system. Four key cytokines involved in this process are TGF?1, VEGF-A, IL-10 and IL-6. In this study we investigated whether these cytokines could be involved in immune avoidance in DFTD. To do this we compared expression of these cytokines in tumour and control tissues using qPCR. We found no significant upregulation of any of these cytokines in tumour tissue. We therefore conclude that these cytokines do not play a role in the spread of DFTD. Further work will be needed to elucidate how DFTD cells avoid immune rejection. PMID:23465357

  5. Amphibian macrophage development and antiviral defenses.

    PubMed

    Grayfer, Leon; Robert, Jacques

    2016-05-01

    Macrophage lineage cells represent the cornerstone of vertebrate physiology and immune defenses. In turn, comparative studies using non-mammalian animal models have revealed that evolutionarily distinct species have adopted diverse molecular and physiological strategies for controlling macrophage development and functions. Notably, amphibian species present a rich array of physiological and environmental adaptations, not to mention the peculiarity of metamorphosis from larval to adult stages of development, involving drastic transformation and differentiation of multiple new tissues. Thus it is not surprising that different amphibian species and their respective tadpole and adult stages have adopted unique hematopoietic strategies. Accordingly and in order to establish a more comprehensive view of these processes, here we review the hematopoietic and monopoietic strategies observed across amphibians, describe the present understanding of the molecular mechanisms driving amphibian, an in particular Xenopus laevis macrophage development and functional polarization, and discuss the roles of macrophage-lineage cells during ranavirus infections. PMID:26705159

  6. Airway defense mechanisms.

    PubMed

    Waterer, Grant W

    2012-06-01

    A multitude of overlapping defenses has evolved to help combat the inventiveness of pathogens seeking to invade us, and because the lung is the most common primary route of infection, it is in the lung that the most varied responses are seen. This article focuses on recent research, particularly in innate immunity, and gives a general overview of the defense systems so far identified. Of particular interest is the markedly increased understanding of the role of small molecules such as defensins, cathelicidins, and collectins. Areas in which abnormalities may be relevant to patients with bronchiectasis are highlighted. PMID:22640840

  7. Gamma interferon, tumor necrosis factor alpha, and nitric oxide synthase 2, key elements of cellular immunity, perform critical protective functions during humoral defense against lethal pulmonary Yersinia pestis infection.

    PubMed

    Parent, Michelle A; Wilhelm, Lindsey B; Kummer, Lawrence W; Szaba, Frank M; Mullarky, Isis K; Smiley, Stephen T

    2006-06-01

    Pulmonary infection by Yersinia pestis causes pneumonic plague, a rapidly progressing and often fatal disease. To aid the development of safe and effective pneumonic plague vaccines, we are deciphering mechanisms used by the immune system to protect against lethal pulmonary Y. pestis infection. In murine pneumonic plague models, passive transfer of convalescent-phase sera confers protection, as does active vaccination with live Y. pestis. Here, we demonstrate that protection by either protocol relies upon both gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) cytokines classically associated with type 1 cellular immunity. In both protocols, abrogating IFN-gamma or TNF-alpha activity significantly decreases survival and increases the bacterial burden in pulmonary, splenic, and hepatic tissues. Neutralization of either cytokine also counteracts challenge-induced, vaccination-dependent upregulation of nitric oxide synthase 2 (NOS2). Moreover, genetic depletion of NOS2 suppresses protection conferred by serotherapy. We conclude that IFN-gamma, TNF-alpha, and NOS2, key elements of cellular immunity, perform critical protective functions during humoral defense against lethal pulmonary Y. pestis challenge. These observations strongly suggest that plague vaccines should strive to maximally prime both cellular and humoral immunity. PMID:16714568

  8. MicroRNA-mediated immune modulation as a therapeutic strategy in host-implant integration.

    PubMed

    Ong, Siew-Min; Biswas, Subhra K; Wong, Siew-Cheng

    2015-07-01

    The concept of implanting an artificial device into the human body was once the preserve of science fiction, yet this approach is now often used to replace lost or damaged biological structures in human patients. However, assimilation of medical devices into host tissues is a complex process, and successful implant integration into patients is far from certain. The body's immediate response to a foreign object is immune-mediated reaction, hence there has been extensive research into biomaterials that can reduce or even ablate anti-implant immune responses. There have also been attempts to embed or coat anti-inflammatory drugs and pro-regulatory molecules onto medical devices with the aim of preventing implant rejection by the host. In this review, we summarize the key immune mediators of medical implant reaction, and we evaluate the potential of microRNAs to regulate these processes to promote wound healing, and prolong host-implant integration. PMID:26024977

  9. Variation in Immune Parameters and Disease Prevalence among Lesser Black-Backed Gulls (Larus fuscus sp.) with Different Migratory Strategies

    PubMed Central

    Arriero, Elena; Müller, Inge; Juvaste, Risto; Martínez, Francisco Javier; Bertolero, Albert

    2015-01-01

    The ability to control infections is a key trait for migrants that must be balanced against other costly features of the migratory life. In this study we explored the links between migration and disease ecology by examining natural variation in parasite exposure and immunity in several populations of Lesser Black-backed Gulls (Larus fuscus) with different migratory strategies. We found higher activity of natural antibodies in long distance migrants from the nominate subspecies L.f.fuscus. Circulating levels of IgY showed large variation at the population level, while immune parameters associated with antimicrobial activity showed extensive variation at the individual level irrespective of population or migratory strategy. Pathogen prevalence showed large geographical variation. However, the seroprevalence of one of the gull-specific subtypes of avian influenza (H16) was associated to the migratory strategy, with lower prevalence among the long-distance migrants, suggesting that migration may play a role in disease dynamics of certain pathogens at the population level. PMID:25679797

  10. Immune memory-boosting dose of rapamycin impairs macrophage vesicle acidification and curtails glycolysis in effector CD8 cells, impairing defense against acute infections

    PubMed Central

    Goldberg, Emily L.; Smithey, Megan J.; Lutes, Lydia K.; Uhrlaub, Jennifer L.; Nikolich-Zugich, Janko

    2014-01-01

    Direct mTORC1 inhibition by short-term low-dose rapamycin treatment has recently been shown to improve CD8 T cell immunological memory. While these studies focused on memory development, the impact of low-dose rapamycin on the primary immune response, particularly as it relates to functional effector immunity, is far less clear. We investigated the impact of acute rapamycin treatment on immune effector cell function during the primary immune response to several acute infections. We found that functional CD8 T cell and macrophage responses to both viral and intracellular bacterial pathogens were depressed in mice in vivo and in humans to phorbol ester and calcium ionophore stimulation in vitro in the face of low-dose rapamycin treatment. Mechanistically, the CD8 defect was linked to impaired glycolytic switch in stimulated nave cells and the reduced formation of short-lived effector cells (SLEC). Therefore, more than one cell type required for a protective effector immune response are impaired by rapamycin in both mice and humans, at the dose shown to improve immune memory and extend lifespan. This urges caution with regard to the relative therapeutic costs and benefits of rapamycin treatment as means to improve immune memory. PMID:24913978

  11. Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

    PubMed Central

    Barquero-Calvo, Elías; Chaves-Olarte, Esteban; Weiss, David S.; Guzmán-Verri, Caterina; Chacón-Díaz, Carlos; Rucavado, Alexandra; Moriyón, Ignacio; Moreno, Edgardo

    2007-01-01

    Background To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-α-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice. Conclusion/Significance We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections. PMID:17637846

  12. Assessment of Different Strategies to Determine MAP-specific Cellular Immune Responses in Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessment of cellular immunity in cattle against Mycobacterium avium ssp. paratuberculosis (MAP) by established methods remains unsatisfactory for diagnostic purposes. Recent studies conclude that analysis of T-cell subset responsiveness may improve diagnostic outcome. Aim of this study was to iden...

  13. Viro-immune therapy: A new strategy for treatment of pancreatic cancer.

    PubMed

    Ibrahim, Andrea Marie; Wang, Yao-He

    2016-01-14

    Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly lethal disease with less than 5% survival at five years. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Even when the primary cancer can be removed by radical surgery, local recurrence occurs within one year in 50%-80% of cases. Therefore, it is imperative to develop new approaches for the treatment of advanced cancer and the prevention of recurrence after surgery. Tumour-targeted oncolytic viruses (TOVs) have become an attractive therapeutic agent as TOVs can kill cancer cells through multiple mechanisms of action, especially via virus-induced engagement of the immune response specifically against tumour cells. To attack tumour cells effectively, tumour-specific T cells need to overcome negative regulatory signals that suppress their activation or that induce tolerance programmes such as anergy or exhaustion in the tumour microenvironment. In this regard, the recent breakthrough in immunotherapy achieved with immune checkpoint blockade agents, such as anti-cytotoxic T-lymphocyte-associate protein 4, programmed death 1 (PD-1) or PD-L1 antibodies, has demonstrated the possibility of relieving immune suppression in PDAC. Therefore, the combination of oncolytic virotherapy and immune checkpoint blockade agents may synergistically function to enhance the antitumour response, lending the opportunity to be the future for treatment of pancreatic cancer. PMID:26811622

  14. Viro-immune therapy: A new strategy for treatment of pancreatic cancer

    PubMed Central

    Ibrahim, Andrea Marie; Wang, Yao-He

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly lethal disease with less than 5% survival at five years. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Even when the primary cancer can be removed by radical surgery, local recurrence occurs within one year in 50%-80% of cases. Therefore, it is imperative to develop new approaches for the treatment of advanced cancer and the prevention of recurrence after surgery. Tumour-targeted oncolytic viruses (TOVs) have become an attractive therapeutic agent as TOVs can kill cancer cells through multiple mechanisms of action, especially via virus-induced engagement of the immune response specifically against tumour cells. To attack tumour cells effectively, tumour-specific T cells need to overcome negative regulatory signals that suppress their activation or that induce tolerance programmes such as anergy or exhaustion in the tumour microenvironment. In this regard, the recent breakthrough in immunotherapy achieved with immune checkpoint blockade agents, such as anti-cytotoxic T-lymphocyte-associate protein 4, programmed death 1 (PD-1) or PD-L1 antibodies, has demonstrated the possibility of relieving immune suppression in PDAC. Therefore, the combination of oncolytic virotherapy and immune checkpoint blockade agents may synergistically function to enhance the antitumour response, lending the opportunity to be the future for treatment of pancreatic cancer. PMID:26811622

  15. HvWRKY10, HvWRKY19, and HvWRKY28 positively regulate Mla-triggered immunity and basal defense to barley powdery mildew

    Technology Transfer Automated Retrieval System (TEKTRAN)

    WRKY proteins represent a large family of transcription factors (TFs), involved in plant development and defense responses. So far, fifty-five unique barley TFs have been annotated that contain the WRKY domain; twenty-six of these are present on the Barley1 GeneChip. We analyzed time-course expres...

  16. POLYCLONAL IMMUNE RESPONSES TO ANTIGENS ASSOCIATED WITH CANCER SIGNALING PATHWAYS AND NEW STRATEGIES TO ENHANCE CANCER VACCINES

    PubMed Central

    Clay, Timothy M.; Osada, Takuya; Hartman, Zachary C.; Hobeika, Amy; Devi, Gayathri; Morse, Michael A.; Lyerly, H. Kim

    2013-01-01

    Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been amongst the most successful. A challenge for these therapies is therapeutic unresponsiveness and acquired resistance due to mutations in the receptors, upregulation of alternate growth and survival pathways or inadequate function of the monoclonal antibodies. Vaccines are able to induce polyclonal responses which can have a multitude of affects against the target molecule. We began to explore therapeutic vaccine development to antigens associated with these signaling pathways. We provide an illustrative example in developing therapeutic cancer vaccines inducing polyclonal adaptive immune responses targeting the ErbB family member HER2. Further, we will discuss new strategies to augment the clinical efficacy of cancer vaccines by enhancing vaccine immunogenicity and reversing the immunosuppressive tumor microenvironment. PMID:21136201

  17. Fighting a losing battle: vigorous immune response countered by pathogen suppression of host defenses in the chytridiomycosis-susceptible frog Atelopus zeteki.

    PubMed

    Ellison, Amy R; Savage, Anna E; DiRenzo, Grace V; Langhammer, Penny; Lips, Karen R; Zamudio, Kelly R

    2014-07-01

    The emergence of the disease chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd) has been implicated in dramatic global amphibian declines. Although many species have undergone catastrophic declines and/or extinctions, others appear to be unaffected or persist at reduced frequencies after Bd outbreaks. The reasons behind this variance in disease outcomes are poorly understood: differences in host immune responses have been proposed, yet previous studies suggest a lack of robust immune responses to Bd in susceptible species. Here, we sequenced transcriptomes from clutch-mates of a highly susceptible amphibian, Atelopus zeteki, with different infection histories. We found significant changes in expression of numerous genes involved in innate and inflammatory responses in infected frogs despite high susceptibility to chytridiomycosis. We show evidence of acquired immune responses generated against Bd, including increased expression of immunoglobulins and major histocompatibility complex genes. In addition, fungal-killing genes had significantly greater expression in frogs previously exposed to Bd compared with Bd-naïve frogs, including chitinase and serine-type proteases. However, our results appear to confirm recent in vitro evidence of immune suppression by Bd, demonstrated by decreased expression of lymphocyte genes in the spleen of infected compared with control frogs. We propose susceptibility to chytridiomycosis is not due to lack of Bd-specific immune responses but instead is caused by failure of those responses to be effective. Ineffective immune pathway activation and timing of antibody production are discussed as potential mechanisms. However, in light of our findings, suppression of key immune responses by Bd is likely an important factor in the lethality of this fungus. PMID:24841130

  18. Fighting a Losing Battle: Vigorous Immune Response Countered by Pathogen Suppression of Host Defenses in the Chytridiomycosis-Susceptible Frog Atelopus zeteki

    PubMed Central

    Ellison, Amy R.; Savage, Anna E.; DiRenzo, Grace V.; Langhammer, Penny; Lips, Karen R.; Zamudio, Kelly R.

    2014-01-01

    The emergence of the disease chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd) has been implicated in dramatic global amphibian declines. Although many species have undergone catastrophic declines and/or extinctions, others appear to be unaffected or persist at reduced frequencies after Bd outbreaks. The reasons behind this variance in disease outcomes are poorly understood: differences in host immune responses have been proposed, yet previous studies suggest a lack of robust immune responses to Bd in susceptible species. Here, we sequenced transcriptomes from clutch-mates of a highly susceptible amphibian, Atelopus zeteki, with different infection histories. We found significant changes in expression of numerous genes involved in innate and inflammatory responses in infected frogs despite high susceptibility to chytridiomycosis. We show evidence of acquired immune responses generated against Bd, including increased expression of immunoglobulins and major histocompatibility complexgenes. In addition, fungal-killing genes had significantly greater expression in frogs previously exposed to Bd compared with Bd-nave frogs, including chitinase and serine-type proteases. However, our results appear to confirm recent in vitro evidence of immune suppression by Bd, demonstrated by decreased expression of lymphocyte genes in the spleen of infected compared with control frogs. We propose susceptibility to chytridiomycosis is not due to lack of Bd-specific immune responses but instead is caused by failure of those responses to be effective. Ineffective immune pathway activation and timing of antibody production are discussed as potential mechanisms. However, in light of our findings, suppression of key immune responses by Bd is likely an important factor in the lethality of this fungus. PMID:24841130

  19. Vaccine Engineering with Dual-Functional Mineral Shell: A Promising Strategy to Overcome Preexisting Immunity.

    PubMed

    Wang, Xiaoyu; Sun, Caijun; Li, Pingchao; Wu, Tongjin; Zhou, Hangyu; Yang, Dong; Liu, Yichu; Ma, Xiuchang; Song, Zhiyong; Nian, Qinggong; Feng, Liqiang; Qin, Chengfeng; Chen, Ling; Tang, Ruikang

    2016-01-01

    Dual-functional biomineral-vaccine core-shell nanohybrids are obtained using recombinant adenovirus serotype 5 (rAd5) as templates, which efficiently masks the neutralizing epitope of vaccines and preserve their original immunogenicity. The versatile vaccine hybrid can evade the preexisting anti-Ad5 immunity, leading to boosted multifunctional antigen-specific cytokine-secreting T cell responses and presenting promising applications of vaccine-material hybrid for the rational design of vaccines. PMID:26607212

  20. De-submergence responses of antioxidative defense systems in two wetland plants having escape and quiescence strategies.

    PubMed

    Luo, Fang-Li; Thiele, Bjrn; Janzik, Ingar; Zeng, Bo; Schurr, Ulrich; Matsubara, Shizue

    2012-11-15

    Fast recovery after de-submergence requires efficient protection against oxidative injuries. We investigated whether de-submergence responses of antioxidant systems differ in two wetland plants, Alternanthera philoxeroides and Hemarthria altissima, characterized by 'escape' and 'quiescence' strategies of flood tolerance, respectively. The antioxidant capacity was assessed in the two species during 10d of recovery following 20d of complete submergence (low light+low O(2)) or severe shading (low light+ambient O(2)). The activities of superoxide dismutase and catalase were measured in leaf and root tissues, along with the concentrations of reduced ascorbate, malondialdehyde, and acetaldehyde. In addition, formation of superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) was detected in leaves by chemical staining. Following de-submergence, plants of A. philoxeroides showed a transient burst of acetaldehyde, while the concentration of acetaldehyde increased slowly and stayed high in leaves of H. altissima. In leaves of A. philoxeroides, the variations in O(2)(-) and H(2)O(2) correlated with the levels of light and O(2), respectively, whereas neither of the two reactive oxygen species was detected in H. altissima. For A. philoxeroides, the antioxidant capacities changed mainly in leaves during the recovery. For H. altissima, changes in reduced ascorbate were found in leaves and those of antioxidant enzyme activities in roots. De-submergence caused some lipid peroxidation in leaves of both species. We conclude that de-submergence responses of the detoxification systems differ between A. philoxeroides and H. altissima, especially in leaves. Dynamic changes were found in A. philoxeroides (having the escape strategy), as opposed to little or slow changes in H. altissima (having the quiescence strategy). Whereas the antioxidant capacities are often strongly influenced by light environments, the toxic compounds and lipid peroxidation indicate harmful effects of changing O(2) concentration which accompanies submergence and de-submergence. PMID:22884406

  1. Iron in Infection and Immunity

    PubMed Central

    Cassat, James E.; Skaar, Eric P.

    2013-01-01

    Iron is an essential nutrient for both humans and pathogenic microbes. Because of its ability to exist in one of two oxidation states, iron is an ideal redox catalyst for diverse cellular processes including respiration and DNA replication. However, the redox potential of iron also contributes to its toxicity, thus iron concentration and distribution must be carefully controlled. Given the absolute requirement for iron by virtually all human pathogens, an important facet of the innate immune system is to limit iron availability to invading microbes in a process termed nutritional immunity. Successful human pathogens must therefore possess mechanisms to circumvent nutritional immunity in order to cause disease. In this review, we discuss regulation of iron metabolism in the setting of infection and delineate strategies used by human pathogens to overcome iron-withholding defenses. PMID:23684303

  2. Stability of Microbiota Facilitated by Host Immune Regulation: Informing Probiotic Strategies to Manage Amphibian Disease

    PubMed Central

    Küng, Denise; Bigler, Laurent; Davis, Leyla R.; Gratwicke, Brian; Griffith, Edgardo; Woodhams, Douglas C.

    2014-01-01

    Microbial communities can augment host immune responses and probiotic therapies are under development to prevent or treat diseases of humans, crops, livestock, and wildlife including an emerging fungal disease of amphibians, chytridiomycosis. However, little is known about the stability of host-associated microbiota, or how the microbiota is structured by innate immune factors including antimicrobial peptides (AMPs) abundant in the skin secretions of many amphibians. Thus, conservation medicine including therapies targeting the skin will benefit from investigations of amphibian microbial ecology that provide a model for vertebrate host-symbiont interactions on mucosal surfaces. Here, we tested whether the cutaneous microbiota of Panamanian rocket frogs, Colostethus panamansis, was resistant to colonization or altered by treatment. Under semi-natural outdoor mesocosm conditions in Panama, we exposed frogs to one of three treatments including: (1) probiotic - the potentially beneficial bacterium Lysinibacillus fusiformis, (2) transplant – skin washes from the chytridiomycosis-resistant glass frog Espadarana prosoblepon, and (3) control – sterile water. Microbial assemblages were analyzed by a culture-independent T-RFLP analysis. We found that skin microbiota of C. panamansis was resistant to colonization and did not differ among treatments, but shifted through time in the mesocosms. We describe regulation of host AMPs that may function to maintain microbial community stability. Colonization resistance was metabolically costly and microbe-treated frogs lost 7–12% of body mass. The discovery of strong colonization resistance of skin microbiota suggests a well-regulated, rather than dynamic, host-symbiont relationship, and suggests that probiotic therapies aiming to enhance host immunity may require an approach that circumvents host mechanisms maintaining equilibrium in microbial communities. PMID:24489847

  3. JASMONATE-TRIGGERED PLANT IMMUNITY

    PubMed Central

    Campos, Marcelo L.; Kang, Jin-Ho; Howe, Gregg A.

    2014-01-01

    The plant hormone jasmonate (JA) exerts direct control over the production of chemical defense compounds that confer resistance to a remarkable spectrum of plant-associated organisms, ranging from microbial pathogens to vertebrate herbivores. The underlying mechanism of JA-triggered immunity (JATI) can be conceptualized as a multi-stage signal transduction cascade involving: i) pattern recognition receptors (PRRs) that couple the perception of danger signals to rapid synthesis of bioactive JA; ii) an evolutionarily conserved JA signaling module that links fluctuating JA levels to changes in the abundance of transcriptional repressor proteins; and iii) activation (de-repression) of transcription factors that orchestrate the expression of myriad chemical and morphological defense traits. Multiple negative feedback loops act in concert to restrain the duration and amplitude of defense responses, presumably to mitigate potential fitness costs of JATI. The convergence of diverse plant- and non-plant-derived signals on the core JA module indicates that JATI is a general response to perceived danger. However, the modular structure of JATI may accommodate attacker-specific defense responses through evolutionary innovation of PRRs (inputs) and defense traits (outputs). The efficacy of JATI as a defense strategy is highlighted by its capacity to shape natural populations of plant attackers, as well as the propensity of plant-associated organisms to subvert or otherwise manipulate JA signaling. As both a cellular hub for integrating informational cues from the environment and a common target of pathogen effectors, the core JA module provides a focal point for understanding immune system networks and the evolution of chemical diversity in the plant kingdom. PMID:24973116

  4. Jasmonate-triggered plant immunity.

    PubMed

    Campos, Marcelo L; Kang, Jin-Ho; Howe, Gregg A

    2014-07-01

    The plant hormone jasmonate (JA) exerts direct control over the production of chemical defense compounds that confer resistance to a remarkable spectrum of plant-associated organisms, ranging from microbial pathogens to vertebrate herbivores. The underlying mechanism of JA-triggered immunity (JATI) can be conceptualized as a multi-stage signal transduction cascade involving: i) pattern recognition receptors (PRRs) that couple the perception of danger signals to rapid synthesis of bioactive JA; ii) an evolutionarily conserved JA signaling module that links fluctuating JA levels to changes in the abundance of transcriptional repressor proteins; and iii) activation (de-repression) of transcription factors that orchestrate the expression of myriad chemical and morphological defense traits. Multiple negative feedback loops act in concert to restrain the duration and amplitude of defense responses, presumably to mitigate potential fitness costs of JATI. The convergence of diverse plant- and non-plant-derived signals on the core JA module indicates that JATI is a general response to perceived danger. However, the modular structure of JATI may accommodate attacker-specific defense responses through evolutionary innovation of PRRs (inputs) and defense traits (outputs). The efficacy of JATI as a defense strategy is highlighted by its capacity to shape natural populations of plant attackers, as well as the propensity of plant-associated organisms to subvert or otherwise manipulate JA signaling. As both a cellular hub for integrating informational cues from the environment and a common target of pathogen effectors, the core JA module provides a focal point for understanding immune system networks and the evolution of chemical diversity in the plant kingdom. PMID:24973116

  5. The New Deal: A Potential Role for Secreted Vesicles in Innate Immunity and Tumor Progression

    PubMed Central

    Benito-Martin, Alberto; Di Giannatale, Angela; Ceder, Sophia; Peinado, Hctor

    2015-01-01

    Tumors must evade the immune system to survive and metastasize, although the mechanisms that lead to tumor immunoediting and their evasion of immune surveillance are far from clear. The first line of defense against metastatic invasion is the innate immune system that provides immediate defense through humoral immunity and cell-mediated components, mast cells, neutrophils, macrophages, and other myeloid-derived cells that protect the organism against foreign invaders. Therefore, tumors must employ different strategies to evade such immune responses or to modulate their environment, and they must do so prior metastasizing. Exosomes and other secreted vesicles can be used for cellcell communication during tumor progression by promoting the horizontal transfer of information. In this review, we will analyze the role of such extracellular vesicles during tumor progression, summarizing the role of secreted vesicles in the crosstalk between the tumor and the innate immune system. PMID:25759690

  6. A novel strategy involved in [corrected] anti-oxidative defense: the conversion of NADH into NADPH by a metabolic network.

    PubMed

    Singh, Ranji; Lemire, Joseph; Mailloux, Ryan J; Appanna, Vasu D

    2008-01-01

    The reduced nicotinamide adenine dinucleotide phosphate (NADPH) is pivotal to the cellular anti-oxidative defence strategies in most organisms. Although its production mediated by different enzyme systems has been relatively well-studied, metabolic networks dedicated to the biogenesis of NADPH have not been fully characterized. In this report, a metabolic pathway that promotes the conversion of reduced nicotinamide adenine dinucleotide (NADH), a pro-oxidant into NADPH has been uncovered in Pseudomonas fluorescens exposed to oxidative stress. Enzymes such as pyruvate carboxylase (PC), malic enzyme (ME), malate dehydrogenase (MDH), malate synthase (MS), and isocitrate lyase (ICL) that are involved in disparate metabolic modules, converged to create a metabolic network aimed at the transformation of NADH into NADPH. The downregulation of phosphoenol carboxykinase (PEPCK) and the upregulation of pyruvate kinase (PK) ensured that this metabolic cycle fixed NADH into NADPH to combat the oxidative stress triggered by the menadione insult. This is the first demonstration of a metabolic network invoked to generate NADPH from NADH, a process that may be very effective in combating oxidative stress as the increase of an anti-oxidant is coupled to the decrease of a pro-oxidant. PMID:18628998

  7. A Novel Strategy Involved Anti-Oxidative Defense: The Conversion of NADH into NADPH by a Metabolic Network

    PubMed Central

    Singh, Ranji; Lemire, Joseph; Mailloux, Ryan J.; Appanna, Vasu D.

    2008-01-01

    The reduced nicotinamide adenine dinucleotide phosphate (NADPH) is pivotal to the cellular anti-oxidative defence strategies in most organisms. Although its production mediated by different enzyme systems has been relatively well-studied, metabolic networks dedicated to the biogenesis of NADPH have not been fully characterized. In this report, a metabolic pathway that promotes the conversion of reduced nicotinamide adenine dinucleotide (NADH), a pro-oxidant into NADPH has been uncovered in Pseudomonas fluorescens exposed to oxidative stress. Enzymes such as pyruvate carboxylase (PC), malic enzyme (ME), malate dehydrogenase (MDH), malate synthase (MS), and isocitrate lyase (ICL) that are involved in disparate metabolic modules, converged to create a metabolic network aimed at the transformation of NADH into NADPH. The downregulation of phosphoenol carboxykinase (PEPCK) and the upregulation of pyruvate kinase (PK) ensured that this metabolic cycle fixed NADH into NADPH to combat the oxidative stress triggered by the menadione insult. This is the first demonstration of a metabolic network invoked to generate NADPH from NADH, a process that may be very effective in combating oxidative stress as the increase of an anti-oxidant is coupled to the decrease of a pro-oxidant. PMID:18628998

  8. Plant defense against insect herbivores.

    PubMed

    Frstenberg-Hgg, Joel; Zagrobelny, Mika; Bak, Sren

    2013-01-01

    Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce several internal signals from the wounded tissues, including calcium ion fluxes, phosphorylation cascades and systemic- and jasmonate signaling. These are perceived in undamaged tissues, which thereafter reinforce their defense by producing different, mostly low molecular weight, defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce defense responses. Plants also apply morphological features like waxes, trichomes and latices to make the feeding more difficult for the insects. Extrafloral nectar, food bodies and nesting or refuge sites are produced to accommodate and feed the predators of the herbivores. Meanwhile, herbivorous insects have adapted to resist plant defenses, and in some cases even sequester the compounds and reuse them in their own defense. Both plant defense and insect adaptation involve metabolic costs, so most plant-insect interactions reach a stand-off, where both host and herbivore survive although their development is suboptimal. PMID:23681010

  9. Plant Defense against Insect Herbivores

    PubMed Central

    Fürstenberg-Hägg, Joel; Zagrobelny, Mika; Bak, Søren

    2013-01-01

    Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce several internal signals from the wounded tissues, including calcium ion fluxes, phosphorylation cascades and systemic- and jasmonate signaling. These are perceived in undamaged tissues, which thereafter reinforce their defense by producing different, mostly low molecular weight, defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce defense responses. Plants also apply morphological features like waxes, trichomes and latices to make the feeding more difficult for the insects. Extrafloral nectar, food bodies and nesting or refuge sites are produced to accommodate and feed the predators of the herbivores. Meanwhile, herbivorous insects have adapted to resist plant defenses, and in some cases even sequester the compounds and reuse them in their own defense. Both plant defense and insect adaptation involve metabolic costs, so most plant-insect interactions reach a stand-off, where both host and herbivore survive although their development is suboptimal. PMID:23681010

  10. Use of immunization as strategy for outbreak control of varicella zoster in an institutional setting

    PubMed Central

    Bhatti, V.K.; Budhathoki, Lee; Kumar, Mahadevan; Singh, Gurpreet; Nath, Amol; Nair, Gen Velu

    2014-01-01

    Background Outbreaks of varicella gets reported often in India. However, outbreak in health care providers living in closed institutional setting and role of vaccination as post exposure prophylaxis for control of outbreak has not been studied extensively. This paper presents epidemiological investigation and control strategy undertaken in such scenario. Methods This is an epidemiological investigation of chickenpox in nursing students which highlights role of early identification and appropriate control strategy to prevent explosive outbreak in high risk vulnerable population. Vaccination of all susceptible in addition to isolation of cases, quarantine of suspects and proper screening for new cases was the major control strategy adopted. Results The index case was imported and all eight cases occurred within the incubation period of the case. Two cases occurred in students previously vaccinated for chickenpox. No second or third wave of infection occurred showing vaccination as effective tool in outbreak control strategy. Conclusion Early identification of cases and vaccination of all susceptible contributed to effective control of the outbreak. PMID:25378773

  11. Intranasal immunization of mice with a bovine respiratory syncytial virus vaccine induces superior immunity and protection compared to those by subcutaneous delivery or combinations of intranasal and subcutaneous prime-boost strategies.

    PubMed

    Mapletoft, John W; Latimer, Laura; Babiuk, Lorne A; van Drunen Littel-van den Hurk, Sylvia

    2010-01-01

    Bovine respiratory syncytial virus (BRSV) infects cells of the respiratory mucosa, so it is desirable to develop a vaccination strategy that induces mucosal immunity. To achieve this, various delivery routes were compared for formalin-inactivated (FI) BRSV formulated with CpG oligodeoxynucleotide (ODN) and polyphosphazene (PP). Intranasal delivery of the FI-BRSV formulation was superior to subcutaneous delivery in terms of antibody, cell-mediated, and mucosal immune responses, as well as reduction in virus replication after BRSV challenge. Although intranasal delivery of FI-BRSV also induced higher serum and lung antibody titers and gamma interferon (IFN-gamma) production in the lungs than intranasal-subcutaneous and/or subcutaneous-intranasal prime-boost strategies, no significant differences were observed in cell-mediated immune responses or virus replication in the lungs of challenged mice. Interleukin 5 (IL-5), eotaxin, and eosinophilia were enhanced after BRSV challenge in the lungs of subcutaneously immunized mice compared to unvaccinated mice, but not in the lungs of mice immunized intranasally or through combinations of the intranasal and subcutaneous routes. These results suggest that two intranasal immunizations with FI-BRSV formulated with CpG ODN and PP are effective and safe as an approach to induce systemic and mucosal responses, as well to reduce virus replication after BRSV challenge. Furthermore, intranasal-subcutaneous and subcutaneous-intranasal prime-boost strategies were also safe and almost as efficacious. In addition to the implications for the development of a protective BRSV vaccine for cattle, formulation with CpG ODN and PP could also prove important in the development of a mucosal vaccine that induces protective immunity against human RSV. PMID:19864487

  12. Effects of lipoic acid on immune function, the antioxidant defense system, and inflammation-related genes expression of broiler chickens fed aflatoxin contaminated diets.

    PubMed

    Li, Yan; Ma, Qiu-Gang; Zhao, Li-Hong; Wei, Hua; Duan, Guo-Xiang; Zhang, Jian-Yun; Ji, Cheng

    2014-01-01

    This study was designed to evaluate the effect of low level of Aflatoxin B1 (AFB1) on oxidative stress, immune reaction and inflammation response and the possible ameliorating effects of dietary alpha-lipoic acid (?-LA) in broilers. Birds were randomly allocated into three groups and assigned to receive different diets: basal diet, diet containing 74 ?g/kg AFB1, and 300 mg/kg ?-LA supplementation in diet containing 74 ?g/kg AFB1 for three weeks. The results showed that the serum levels of malondialdehyde, tumor necrosis factor alpha (TNF?) and interferon gamma (IFN?) in the AFB1-treated group were significantly increased than the control group. In addition, the increased expressions of interleukin 6 (IL6), TNF? and IFN? were observed in birds exposed to the AFB1-contaminated diet. These degenerative changes were inhibited by ?-LA-supplement. The activities of total superoxide dismutase and glutathione peroxidase, the levels of humoral immunity, and the expressions of nuclear factor-?B p65 and heme oxygenase-1, however, were not affected by AFB1. The results suggest that ?-LA alleviates AFB1 induced oxidative stress and immune changes and modulates the inflammatory response at least partly through changes in the expression of proinflammatory cytokines of spleen such as IL6 and TNF? in broiler chickens. PMID:24699046

  13. Effects of Lipoic Acid on Immune Function, the Antioxidant Defense System, and Inflammation-Related Genes Expression of Broiler Chickens Fed Aflatoxin Contaminated Diets

    PubMed Central

    Li, Yan; Ma, Qiu-Gang; Zhao, Li-Hong; Wei, Hua; Duan, Guo-Xiang; Zhang, Jian-Yun; Ji, Cheng

    2014-01-01

    This study was designed to evaluate the effect of low level of Aflatoxin B1 (AFB1) on oxidative stress, immune reaction and inflammation response and the possible ameliorating effects of dietary alpha-lipoic acid (?-LA) in broilers. Birds were randomly allocated into three groups and assigned to receive different diets: basal diet, diet containing 74 ?g/kg AFB1, and 300 mg/kg ?-LA supplementation in diet containing 74 ?g/kg AFB1 for three weeks. The results showed that the serum levels of malondialdehyde, tumor necrosis factor alpha (TNF?) and interferon gamma (IFN?) in the AFB1-treated group were significantly increased than the control group. In addition, the increased expressions of interleukin 6 (IL6), TNF? and IFN? were observed in birds exposed to the AFB1-contaminated diet. These degenerative changes were inhibited by ?-LA-supplement. The activities of total superoxide dismutase and glutathione peroxidase, the levels of humoral immunity, and the expressions of nuclear factor-?B p65 and heme oxygenase-1, however, were not affected by AFB1. The results suggest that ?-LA alleviates AFB1 induced oxidative stress and immune changes and modulates the inflammatory response at least partly through changes in the expression of proinflammatory cytokines of spleen such as IL6 and TNF? in broiler chickens. PMID:24699046

  14. Balancing Innate Immunity and Inflammatory State via Modulation of Neutrophil Function: A Novel Strategy to Fight Sepsis.

    PubMed

    Fang, Haoshu; Jiang, Wei; Cheng, Jin; Lu, Yan; Liu, Anding; Kan, Lixin; Dahmen, Uta

    2015-01-01

    Sepsis and SIRS (systemic inflammatory response syndrome) belong to a severe disease complex characterized by infection and/or a whole-body inflammatory state. There is a growing body of evidence that neutrophils are actively involved in sepsis and are responsible for both release of cytokines and phagocytosis of pathogens. The neutrophil level is mainly regulated by G-CSF, a cytokine and drug, which is widely used in the septic patient with neutropenia. This review will briefly summarize the role of neutrophils and the therapeutic effect of G-CSF in sepsis. We further suggest that targeting neutrophil function to modulate the balance between innate immunity and inflammatory injury could be a worthwhile therapeutic strategy for sepsis. PMID:26798659

  15. Balancing Innate Immunity and Inflammatory State via Modulation of Neutrophil Function: A Novel Strategy to Fight Sepsis

    PubMed Central

    Fang, Haoshu; Jiang, Wei; Cheng, Jin; Lu, Yan; Liu, Anding; Kan, Lixin; Dahmen, Uta

    2015-01-01

    Sepsis and SIRS (systemic inflammatory response syndrome) belong to a severe disease complex characterized by infection and/or a whole-body inflammatory state. There is a growing body of evidence that neutrophils are actively involved in sepsis and are responsible for both release of cytokines and phagocytosis of pathogens. The neutrophil level is mainly regulated by G-CSF, a cytokine and drug, which is widely used in the septic patient with neutropenia. This review will briefly summarize the role of neutrophils and the therapeutic effect of G-CSF in sepsis. We further suggest that targeting neutrophil function to modulate the balance between innate immunity and inflammatory injury could be a worthwhile therapeutic strategy for sepsis. PMID:26798659

  16. Enhancing Artificial Bee Colony Algorithm with Self-Adaptive Searching Strategy and Artificial Immune Network Operators for Global Optimization

    PubMed Central

    Chen, Tinggui; Xiao, Renbin

    2014-01-01

    Artificial bee colony (ABC) algorithm, inspired by the intelligent foraging behavior of honey bees, was proposed by Karaboga. It has been shown to be superior to some conventional intelligent algorithms such as genetic algorithm (GA), artificial colony optimization (ACO), and particle swarm optimization (PSO). However, the ABC still has some limitations. For example, ABC can easily get trapped in the local optimum when handing in functions that have a narrow curving valley, a high eccentric ellipse, or complex multimodal functions. As a result, we proposed an enhanced ABC algorithm called EABC by introducing self-adaptive searching strategy and artificial immune network operators to improve the exploitation and exploration. The simulation results tested on a suite of unimodal or multimodal benchmark functions illustrate that the EABC algorithm outperforms ACO, PSO, and the basic ABC in most of the experiments. PMID:24772023

  17. Breaking the mould - novel diagnostic and therapeutic strategies for invasive pulmonary aspergillosis in the immune deficient patient.

    PubMed

    Thornton, Christopher R

    2014-06-01

    Invasive pulmonary aspergillosis (IPA) caused by the ubiquitous environmental fungus Aspergillus is a frequently fatal lung disease of immunocompromised humans accounting for more than 200,000 infections each year, with an associated mortality rate of 30-90%. This review addresses the current status of IPA diagnosis and treatment and the urgent need to develop accurate, non-invasive strategies for identifying pulmonary infections in the ever-expanding population of immune deficient patients at risk of acquiring opportunistic fungal infections including hematological malignancy and hematopoetic stem cell transplant patients. Recent advances in the use of an Aspergillus-specific monoclonal antibody, JF5, for point-of-care diagnosis of IPA using lateral-flow technology is examined, as is its use in PET/MRI bioimaging and radio-immunotherapy using radionuclide-labeled single chain antibody fragments, Fab fragments, and a fully humanized JF5 derivative. PMID:24689528

  18. The Complex Contributions of Genetics and Nutrition to Immunity in Drosophila melanogaster

    PubMed Central

    Unckless, Robert L.; Rottschaefer, Susan M.; Lazzaro, Brian P.

    2015-01-01

    Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and nutritional immunology has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional immune system that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment. PMID:25764027

  19. The complex contributions of genetics and nutrition to immunity in Drosophila melanogaster.

    PubMed

    Unckless, Robert L; Rottschaefer, Susan M; Lazzaro, Brian P

    2015-03-01

    Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and "nutritional immunology" has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional "immune system" that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment. PMID:25764027

  20. On the Mechanism Determining the Th1/Th2 Phenotype of an Immune Response, and its Pertinence to Strategies for the Prevention, and Treatment, of Certain Infectious Diseases

    PubMed Central

    Bretscher, P A

    2014-01-01

    It is well recognized that the physiological/pathological consequences of an immune response, against a foreign or a self-antigen, are often critically dependent on the class of immunity generated. Here we focus on how antigen interacts with the cells of the immune system to determine whether antigen predominantly generates Th1 or Th2 cells. We refer to this mechanism as the ‘decision criterion’ controlling the Th1/Th2 phenotype of the immune response. A plausible decision criterion should account for the variables of immunization known to affect the Th1/Th2 phenotype of the ensuing immune response. Documented variables include the nature of the antigen, in terms of its degree of foreignness, the dose of antigen and the time after immunization at which the Th1/Th2 phenotype of the immune response is assessed. These are quantitative variables made at the level of the system. In addition, the route of immunization is also critical. I describe a quantitative hypothesis as to the nature of the decision criterion, referred to as the Threshold Hypothesis. This hypothesis accounts for the quantitative variables of immunization known to affect the Th1/Th2 phenotype of the immune response generated. I suggest and illustrate how this is not true of competing, contemporary hypotheses. I outline studies testing predictions of the hypothesis and illustrate its potential utility in designing strategies to prevent or treat medical situations where a predominant Th1 response is required to contain an infection, such as those caused by HIV-1 and by Mycobacterium tuberculosis, or to contain cancers. PMID:24684592

  1. On the mechanism determining the TH1/TH2 phenotype of an immune response, and its pertinence to strategies for the prevention, and treatment, of certain infectious diseases.

    PubMed

    Bretscher, P A

    2014-06-01

    It is well recognized that the physiological/pathological consequences of an immune response, against a foreign or a self-antigen, are often critically dependent on the class of immunity generated. Here we focus on how antigen interacts with the cells of the immune system to determine whether antigen predominantly generates Th1 or Th2 cells. We refer to this mechanism as the 'decision criterion' controlling the Th1/Th2 phenotype of the immune response. A plausible decision criterion should account for the variables of immunization known to affect the Th1/Th2 phenotype of the ensuing immune response. Documented variables include the nature of the antigen, in terms of its degree of foreignness, the dose of antigen and the time after immunization at which the Th1/Th2 phenotype of the immune response is assessed. These are quantitative variables made at the level of the system. In addition, the route of immunization is also critical. I describe a quantitative hypothesis as to the nature of the decision criterion, referred to as the Threshold Hypothesis. This hypothesis accounts for the quantitative variables of immunization known to affect the Th1/Th2 phenotype of the immune response generated. I suggest and illustrate how this is not true of competing, contemporary hypotheses. I outline studies testing predictions of the hypothesis and illustrate its potential utility in designing strategies to prevent or treat medical situations where a predominant Th1 response is required to contain an infection, such as those caused by HIV-1 and by Mycobacterium tuberculosis, or to contain cancers. PMID:24684592

  2. Cryptococcal Interactions with the Host Immune System ?

    PubMed Central

    Voelz, Kerstin; May, Robin C.

    2010-01-01

    Opportunistic pathogens have become of increasing medical importance over the last decade due to the AIDS pandemic. Not only is cryptococcosis the fourth-most-common fatal infectious disease in sub-Saharan Africa, but also Cryptococcus is an emerging pathogen of immunocompetent individuals. The interaction between Cryptococcus and the host's immune system is a major determinant for the outcome of disease. Despite initial infection in early childhood with Cryptococcus neoformans and frequent exposure to C. neoformans within the environment, immunocompetent individuals are generally able to contain the fungus or maintain the yeast in a latent state. However, immune deficiencies lead to disseminating infections that are uniformly fatal without rapid clinical intervention. This review will discuss the innate and adaptive immune responses to Cryptococcus and cryptococcal strategies to evade the host's defense mechanisms. It will also address the importance of these strategies in pathogenesis and the potential of immunotherapy in cryptococcosis treatment. PMID:20382758

  3. Exploiting host immunity: the Salmonella paradigm

    PubMed Central

    Behnsen, Judith; Perez-Lopez, Araceli; Nuccio, Sean-Paul; Raffatellu, Manuela

    2014-01-01

    Pathogens have evolved clever strategies to evade and in some cases exploit the attacks of an activated immune system. Salmonella enterica is one such pathogen, exploiting multiple aspects of host defense to promote its replication in the host. Here we review recent findings on the mechanisms by which Salmonella establishes systemic and chronic infection, including strategies involving manipulation of innate immune signaling and inflammatory forms of cell death, as well as immune evasion by establishing residency in M2 macrophages. We also examine recent evidence showing that the oxidative environment and the high levels of antimicrobial proteins produced in response to localized Salmonella gastrointestinal infection enable the pathogen to successfully outcompete the resident gut microbiota. PMID:25582038

  4. Exploiting host immunity: the Salmonella paradigm.

    PubMed

    Behnsen, Judith; Perez-Lopez, Araceli; Nuccio, Sean-Paul; Raffatellu, Manuela

    2015-02-01

    Pathogens have evolved clever strategies to evade and in some cases exploit the attacks of an activated immune system. Salmonella enterica is one such pathogen, exploiting multiple aspects of host defense to promote its replication in the host. Here we review recent findings on the mechanisms by which Salmonella establishes systemic and chronic infection, including strategies involving manipulation of innate immune signaling and inflammatory forms of cell death, as well as immune evasion by establishing residency in M2 macrophages. We also examine recent evidence showing that the oxidative environment and the high levels of antimicrobial proteins produced in response to localized Salmonella gastrointestinal infection enable the pathogen to successfully outcompete the resident gut microbiota. PMID:25582038

  5. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system.

    PubMed

    Pelaseyed, Thaher; Bergström, Joakim H; Gustafsson, Jenny K; Ermund, Anna; Birchenough, George M H; Schütte, André; van der Post, Sjoerd; Svensson, Frida; Rodríguez-Piñeiro, Ana M; Nyström, Elisabeth E L; Wising, Catharina; Johansson, Malin E V; Hansson, Gunnar C

    2014-07-01

    The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine, mucus limits the number of bacteria that can reach the epithelium and the Peyer's patches. In the large intestine, the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate-keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103(+) type. In addition to the gel-forming mucins, the transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization, suggesting that enterocytes might control and report epithelial microbial challenge. There is communication not only from the epithelial cells to the immune system but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy. PMID:24942678

  6. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system

    PubMed Central

    Pelaseyed, Thaher; Bergström, Joakim H.; Gustafsson, Jenny K.; Ermund, Anna; Birchenough, George M. H.; Schütte, André; van der Post, Sjoerd; Svensson, Frida; Rodríguez-Piñeiro, Ana M.; Nyström, Elisabeth E.L.; Wising, Catharina; Johansson, Malin E.V.; Hansson, Gunnar C.

    2014-01-01

    Summary The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine and colon. The large highly glycosylated gel-forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine mucus limits the number of bacteria that can reach the epithelium and the Peyer’s patches. In the large intestine the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells not only secrete the MUC2 mucin, but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate-keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103+-type. In addition to the gel forming mucins, the transmembrane mucins MUC3, MUC12 and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization suggesting that enterocytes might control and report epithelial microbial challenge. There is not only communication from the epithelial cells to the immune system, but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy. PMID:24942678

  7. Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression

    PubMed Central

    Kimberlin, Christopher R.; Bornholdt, Zachary A.; Li, Sheng; Woods, Virgil L.; MacRae, Ian J.; Saphire, Erica Ollmann

    2009-01-01

    Ebolavirus causes a severe hemorrhagic fever and is divided into five distinct species, of which Reston ebolavirus is uniquely nonpathogenic to humans. Disease caused by ebolavirus is marked by early immunosuppression of innate immune signaling events, involving silencing and sequestration of double-stranded RNA (dsRNA) by the viral protein VP35. Here we present unbound and dsRNA-bound crystal structures of the dsRNA-binding domain of Reston ebolavirus VP35. The structures show that VP35 forms an unusual, asymmetric dimer on dsRNA binding, with each of the monomers binding dsRNA in a different way: one binds the backbone whereas the other caps the terminus. Additional SAXS, DXMS, and dsRNA-binding experiments presented here support a model of cooperative dsRNA recognition in which binding of the first monomer assists binding of the next monomer of the oligomeric VP35 protein. This work illustrates how ebolavirus VP35 could mask key recognition sites of molecules such as RIG-I, MDA-5, and Dicer to silence viral dsRNA in infection. PMID:20018665

  8. Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression

    SciTech Connect

    Kimberlin, Christopher R.; Bornholdt, Zachary A.; Li, Sheng; Woods, Jr., Virgil L.; MacRae, Ian J.; Saphire, Erica Ollmann

    2010-03-12

    Ebolavirus causes a severe hemorrhagic fever and is divided into five distinct species, of which Reston ebolavirus is uniquely nonpathogenic to humans. Disease caused by ebolavirus is marked by early immunosuppression of innate immune signaling events, involving silencing and sequestration of double-stranded RNA (dsRNA) by the viral protein VP35. Here we present unbound and dsRNA-bound crystal structures of the dsRNA-binding domain of Reston ebolavirus VP35. The structures show that VP35 forms an unusual, asymmetric dimer on dsRNA binding, with each of the monomers binding dsRNA in a different way: one binds the backbone whereas the other caps the terminus. Additional SAXS, DXMS, and dsRNA-binding experiments presented here support a model of cooperative dsRNA recognition in which binding of the first monomer assists binding of the next monomer of the oligomeric VP35 protein. This work illustrates how ebolavirus VP35 could mask key recognition sites of molecules such as RIG-I, MDA-5, and Dicer to silence viral dsRNA in infection.

  9. Developing strategies to enhance and focus humoral immune responses using filamentous phage as a model antigen

    PubMed Central

    Henry, Kevin A; Murira, Armstrong; van Houten, Nienke E

    2011-01-01

    Filamentous bacteriophage are commonly used as immunogenic carriers for peptides and proteins displayed on the phage surface. Previously, we showed that immunization with phage to which peptides had been chemically conjugated can elicit a focused anti-peptide antibody response compared with traditional carrier molecules bearing the same peptide, perhaps due to the low surface complexity of the phage. The regularity of its surface also gives the phage other advantages as a carrier, including immunological simplicity and thousands of well-defined sites for chemical conjugation. More recently, we showed that focusing of antibody responses against ‘target’ peptides was enhanced when the phage's molecular surface was simplified by removal of immunodominant B-cell epitopes present on the minor coat protein, pIII. The pIII-truncated variant elicits an antibody response that is largely restricted to the exposed N-terminus of the major coat protein, pVIII, and to phage-associated bacterial lipopolysaccharide, and a significant fraction of this response crossreacts with a 12-residue peptide covering the surface-exposed region of pVIII. This allows one to track antibody responses against the phage (and any associated haptens) as they develop over time, and characterize them using a combination of serological, flow cytometric, cellular and immunogenetic assays. The filamentous phage thus provides an excellent model system for studying various aspects of the antibody response, all with the goal of targeting antibody production against weakly immunogenic peptides, proteins and carbohydrates. PMID:22008640

  10. Quantal and graded stimulation of B lymphocytes as alternative strategies for regulating adaptive immune responses

    PubMed Central

    Hawkins, E.D.; Turner, M.L.; Wellard, C.J.; Zhou, J.H.S.; Dowling, M.R.; Hodgkin, P.D.

    2013-01-01

    Lymphocytes undergo a typical response pattern following stimulation in vivo: they proliferate, differentiate to effector cells, cease dividing and predominantly die, leaving a small proportion of long-lived memory and effector cells. This pattern results from cell-intrinsic processes following activation and the influence of external regulation. Here we apply quantitative methods to study B-cell responses in vitro. Our results reveal that B cells stimulated through two Toll-like receptors (TLRs) require minimal external direction to undergo the basic pattern typical of immunity. Altering the stimulus strength regulates the outcome in a quantal manner by varying the number of cells that participate in the response. In contrast, the T-cell-dependent CD40 activation signal induces a response where division times and differentiation rates vary in relation to stimulus strength. These studies offer insight into how the adaptive antibody response may have evolved from simple autonomous response patterns to the highly regulable state that is now observed in mammals. PMID:24009041

  11. Kinetics of rabies antibodies as a strategy for canine active immunization

    PubMed Central

    2014-01-01

    Background Rabies, a zoonosis found throughout the globe, is caused by a virus of the Lyssavirus genus. The disease is transmitted to humans through the inoculation of the virus present in the saliva of infected mammals. Since its prognosis is usually fatal for humans, nationwide public campaigns to vaccinate dogs and cats against rabies aim to break the epidemiological link between the virus and its reservoirs in Brazil. Findings During 12months we evaluated the active immunity of dogs first vaccinated (booster shot at 30days after first vaccination) against rabies using the Fuenzalida-Palcios modified vaccine in the urban area of Botucatu city, So Pauto state, Brazil. Of the analyzed dogs, 54.7% maintained protective titers (?0.5IU/mL) for 360days after the first vaccination whereas 51.5% during all the study period. Conclusions The present results suggest a new vaccination schedule for dogs that have never been vaccinated. In addition to the first dose of vaccine, two others are recommended: the second at 30days after the first and the third dose at 180days after the first for the maintenance of protective titers during 12months. PMID:26413082

  12. New Strategies for Overcoming Limitations of Mesenchymal Stem Cell-Based Immune Modulation

    PubMed Central

    Kim, Nayoun; Cho, Seok-Goo

    2015-01-01

    Mesenchymal stem cells (MSCs) have rapidly been applied in a broad field of immune-mediated disorders since the first successful clinical use of MSCs for treatment of graft-versus-host disease. Despite the lack of supporting data, expectations that MSCs could potentially treat most inflammatory conditions led to rushed application and development of commercialized products. Today, both pre-clinical and clinical studies present mixed results for MSC therapy and the discrepancy between expected and actual efficacy of MSCs in various diseases has evoked a sense of discouragement. Therefore, we believe that MSC therapy may now be at a critical milestone for re-evaluation and re-consideration. In this review, we summarize the current status of MSC-based clinical trials and focus on the discrepancy between expected and actual outcome of MSC therapy from bench to bedside. Importantly, we discuss the underlying limitations of MSCs and suggest a new guideline for MSC therapy in hopes of improving their therapeutic efficacy. PMID:26019755

  13. The genome of obligately intracellular Ehrlichia canis revealsthemes of complex membrane structure and immune evasion strategies

    SciTech Connect

    Mavromatis, K.; Kuyler Doyle, C.; Lykidis, A.; Ivanova, N.; Francino, P.; Chain, P.; Shin, M.; Malfatti, S.; Larimer, F.; Copeland,A.; Detter, J.C.; Land, M.; Richardson, P.M.; Yu, X.J.; Walker, D.H.; McBride, J.W.; Kyrpides, N.C.

    2005-09-01

    Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, a-proteobacterium is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, and 17 putative pseudogenes, and a substantial proportion of non-coding sequence (27 percent). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences, and a unique serine-threonine bias associated with the potential for O-glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly G:C tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Proteins associated with pathogen-host interactions were identified including a small group of proteins (12) with tandem repeats and another with eukaryotic-like ankyrin domains (7).

  14. Enteral nutrition and mucosal immunity: implications for feeding strategies in surgery and trauma

    PubMed Central

    Sigalet, David L.; Mackenzie, Shannon L.; Hameed, S. Morad

    2004-01-01

    Systemic inflammatory responses to severe trauma and surgical illnesses may be partly responsible for numerous complications, including sepsis, multiple organ failure and unregulated hypermetabolism leading to protein-calorie malnutrition. The integrity of the gastrointestinal tract appears to be an important factor in the pathogenesis of the systemic inflammatory response and sepsis. Resuscitation and nutrition support strategies for preserving gut mucosal integrity have therefore been strongly promoted. This review summarizes the scientific rationale for emphasizing enteral nutritional support of surgical patients, discusses some important limitations of enteral feeding and argues for a flexible approach to nutrition support for these complex patients. PMID:15132464

  15. A Novel Vaccination Strategy Mediating the Induction of Lung-Resident Memory CD8 T Cells Confers Heterosubtypic Immunity against Future Pandemic Influenza Virus.

    PubMed

    Lee, Yu-Na; Lee, Young-Tae; Kim, Min-Chul; Gewirtz, Andrew T; Kang, Sang-Moo

    2016-03-15

    The currently used vaccine strategy to combat influenza A virus (IAV) aims to provide highly specific immunity to circulating seasonal IAV strains. However, the outbreak of 2009 influenza pandemic highlights the danger in this strategy. In this study, we tested the hypothesis that universal vaccination that offers broader but weaker protection would result in cross protective T cell responses after primary IAV infection, which would subsequently provide protective immunity against future pandemic strains. Specifically, we used tandem repeat extracellular domain of M2 (M2e) epitopes on virus-like particles (M2e5x VLP) that induced heterosubtypic immunity by eliciting Abs to a conserved M2e epitope. M2e5x VLP was found to be superior to strain-specific current split vaccine in conferring heterosubtypic cross protection and in equipping the host with cross-protective lung-resident nucleoprotein-specific memory CD8(+) T cell responses to a subsequent secondary infection with a new pandemic potential strain. Immune correlates for subsequent heterosubtypic immunity by M2e5x VLP vaccination were found to be virus-specific CD8(+) T cells secreting IFN-γ and expressing lung-resident memory phenotypic markers CD69(+) and CD103(+) as well as M2e Abs. Hence, vaccination with M2e5x VLP may be developable as a new strategy to combat future pandemic outbreaks. PMID:26864033

  16. The personal touch: strategies toward personalized vaccines and predicting immune responses to them.

    PubMed

    Kennedy, Richard B; Ovsyannikova, Inna G; Lambert, Nathaniel D; Haralambieva, Iana H; Poland, Gregory A

    2014-05-01

    The impact of vaccines on public health and wellbeing has been profound. Smallpox has been eradicated, polio is nearing eradication, and multiple diseases have been eliminated from certain areas of the world. Unfortunately, we now face diseases such as hepatitis C, malaria or tuberculosis, as well as new and re-emerging pathogens for which we lack effective vaccines. Empirical approaches to vaccine development have been successful in the past, but may not be up to the current infectious disease challenges facing us. New, directed approaches to vaccine design, development, and testing need to be developed. Ideally these approaches will capitalize on cutting-edge technologies, advanced analytical and modeling strategies, and up-to-date knowledge of both pathogen and host. These approaches will pay particular attention to the causes of inter-individual variation in vaccine response in order to develop new vaccines tailored to the unique needs of individuals and communities within the population. PMID:24702429

  17. A risk-based bioanalytical strategy for the assessment of antibody immune responses against biological drugs.

    PubMed

    Shankar, Gopi; Pendley, Charles; Stein, Kathryn E

    2007-05-01

    Bioanalytical assessments of anti-drug antibodies (ADAs) provide an understanding of the immunogenicity of biological drug molecules. The potential to induce ADAs after treatment with biologics is a safety issue that has become an important consideration in the development of biologics and a critical aspect of regulatory filings. US and European regulatory agencies are recommending that sponsors study immunogenicity using a risk-based approach, encouraging sponsors to formulate and implement their own risk management plans and to conduct discussions with the agencies when necessary. It follows from this that the greater the safety risks of ADAs, the more diligently one should clarify the immunogenicity of the product. Here we propose a general strategy to broadly assign immunogenicity risk levels to biological drug products, and present risk level-based 'fit-for-purpose' bioanalytical schemes for the investigations of treatment-related ADAs in clinical and nonclinical studies. PMID:17483842

  18. Passive immune neutralization strategies for prevention and control of influenza A infections

    PubMed Central

    Ye, Jianqiang; Shao, Hongxia; Perez, Daniel R

    2012-01-01

    Although vaccination significantly reduces influenza severity, seasonal human influenza epidemics still cause more than 250,000 deaths annually. Vaccine efficacy is limited in high-risk populations such as infants, the elderly and immunosuppressed individuals. In the event of an influenza pandemic (such as the 2009 H1N1 pandemic), a significant delay in vaccine availability represents a significant public health concern, particularly in high-risk groups. The increasing emergence of strains resistant to the two major anti-influenza drugs, adamantanes and neuraminidase inhibitors, and the continuous circulation of avian influenza viruses with pandemic potential in poultry, strongly calls for alternative prophylactic and treatment options. In this review, we focus on passive virus neutralization strategies for the prevention and control of influenza type A viruses. PMID:22339460

  19. The personal touch: strategies toward personalized vaccines and predicting immune responses to them

    PubMed Central

    Kennedy, Richard B.; Ovsyannikova, Inna G.; Lambert, Nathaniel D.; Haralambieva, Iana H.; Poland, Gregory A.

    2014-01-01

    The impact of vaccines on public health and well-being has been profound. Smallpox has been eradicated, polio is nearing eradication, and multiple diseases have been eliminated from certain areas of the world. Unfortunately, we now face diseases such as: hepatitis C, malaria, or tuberculosis, as well as new and re-emerging pathogens for which lack effective vaccines. Empirical approaches to vaccine development have been successful in the past, but may not be up to the current infectious disease challenges facing us. New, directed approaches to vaccine design, development, and testing need to be developed. Ideally these approaches will capitalize on cutting-edge technologies, advanced analytical and modeling strategies, and up-to-date knowledge of both pathogen and host. These approaches will pay particular attention to the causes of inter-individual variation in vaccine response in order to develop new vaccines tailored to the unique needs of individuals and communities within the population. PMID:24702429

  20. HIV-1 Envelope Trimer Design and Immunization Strategies To Induce Broadly Neutralizing Antibodies.

    PubMed

    de Taeye, Steven W; Moore, John P; Sanders, Rogier W

    2016-03-01

    The identification of multiple broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) trimer has facilitated its structural characterization and guided Env immunogen design. Several recent studies constitute progress in utilizing this knowledge for the development of an HIV-1 vaccine that induces bNAbs. Native-like Env trimers can induce autologous NAb responses against resistant (Tier-2) viruses in several animal models. Here we review recent studies aimed at addressing the challenge of driving the strong but narrowly focused NAb responses to Env trimers towards ones with much greater breadth. Among strategies that merit pursuing are using multiple trimers as sequential or simultaneous immunogens, targeting the germline precursors of bNAbs, delivering sequential lineages of trimers derived from infected individuals who developed bNAbs, and presenting trimers as particulate antigens. PMID:26869204

  1. Synthetic plant defense elicitors

    PubMed Central

    Bektas, Yasemin; Eulgem, Thomas

    2015-01-01

    To defend themselves against invading pathogens plants utilize a complex regulatory network that coordinates extensive transcriptional and metabolic reprogramming. Although many of the key players of this immunity-associated network are known, the details of its topology and dynamics are still poorly understood. As an alternative to forward and reverse genetic studies, chemical genetics-related approaches based on bioactive small molecules have gained substantial popularity in the analysis of biological pathways and networks. Use of such molecular probes can allow researchers to access biological space that was previously inaccessible to genetic analyses due to gene redundancy or lethality of mutations. Synthetic elicitors are small drug-like molecules that induce plant defense responses, but are distinct from known natural elicitors of plant immunity. While the discovery of some synthetic elicitors had already been reported in the 1970s, recent breakthroughs in combinatorial chemical synthesis now allow for inexpensive high-throughput screens for bioactive plant defense-inducing compounds. Along with powerful reverse genetics tools and resources available for model plants and crop systems, comprehensive collections of new synthetic elicitors will likely allow plant scientists to study the intricacies of plant defense signaling pathways and networks in an unparalleled fashion. As synthetic elicitors can protect crops from diseases, without the need to be directly toxic for pathogenic organisms, they may also serve as promising alternatives to conventional biocidal pesticides, which often are harmful for the environment, farmers and consumers. Here we are discussing various types of synthetic elicitors that have been used for studies on the plant immune system, their modes-of-action as well as their application in crop protection. PMID:25674095

  2. RNAi and Antiviral Defense in the Honey Bee.

    PubMed

    Brutscher, Laura M; Flenniken, Michelle L

    2015-01-01

    Honey bees play an important agricultural and ecological role as pollinators of numerous agricultural crops and other plant species. Therefore, investigating the factors associated with high annual losses of honey bee colonies in the US is an important and active area of research. Pathogen incidence and abundance correlate with Colony Collapse Disorder- (CCD-) affected colonies in the US and colony losses in the US and in some European countries. Honey bees are readily infected by single-stranded positive sense RNA viruses. Largely dependent on the host immune response, virus infections can either remain asymptomatic or result in deformities, paralysis, or death of adults or larvae. RNA interference (RNAi) is an important antiviral defense mechanism in insects, including honey bees. Herein, we review the role of RNAi in honey bee antiviral defense and highlight some parallels between insect and mammalian immune systems. A more thorough understanding of the role of pathogens on honey bee health and the immune mechanisms bees utilize to combat infectious agents may lead to the development of strategies that enhance honey bee health and result in the discovery of additional mechanisms of immunity in metazoans. PMID:26798663

  3. RNAi and Antiviral Defense in the Honey Bee

    PubMed Central

    Brutscher, Laura M.; Flenniken, Michelle L.

    2015-01-01

    Honey bees play an important agricultural and ecological role as pollinators of numerous agricultural crops and other plant species. Therefore, investigating the factors associated with high annual losses of honey bee colonies in the US is an important and active area of research. Pathogen incidence and abundance correlate with Colony Collapse Disorder- (CCD-) affected colonies in the US and colony losses in the US and in some European countries. Honey bees are readily infected by single-stranded positive sense RNA viruses. Largely dependent on the host immune response, virus infections can either remain asymptomatic or result in deformities, paralysis, or death of adults or larvae. RNA interference (RNAi) is an important antiviral defense mechanism in insects, including honey bees. Herein, we review the role of RNAi in honey bee antiviral defense and highlight some parallels between insect and mammalian immune systems. A more thorough understanding of the role of pathogens on honey bee health and the immune mechanisms bees utilize to combat infectious agents may lead to the development of strategies that enhance honey bee health and result in the discovery of additional mechanisms of immunity in metazoans. PMID:26798663

  4. Innate immunity activation on biomaterial surfaces: A mechanistic model and coping strategies

    PubMed Central

    Ekdahl, Kristina N; Lambris, John D.; Elwing, Hans; Ricklin, Daniel; Nilsson, Per H.; Teramura, Yuji; Nicholls, Ian A.; Nilsson, Bo

    2011-01-01

    When an artificial biomaterial (e.g., a stent or implantable pump) is exposed to blood, plasma proteins immediately adhere to the surface, creating a new interface between the biomaterial and the blood. The recognition proteins within the complement and contact activation/coagulation cascade systems of the blood will be bound to, or inserted into, this protein film and generate different mediators that will activate polymorphonuclear leukocytes and monocytes, as well as platelets. Under clinical conditions, the ultimate outcome of these processes may be thrombotic and inflammatory reactions, and consequently the composition and conformation of the proteins in the initial layer formed on the surface will to a large extent determine the outcome of a treatment involving the biomaterial, affecting both the functionality of the material and the patients life quality. This review presents models of biomaterial-induced activation processes and describes various strategies to attenuate potential adverse reactions by conjugating bioactive molecules to surfaces or by introducing nanostructures. PMID:21771620

  5. The distribution of the phenolic metabolites barbaloin, aloeresin and aloenin as a peripheral defense strategy in the succulent leaf parts of Aloe arborescens.

    PubMed

    Gutterman; Chauser-Volfson

    2000-11-01

    Aloe arborescens is a large, multi-stemmed shrub. It is used as hedge plants to protect agricultural fields or stock and as horticultural plants in gardens. In natural habitats it is one of the very common Aloe species along the Indian Ocean coast of southern Africa, from the Cape, in the south, to Zimbabwe and Malawi in the north. Secondary phenolic metabolites such as barbaloin (Rf 0.31-0.35), aloeresin (Rf 0.25-0.3) and aloenin (Rf 0.51-0.55) have been found to be distributed in the succulent leaves of Aloe arborescens in a peripheral defense strategy. The youngest leaves have the highest content. The terminal third of each leaf has the highest content and the basal third, the lowest. Along the leaf margins, on the top third and adaxial side, the content is the highest and in the base third, the lowest along the leaf center on the abaxial side. Similar relative amounts of these three secondary phenolic metabolites were found in the different leaf locations. The leaf orientation may affect the total content of these three phenols but not their relative amounts in the different parts of the leaves. It is possible that the more often the plant parts are damaged by consumption by animals such as elephants, kudu or insects, the greater the increase of their phenolic metabolites. This increase may reduce or prevent further consumption when the content of the metabolites reaches a certain level. The plants then have a chance to renew themselves. PMID:10913844

  6. Sequestration of host-CD59 as potential immune evasion strategy of Trichomonas vaginalis.

    PubMed

    Ibez-Escribano, Alexandra; Nogal-Ruiz, Juan Jos; Prez-Serrano, Jorge; Gmez-Barrio, Alicia; Escario, J Antonio; Alderete, J F

    2015-09-01

    Trichomonas vaginalis is known to evade complement-mediated lysis. Because the genome of T. vaginalis does not possess DNA sequence with homology to human protectin (CD59), a complement lysis restricting factor, we tested the hypothesis that host CD59 acquisition by T. vaginalis organisms mediates resistance to complement killing. This hypothesis was based on the fact that trichomonads are known to associate with host proteins. No CD59 was detected on the surface of T. vaginalis grown in serum-based medium using as probe anti-CD59 monoclonal antibody (MAb). We, therefore, infected mice intraperitoneally with live T. vaginalis, and trichomonads harvested from ascites were tested for binding of CD59. Immunofluorescence showed that parasites had surface CD59. Furthermore, as mouse erythrocytes (RBCs) possess membrane-associated CD59, and trichomonads use RBCs as a nutrient source, organisms were co-cultured with murine RBCs for one week. Parasites were shown to have detectable surface CD59. Importantly, live T. vaginalis with bound CD59 were compared with batch-grown parasites without surface-associated CD59 for sensitivity to complement in human serum. Trichomonads without surface-bound CD59 had a higher level of killing by complement than did parasites with surface CD59. These data show that host CD59 acquired onto the surface by live T. vaginalis may be an alternative mechanism for complement evasion. We describe a novel strategy by T. vaginalis consistent with host protein procurement by this parasite to evade the lytic action of complement. PMID:25976413

  7. Identifying genetic loci controlling neonatal passive transfer of immunity using a hybrid genotyping strategy.

    PubMed

    Rohrer, G A; Rempel, L A; Miles, J R; Keele, J W; Wiedmann, R T; Vallet, J L

    2014-06-01

    Colostrum intake is critical to a piglet's survival and can be measured by precipitating out the ?-immunoglobulins from serum with ammonium sulfate (immunocrit). Genetic analysis of immunocrits on 5312 piglets indicated that the heritabilities (se) for direct and maternal effects were 0.13 (0.06) and 0.53 (0.08) respectively. To identify QTL for direct genetic effects, piglets with the highest and lowest immunocrits from 470 litters were selected. Six sets of DNA pools were created based on sire of the litter. These 12 DNA pools were applied to Illumina Porcine SNP60 BeadChips. Normalized X and Y values were analyzed. Three different SNP selection methods were used: deviation of the mean from high vs. low pools, the deviation adjusted for variance based on binomial theory and ANOVA. The 25 highest ranking SNPs were selected from each evaluation for further study along with 12 regions selected based on a five-SNP window approach. Selected SNPs were individually genotyped in the 988 piglets included in pools as well as in 524 piglets that had intermediate immunocrits. Association analyses were conducted fitting an animal model using the estimated genetic parameters. Nineteen SNPs were nominally associated (P < 0.01) with immunocrit values, of which nine remained significant (P < 0.05) after Bonferroni correction, located in 16 genomic regions on 13 chromosomes. In conclusion, the pooling strategy reduced the cost to scan the genome by more than 80% and identified genomic regions associated with a piglet's ability to acquire ?-immunoglobulin from colostrum. Each method to rank SNPs from the pooled analyses contributed unique validated markers, suggesting that multiple analyses will reveal more QTL than a single analysis. PMID:24779640

  8. Plant immunity to insect herbivores.

    PubMed

    Howe, Gregg A; Jander, Georg

    2008-01-01

    Herbivorous insects use diverse feeding strategies to obtain nutrients from their host plants. Rather than acting as passive victims in these interactions, plants respond to herbivory with the production of toxins and defensive proteins that target physiological processes in the insect. Herbivore-challenged plants also emit volatiles that attract insect predators and bolster resistance to future threats. This highly dynamic form of immunity is initiated by the recognition of insect oral secretions and signals from injured plant cells. These initial cues are transmitted within the plant by signal transduction pathways that include calcium ion fluxes, phosphorylation cascades, and, in particular, the jasmonate pathway, which plays a central and conserved role in promoting resistance to a broad spectrum of insects. A detailed understanding of plant immunity to arthropod herbivores will provide new insights into basic mechanisms of chemical communication and plant-animal coevolution and may also facilitate new approaches to crop protection and improvement. PMID:18031220

  9. Novel Antitumor Strategy Utilizing a Plasmid Expressing a Mycobacterium tuberculosis Antigen as a “Danger Signal” to Block Immune Escape of Tumor Cells

    PubMed Central

    Koyama, Yoshiyuki; Yoshihara, Chieko; Ito, Tomoko

    2015-01-01

    Immune escape of tumor cells is one of the main obstacles hindering the effectiveness of cancer immunotherapy. We developed a novel strategy to block immune escape by transfecting tumor cells in vivo with genes of pathogenic antigens from Mycobacterium tuberculosis (TB). This induces presentation of the TB antigen on tumor cell surfaces, which can be recognized by antigen presenting cells (APCs) as a “danger signal” to stimulate antitumor immune response. This strategy is also expected to amplify the immune response against tumor-associated antigens, and block immune escape of the tumor. DNA/PEI/chondroitin sulfate ternary complex is a highly effective non-viral gene vector system for in vivo transfection. A therapeutic complex was prepared using a plasmid encoding the TB antigen, early secretory antigenic target-6 (ESAT-6). This was injected intratumorally into syngeneic tumor-bearing mice, and induced significant tumor growth suppression comparable to or higher than similar complexes expressing cytokines such as interleukin-2 (IL-2) and interleukin-12 (IL-12). Co-transfection of the cytokine-genes and the ESAT-6-gene enhanced the antitumor efficacy of either treatment alone. In addition, complete tumor regression was achieved with the combination of ESAT-6 and IL-2 genes. PMID:26213962

  10. Pattern-recognition receptors in pulp defense.

    PubMed

    Staquet, M-J; Carrouel, F; Keller, J-F; Baudouin, C; Msika, P; Bleicher, F; Kufer, T A; Farges, J-C

    2011-07-01

    Initial sensing of infection is mediated by germline-encoded pattern-recognition receptors (PRRs), the activation of which leads to the expression of inflammatory mediators responsible for the elimination of pathogens and infected cells. PRRs act as immune sensors that provide immediate cell responses to pathogen invasion or tissue injury. Here, we review the expression of PRRs in human dental pulp cells, namely, receptors from the Toll-like (TLR) and Nod-like NLR families, by which cells recognize bacteria. Particular attention is given to odontoblasts, which are the first cells encountered by pathogens and represent, in the tooth, the first line of defense for the host. Understanding cellular and molecular mechanisms associated with the recognition of bacterial pathogens by odontoblasts is critical for the development of therapeutic strategies that aim at preventing excessive pulp inflammation and related deleterious effects. PMID:21677082

  11. The Impact of Two Different Transfusion Strategies on Patient Immune Response during Major Abdominal Surgery: A Preliminary Report

    PubMed Central

    Markatou, Maria; Rizos, Demetrios; Fassoulaki, Argyro

    2014-01-01

    Blood transfusion is associated with well-known risks. We investigated the difference between a restrictive versus a liberal transfusion strategy on the immune response, as expressed by the production of inflammatory mediators, in patients subjected to major abdominal surgery procedures. Fifty-eight patients undergoing major abdominal surgery were randomized preoperatively to either a restrictive transfusion protocol or a liberal transfusion protocol (with transfusion if hemoglobin dropped below 7.7?g?dL?1 or 9.9?g?dL?1, respectively). In a subgroup of 20 patients randomly selected from the original allocation groups, blood was sampled for measurement of IL-6, IL-10, and TNF?. Postoperative levels of IL-10 were higher in the liberal transfusion group on the first postoperative day (49.82 29.07 vs. 15.83 13.22?pg?mL?1, P < 0.05). Peak postoperative IL-10 levels correlated with the units of blood transfused as well as the mean duration of storage and the storage time of the oldest unit transfused (r2 = 0.38, P = 0.032, r2 = 0.52, P = 0.007, and r2 = 0.68, P<0.001, respectively). IL-10 levels were elevated in patients with a more liberal red blood cell transfusion strategy. The strength of the association between anti-inflammatory IL-10 and transfusion variables indicates that IL-10 may be an important factor in transfusion-associated immunomodulation. This trial is registered under ClinicalTrials.gov Identifier: NCT02020525. PMID:24804272

  12. Immunity and Nutrition.

    ERIC Educational Resources Information Center

    Dupin, Henri; Guerin, Nicole

    1990-01-01

    The three articles in this issue of a periodical focussed on various aspects of the life and health of children in the tropics concern: (1) immune defenses; (2) interactions between nutrition disorders and infection; and (3) immunity and vaccination. The science of immunology has progressed rapidly in recent years. A brief review of present

  13. Immunity and Nutrition.

    ERIC Educational Resources Information Center

    Dupin, Henri; Guerin, Nicole

    1990-01-01

    The three articles in this issue of a periodical focussed on various aspects of the life and health of children in the tropics concern: (1) immune defenses; (2) interactions between nutrition disorders and infection; and (3) immunity and vaccination. The science of immunology has progressed rapidly in recent years. A brief review of present…

  14. Evaluability Assessment of an immunization improvement strategy in rural Burkina Faso: intervention theory versus reality, information need and evaluations.

    PubMed

    Sanou, Aboubakary; Kouyat, Bocar; Bibeau, Gilles; Nguyen, Vinh-Kim

    2011-08-01

    An innovative immunization improvement strategy was proposed by the CRSN (Centre de Recherche en Sant de Nouna) to improve the low coverage rate for children aged 0-11 months in the health district of Nouna in Burkina Faso. This article reports on the Evaluability Assessment (EA) study that aimed to orient decisions for its evaluation in close relationship with the information needs of the stakeholders. Various methods were used, including document reviews, individual interviews, focus group discussions, meetings, literature reviews and site visits. A description of the intervention theory and philosophy is provided with its logic models and its reality documented. Lessons on the procedure include the importance of the position of the evaluability assessor, the value of replicating some steps of the assessment and the relationships between EA and process evaluation. The evaluability study concludes that the intervention had some evaluable components. To satisfy the stakeholders' needs, the initially planned community randomized controlled trial can be maintained and complemented with a process evaluation. There is a need to provide sufficient information on the cost of the intervention. This will inform decision makers on the possibility of replicating the intervention in other contexts. PMID:21168211

  15. The CAP superfamily: cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins--roles in reproduction, cancer, and immune defense.

    PubMed

    Gibbs, Gerard M; Roelants, Kim; O'Bryan, Moira K

    2008-12-01

    The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily members are found in a remarkable range of organisms spanning each of the animal kingdoms. Within humans and mice, there are 31 and 33 individual family members, respectively, and although many are poorly characterized, the majority show a notable expression bias to the reproductive tract and immune tissues or are deregulated in cancers. CAP superfamily proteins are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumor suppressor or prooncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilization. This review describes mammalian CAP superfamily gene expression profiles, phylogenetic relationships, protein structural properties, and biological functions, and it draws into focus their potential role in health and disease. The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. We conclude that overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters target specificity and, therefore, the biological consequences. PMID:18824526

  16. Extensive Central Nervous System Cryptococcal Disease Presenting as Immune Reconstitution Syndrome in a Patient with Advanced HIV: Report of a Case and Review of Management Dilemmas and Strategies

    PubMed Central

    Ogbuagu, Onyema; Villanueva, Merceditas

    2014-01-01

    One of the complications of the use of antiretroviral therapy (ART), immune reconstitution inflammatory syndrome (IRIS), is particularly problematic in the management of cryptococcal meningitis. We present the case of a 35-year-old male with acquired immune deficiency syndrome diagnosed with extensive central nervous system (CNS) cryptococcal disease, including meningitis and multiple intracranial cysts, diagnosed eight weeks after the initiation of ART. The patient experienced a relapsing and remitting clinical course despite repeated courses of potent antifungal therapy and aggressive management of raised intracranial pressure. This review highlights therapeutic dilemmas and strategies in the management of CNS cryptococcosis complicated with IRIS and highlights gaps in available treatment guidelines. PMID:25568756

  17. Signature Patterns of MHC Diversity in Three Gombe Communities of Wild Chimpanzees Reflect Fitness in Reproduction and Immune Defense against SIVcpz

    PubMed Central

    Wroblewski, Emily E.; Norman, Paul J.; Guethlein, Lisbeth A.; Rudicell, Rebecca S.; Ramirez, Miguel A.; Li, Yingying; Hahn, Beatrice H.; Pusey, Anne E.; Parham, Peter

    2015-01-01

    Major histocompatibility complex (MHC) class I molecules determine immune responses to viral infections. These polymorphic cell-surface glycoproteins bind peptide antigens, forming ligands for cytotoxic T and natural killer cell receptors. Under pressure from rapidly evolving viruses, hominoid MHC class I molecules also evolve rapidly, becoming diverse and species-specific. Little is known of the impact of infectious disease epidemics on MHC class I variant distributions in human populations, a context in which the chimpanzee is the superior animal model. Population dynamics of the chimpanzees inhabiting Gombe National Park, Tanzania have been studied for over 50 years. This population is infected with SIVcpz, the precursor of human HIV-1. Because HLA-B is the most polymorphic human MHC class I molecule and correlates strongly with HIV-1 progression, we determined sequences for its ortholog, Patr-B, in 125 Gombe chimpanzees. Eleven Patr-B variants were defined, as were their frequencies in Gombe’s three communities, changes in frequency with time, and effect of SIVcpz infection. The growing populations of the northern and central communities, where SIVcpz is less prevalent, have stable distributions comprising a majority of low-frequency Patr-B variants and a few high-frequency variants. Driving the latter to high frequency has been the fecundity of immigrants to the northern community, whereas in the central community, it has been the fecundity of socially dominant individuals. In the declining population of the southern community, where greater SIVcpz prevalence is associated with mortality and emigration, Patr-B variant distributions have been changing. Enriched in this community are Patr-B variants that engage with natural killer cell receptors. Elevated among SIVcpz-infected chimpanzees, the Patr-B*06:03 variant has striking structural and functional similarities to HLA-B*57, the human allotype most strongly associated with delayed HIV-1 progression. Like HLA-B*57, Patr-B*06:03 correlates with reduced viral load, as assessed by detection of SIVcpz RNA in feces. PMID:26020813

  18. Immunity to fungi.

    PubMed

    LeibundGut-Landmann, Salomé; Wüthrich, Marcel; Hohl, Tobias M

    2012-08-01

    The global increase in fungal disease burden, the emergence of novel pathogenic fungi, and the lack of fungal vaccines have focused intense interest in elucidating immune defense mechanisms against fungi. Recent studies in animal models and in humans identify an integrated role for C-type lectin and Toll-like receptor signaling in activating innate and adaptive responses that control medically relevant fungi. Beyond the critical role of phagocytes in host defense, the generation and balance of specific T helper subsets contributes to sterilizing immunity. These advances form a basis for the development of fungal vaccines and immune-based therapeutic adjuncts. PMID:22613091

  19. Immunization with Recombinant Adenoviral Vectors Expressing HCV Core or F Proteins Leads to T Cells with Reduced Effector Molecules Granzyme B and IFN-?: A Potential New Strategy for Immune Evasion in HCV Infection.

    PubMed

    Samrat, Subodh Kumar; Vedi, Satish; Singh, Shakti; Li, Wen; Kumar, Rakesh; Agrawal, Babita

    2015-01-01

    Multispecific, broad, and potent T cell responses have been correlated with viral clearance in hepatitis C virus (HCV) infection. However, the majority of infected patients develop chronic infection, suggesting that natural infection mostly leads to development of inefficient T cell immunity. Multiple mechanisms of immune modulation and evasion have been shown in HCV infection through various investigations. This study examined the generation and modulation of T cell responses against core and frameshift (F) proteins of HCV. A single immunization of mice with replication incompetent recombinant adenovirus vectors encoding for F or core antigens induces poor T cell responses and leads to generation of CD4+ and CD8+ T cells with low granzyme B (GrB) expression. These T cells have impaired GrB enzyme activity and are unable to kill peptide loaded target cells. The low intracellular expression of GrB is not due to degranulation of cytotoxic granules containing cytotoxic T cells. Addition of exogenous IL-2 in in vitro cultures leads to partial recovery of GrB production, whereas immunization with the Toll-like receptor (TLR) agonist poly I:C leads to complete restoration of GrB expression in both CD4+ and CD8+ T cells. Thus, a possible new strategy of T cell modulation is recognized wherein effector T cells are caused to be dysfunctional by HCV-derived antigens F or core, and strategies are also delineated to overcome this dysfunction. These studies are important in the investigation of prophylactic vaccine and immunotherapy strategies for HCV infection. PMID:26133045

  20. Antipredator defenses predict diversification rates.

    PubMed

    Arbuckle, Kevin; Speed, Michael P

    2015-11-01

    The "escape-and-radiate" hypothesis predicts that antipredator defenses facilitate adaptive radiations by enabling escape from constraints of predation, diversified habitat use, and subsequently speciation. Animals have evolved diverse strategies to reduce the direct costs of predation, including cryptic coloration and behavior, chemical defenses, mimicry, and advertisement of unprofitability (conspicuous warning coloration). Whereas the survival consequences of these alternative defenses for individuals are well-studied, little attention has been given to the macroevolutionary consequences of alternative forms of defense. Here we show, using amphibians as the first, to our knowledge, large-scale empirical test in animals, that there are important macroevolutionary consequences of alternative defenses. However, the escape-and-radiate hypothesis does not adequately describe them, due to its exclusive focus on speciation. We examined how rates of speciation and extinction vary across defensive traits throughout amphibians. Lineages that use chemical defenses show higher rates of speciation as predicted by escape-and-radiate but also show higher rates of extinction compared with those without chemical defense. The effect of chemical defense is a net reduction in diversification compared with lineages without chemical defense. In contrast, acquisition of conspicuous coloration (often used as warning signals or in mimicry) is associated with heightened speciation rates but unchanged extinction rates. We conclude that predictions based on the escape-and-radiate hypothesis must incorporate the effect of traits on both speciation and extinction, which is rarely considered in such studies. Our results also suggest that knowledge of defensive traits could have a bearing on the predictability of extinction, perhaps especially important in globally threatened taxa such as amphibians. PMID:26483488

  1. Adenoviral vectors elicit humoral immunity against variable loop 2 of clade C HIV-1 gp120 via "Antigen Capsid-Incorporation" strategy.

    PubMed

    Gu, Linlin; Krendelchtchikova, Valentina; Krendelchtchikov, Alexandre; Farrow, Anitra L; Derdeyn, Cynthia A; Matthews, Qiana L

    2016-01-01

    Adenoviral (Ad) vectors in combination with the "Antigen Capsid-Incorporation" strategy have been applied in developing HIV-1 vaccines, due to the vectors? abilities in incorporating and inducing immunity of capsid-incorporated antigens. Variable loop 2 (V2)-specific antibodies were suggested in the RV144 trial to correlate with reduced HIV-1 acquisition, which highlights the importance of developing novel HIV-1 vaccines by targeting the V2 loop. Therefore, the V2 loop of HIV-1 has been incorporated into the Ad capsid protein. We generated adenovirus serotype 5 (Ad5) vectors displaying variable loop 2 (V2) of HIV-1 gp120, with the "Antigen Capsid-Incorporation" strategy. To assess the incorporation capabilities on hexon hypervariable region1 (HVR1) and protein IX (pIX), 20aa or full length (43aa) of V2 and V1V2 (67aa) were incorporated, respectively. Immunizations with the recombinant vectors significantly generated antibodies against both linear and discontinuous V2 epitopes. The immunizations generated durable humoral immunity against V2. This study will lead to more stringent development of various serotypes of adenovirus-vectored V2 vaccine candidates, based on breakthroughs regarding the immunogenicity of V2. PMID:26499044

  2. Cytosolic Innate Immune Sensing and Signaling upon Infection.

    PubMed

    Radoshevich, Lilliana; Dussurget, Olivier

    2016-01-01

    Cytosolic sensing of pathogens is essential to a productive immune response. Recent reports have emphasized the importance of signaling platforms emanating from organelles and cytosolic sensors, particularly during the response to intracellular pathogens. Here, we highlight recent discoveries identifying the key mediators of nucleic acid and cyclic nucleotide sensing and discuss their importance in host defense. This review will also cover strategies evolved by pathogens to manipulate these pathways. PMID:27014235

  3. Cytosolic Innate Immune Sensing and Signaling upon Infection

    PubMed Central

    Radoshevich, Lilliana; Dussurget, Olivier

    2016-01-01

    Cytosolic sensing of pathogens is essential to a productive immune response. Recent reports have emphasized the importance of signaling platforms emanating from organelles and cytosolic sensors, particularly during the response to intracellular pathogens. Here, we highlight recent discoveries identifying the key mediators of nucleic acid and cyclic nucleotide sensing and discuss their importance in host defense. This review will also cover strategies evolved by pathogens to manipulate these pathways. PMID:27014235

  4. [Recent advances in understanding the innate immune mechanisms and developing new disease resistance breeding strategies against the rice blast fungus Magnaporthe oryzae in rice].

    PubMed

    He, Feng; Zhang, Hao; Liu, Jinling; Wang, Zhilong; Wang, Guoliang

    2014-08-01

    Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most destructive diseases in rice. Utilization of resistant cultivars is the most effective and economic strategy against the disease. Recently, rice blast has become an advanced model system for elucidating the molecular mechanisms of plant-fungal interactions. Significant progress has been made in the molecular biology, genomics and proteomics of the rice-M. oryzae interaction and host resistance in the last few years. In this review, we summarize the recent advances in understanding the molecular basis of PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI) in rice against M. oryzae, and propose the new strategies for blast resistance molecular breeding. We also discuss the new challenges for future investigations. PMID:25143273

  5. One-prime multi-boost strategy immunization with recombinant DNA, adenovirus, and MVA vector vaccines expressing HPV16 L1 induces potent, sustained, and specific immune response in mice.

    PubMed

    Li, Li-Li; Wang, He-Rong; Zhou, Zhi-Yi; Luo, Jing; Xiao, Xiang-Qian; Wang, Xiao-Li; Li, Jin-Tao; Zhou, Yu-Bai; Zeng, Yi

    2016-04-01

    Human papillomavirus (HPV) is associated with various human diseases, including cancer, and developing vaccines is a cost-efficient strategy to prevent HPV-related disease. The major capsid protein L1, which an increasing number of studies have confirmed is typically expressed early in infection, is a promising antigen for such a vaccine, although the E6 and E7 proteins have been characterized more extensively. Thus, the L1 gene from HPV16 was inserted into a recombinant vector, AdHu5, and MVA viral vectors, and administered by prime-boost immunization. Virus-like particles were used as control antigens. Our results indicate that prime-boost immunization with heterologous vaccines induced robust and sustained cellular and humoral response specific to HPV16 L1. In particular, sera obtained from mice immunized with DNA + DNA + Ad + MVA had excellent antitumor activity in vivo. However, the data also confirm that virus-like particles can only elicit low levels cellular immunity and not be long-lasting, and are therefore unsuitable for treatment of existing HPV infections. PMID:26821205

  6. Plant Innate Immunity Multicomponent Model

    PubMed Central

    Andolfo, Giuseppe; Ercolano, Maria R.

    2015-01-01

    Our understanding of plantpathogen interactions is making rapid advances in order to address issues of global importance such as improving agricultural productivity and sustainable food security. Innate immunity has evolved in plants, resulting in a wide diversity of defense mechanisms adapted to specific threats. The postulated PTI/ETI model describes two perception layers of plant innate immune system, which belong to a first immunity component of defense response activation. To better describe the sophisticated defense system of plants, we propose a new model of plant immunity. This model considers the plants ability to distinguish the feeding behavior of their many foes, such as a second component that modulates innate immunity. This hypothesis provides a new viewpoint highlighting the relevance of hormone crosstalk and primary metabolism in regulating plant defense against the different behaviors of pathogens with the intention to stimulate further interest in this research area. PMID:26617626

  7. Evidence-based strategies to improve immunization compliance of postgraduate medical trainees at large academic-medical facilities.

    PubMed

    Kanagasabai, Thirumagal; Muharuma, Loreta; McGuire, Joy; Russell, Melanie; Vearncombe, Mary; Urowitz, Murray

    2007-01-01

    The purpose of this evaluation is to assess the effectiveness of the modifications made by the University of Toronto Postgraduate Medical Education to improve medical trainee compliance with the immunization standards set forth in national guidelines, provincial regulations and protocols and university policy. Trainee compliance with immunization requirements were evaluated as of January 2003, 2004 and 2005. Statistically significant increases in compliance rates for all required immunizations--hepatitis B virus, measles, rubella and chicken pox--and tuberculosis skin tests were observed. University of Toronto postgraduate medical trainees are now highly compliant with the Hospital Management Regulation 965 of the Ontario Public Hospitals Act, Canadian Immunization Guide, Public Health Agency of Canada guidelines for prevention and control of occupational infections in healthcare and the University of Toronto Faculty of Medicine immunization policy. PMID:17491572

  8. Innate Immunity to Adenovirus

    PubMed Central

    Hendrickx, Rodinde; Stichling, Nicole; Koelen, Jorien; Kuryk, Lukasz; Lipiec, Agnieszka

    2014-01-01

    Abstract Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limiting in immunocompetent individuals. Here we describe how adenoviruses are recognized by the host innate defense system during entry and replication in immune and nonimmune cells. Innate defense protects the host and represents a major barrier to using adenoviruses as therapeutic interventions in humans. Innate response against adenoviruses involves intrinsic factors present at constant levels, and innate factors mounted by the host cell upon viral challenge. These factors exert antiviral effects by directly binding to viruses or viral components, or shield the virus, for example, soluble factors, such as blood clotting components, the complement system, preexisting immunoglobulins, or defensins. In addition, Toll-like receptors and lectins in the plasma membrane and endosomes are intrinsic factors against adenoviruses. Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins, nucleotide-binding oligomerization domain-like inflammatory receptors, and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine monophosphate–adenosine monophosphate synthase. Adenovirus tunes the function of antiviral autophagy, and counters innate defense by virtue of its early proteins E1A, E1B, E3, and E4 and two virus-associated noncoding RNAs VA-I and VA-II. We conclude by discussing strategies to engineer adenovirus vectors with attenuated innate responses and enhanced delivery features. PMID:24512150

  9. Dietary supplementation with lacto-wolfberry enhances the immune response and reduces pathogenesis to influenza infection in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite the availability of vaccines, influenza is a significant public health problem, emphasizing the need for development of additional strategies to enhance host defense against influenza. Wolfberry or Goji berry, long used as a medicinal food in China, has recently been shown to improve immune ...

  10. Integrated Immune Experiment

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2009-01-01

    This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  11. The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

    PubMed

    Fecci, Peter E; Mitchell, Duane A; Archer, Gary E; Morse, Michael A; Lyerly, H Kim; Bigner, Darell D; Sampson, John H

    2003-01-01

    Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration. PMID:12952297

  12. Humoral immune responses are maintained with age in a long-lived ectotherm, the red-eared slider turtle.

    PubMed

    Zimmerman, Laura M; Clairardin, Sandrine G; Paitz, Ryan T; Hicke, Justin W; LaMagdeleine, Katie A; Vogel, Laura A; Bowden, Rachel M

    2013-02-15

    Aging is typically associated with a decrease in immune function. However, aging does not affect each branch of the immune system equally. Because of these varying effects of age on immune responses, aging could affect taxa differently based on how the particular taxon employs its resources towards different components of immune defense. An example of this is found in the humoral immune system. Specific responses tend to decrease with age while non-specific, natural antibody responses increase with age. Compared with mammals, reptiles of all ages have a slower and less robust humoral immune system. Therefore, they may invest more in non-specific responses and thus avoid the negative consequences of age on the immune system. We examined how the humoral immune system of reptiles is affected by aging and investigated the roles of non-specific, natural antibody responses and specific responses by examining several characteristics of antibodies against lipopolysaccharide (LPS) in the red-eared slider turtle. We found very little evidence of immunosenescence in the humoral immune system of the red-eared slider turtle, Trachemys scripta, which supports the idea that non-specific, natural antibody responses are an important line of defense in reptiles. Overall, this demonstrates that a taxon's immune strategy can influence how the immune system is affected by age. PMID:23077164

  13. Aging and Immune Function: Molecular Mechanisms to Interventions

    PubMed Central

    Ponnappan, Subramaniam

    2011-01-01

    Abstract The immune system of an organism is an essential component of the defense mechanism aimed at combating pathogenic stress. Age-associated immune dysfunction, also dubbed “immune senescence,” manifests as increased susceptibility to infections, increased onset and progression of autoimmune diseases, and onset of neoplasia. Over the years, extensive research has generated consensus in terms of the phenotypic and functional defects within the immune system in various organisms, including humans. Indeed, age-associated alterations such as thymic involution, T cell repertoire skewing, decreased ability to activate naïve T cells and to generate robust memory responses, have been shown to have a causative role in immune decline. Further, understanding the molecular mechanisms underlying the generation of proteotoxic stress, DNA damage response, modulation of ubiquitin proteasome pathway, and regulation of transcription factor NFκB activation, in immune decline, have paved the way to delineating signaling pathways that cross-talk and impact immune senescence. Given the role of the immune system in combating infections, its effectiveness with age may well be a marker of health and a predictor of longevity. It is therefore believed that a better understanding of the mechanisms underlying immune senescence will lead to an effective interventional strategy aimed at improving the health span of individuals. Antioxid. Redox Signal. 14, 1551–1585. PMID:20812785

  14. [Innate immunity against viruses].

    PubMed

    Drutskaia, M S; Belousov, P V; Nedospasov, S A

    2011-01-01

    Viruses are obligate parasites which are able to infect cells of all living organisms. Multiple antiviral defense mechanisms have appeared early in evolution of the immune system. Higher vertebrates have the most complex antiviral immunity which is based on both innate and adoptive immune responses. However, majority of living organisms, including plants and invertebrates, rely exclusively on innate immune mechanisms for protection against viral infections. There are some striking similarities in several components of the innate immune recognition between mammals, plants and insects, rendering these signaling cascades as highly conserved in the evolution of the immune system. This review summarizes recent advances in the field of innate immune recognition of viruses, with particular interest on pattern-recognition receptors. PMID:21485493

  15. Cellular immune defenses of Drosophila melanogaster.

    PubMed

    Parsons, Brendon; Foley, Edan

    2016-05-01

    Drosophila melanogaster is a widely used model for the characterization of blood cell development and function, with an array of protocols for the manipulation and visualization of fixed or live cells in vitro or in vivo. Researchers have deployed these techniques to reveal Drosophila hemocytes as a remarkably versatile cell type that engulfs apoptotic corpses; neutralizes invading parasites; seals epithelial wounds; and deposits extracellular matrix proteins. In this review, we will discuss the key features of Drosophila hemocyte development and function, and identify similarities with vertebrate counterparts. PMID:26748247

  16. Has innate immunity evolved through different routes?

    NASA Astrophysics Data System (ADS)

    Parrinello, Nicolò

    2010-03-01

    Invertebrate self/non-self recognition, defense responses, mating and development share innate immune surveillance and functions challenged by competition and linked to fitness. Independent evolutionary branches of immune responses may use conserved gene traits. On the other hand immunity genes may be conserved due to their role in development. Finally, upregulation of innate immunity genes during ascidian metamorphosis supports the danger hypothesis.

  17. Host Cell Autophagy in Immune Response to Zoonotic Infections

    PubMed Central

    Skendros, Panagiotis; Mitroulis, Ioannis

    2012-01-01

    Autophagy is a fundamental homeostatic process in which cytoplasmic targets are sequestered within double-membraned autophagosomes and subsequently delivered to lysosomes for degradation. Accumulating evidence supports the pivotal role of autophagy in host defense against intracellular pathogens implicating both innate and adaptive immunity. Many of these pathogens cause common zoonotic infections worldwide. The induction of the autophagic machinery by innate immune receptors signaling, such as TLRs, NOD1/2, and p62/SQSTM1 in antigen-presenting cells results in inhibition of survival and elimination of invading pathogens. Furthermore, Th1 cytokines induce the autophagic process, whereas autophagy also contributes to antigen processing and MHC class II presentation, linking innate to adaptive immunity. However, several pathogens have developed strategies to avoid autophagy or exploit autophagic machinery to their advantage. This paper focuses on the role of host cell autophagy in the regulation of immune response against intracellular pathogens, emphasizing on selected bacterial and protozoan zoonoses. PMID:22110539

  18. Immune response from a resource allocation perspective

    PubMed Central

    Rauw, Wendy M.

    2012-01-01

    The immune system is a life history trait that can be expected to trade off against other life history traits. Whether or not a trait is considered to be a life history trait has consequences for the expectation on how it responds to natural selection and evolution; in addition, it may have consequences for the outcome of artificial selection when it is included in the breeding objective. The immune system involved in pathogen resistance comprises multiple mechanisms that define a host's defensive capacity. Immune resistance involves employing mechanisms that either prevent pathogens from invading or eliminate the pathogens when they do invade. On the other hand, tolerance involves limiting the damage that is caused by the infection. Both tolerance and resistance traits require (re)allocation of resources and carry physiological costs. Examples of trade-offs between immune function and growth, reproduction and stress response are provided in this review, in addition to consequences of selection for increased production on immune function and vice versa. Reaction norms are used to deal with questions of immune resistance vs. tolerance to pathogens that relate host health to infection intensity. In essence, selection for immune tolerance in livestock is a particular case of selection for animal robustness. Since breeding goals that include robustness traits are required in the implementation of more sustainable agricultural production systems, it is of interest to investigate whether immune tolerance is a robustness trait that is positively correlated with overall animal robustness. Considerably more research is needed to estimate the shapes of the cost functions of different immune strategies, and investigate trade-offs and cross-over benefits of selection for disease resistance and/or disease tolerance in livestock production. PMID:23413205

  19. Tumor antigen-targeting monoclonal antibody-based immunotherapy: Orchestrating combined strategies for the development of long-term antitumor immunity

    PubMed Central

    Michaud, Henri-Alexandre; Eliaou, Jean-Franois; Lafont, Virginie; Bonnefoy, Nathalie; Gros, Laurent

    2014-01-01

    Tumor antigen (TA)-targeting monoclonal antibody (mAb)-based treatments are considered to be one of the most successful strategies in cancer therapy. Besides targeting TAs and inducing tumor cell death, such antibodies interact with immune cells through Fc-dependent mechanisms to induce adaptive memory immune responses. However, multiple inhibitory/immunosuppressive pathways can be induced by tumor cells to limit the establishment of an efficient antitumor response and consequently a sustained clinical response to TA-targeting mAbs. Here, we provide an overview on how TA-targeting mAbs in combination with conventional cancer therapies and/or inhibitors of key immunosuppressive pathways might represent promising approaches to achieve long-term tumor control. PMID:25941618

  20. A Heterologous DNA Priming-Mycobacterium bovis BCG Boosting Immunization Strategy Using Mycobacterial Hsp70, Hsp65, and Apa Antigens Improves Protection against Tuberculosis in Mice

    PubMed Central

    Ferraz, Jose C.; Stavropoulos, Evangelos; Yang, Min; Coade, Steve; Espitia, Clara; Lowrie, Douglas B.; Colston, M. Joseph; Tascon, Ricardo E.

    2004-01-01

    Tuberculosis is responsible for >2 million deaths a year, and the number of new cases is rising worldwide. DNA vaccination combined with Mycobacterium bovis bacillus Calmette Gurin (BCG) represents a potential strategy for prevention of this disease. Here, we used a heterologous prime-boost immunization approach using a combination of DNA plasmids and BCG in order to improve the efficacy of vaccination against Mycobacterium tuberculosis infection in mice. As model antigens, we selected the M. tuberculosis Apa (for alanine-proline-rich antigen) and the immunodominant Hsp65 and Hsp70 mycobacterial antigens combined with BCG. We demonstrated that animals injected with a combination of DNA vectors expressing these antigens, when boosted with BCG, showed increased specific antimycobacterial immune responses compared to animals vaccinated with BCG alone. More importantly, the protection achieved with this regimen was also significantly better than with BCG alone. PMID:15557616

  1. Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus

    PubMed Central

    Yeaman, Michael R.; Filler, Scott G.; Schmidt, Clint S.; Ibrahim, Ashraf S.; Edwards, John E.; Hennessey, John P.

    2014-01-01

    Recent perspectives forecast a new paradigm for future “third generation” vaccines based on commonalities found in diverse pathogens or convergent immune defenses to such pathogens. For Staphylococcus aureus, recurring infections and a limited success of vaccines containing S. aureus antigens imply that native antigens induce immune responses insufficient for optimal efficacy. These perspectives exemplify the need to apply novel vaccine strategies to high-priority pathogens. One such approach can be termed convergent immunity, where antigens from non-target organisms that contain epitope homologs found in the target organism are applied in vaccines. This approach aims to evoke atypical immune defenses via synergistic processes that (1) afford protective efficacy; (2) target an epitope from one organism that contributes to protective immunity against another; (3) cross-protect against multiple pathogens occupying a common anatomic or immunological niche; and/or (4) overcome immune subversion or avoidance strategies of target pathogens. Thus, convergent immunity has a potential to promote protective efficacy not usually elicited by native antigens from a target pathogen. Variations of this concept have been mainstays in the history of viral and bacterial vaccine development. A more far-reaching example is the pre-clinical evidence that specific fungal antigens can induce cross-kingdom protection against bacterial pathogens. This trans-kingdom protection has been demonstrated in pre-clinical studies of the recombinant Candida albicans agglutinin-like sequence 3 protein (rAls3) where it was shown that a vaccine containing rAls3 provides homologous protection against C. albicans, heterologous protection against several other Candida species, and convergent protection against several strains of S. aureus. Convergent immunity reflects an intriguing new approach to designing and developing vaccine antigens and is considered here in the context of vaccines to target S. aureus. PMID:25309545

  2. Responses of innate immune cells to group A Streptococcus

    PubMed Central

    Fieber, Christina; Kovarik, Pavel

    2014-01-01

    Group A Streptococcus (GAS), also called Streptococcus pyogenes, is a Gram-positive beta-hemolytic human pathogen which causes a wide range of mostly self-limiting but also several life-threatening diseases. Innate immune responses are fundamental for defense against GAS, yet their activation by pattern recognition receptors (PRRs) and GAS-derived pathogen-associated molecular patterns (PAMPs) is incompletely understood. In recent years, the use of animal models together with the powerful tools of human molecular genetics began shedding light onto the molecular mechanisms of innate immune defense against GAS. The signaling adaptor MyD88 was found to play a key role in launching the immune response against GAS in both humans and mice, suggesting that PRRs of the Toll-like receptor (TLR) family are involved in sensing this pathogen. The specific TLRs and their ligands have yet to be identified. Following GAS recognition, induction of cytokines such as TNF and type I interferons (IFNs), leukocyte recruitment, phagocytosis, and the formation of neutrophil extracellular traps (NETs) have been recognized as key events in host defense. A comprehensive knowledge of these mechanisms is needed in order to understand their frequent failure against GAS immune evasion strategies. PMID:25325020

  3. Responses of innate immune cells to group A Streptococcus.

    PubMed

    Fieber, Christina; Kovarik, Pavel

    2014-01-01

    Group A Streptococcus (GAS), also called Streptococcus pyogenes, is a Gram-positive beta-hemolytic human pathogen which causes a wide range of mostly self-limiting but also several life-threatening diseases. Innate immune responses are fundamental for defense against GAS, yet their activation by pattern recognition receptors (PRRs) and GAS-derived pathogen-associated molecular patterns (PAMPs) is incompletely understood. In recent years, the use of animal models together with the powerful tools of human molecular genetics began shedding light onto the molecular mechanisms of innate immune defense against GAS. The signaling adaptor MyD88 was found to play a key role in launching the immune response against GAS in both humans and mice, suggesting that PRRs of the Toll-like receptor (TLR) family are involved in sensing this pathogen. The specific TLRs and their ligands have yet to be identified. Following GAS recognition, induction of cytokines such as TNF and type I interferons (IFNs), leukocyte recruitment, phagocytosis, and the formation of neutrophil extracellular traps (NETs) have been recognized as key events in host defense. A comprehensive knowledge of these mechanisms is needed in order to understand their frequent failure against GAS immune evasion strategies. PMID:25325020

  4. Adenosine Signaling and the Energetic Costs of Induced Immunity

    PubMed Central

    Lazzaro, Brian P.

    2015-01-01

    Life history theory predicts that trait evolution should be constrained by competing physiological demands on an organism. Immune defense provides a classic example in which immune responses are presumed to be costly and therefore come at the expense of other traits related to fitness. One strategy for mitigating the costs of expensive traits is to render them inducible, such that the cost is paid only when the trait is utilized. In the current issue of PLOS Biology, Bajgar and colleagues elegantly demonstrate the energetic and life history cost of the immune response that Drosophila melanogaster larvae induce after infection by the parasitoid wasp Leptopilina boulardi. These authors show that infection-induced proliferation of defensive blood cells commands a diversion of dietary carbon away from somatic growth and development, with simple sugars instead being shunted to the hematopoetic organ for rapid conversion into the raw energy required for cell proliferation. This metabolic shift results in a 15% delay in the development of the infected larva and is mediated by adenosine signaling between the hematopoietic organ and the central metabolic control organ of the host fly. The adenosine signal thus allows D. melanogaster to rapidly marshal the energy needed for effective defense and to pay the cost of immunity only when infected. PMID:25915419

  5. Immune responses against hepatitis C virus genotype 3a virus-like particles in mice: A novel VLP prime-adenovirus boost strategy.

    PubMed

    Kumar, Anuj; Das, Soma; Mullick, Ranajoy; Lahiri, Priyanka; Tatineni, Ranjitha; Goswami, Debashree; Bhat, Prasanna; Torresi, Joseph; Gowans, Eric James; Karande, Anjali Anoop; Das, Saumitra

    2016-02-17

    Chronic hepatitis C virus (HCV) infection represents a major health threat to global population. In India, approximately 15-20% of cases of chronic liver diseases are caused by HCV infection. Although, new drug treatments hold great promise for HCV eradication in infected individuals, the treatments are highly expensive. A vaccine for preventing or treating HCV infection would be of great value, particularly in developing countries. Several preclinical trials of virus-like particle (VLP) based vaccine strategies are in progress throughout the world. Previously, using baculovirus based system, we have reported the production of hepatitis C virus-like particles (HCV-LPs) encoding structural proteins for genotype 3a, which is prevalent in India. In the present study, we have generated HCV-LPs using adenovirus based system and tried different immunization strategies by using combinations of both kinds of HCV-LPs with other genotype 3a-based immunogens. HCV-LPs and peptides based ELISAs were used to evaluate antibody responses generated by these combinations. Cell-mediated immune responses were measured by using T-cell proliferation assay and intracellular cytokine staining. We observed that administration of recombinant adenoviruses expressing HCV structural proteins as final booster enhances both antibody as well as T-cell responses. Additionally, reduction of binding of VLP and JFH1 virus to human hepatocellular carcinoma cells demonstrated the presence of neutralizing antibodies in immunized sera. Taken together, our results suggest that the combined regimen of VLP followed by recombinant adenovirus could more effectively inhibit HCV infection, endorsing the novel vaccine strategy. PMID:26700891

  6. Immunity to plant pathogens and iron homeostasis.

    PubMed

    Aznar, Aude; Chen, Nicolas W G; Thomine, Sebastien; Dellagi, Alia

    2015-11-01

    Iron is essential for metabolic processes in most living organisms. Pathogens and their hosts often compete for the acquisition of this nutrient. However, iron can catalyze the formation of deleterious reactive oxygen species. Hosts may use iron to increase local oxidative stress in defense responses against pathogens. Due to this duality, iron plays a complex role in plant-pathogen interactions. Plant defenses against pathogens and plant response to iron deficiency share several features, such as secretion of phenolic compounds, and use common hormone signaling pathways. Moreover, fine tuning of iron localization during infection involves genes coding iron transport and iron storage proteins, which have been shown to contribute to immunity. The influence of the plant iron status on the outcome of a given pathogen attack is strongly dependent on the nature of the pathogen infection strategy and on the host species. Microbial siderophores emerged as important factors as they have the ability to trigger plant defense responses. Depending on the plant species, siderophore perception can be mediated by their strong iron scavenging capacity or possibly via specific recognition as pathogen associated molecular patterns. This review highlights that iron has a key role in several plant-pathogen interactions by modulating immunity. PMID:26475190

  7. DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response

    PubMed Central

    Smith, Trevor RF; Schultheis, Katherine; Kiosses, William B; Amante, Dinah H; Mendoza, Janess M; Stone, John C; McCoy, Jay R; Sardesai, Niranjan Y; Broderick, Kate E

    2014-01-01

    The immunocompetence and clinical accessibility of dermal tissue offers an appropriate and attractive target for vaccination. We previously demonstrated that pDNA injection into the skin in combination with surface electroporation (SEP), results in rapid and robust expression of the encoded antigen in the epidermis. Here, we demonstrate that intradermally EP-enhanced pDNA vaccination results in the rapid induction of a host humoral immune response. In the dermally relevant guinea pig model, we used high-resolution laser scanning confocal microscopy to observe direct dendritic cell (DC) transfections in the epidermis, to determine the migration kinetics of these cells from the epidermal layer into the dermis, and to follow them sequentially to the immediate draining lymph nodes. Furthermore, we delineate the relationship between the migration of directly transfected epidermal DCs and the generation of the host immune response. In summary, these data indicate that direct presentation of antigen to the immune system by DCs through SEP-based in vivo transfection in the epidermis, is related to the generation of a humoral immune response. PMID:26052522

  8. Release of Soluble Ligands for the Activating NKG2D Receptor: One More Immune Evasion Strategy Evolved by HIV-1 ?

    PubMed

    Giuliani, Erica; Vassena, Lia; Cerboni, Cristina; Doria, Margherita

    2016-01-01

    Increasing lines of evidence indicate that NKG2D, an activating receptor of natural killer (NK) and CD8(+) T cells, plays an important role in immune responses against HIV-1. Through its ability to recognize a diverse array of ligands (NKG2DLs) induced by cell 'stress' such as viral infection, NKG2D delivers activating and co-stimulatory signals resulting in cytotoxicity and release of cytokines. Therefore, HIV-1 and other viruses have evolved clever mechanisms to counteract NKG2D-dependent immune responses. While, on one hand, the HIV-1 Vpr protein up-regulates NKG2DLs expression by activating the DNA damage response (DDR) pathway, other viral proteins (Nef and Vif) have developed the capacity to reduce NKG2DLs expression levels. In addition, recent evidences suggest that HIV-1-infected CD4(+) T cells may release NKG2DLs, particularly MICA, in soluble form, a phenomenon that has the potential to down-modulate NKG2D on circulating lymphocytes and allow evasion of NKG2D-mediated immune responses. Indeed, despite controversial, lower NKG2D expression was found on both NK and CD8(+) T cells in HIV-1-infected patients. This review discusses recent advances in the understanding of how HIV-1 affects the NKG2D/NKG2DLs system, with a special focus on virus-induced release of soluble NKG2DLs and its functional implications for the immune surveillance of the infected host. PMID:26122035

  9. Inhibition of Translation Initiation by Protein 169: A Vaccinia Virus Strategy to Suppress Innate and Adaptive Immunity and Alter Virus Virulence.

    PubMed

    Strnadova, Pavla; Ren, Hongwei; Valentine, Robert; Mazzon, Michela; Sweeney, Trevor R; Brierley, Ian; Smith, Geoffrey L

    2015-09-01

    Vaccinia virus (VACV) is the prototypic orthopoxvirus and the vaccine used to eradicate smallpox. Here we show that VACV strain Western Reserve protein 169 is a cytoplasmic polypeptide expressed early during infection that is excluded from virus factories and inhibits the initiation of cap-dependent and cap-independent translation. Ectopic expression of protein 169 causes the accumulation of 80S ribosomes, a reduction of polysomes, and inhibition of protein expression deriving from activation of multiple innate immune signaling pathways. A virus lacking 169 (vΔ169) replicates and spreads normally in cell culture but is more virulent than parental and revertant control viruses in intranasal and intradermal murine models of infection. Intranasal infection by vΔ169 caused increased pro-inflammatory cytokines and chemokines, infiltration of pulmonary leukocytes, and lung weight. These alterations in innate immunity resulted in a stronger CD8+ T-cell memory response and better protection against virus challenge. This work illustrates how inhibition of host protein synthesis can be a strategy for virus suppression of innate and adaptive immunity. PMID:26334635

  10. Inhibition of Translation Initiation by Protein 169: A Vaccinia Virus Strategy to Suppress Innate and Adaptive Immunity and Alter Virus Virulence

    PubMed Central

    Strnadova, Pavla; Ren, Hongwei; Valentine, Robert; Mazzon, Michela; Sweeney, Trevor R.; Brierley, Ian; Smith, Geoffrey L.

    2015-01-01

    Vaccinia virus (VACV) is the prototypic orthopoxvirus and the vaccine used to eradicate smallpox. Here we show that VACV strain Western Reserve protein 169 is a cytoplasmic polypeptide expressed early during infection that is excluded from virus factories and inhibits the initiation of cap-dependent and cap-independent translation. Ectopic expression of protein 169 causes the accumulation of 80S ribosomes, a reduction of polysomes, and inhibition of protein expression deriving from activation of multiple innate immune signaling pathways. A virus lacking 169 (vΔ169) replicates and spreads normally in cell culture but is more virulent than parental and revertant control viruses in intranasal and intradermal murine models of infection. Intranasal infection by vΔ169 caused increased pro-inflammatory cytokines and chemokines, infiltration of pulmonary leukocytes, and lung weight. These alterations in innate immunity resulted in a stronger CD8+ T-cell memory response and better protection against virus challenge. This work illustrates how inhibition of host protein synthesis can be a strategy for virus suppression of innate and adaptive immunity. PMID:26334635

  11. Regulation of the Intestinal Barrier Function by Host Defense Peptides

    PubMed Central

    Robinson, Kelsy; Deng, Zhuo; Hou, Yongqing; Zhang, Guolong

    2015-01-01

    Intestinal barrier function is achieved primarily through regulating the synthesis of mucins and tight junction (TJ) proteins, which are critical for maintaining optimal gut health and animal performance. An aberrant expression of TJ proteins results in increased paracellular permeability, leading to intestinal and systemic disorders. As an essential component of innate immunity, host defense peptides (HDPs) play a critical role in mucosal defense. Besides broad-spectrum antimicrobial activities, HDPs promotes inflammation resolution, endotoxin neutralization, wound healing, and the development of adaptive immune response. Accumulating evidence has also indicated an emerging role of HDPs in barrier function and intestinal homeostasis. HDP deficiency in the intestinal tract is associated with barrier dysfunction and dysbiosis. Several HDPs were recently shown to enhance mucosal barrier function by directly inducing the expression of multiple mucins and TJ proteins. Consistently, dietary supplementation of HDPs often leads to an improvement in intestinal morphology, production performance, and feed efficiency in livestock animals. This review summarizes current advances on the regulation of epithelial integrity and homeostasis by HDPs. Major signaling pathways mediating HDP-induced mucin and TJ protein synthesis are also discussed. As an alternative strategy to antibiotics, supplementation of exogenous HDPs or modulation of endogenous HDP synthesis may have potential to improve intestinal barrier function and animal health and productivity. PMID:26664984

  12. Small RNAs in plant defense responses during viral and bacterial interactions: similarities and differences

    PubMed Central

    Pelez, Pablo; Sanchez, Federico

    2013-01-01

    Small non-coding RNAs constitute an important class of gene expression regulators that control different biological processes in most eukaryotes. In plants, several small RNA (sRNA) silencing pathways have evolved to produce a wide range of small RNAs with specialized functions. Evidence for the diverse mode of action of the small RNA pathways has been highlighted during plantmicrobe interactions. Host sRNAs and small RNA silencing pathways have been recognized as essential components of plant immunity. One way plants respond and defend against pathogen infections is through the small RNA silencing immune system. To deal with plant defense responses, pathogens have evolved sophisticated mechanisms to avoid and counterattack this defense strategy. The relevance of the small RNA-mediated plant defense responses during viral infections has been well-established. Recent evidence points out its importance also during plantbacteria interactions. Herein, this review discusses recent findings, similarities and differences about the small RNA-mediated arms race between plants and these two groups of microbes, including the small RNA silencing pathway components that contribute to plant immune responses, the pathogen-responsive endogenous sRNAs and the pathogen-delivered effector proteins. PMID:24046772

  13. Making sense of hormone-mediated defense networking: from rice to Arabidopsis

    PubMed Central

    De Vleesschauwer, David; Xu, Jing; Höfte, Monica

    2014-01-01

    Phytohormones are not only essential for plant growth and development but also play central roles in triggering the plant immune signaling network. Historically, research aimed at elucidating the defense-associated role of hormones has tended to focus on the use of experimentally tractable dicot plants such as Arabidopsis thaliana. Emerging from these studies is a picture whereby complex crosstalk and induced hormonal changes mold plant health and disease, with outcomes largely dependent on the lifestyle and infection strategy of invading pathogens. However, recent studies in monocot plants are starting to provide additional important insights into the immune-regulatory roles of hormones, often revealing unique complexities. In this review, we address the latest discoveries dealing with hormone-mediated immunity in rice, one of the most important food crops and an excellent model for molecular genetic studies in monocots. Moreover, we highlight interactions between hormone signaling, rice defense and pathogen virulence, and discuss the differences and similarities with findings in Arabidopsis. Finally, we present a model for hormone defense networking in rice and describe how detailed knowledge of hormone crosstalk mechanisms can be used for engineering durable rice disease resistance. PMID:25426127

  14. Innate Immune Sensing and Response to Influenza

    PubMed Central

    Pulendran, Bali; Maddur, Mohan S.

    2015-01-01

    Influenza viruses pose a substantial threat to human and animal health worldwide. Recent studies in mouse models have revealed an indispensable role for the innate immune system in defense against influenza virus. Recognition of the virus by innate immune receptors in a multitude of cell types activates intricate signaling networks, functioning to restrict viral replication. Downstream effector mechanisms include activation of innate immune cells and, induction and regulation of adaptive immunity. However, uncontrolled innate responses are associated with exaggerated disease, especially in pandemic influenza virus infection. Despite advances in the understanding of innate response to influenza in the mouse model, there is a large knowledge gap in humans, particularly in immunocom-promised groups such as infants and the elderly. We propose here, the need for further studies in humans to decipher the role of innate immunity to influenza virus, particularly at the site of infection. These studies will complement the existing work in mice and facilitate the quest to design improved vaccines and therapeutic strategies against influenza. PMID:25078919

  15. The costs, effects and cost-effectiveness of strategies to increase coverage of routine immunizations in low- and middle-income countries: systematic review of the grey literature.

    PubMed Central

    Batt, Katherine; Fox-Rushby, J. A.; Castillo-Riquelme, Marianela

    2004-01-01

    Evidence-based reviews of published literature can be subject to several biases. Grey literature, however, can be of poor quality and expensive to access. Effective search strategies also vary by topic and are rarely known in advance. This paper complements a systematic review of the published literature on the costs and effects of expanding immunization services in developing countries. The quality of data on the effectiveness and cost-effectiveness of strategies to increase immunization coverage is shown to be similar across literatures, but the quality of information on costing is much lower in the grey literature. After excluding poorer quality studies from this review we found the quantity of available evidence almost doubled, particularly for more complex health-system interventions and cost or cost-effectiveness analyses. Interventions in the grey literature are more up to date and cover a different geographical spread. Consequently the conclusions of the published and grey literatures differ, although the number of papers is still too low to account for differences across types of interventions. We recommend that in future researchers consider using non-English keywords in their searches. PMID:15628207

  16. A Two-Component DNA-Prime/Protein-Boost Vaccination Strategy for Eliciting Long-Term, Protective T Cell Immunity against Trypanosoma cruzi

    PubMed Central

    Gupta, Shivali; Garg, Nisha J.

    2015-01-01

    In this study, we evaluated the long-term efficacy of a two-component subunit vaccine against Trypanosoma cruzi infection. C57BL/6 mice were immunized with TcG2/TcG4 vaccine delivered by a DNA-prime/Protein-boost (D/P) approach and challenged with T. cruzi at 120 or 180 days post-vaccination (dpv). We examined whether vaccine-primed T cell immunity was capable of rapid expansion and intercepting the infecting T. cruzi. Our data showed that D/P vaccine elicited CD4+ (30-38%) and CD8+ (22-42%) T cells maintained an effector phenotype up to 180 dpv, and were capable of responding to antigenic stimulus or challenge infection by a rapid expansion (CD8>CD4) with type 1 cytokine (IFNγ+ and TFNα+) production and cytolytic T lymphocyte (CTL) activity. Subsequently, challenge infection at 120 or 180 dpv, resulted in 2-3-fold lower parasite burden in vaccinated mice than was noted in unvaccinated/infected mice. Co-delivery of IL-12- and GMCSF-encoding expression plasmids provided no significant benefits in enhancing the anti-parasite efficacy of the vaccine-induced T cell immunity. Booster immunization (bi) with recombinant TcG2/TcG4 proteins 3-months after primary vaccine enhanced the protective efficacy, evidenced by an enhanced expansion (1.2-2.8-fold increase) of parasite-specific, type 1 CD4+ and CD8+ T cells and a potent CTL response capable of providing significantly improved (3-4.5-fold) control of infecting T. cruzi. Further, CD8+T cells in vaccinated/bi mice were predominantly of central memory phenotype, and capable of responding to challenge infection 4-6-months post bi by a rapid expansion to a poly-functional effector phenotype, and providing a 1.5-2.3-fold reduction in tissue parasite replication. We conclude that the TcG2/TcG4 D/P vaccine provided long-term anti-T. cruzi T cell immunity, and bi would be an effective strategy to maintain or enhance the vaccine-induced protective immunity against T. cruzi infection and Chagas disease. PMID:25951312

  17. Immune checkpoint blockade as a novel immunotherapeutic strategy for renal cell carcinoma: a review of clinical trials.

    PubMed

    Godwin, J Luke; Zibelman, Matthew; Plimack, Elizabeth R; Geynisman, Daniel M

    2014-12-01

    Renal cell carcinoma (RCC) is a common genitourinary malignancy; when metastatic, it is almost uniformly fatal. For many years non-specific immunotherapy was the mainstay of treatment for metastatic RCC, but led to only modest success and significant side-effects. More recently, seven targeted therapy drugs have been approved to treat metastatic RCC; these drugs impede RCC cell growth, proliferation, and angiogenesis and have had a significant impact on patient outcomes, but with infrequent long term responders. Thus, a renewed emphasis on immunotherapy has emerged over the last several years with the development and testing of a novel class of immunotherapeutic agents called checkpoint inhibitors. These drugs have targeted the programmed cell death 1 (PD-1) and cytotoxic leukocyte antigen 4 (CTLA-4) pathways on regulatory T cells, leading to immune response enhancement and immune-mediated anti-tumor effects in multiple malignancies, including RCC. A number of studies recently reported utilizing checkpoint inhibitors, either alone or in combination with other checkpoint inhibitors or vascular endothelial growth factor targeting agents, and these studies have shown significant and at times durable responses in RCC patients. This has led to the development of further phase I, II, and III trials and this review will discuss the history and currently available data for immune checkpoint blockade in RCC. PMID:25549705

  18. Bacteria Fighting Back How Pathogens Target and Subvert the Host Innate Immune System

    PubMed Central

    Reddick, L. Evan; Alto, Neal M.

    2014-01-01

    The innate immune system has evolved under selective pressure since the radiation of multicellular life approximately six hundred million years ago. Because of this long history, innate immune mechanisms found in modern eukaryotic organisms today are highly complex, yet are built from common molecular strategies. It is now clear that evolution has selected a conserved set of anti-microbial peptides as well as Pattern Recognition Receptors (PRRs) that initiate cellular-based signals as a first line of defense against invading pathogens. Conversely, microbial pathogens employ their own strategies to evade, inhibit, or otherwise manipulate the innate immune response. Here, we discuss recent discoveries that have changed our view of immune modulatory mechanisms employed by bacterial pathogens, focusing specifically on the initial sites of microbial recognition and extending to host cellular signal transduction, pro-inflammatory cytokine production, and alteration of protein trafficking and secretion. PMID:24766896

  19. Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Wang, Rong; Zhang, Yan-Jin

    2014-01-01

    Interferons (IFNs) are important components in innate immunity involved in the first line of defense to protect host against viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) leads to severe economic losses for swine industry since being first identified in early 1990s. PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. PRRSV encodes several proteins that act as antagonists for the IFN signaling. In this review, we summarized the various strategies used by PRRSV to antagonize IFN production and thwart IFN-activated antiviral signaling, as well as the variable interference with IFN-mediated immune response by different PRRSV strains. Thorough understanding of the interaction between PRRSV and host innate immune response will facilitate elucidation of PRRSV pathogenesis and development of a better strategy to control PRRS. PMID:25101271

  20. B cells and Antibodies in the Defense against Mycobacterium tuberculosis infection

    PubMed Central

    Achkar, Jacqueline M.; Chan, John; Casadevall, Arturo

    2015-01-01

    Summary Better understanding of the immunological components and their interactions necessary to prevent or control Mycobacterium tuberculosis (Mtb) infection in humans is critical for tuberculosis (TB) vaccine development strategies. While the contributory role of humoral immunity in the protection against Mtb infection and disease is less defined than the role of T cells, it has been well established for many other intracellular pathogens. Here we update and discuss the increasing evidence and the mechanisms of B cells and antibodies in the defense against Mtb infection. We posit that B cells and antibodies have a variety of potential protective roles at each stage of Mtb infection, and postulate that such roles should be considered in the development strategies for TB vaccines and other immune-based interventions. PMID:25703559

  1. Hepatitis C virus and antiviral innate immunity: Who wins at tug-of-war?

    PubMed Central

    Yang, Da-Rong; Zhu, Hai-Zhen

    2015-01-01

    Hepatitis C virus (HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon (IFN) system plays an essential role in the restriction of HCV infection via the induction of hundreds of IFN-stimulated genes (ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HCV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HCV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HCV infection. PMID:25852264

  2. Neonatal Host Defense against Staphylococcal Infections

    PubMed Central

    Power Coombs, Melanie R.; Kronforst, Kenny; Levy, Ofer

    2013-01-01

    Preterm infants are especially susceptible to late-onset sepsis that is often due to Gram-positive bacterial infections resulting in substantial morbidity and mortality. Herein, we will describe neonatal innate immunity to Staphylococcus spp. comparing differences between preterm and full-term newborns with adults. Newborn innate immunity is distinct demonstrating diminished skin integrity, impaired Th1-polarizing responses, low complement levels, and diminished expression of plasma antimicrobial proteins and peptides, especially in preterm newborns. Characterization of distinct aspects of the neonatal immune response is defining novel approaches to enhance host defense to prevent and/or treat staphylococcal infection in this vulnerable population. PMID:23935651

  3. Defense system shortcuts and limits of scope.

    PubMed

    Rewald, E; Francischetti, M M

    2000-10-01

    Defense, as a key factor of life, shares the biological tendencies of simplicity and energy saving. We propose that, like the mind, defense tends to rely on shortcuts via immune memes. Also, response repetition may induce the formation of virtual 'modules' [toolkits] to simplify and perfect performance. Engaged modules may expand by proliferating or by capturing immune components from the 'dormant' and even perhaps from active ones. With regard to recovery and/or survival, complexity of the integrated defense system (IDS) (1) requires to be inside of what we call the 'functional window'. In contrast to the physiological and common disease repair, energy is squandered when IDS perceives real danger. Our concern is the uncertain transition to conditions that do not fit into the IDS routine and, even worse, that are outside the functional window where the system is lacking. PMID:11000052

  4. Comparative genomics of defense systems in archaea and bacteria

    PubMed Central

    Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.

    2013-01-01

    Our knowledge of prokaryotic defense systems has vastly expanded as the result of comparative genomic analysis, followed by experimental validation. This expansion is both quantitative, including the discovery of diverse new examples of known types of defense systems, such as restriction-modification or toxin-antitoxin systems, and qualitative, including the discovery of fundamentally new defense mechanisms, such as the CRISPR-Cas immunity system. Large-scale statistical analysis reveals that the distribution of different defense systems in bacterial and archaeal taxa is non-uniform, with four groups of organisms distinguishable with respect to the overall abundance and the balance between specific types of defense systems. The genes encoding defense system components in bacterial and archaea typically cluster in defense islands. In addition to genes encoding known defense systems, these islands contain numerous uncharacterized genes, which are candidates for new types of defense systems. The tight association of the genes encoding immunity systems and dormancy- or cell death-inducing defense systems in prokaryotic genomes suggests that these two major types of defense are functionally coupled, providing for effective protection at the population level. PMID:23470997

  5. Does AIDS involve some collusion by the neuro-immune system because of positive learning of the disarmament strategy?

    PubMed

    Sandoz, Patrick

    2013-04-01

    Korzybski's general semantics recommends considering living beings as organisms-as-a-whole in their environment. Our cognitive abilities, specific to the human species, have thus to be taken into account. In this framework we establish a semantic similarity between particular stressful events of the 20th century and AIDS in which the immune-deficiency-caused is semiotically seen as a biological state of disarmament of the organism. It then appears that: These observations suggest that AIDS could benefit from some collusion by the neuro-immune system because of positive learning of the semiotic concept of disarmament, thus making the terrain favorable to the germ in response to intense stress. The disease would then result from a conditioning process based on semiotics and involve some confusion at the level of the unconscious cognitive system between disarmament toward outside the body and disarmament toward inside the body. This hypothesis is discussed within a multidisciplinary perspective considering the specificities of our modern lifestyles, the cybernetic ability of signs to control metabolism and behavior, and the recent advances of epigenetics and cognition sciences. This hypothesis may explain the multiple cross-species transmissions of the immunodeficiency virus into humans during the 20th century. Further research is suggested for evaluating this hypothesis. PMID:23317541

  6. Behavioral Immunity in Insects

    PubMed Central

    de Roode, Jacobus C.; Lefèvre, Thierry

    2012-01-01

    Parasites can dramatically reduce the fitness of their hosts, and natural selection should favor defense mechanisms that can protect hosts against disease. Much work has focused on understanding genetic and physiological immunity against parasites, but hosts can also use behaviors to avoid infection, reduce parasite growth or alleviate disease symptoms. It is increasingly recognized that such behaviors are common in insects, providing strong protection against parasites and parasitoids. We review the current evidence for behavioral immunity in insects, present a framework for investigating such behavior, and emphasize that behavioral immunity may act through indirect rather than direct fitness benefits. We also discuss the implications for host-parasite co-evolution, local adaptation, and the evolution of non-behavioral physiological immune systems. Finally, we argue that the study of behavioral immunity in insects has much to offer for investigations in vertebrates, in which this topic has traditionally been studied. PMID:26466629

  7. Evolutionary genetics of insect innate immunity

    PubMed Central

    2015-01-01

    Patterns of evolution in immune defense genes help to understand the evolutionary dynamics between hosts and pathogens. Multiple insect genomes have been sequenced, with many of them having annotated immune genes, which paves the way for a comparative genomic analysis of insect immunity. In this review, I summarize the current state of comparative and evolutionary genomics of insect innate immune defense. The focus is on the conserved and divergent components of immunity with an emphasis on gene family evolution and evolution at the sequence level; both population genetics and molecular evolution frameworks are considered. PMID:25750410

  8. Obligate brood parasites show more functionally effective innate immune responses: an eco-immunological hypothesis

    USGS Publications Warehouse

    Hahn, D. Caldwell; Summers, Scott G.; Genovese, Kenneth J.; He, Haiqi; Kogut, Michael H.

    2013-01-01

    Immune adaptations of obligate brood parasites attracted interest when three New World cowbird species (Passeriformes, Icteridae, genus Molothrus) proved unusually resistant to West Nile virus. We have used cowbirds as models to investigate the eco-immunological hypothesis that species in parasite-rich environments characteristically have enhanced immunity as a life history adaptation. As part of an ongoing program to understand the cowbird immune system, in this study we measured degranulation and oxidative burst, two fundamental responses of the innate immune system. Innate immunity provides non-specific, fast-acting defenses against a variety of invading pathogens, and we hypothesized that innate immunity experiences particularly strong selection in cowbirds, because their life history strategy exposes them to diverse novel and unpredictable parasites. We compared the relative effectiveness of degranulation and oxidative burst responses in two cowbird species and one related, non-parasitic species. Both innate immune defenses were significantly more functionally efficient in the two parasitic cowbird species than in the non-parasitic red-winged blackbird (Icteridae, Agelaius phoeniceus). Additionally, both immune defenses were more functionally efficient in the brown-headed cowbird (M. ater), an extreme host-generalist brood parasite, than in the bronzed cowbird (M. aeneus), a moderate host-specialist with lower exposure to other species and their parasites. Thus the relative effectiveness of these two innate immune responses corresponds to the diversity of parasites in the niche of each species and to their relative resistance to WNV. This study is the first use of these two specialized assays in a comparative immunology study of wild avian species.

  9. CRISPR/Cas, the immune system of bacteria and archaea.

    PubMed

    Horvath, Philippe; Barrangou, Rodolphe

    2010-01-01

    Microbes rely on diverse defense mechanisms that allow them to withstand viral predation and exposure to invading nucleic acid. In many Bacteria and most Archaea, clustered regularly interspaced short palindromic repeats (CRISPR) form peculiar genetic loci, which provide acquired immunity against viruses and plasmids by targeting nucleic acid in a sequence-specific manner. These hypervariable loci take up genetic material from invasive elements and build up inheritable DNA-encoded immunity over time. Conversely, viruses have devised mutational escape strategies that allow them to circumvent the CRISPR/Cas system, albeit at a cost. CRISPR features may be exploited for typing purposes, epidemiological studies, host-virus ecological surveys, building specific immunity against undesirable genetic elements, and enhancing viral resistance in domesticated microbes. PMID:20056882

  10. Innate and Adaptive Immune Responses in Wound Epithelialization

    PubMed Central

    Strbo, Natasa; Yin, Natalie; Stojadinovic, Olivera

    2014-01-01

    Significance: Over the years, it has become clear that, in addition to performing their regular duties in immune defense, the innate and adaptive arms of the immune system are important regulators of the complex series of events that lead to wound healing. Immune cells modulate wound healing by promoting cellular cross-talk; they secrete signaling molecules, including cytokines, chemokines, and growth factors. In line with the major effort in wound healing research to find efficient therapeutic agents for the constantly increasing number of patients with chronic wounds, findings regarding the contributions of innate and adaptive immune responses to the re-epithelialization of damaged skin may bring novel therapeutics. Recent Advances: Increasing evidence suggests that induction of the adaptive immune response requires activation of innate immunity and that there is a dependent relationship between the two systems. Consequently, the bridge between the innate and the acquired immune systems has become an area of emerging exploration. It is clear that a better understanding of the epithelial cells (keratinocytes), immune cells, and mechanisms that contribute to an effective wound healing process is necessary so that new strategies for successful wounds treatment can be devised. Critical Issues: A greater understanding of the biology of skin innate and adaptive immune cells during wound epithelialization may have an impact on development of novel strategies for significant improvements in the quality of tissue repair. Future Directions: Future studies should clarify the importance of particular molecules and mechanisms utilized for development and functions of skin-resident ??T and Langerhans cells, as well as identify therapeutic targets for manipulation of these cells to combat epithelial diseases. PMID:25032069

  11. Hepcidin and Host Defense against Infectious Diseases

    PubMed Central

    Michels, Kathryn; Nemeth, Elizabeta; Ganz, Tomas; Mehrad, Borna

    2015-01-01

    Hepcidin is the master regulator of iron homeostasis in vertebrates. The synthesis of hepcidin is induced by systemic iron levels and by inflammatory stimuli. While the role of hepcidin in iron regulation is well established, its contribution to host defense is emerging as complex and multifaceted. In this review, we summarize the literature on the role of hepcidin as a mediator of antimicrobial immunity. Hepcidin induction during infection causes depletion of extracellular iron, which is thought to be a general defense mechanism against many infections by withholding iron from invading pathogens. Conversely, by promoting iron sequestration in macrophages, hepcidin may be detrimental to cellular defense against certain intracellular infections, although critical in vivo studies are needed to confirm this concept. It is not yet clear whether hepcidin exerts any iron-independent effects on host defenses. PMID:26291319

  12. Innate Immune Recognition of HIV-1

    PubMed Central

    Iwasaki, Akiko

    2012-01-01

    In contrast to the extraordinary body of knowledge gained over the past three decades on the virology, pathogenesis, and immunology of HIV-1 infection, innate sensors that detect HIV-1 had remained elusive until recently. By virtue of integration, retroviridae makes up a substantial portion of our genome. Thus, immune strategies that deal with endogenous retroviruses are, by necessity, those of self-preservation and not of virus elimination. Some of the principles of such strategies may also apply for defense against exogenous retroviruses including HIV-1. Here, I highlight several sensors that have recently been revealed to be capable of recognizing distinct features of HIV-1 infection, while taking into account the host-retrovirus relationship that converges on avoiding pathogenic inflammatory consequences. PMID:22999945

  13. Phosphorylation of Mouse Immunity-Related GTPase (IRG) Resistance Proteins Is an Evasion Strategy for Virulent Toxoplasma gondii

    PubMed Central

    Steinfeldt, Tobias; Knen-Waisman, Stephanie; Tong, Lan; Pawlowski, Nikolaus; Lamkemeyer, Tobias; Sibley, L. David; Hunn, Julia P.; Howard, Jonathan C.

    2010-01-01

    Virulence of complex pathogens in mammals is generally determined by multiple components of the pathogen interacting with the functional complexity and multiple layering of the mammalian immune system. It is most unusual for the resistance of a mammalian host to be overcome by the defeat of a single defence mechanism. In this study we uncover and analyse just such a case at the molecular level, involving the widespread intracellular protozoan pathogen Toxoplasma gondii and one of its most important natural hosts, the house mouse (Mus musculus). Natural polymorphism in virulence of Eurasian T. gondii strains for mice has been correlated in genetic screens with the expression of polymorphic rhoptry kinases (ROP kinases) secreted into the host cell during infection. We show that the molecular targets of the virulent allelic form of ROP18 kinase are members of a family of cellular GTPases, the interferon-inducible IRG (immunity-related GTPase) proteins, known from earlier work to be essential resistance factors in mice against avirulent strains of T. gondii. Virulent T. gondii strain ROP18 kinase phosphorylates several mouse IRG proteins. We show that the parasite kinase phosphorylates host Irga6 at two threonines in the nucleotide-binding domain, biochemically inactivating the GTPase and inhibiting its accumulation and action at the T. gondii parasitophorous vacuole membrane. Our analysis identifies the conformationally active switch I region of the GTP-binding site as an Achilles' heel of the IRG protein pathogen-resistance mechanism. The polymorphism of ROP18 in natural T. gondii populations indicates the existence of a dynamic, rapidly evolving ecological relationship between parasite virulence factors and host resistance factors. This system should be unusually fruitful for analysis at both ecological and molecular levels since both T. gondii and the mouse are widespread and abundant in the wild and are well-established model species with excellent analytical tools available. PMID:21203588

  14. Phosphorylation of mouse immunity-related GTPase (IRG) resistance proteins is an evasion strategy for virulent Toxoplasma gondii.

    PubMed

    Steinfeldt, Tobias; Könen-Waisman, Stephanie; Tong, Lan; Pawlowski, Nikolaus; Lamkemeyer, Tobias; Sibley, L David; Hunn, Julia P; Howard, Jonathan C

    2010-01-01

    Virulence of complex pathogens in mammals is generally determined by multiple components of the pathogen interacting with the functional complexity and multiple layering of the mammalian immune system. It is most unusual for the resistance of a mammalian host to be overcome by the defeat of a single defence mechanism. In this study we uncover and analyse just such a case at the molecular level, involving the widespread intracellular protozoan pathogen Toxoplasma gondii and one of its most important natural hosts, the house mouse (Mus musculus). Natural polymorphism in virulence of Eurasian T. gondii strains for mice has been correlated in genetic screens with the expression of polymorphic rhoptry kinases (ROP kinases) secreted into the host cell during infection. We show that the molecular targets of the virulent allelic form of ROP18 kinase are members of a family of cellular GTPases, the interferon-inducible IRG (immunity-related GTPase) proteins, known from earlier work to be essential resistance factors in mice against avirulent strains of T. gondii. Virulent T. gondii strain ROP18 kinase phosphorylates several mouse IRG proteins. We show that the parasite kinase phosphorylates host Irga6 at two threonines in the nucleotide-binding domain, biochemically inactivating the GTPase and inhibiting its accumulation and action at the T. gondii parasitophorous vacuole membrane. Our analysis identifies the conformationally active switch I region of the GTP-binding site as an Achilles' heel of the IRG protein pathogen-resistance mechanism. The polymorphism of ROP18 in natural T. gondii populations indicates the existence of a dynamic, rapidly evolving ecological relationship between parasite virulence factors and host resistance factors. This system should be unusually fruitful for analysis at both ecological and molecular levels since both T. gondii and the mouse are widespread and abundant in the wild and are well-established model species with excellent analytical tools available. PMID:21203588

  15. [Cathelicidins: multifunctional defense molecules of the skin].

    PubMed

    Peric, M; Koglin, S; Ruzicka, T; Schauber, J

    2009-01-01

    The human skin is constantly exposed to microbial pathogens but infections only rarely occur. Innate cutaneous immunity is a primary system for protection against infection, and antimicrobial peptides (AMPs) expressed in skin are essential defence molecules. The AMPs include molecules such as the defensins that were first characterized for their antimicrobial properties as well as other peptides and proteins first known for their activity as chemokines, enzymes, enzyme inhibitors and neuropeptides. Cathelicidins are unique AMPs that act as defensive and signalling molecules. Two different pathways are involved in this function: cathelicidins have direct antimicrobial activity and they also initiate a host of cellular responses in cytokine release, inflammation and angiogenesis. Several skin diseases are associated with cathelicidin dysfunction. In atopic eczema, for example, cathelicidin expression is suppressed, whereas in rosacea cathelicidin peptides are abnormally processed to forms that induce cutaneous inflammation and a vascular response. In psoriasis cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Current studies have unexpectedly identified vitamin D3 as a major factor for the regulation of cathelicidin expression. This finding may provide new strategies in the management of infectious and inflammatory diseases of the skin by targeting control of the expression and function of cathelicidin and other AMPs. PMID:19090451

  16. Rhamnolipid Biosurfactants as New Players in Animal and Plant Defense against Microbes

    PubMed Central

    Vatsa, Parul; Sanchez, Lisa; Clement, Christophe; Baillieul, Fabienne; Dorey, Stephan

    2010-01-01

    Rhamnolipids are known as very efficient biosurfactant molecules. They are used in a wide range of industrial applications including food, cosmetics, pharmaceutical formulations and bioremediation of pollutants. The present review provides an overview of the effect of rhamnolipids in animal and plant defense responses. We describe the current knowledge on the stimulation of plant and animal immunity by these molecules, as well as on their direct antimicrobial properties. Given their ecological acceptance owing to their low toxicity and biodegradability, rhamnolipids have the potential to be useful molecules in medicine and to be part of alternative strategies in order to reduce or replace pesticides in agriculture. PMID:21614194

  17. A reasonable defense

    SciTech Connect

    Kaufmann, W.W.

    1986-01-01

    The author traces the growth of defense spending from 1929 to the present and discusses changes in spending and emphasis on programs brought about by President Reagan. He constructs three possible defense postures and budgets and compares their costs and effectiveness, discussing the conditions necessary to adopt a reasonable defense capability and budget.

  18. Radiological Defense. Textbook.

    ERIC Educational Resources Information Center

    Defense Civil Preparedness Agency (DOD), Washington, DC.

    This textbook has been prepared under the direction of the Defense Civil Preparedness Agency (DCPA) Staff College for use as a student reference manual in radiological defense (RADEF) courses. It provides much of the basic technical information necessary for a proper understanding of radiological defense and summarizes RADEF planning and expected…

  19. A Prime Time for Trained Immunity: Innate Immune Memory in Newborns & Infants

    PubMed Central

    Levy, Ofer; Wynn, James L.

    2014-01-01

    The newborn and infant periods of early life are associated with heightened vulnerability to infection. Limited antigen exposure and distinct adaptive immune function compared to the adult places a greater burden on innate immunity for host defense to microbial challenge during this time. Trained immunity describes the phenomenon of augmented innate immune function following a stimulus that is not specific to the original stimulus. We review the concept of trained immunity in the context of the newborns unique innate immune system function, the preclinical and clinical evidence that support the tenet of innate immune memory in early life, and potential consequences of altered innate immune host responses. PMID:24356292

  20. Exchange of Computable Patient Data between the Department of Veterans Affairs (VA) and the Department of Defense (DoD): Terminology Mediation Strategy

    PubMed Central

    Bouhaddou, Omar; Warnekar, Pradnya; Parrish, Fola; Do, Nhan; Mandel, Jack; Kilbourne, John; Lincoln, Michael J.

    2008-01-01

    Complete patient health information that is available where and when it is needed is essential to providers and patients and improves healthcare quality and patient safety. VA and DoD have built on their previous experience in patient data exchange to establish data standards and terminology services to enable real-time bi-directional computable (i.e., encoded) data exchange and achieve semantic interoperability in compliance with recommended national standards and the eGov initiative. The project uses RxNorm, UMLS, and SNOMED CT terminology standards to mediate codified pharmacy and allergy data with greater than 92 and 60 percent success rates respectively. Implementation of the project has been well received by users and is being expanded to multiple joint care sites. Stable and mature standards, mediation strategies, and a close relationship between healthcare institutions and Standards Development Organizations are recommended to achieve and maintain semantic interoperability in a clinical setting. PMID:18096911

  1. Common loon nest defense against an American mink

    USGS Publications Warehouse

    McCarthy, K.P.; DeStefano, S.

    2011-01-01

    We describe a successful nest defense strategy of an adult Gavia immer (Common Loon) during an attempted predation event by a Nevison vison (American Mink) at Umbagog National Wildlife Refuge, NH. It is suspected that mink occasionally depredate loon nests, but defense strategies have not been described previously.

  2. Immune System

    MedlinePLUS

    ... How Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  3. A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4.

    PubMed

    Rosadini, Charles V; Zanoni, Ivan; Odendall, Charlotte; Green, Erin R; Paczosa, Michelle K; Philip, Naomi H; Brodsky, Igor E; Mecsas, Joan; Kagan, Jonathan C

    2015-12-01

    During bacterial infections, Toll-like receptor 4 (TLR4) signals through the MyD88- and TRIF-dependent pathways to promote pro-inflammatory and interferon (IFN) responses, respectively. Bacteria can inhibit the MyD88 pathway, but if the TRIF pathway is also targeted is unclear. We demonstrate that, in addition to MyD88, Yersinia pseudotuberculosis inhibits TRIF signaling through the type III secretion system effector YopJ. Suppression of TRIF signaling occurs during dendritic cell (DC) and macrophage infection and prevents expression of type I IFN and pro-inflammatory cytokines. YopJ-mediated inhibition of TRIF prevents DCs from inducing natural killer (NK) cell production of antibacterial IFN?. During infection of DCs, YopJ potently inhibits MAPK pathways but does not prevent activation of IKK- or TBK1-dependent pathways. This singular YopJ activity efficiently inhibits TLR4 transcription-inducing activities, thus illustrating a simple means by which pathogens impede innate immunity. PMID:26651944

  4. The Genome of the Obligately Intracellular Bacterium Ehrlichia canis Reveals Themes of Complex Membrane Structure and Immune Evasion Strategies

    SciTech Connect

    Mavromatis, K; Doyle, C Kuyler; Lykidis, A; Ivanova, N; Francino, M P; Chain, Patrick S; Shin, M; Malfatti, Stephanie; Larimer, Frank W; Copeland, A; Detter, J C; Land, Miriam L; Richardson, P M; Yu, X J; Walker, D H; McBride, J W; Kyripides, N C

    2006-01-01

    Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, {alpha}-proteobacterium, is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, 17 putative pseudogenes, and a substantial proportion of noncoding sequence (27%). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences and a unique serine-threonine bias associated with the potential for O glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly(G-C) tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Genes associated with pathogen-host interactions were identified, including a small group encoding proteins (n = 12) with tandem repeats and another group encoding proteins with eukaryote-like ankyrin domains (n = 7).

  5. Regulatory T cells and the immune pathogenesis of prenatal infection

    PubMed Central

    Rowe, Jared H.; Ertelt, James M.; Xin, Lijun; Way, Sing Sing

    2013-01-01

    Pregnancy in placental mammals offers exceptional comprehensive benefits of in utero protection, nutrition, and elimination of metabolic waste for the developing fetus. However, these advantages also require durable strategies to mitigate maternal rejection of fetal tissue expressing foreign paternal antigens. Since the initial postulate of expanded maternal immune tolerance by Sir Peter Medawar 60 years ago, an amazingly elaborate assortment of molecular and cellular modifications acting both locally at the maternal placental interface and systemically have been shown to silence potentially detrimental maternal immune responses. In turn, simultaneously maintaining host defense against the infinite array of potential pathogens during pregnancy is equally important. Fortunately, resistance against most infections is preserved seamlessly throughout gestation. On the other hand, recent studies on pathogens with unique predisposition for prenatal infection have uncovered distinctive holes in host defense associated with the reproductive process. Using these infections to probe the response during pregnancy, the immune suppressive regulatory subset of maternal CD4 T cells has been increasingly shown to dictate the inter-workings between prenatal infection susceptibility and pathogenesis of ensuing pregnancy complications. Herein, the recent literature suggesting a necessity for maternal regulatory T cells in pregnancy induced immunological shifts that sustain fetal tolerance is reviewed. Additional discussion is focused on how expansion of maternal regulatory T cell suppression may become exploited by pathogens that cause prenatal infection, and the perilous potential of infection induced immune activation that may mitigate fetal tolerance and inadvertently inject hostility into the protective in utero environment. PMID:23929902

  6. Toward understanding of rice innate immunity against Magnaporthe oryzae.

    PubMed

    Azizi, P; Rafii, M Y; Abdullah, S N A; Nejat, N; Maziah, M; Hanafi, M M; Latif, M A; Sahebi, M

    2016-02-01

    The blast fungus, Magnaporthe oryzae, causes serious disease on a wide variety of grasses including rice, wheat and barley. The recognition of pathogens is an amazing ability of plants including strategies for displacing virulence effectors through the adaption of both conserved and variable pathogen elicitors. The pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) were reported as two main innate immune responses in plants, where PTI gives basal resistance and ETI confers durable resistance. The PTI consists of extracellular surface receptors that are able to recognize PAMPs. PAMPs detect microbial features such as fungal chitin that complete a vital function during the organism's life. In contrast, ETI is mediated by intracellular receptor molecules containing nucleotide-binding (NB) and leucine rich repeat (LRR) domains that specifically recognize effector proteins produced by the pathogen. To enhance crop resistance, understanding the host resistance mechanisms against pathogen infection strategies and having a deeper knowledge of innate immunity system are essential. This review summarizes the recent advances on the molecular mechanism of innate immunity systems of rice against M. oryzae. The discussion will be centered on the latest success reported in plant-pathogen interactions and integrated defense responses in rice. PMID:25198435

  7. Strategic defense initiative: Folly or future

    SciTech Connect

    Haley, P.E.; Merritt, J.

    1986-01-01

    This collection of analyses is a guide through the maze of claims and criticisms about ''Star Wars,'' the controversial effort of the Reagan administration to reorient United States nuclear strategy to strategic defense. The text starts with an introduction by the editors followed by individual chapters outlining the strategic defense initiative as originally conceived and subsequently modified by the Reagan administration; the arguments for and against the plan's strategic and technical feasibility; and assessments of the harmful and constructive effects of strategic defense on U.S.-Soviet and U.S.-allied relations.

  8. Cascade defense via routing in complex networks

    NASA Astrophysics Data System (ADS)

    Xu, Xiao-Lan; Du, Wen-Bo; Hong, Chen

    2015-05-01

    As the cascading failures in networked traffic systems are becoming more and more serious, research on cascade defense in complex networks has become a hotspot in recent years. In this paper, we propose a traffic-based cascading failure model, in which each packet in the network has its own source and destination. When cascade is triggered, packets will be redistributed according to a given routing strategy. Here, a global hybrid (GH) routing strategy, which uses the dynamic information of the queue length and the static information of nodes' degree, is proposed to defense the network cascade. Comparing GH strategy with the shortest path (SP) routing, efficient routing (ER) and global dynamic (GD) routing strategies, we found that GH strategy is more effective than other routing strategies in improving the network robustness against cascading failures. Our work provides insight into the robustness of networked traffic systems.

  9. A sophisticated network of signaling pathways regulates stomatal defenses to bacterial pathogens.

    PubMed

    Arnaud, Dominique; Hwang, Ildoo

    2015-04-01

    Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. Stomata have been shown to play an important role in plant defense as a part of the innate immune response. Plants actively close their stomata upon contact with microbe