Sample records for immune defense strategies

  1. Immunizing Strategies and Epistemic Defense Mechanisms

    Microsoft Academic Search

    Maarten Boudry; Johan Braeckman

    2011-01-01

    An immunizing strategy is an argument brought forward in support of a belief system, though independent from that belief system, which makes it more or less invulnerable to rational argumentation and\\/or empirical evidence. By contrast,\\u000a an epistemic defense mechanism is defined as a structural feature of a belief system which has the same effect of deflecting arguments and evidence. We

  2. Body Defenses Immune System

    E-print Network

    Cochran-Stafira, D. Liane

    1 1 Body Defenses Immune System Part 2 2 Adaptive Immune Defenses When innate defenses have failed defenses respond to antigens Molecules the immune system recognizes as foreign to the body. Adaptive strongly to the body's own cells are eliminated in order to minimize an immune response against the body

  3. Dual strategy for immune defense in the land snail Cornu aspersum (Gastropoda, Pulmonata).

    PubMed

    Russo, Jacqueline; Madec, Luc

    2011-01-01

    Immune defenses have been shown to be heavily involved in the evolution of physiological trade-offs. In this study, we compared the internal defense systems in two subspecies of the land snail Cornu aspersum that exhibit contrasting life-history strategies. The "fast-living" Cornu aspersum subsp. aspersa is widespread throughout the world, especially in ecosystems disturbed by man, whereas natural populations of the giant Cornu aspersum subsp. maxima, characterized by a longer life span, are present only in north Africa. Snails were experimentally challenged with Escherichia coli; the measurements used to assess their internal defense for cell- and humoral-mediated immune responses were bacterial clearance, hemocyte density, reactive oxygen species (ROS) production, and plasma antibacterial activity. Both subspecies showed a similar ability to clear bacteria from their hemolymph; however, they varied in the robustness of different individual immune components. Cornu aspersum aspersa had higher ROS activity than did C. a. maxima and lower plasma bactericidal activity. These results suggest that ecological factors can sculpt the immune response. One interpretation is that shorter life span selects for immune defenses such as ROS that, although effective, can cause long-term damage. Such different immune patterns obviously entail various costs involved in the strong intraspecific variation of life-history trade-offs we previously observed. We also have to consider that such variation might be related to intraspecific differences in the relative strength of resistance and tolerance mechanisms. PMID:21460532

  4. Special issue on Avoidance, Resistance and Tolerance: Strategies in Host Defense Rethinking the role of immunity

    E-print Network

    the role of immunity: lessons from Hydra Thomas C.G. Bosch Zoological Institute, Christian our current understanding of the evolution of epithelial- based innate immunity in Hydra highlight growing evi- dence that the innate immune system with its host- specific antimicrobial peptides

  5. Innate Immune Defense Through RNA Interference

    NSDL National Science Digital Library

    Jorg H. Fritz (University of Toronto; Department of Immunology REV)

    2006-06-13

    RNA interference (RNAi, also known as RNA silencing) has recently emerged as a fundamental and widespread regulator of gene expression. New developments in this field implicate RNAi in the innate immune response to infection in plants and animals. Evidence from plants, tissue culture cells, and Caenorhabditis elegans–based systems previously suggested that RNAi plays a role in the defense against viral infection, but definitive evidence using viruses and whole animals has been lacking. Two recent reports now show that both Drosophila embryos and adult flies mount a substantial innate immune response to insect viruses that requires the RNAi machinery. This innate response is distinct from known bacterial and fungal defense systems provided by the Toll and immune deficiency (Imd) pathways, thus defining a previously unrecognized strategy to fight viral infection. Whether RNAi, aside from its function in counteracting viruses, is also used to fight bacterial infection remained enigmatic. New evidence, however, now shows that in Arabidopsis, the bacterial component, flagellin, induces the expression of a specific microRNA, which in turn leads to the down-regulation of the signaling pathways that are implicated in disease susceptibility. This down-regulation then increases the plant's resistance to infection. Whether RNAi mechanisms also exist for combating bacterial diseases in animals remains an intriguing question for future studies.

  6. Defensive strategies in rugby union.

    PubMed

    Hendricks, Sharief; Roode, Brad; Matthews, Bevan; Lambert, Michael

    2013-08-01

    Success in rugby union competition is dependent partly on the defensive strategies of a team. Despite this, little empirical evidence exists about effective defensive strategies used during play. This study attempted to identify defensive characteristics associated with increased likelihood of a successful outcome in rugby union, while considering the game situation. Twenty-one matches of the 2010 Super 14 competition were analysed, amounting to 2,394 coded tackle contacts. The likelihood of the defending team winning the breakdown (the post-tackle contact situation where opposing teams compete for possession of the ball) increased as the match progressed. Defensive speed, measured as the speed of the defence in response to the attacking line, was a statistically significant predictor of breakdown wins and preventing the attacking team from advancing towards the gain line. Identifying the relative effectiveness of such strategies allows understanding of rugby match behaviour and may be applied to improve organisation, design, training, teaching and learning the game. PMID:24422340

  7. Testicular defense systems: immune privilege and innate immunity

    PubMed Central

    Zhao, Shutao; Zhu, Weiwei; Xue, Shepu; Han, Daishu

    2014-01-01

    The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation. PMID:24954222

  8. 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.

  9. Mosquito immune defenses against Plasmodium infection

    PubMed Central

    Cirimotich, Chris M.; Dong, Yuemei; Garver, Lindsey S.; Sim, Shuzhen

    2012-01-01

    The causative agent of malaria, Plasmodium, has to undergo complex developmental transitions and survive attacks from the mosquito's innate immune system to achieve transmission from one host to another through the vector. Here we discuss recent findings on the role of the mosquito's innate immune signaling pathways in preventing infection by the Plasmodium parasite, the identification and mechanistic description of novel anti-parasite molecules, the role that natural bacteria harbored in the mosquito midgut might play in this immune defense, and the crucial parasite and vector molecules that mediate midgut infection. PMID:20026176

  10. Defense display strategy and roadmaps

    NASA Astrophysics Data System (ADS)

    Hopper, Darrel G.

    2002-08-01

    The Department of Defense (DoD) is developing a new strategy for displays. The new displays science and technology roadmap will incorporate urgent warfighter needs as well as investment opportunities where military advantage is foreseen. Thrusts now ending include the High Definition System (HDS) program and related initiatives, like flexible displays, at the Defense Advanced Research Projects Agency (DARPA). Continuing thrusts include a variety of Serviceled programs to develop micro-displays for virtual image helmet-/rifle-mounted systems for pilots and soldiers, novel displays, materials, and basic research. New thrusts are being formulated for ultra-resolution, true 3D, and intelligent displays (integration of computers and communication functions into screens). The new strategy is Service-led.

  11. Evolving meningococcal immunization strategies.

    PubMed

    Sáfadi, Marco Aurélio; Bettinger, Julie A; Maturana, Gabriela Moreno; Enwere, Godwin; Borrow, Ray

    2015-04-01

    Meningococcal disease is a major public health problem and immunization is considered the best strategy for prevention. The introduction of meningococcal C conjugate immunization schedules that targeted adolescents, with catch-up programs in several European countries, Australia and Canada proved to be highly effective, with dramatic reduction in the incidence of serogroup C disease, not only in vaccinated, but also in unvaccinated individuals. Meningococcal quadrivalent (A, C, W, Y) conjugate vaccines are now licensed and are being used in adolescent programs in North America and to control serogroup W disease in South America. In the African meningitis belt, a mass immunization campaign against serogroup A disease using a meningococcal A conjugate vaccine is now controlling the devastating epidemics of meningococcal disease. After introducing new immunization programs, it is of importance to maintain enhanced surveillance for a better understanding of the changing nature of disease epidemiology. This information is crucial for identifying optimal immunization policies. PMID:25494168

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

    PubMed

    Vogelweith, Fanny; Thiéry, Denis; Moret, Yannick; Colin, Eloïse; Motreuil, Sébastien; Moreau, Jérôme

    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

  13. Immune defense mechanisms of the dental pulp.

    PubMed

    Jontell, M; Okiji, T; Dahlgren, U; Bergenholtz, G

    1998-01-01

    Defense reactions of the dentin/pulp complex involve a variety of biological systems, in which the immune system plays a pivotal role. The knowledge of the organization and function of pulpal immunocompetent cells has been sparse, but in recent years a significant body of information of immune mechanisms in general has provided a footing for substantial new knowledge of the immune mechanisms of the dental pulp. The identification of pulpal dendritic cells (DCs) has generated research activities which have led to a concept of how an antigenic challenge may evoke a pulpal inflammatory response. Although DCs are not able to identify foreign antigens specifically, they provide necessary signals to activate T-lymphocytes which in turn will orchestrate other immunocompetent cells to mount the local immune defense of the dental pulp. The purpose of this review is to accent the organization and function of pulpal DCs and other tissue and cellular components and to provide a basis for how they may interact to instigate pulpal defense mechanisms. PMID:9603235

  14. 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

  15. Hyaluronan Breakdown Contributes to Immune Defense against Group A Streptococcus*

    E-print Network

    Nizet, Victor

    Hyaluronan Breakdown Contributes to Immune Defense against Group A Streptococcus* Received, La Jolla, California 92093 Background: The role of hyaluronan catabolism in group A Streptococcus be a previously unrecognized mechanism for host defense. Group A Streptococcus (GAS) commonly infects human skin

  16. 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.…

  17. 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

  18. 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

  19. A Chromosome-based Evaluation Model for Computer Defense Immune Systems

    E-print Network

    McKay, Robert Ian

    - 1 - A Chromosome-based Evaluation Model for Computer Defense Immune Systems Zejun Wu, Hongbin,hbdong}@whu.edu.cn rim@cs.adfa.edu.au Abstract- The Computer Defense Immune System (CDIS) is an artificial immune system on systems in which they were incorporated. 1 Introduction The Computer Defense Immune System (CDIS

  20. A recent perspective on alcohol, immunity and host defense

    PubMed Central

    Szabo, Gyongyi; Mandrekar, Pranoti

    2013-01-01

    Overview Multiple line of clinical and experimental evidence demonstrates that both acute, moderate and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system. Altered inflammatory cell and adaptive immune responses in turn result in increased incidence and poor outcome of infections and other organ effects after alcohol use. This review article summarizes recent findings relevant to immunomodulation by alcohol and its consequences on host defense against microbial pathogens and tissue injury. PMID:19053973

  1. Immune Building Technology and Bioterrorism Defense

    NSDL National Science Digital Library

    Bahnfleth, William P. (William Parry), 1957-

    In the wake of the 2001 anthrax scare, a research project at Pennsylvania State University has garnered significant attention. This paper introduces immune buildings, which have advanced ventilation and air filtration systems that can mitigate the danger caused by airborne pathogens. Experimental results from the project are also presented.

  2. 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...

  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. Mucosal immunity: its role in defense and allergy.

    PubMed

    Tlaskalová-Hogenová, Helena; Tucková, Ludmila; Lodinová-Zádniková, Rája; Stepánková, Renata; Cukrowska, Bozena; Funda, David P; Striz, Ilja; Kozáková, Hana; Trebichavský, Ilja; Sokol, Dan; Reháková, Zuzana; Sinkora, Jirí; Fundová, Petra; Horáková, Dana; Jelínková, Lenka; Sánchez, Daniel

    2002-06-01

    The interface between the organism and the outside world, which is the site of exchange of nutrients, export of products and waste components, must be selectively permeable and at the same time, it must constitute a barrier equipped with local defense mechanisms against environmental threats (e.g. invading pathogens). The boundaries with the environment (mucosal and skin surfaces) are therefore covered with special epithelial layers which support this barrier function. The immune system, associated with mucosal surfaces covering the largest area of the body (200-300 m(2)), evolved mechanisms discriminating between harmless antigens and commensal microorganisms and dangerous pathogens. The innate mucosal immune system, represented by epithelial and other mucosal cells and their products, is able to recognize the conserved pathogenic patterns on microbes by pattern recognition receptors such as Toll-like receptors, CD14 and others. As documented in experimental gnotobiotic models, highly protective colonization of mucosal surfaces by commensals has an important stimulatory effect on postnatal development of immune responses, metabolic processes (e.g. nutrition) and other host activities; these local and systemic immune responses are later replaced by inhibition, i.e. by induction of mucosal (oral) tolerance. Characteristic features of mucosal immunity distinguishing it from systemic immunity are: strongly developed mechanisms of innate defense, the existence of characteristic populations of unique types of lymphocytes, colonization of the mucosal and exocrine glands by cells originating from the mucosal organized tissues ('common mucosal system') and preferential induction of inhibition of the responses to nondangerous antigens (mucosal tolerance). Many chronic diseases, including allergy, may occur as a result of genetically based or environmentally induced changes in mechanisms regulating mucosal immunity and tolerance; this leads to impaired mucosal barrier function, disturbed exclusion and increased penetration of microbial, food or airborne antigens into the circulation and consequently to exaggerated and generalized immune responses to mucosally occurring antigens, allergens, superantigens and mitogens. PMID:12065907

  5. 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.

  6. Border maneuvers: deployment of mucosal immune defenses against Toxoplasma gondii.

    PubMed

    Cohen, S B; Denkers, E Y

    2014-07-01

    Toxoplasma gondii is a highly prevalent protozoan pathogen that is transmitted through oral ingestion of infectious cysts. As such, mucosal immune defenses in the intestine constitute the first and arguably most important line of resistance against the parasite. The response to infection is now understood to involve complex three-way interactions between Toxoplasma, the mucosal immune system, and the host intestinal microbiota. Productive outcome of these interactions ensures resolution of infection in the intestinal mucosa. Nonsuccessful outcome may result in emergence of proinflammatory damage that can spell death for the host. Here, we discuss new advances in our understanding of the mechanisms underpinning these disparate outcomes, with particular reference to initiators, effectors, and regulators of mucosal immunity stimulated by Toxoplasma in the intestine. PMID:24717355

  7. Antiviral defense in shrimp: from innate immunity to viral infection.

    PubMed

    Wang, Pei-Hui; Huang, Tianzhi; Zhang, Xiaobo; He, Jian-Guo

    2014-08-01

    The culture of penaeid shrimp is rapidly developing as a major business endeavor worldwide. However, viral diseases have caused huge economic loss in penaeid shrimp culture industries. Knowledge of shrimp innate immunity and antiviral responses has made important progress in recent years, allowing the design of better strategies for the prevention and control of shrimp diseases. In this study, we have updated information on shrimp antiviral immunity and interactions between shrimp hosts and viral pathogens. Current knowledge and recent progress in immune signaling pathways (e.g., Toll/IMD-NF-?B and JAK-STAT signaling pathways), RNAi, phagocytosis, and apoptosis in shrimp antiviral immunity are discussed. The mechanism of viral infection in shrimp hosts and the interactions between viruses and shrimp innate immune systems are also analyzed. PMID:24886688

  8. 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.

  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. Thermoregulatory strategy may shape immune investment in Drosophila melanogaster.

    PubMed

    Kutch, Ian C; Sevgili, Hasan; Wittman, Tyler; Fedorka, Kenneth M

    2014-10-15

    As temperatures change, insects alter the amount of melanin in their cuticle to improve thermoregulation. However, melanin is also central to insect immunity, suggesting that thermoregulatory strategy may indirectly impact immune defense by altering the abundance of melanin pathway components (a hypothesis we refer to as thermoregulatory-dependent immune investment). This may be the case in the cricket Allonemobius socius, where warm environments (both seasonal and geographical) produced crickets with lighter cuticles and increased pathogen susceptibility. Unfortunately, the potential for thermoregulatory strategy to influence insect immunity has not been widely explored. Here we address the relationships between temperature, thermoregulatory strategy and immunity in the fruit fly Drosophila melanogaster. To this end, flies from two separate Canadian populations were reared in either a summer- or autumn-like environment. Shortly after adult eclosion, flies were moved to a common environment where their cuticle color and susceptibility to a bacterial pathogen (Pseudomonas aeruginosa) were measured. As with A. socius, individuals from summer-like environments exhibited lighter cuticles and increased pathogen susceptibility, suggesting that the thermoregulatory-immunity relationship is evolutionarily conserved across the hemimetabolous and holometabolous clades. If global temperatures continue to rise as expected, then thermoregulation might play an important role in host infection and mortality rates in systems that provide critical ecosystem services (e.g. pollination), or influence the prevalence of insect-vectored disease (e.g. malaria). PMID:25147243

  11. Racquetball Beginner Strategies: Reading the Defense

    ERIC Educational Resources Information Center

    Strand, Brad; Albrecht, Jay; Traschel, Jamie

    2007-01-01

    Racquetball is a constant game of cat and mouse, creating a situation where players make a transition between offensive and defensive play, or trap themselves in a game of uncertainty and misdirection because they do understand some basic racquetball fundamentals. A first step in learning the sport of racquetball is to understand terminology. This…

  12. Garland Science 2009 The concept of an immune system-the defense of

    E-print Network

    Utrecht, Universiteit

    6/29/11 1 © Garland Science 2009 · The concept of an immune system-the defense of the individual. As a consequence we will focuss on the evolution of an immune system in multicellular organisms © Garland Science 2009 · The evolution of the immune system can be studied by comparing the genes expressed

  13. Innate immunity probed by lipopolysaccharides affinity strategy and proteomics.

    PubMed

    Giangrande, Chiara; Colarusso, Lucia; Lanzetta, Rosa; Molinaro, Antonio; Pucci, Piero; Amoresano, Angela

    2013-01-01

    Lipopolysaccharides (LPSs) are ubiquitous and vital components of the cell surface of Gram-negative bacteria that have been shown to play a relevant role in the induction of the immune-system response. In animal and plant cells, innate immune defenses toward microorganisms are triggered by the perception of pathogen associated molecular patterns. These are conserved and generally indispensable microbial structures such as LPSs that are fundamental in the Gram-negative immunity recognition. This paper reports the development of an integrated strategy based on lipopolysaccharide affinity methodology that represents a new starting point to elucidate the molecular mechanisms elicited by bacterial LPS and involved in the different steps of innate immunity response. Biotin-tagged LPS was immobilized on streptavidin column and used as a bait in an affinity capture procedure to identify protein partners from human serum specifically interacting with this effector. The complex proteins/lipopolysaccharide was isolated and the protein partners were fractionated by gel electrophoresis and identified by mass spectrometry. This procedure proved to be very effective in specifically binding proteins functionally correlated with the biological role of LPS. Proteins specifically bound to LPS essentially gathered within two functional groups, regulation of the complement system (factor H, C4b, C4BP, and alpha 2 macroglobulin) and inhibition of LPS-induced inflammation (HRG and Apolipoproteins). The reported strategy might have important applications in the elucidation of biological mechanisms involved in the LPSs-mediated molecular recognition and anti-infection responses. PMID:22752448

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

    PubMed Central

    Pigeon, Gabriel; Bélisle, 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

  15. Accessory cells in the immune defense of the dental pulp.

    PubMed

    Jontell, M; Bergenholtz, G

    1992-01-01

    This communication focuses on the participation of accessory cells in the initial recognition and processing of antigenic substances in the dental pulp. Immunohistochemical analyses have demonstrated the presence of two types of accessory cells--one with a dendritic morphology located in the periphery of the pulp and one with a macrophage-like appearance located more centrally. Functional studies in vitro have provided evidence for the dendritic cells being the most significant of the two cells regarding their capacity to induce T-cell proliferation. Studies on ontogeny have revealed that the appearance of pulp accessory cells is delayed compared to other peripheral tissues. In experimentally induced pulp lesions a rapid increase of cells with morphologic and phenotypic features similar to normally occurring accessory cells was found. These data demonstrate that the dental pulp contains the necessary cellular constituents to mount an immunologic defense reaction. Future studies should focus on elucidating possible interactions between these immune cells and the neurovascular system of the pulp. PMID:1508890

  16. Impaired immune defense in hemodialysis patients: role of ?-defensins?

    PubMed

    Grupp, Clemens; Troche-Polzien, Ilka; Noeding, Christian; Mueller, Claudia A; Mueller, Gerhard A

    2014-04-01

    The mechanisms underlying the impaired immune response in hemodialysis (HD) patients are not completely understood. The ?-defensins human neutrophil peptides-1, 2, and 3 are low molecular weight peptides with antimicrobial activity and important effector molecules of innate immune responses. We now examined the expression of these peptides in HD patients. Seventy-six patients on chronic HD treatment (mean time on HD 5.8 years; mean age 70 years) were studied and compared with 38 healthy volunteers and 20 patients with infections and normal renal function. Expression of ?-defensins was analyzed semiquantitatively in leukocytes on the messenger RNA (mRNA) level by reverse transcriptase polymerase chain reaction; the ?-defensin protein levels in serum were detected by enzyme-linked immunosorbent assay. ?-Defensin concentrations (140 ± 10.5 ng/mL; mean ± standard error of the mean) as well as mRNA levels in leukocytes (82.9 ± 7.9 arbitrary units [a.u.]) in HD patients were not significantly different from those in healthy volunteers (156 ± 15.2 ng/mL; 81.4 ± 11.3 a.u.). Defensin levels were independent of the time of the patient on HD and their age. During infection periods (mean increase of the C-reactive protein to 161 ± 17.3 mg/L), defensin serum levels increased to 321 ± 65 ng/mL (P < 0.005) and mRNA expression in leukocytes to 159 ± 19.2 a.u. (P < 0.05). These increases were not significantly different from those in patients with normal renal function (298 ± 46.8 ng/mL and 128 ± 9.1 a.u., respectively) suffering from infections (C-reactive protein 222 ± 26.6 mg/L). Our results suggest that the impaired immune defense in dialysis patients is not due to a deficiency in ?-defensins in these patients as neither basal levels nor expression during infections were reduced compared with subjects with normal renal function. PMID:24341412

  17. ALD1 Regulates Basal Immune Components and Early Inducible Defense Responses in Arabidopsis.

    PubMed

    Cecchini, Nicolás M; Jung, Ho Won; Engle, Nancy L; Tschaplinski, Timothy J; Greenberg, Jean T

    2015-04-01

    Robust immunity requires basal defense machinery to mediate timely responses and feedback cycles to amplify defenses against potentially spreading infections. AGD2-LIKE DEFENSE RESPONSE PROTEIN 1 (ALD1) is needed for the accumulation of the plant defense signal salicylic acid (SA) during the first hours after infection with the pathogen Pseudomonas syringae and is also upregulated by infection and SA. ALD1 is an aminotransferase with multiple substrates and products in vitro. Pipecolic acid (Pip) is an ALD1-dependent bioactive product induced by P. syringae. Here, we addressed roles of ALD1 in mediating defense amplification as well as the levels and responses of basal defense machinery. ALD1 needs immune components PAD4 and ICS1 (an SA synthesis enzyme) to confer disease resistance, possibly through a transcriptional amplification loop between them. Furthermore, ALD1 affects basal defense by controlling microbial-associated molecular pattern (MAMP) receptor levels and responsiveness. Vascular exudates from uninfected ALD1-overexpressing plants confer local immunity to the wild type and ald1 mutants yet are not enriched for Pip. We infer that, in addition to affecting Pip accumulation, ALD1 produces non-Pip metabolites that play roles in immunity. Thus, distinct metabolite signals controlled by the same enzyme affect basal and early defenses versus later defense responses, respectively. PMID:25372120

  18. 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

  19. Strategy and the defense dilemma: nuclear policies and alliance politics

    Microsoft Academic Search

    Garvey

    1984-01-01

    Focusing on the emerging dilemmas of US defense, foreign and international economic policies, Professor Garvey calls for a realignment of military alliance strategies consistent with the new realities. He describes the nature of the US's dilemmas and posits the need for decoupling and relinking various facets of American strategic policy that will emphasize Asia and the relationship between commercial and

  20. Plagiarizing Smartphone Applications: Attack Strategies and Defense Techniques

    E-print Network

    Nita-Rotaru, Cristina

    can launch malware onto a large number of smartphone users by plagiarizing Android appli- cationsPlagiarizing Smartphone Applications: Attack Strategies and Defense Techniques Rahul Potharaju,000 smartphone applications meta- information indicates that 29.4% of the applications are more likely

  1. Defensive strategy framework in global markets : A mental models approach

    Microsoft Academic Search

    Fahri Karakaya; Peter Yannopoulos

    2010-01-01

    Purpose – The purpose of this study is to develop a conceptual framework for defensive strategy by integrating market entry modes and the typology of firms suggested by Day and Nedungandi, and to attempt to propose how local incumbent firms utilize their mental models in order to react against market entry of new competition in global markets. Design\\/methodology\\/approach – The

  2. 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

  3. Agent-Based Modeling Approach of Immune Defense Against Spores of Opportunistic Human Pathogenic Fungi

    PubMed Central

    Tokarski, Christian; Hummert, Sabine; Mech, Franziska; Figge, Marc Thilo; Germerodt, Sebastian; Schroeter, Anja; Schuster, Stefan

    2012-01-01

    Opportunistic human pathogenic fungi like the ubiquitous fungus Aspergillus fumigatus are a major threat to immunocompromised patients. An impaired immune system renders the body vulnerable to invasive mycoses that often lead to the death of the patient. While the number of immunocompromised patients is rising with medical progress, the process, and dynamics of defense against invaded and ready to germinate fungal conidia are still insufficiently understood. Besides macrophages, neutrophil granulocytes form an important line of defense in that they clear conidia. Live imaging shows the interaction of those phagocytes and conidia as a dynamic process of touching, dragging, and phagocytosis. To unravel strategies of phagocytes on the hunt for conidia an agent-based modeling approach is used, implemented in NetLogo. Different modes of movement of phagocytes are tested regarding their clearing efficiency: random walk, short-term persistence in their recent direction, chemotaxis of chemokines excreted by conidia, and communication between phagocytes. While the short-term persistence hunting strategy turned out to be superior to the simple random walk, following a gradient of chemokines released by conidial agents is even better. The advantage of communication between neutrophilic agents showed a strong dependency on the spatial scale of the focused area and the distribution of the pathogens. PMID:22557995

  4. Phylogenetic escalation and decline of plant defense strategies.

    PubMed

    Agrawal, Anurag A; Fishbein, Mark

    2008-07-22

    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

  5. 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

  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. Defense strategies and insurance coverage issues in a Superfund case

    SciTech Connect

    Kaplan, H.L.; Balloun, J.E.; Stigall, S.R.

    1986-10-01

    The handling of Comprehensive Environmental Response Compensation and Liability Act (CERCLA) litigation introduces a new challenge to defense attorneys and insurance claims personnel. The authors focus on those aspects of the CERCLA case which are unique in comparison to other property damage or personal injury litigation, and discuss the effect upon defense strategies and insurance coverage issues. They note in conclusion that alternative claims are often raised by the government based upon other federal and state statutes and common law. Private individuals may also file a separate but related suit.

  9. 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 plant–pathogen 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 plant’s 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

  10. Microbial Symbiosis with the Innate Immune Defense System of the Skin

    Microsoft Academic Search

    Richard L Gallo; Teruaki Nakatsuji

    2011-01-01

    Skin protects itself against infection through a variety of mechanisms. Antimicrobial peptides (AMPs) are major contributors to cutaneous innate immunity, and this system, combined with the unique ionic, lipid, and physical barrier of the epidermis, is the first-line defense against invading pathogens. However, recent studies have revealed that our skin's innate immune system is not solely of human origin. Staphylococcus

  11. Regulation of actin dynamics by protein kinase R control of gelsolin enforces basal innate immune defense.

    PubMed

    Irving, Aaron T; Wang, Die; Vasilevski, Oliver; Latchoumanin, Olivier; Kozer, Noga; Clayton, Andrew H A; Szczepny, Anette; Morimoto, Hiroyuki; Xu, Dakang; Williams, Bryan R G; Sadler, Anthony J

    2012-05-25

    Primary resistance to pathogens is reliant on both basal and inducible immune defenses. To date, research has focused upon inducible innate immune responses. In contrast to resistance via cytokine induction, basal defense mechanisms are less evident. Here we showed that the antiviral protein kinase R (PKR) inhibited the key actin-modifying protein gelsolin to regulate actin dynamics and control cytoskeletal cellular functions under homeostatic conditions. Through this mechanism, PKR controlled fundamental innate immune, actin-dependent processes that included membrane ruffling and particle engulfment. Accordingly, PKR counteracted viral entry into the cell. These findings identify a layer of host resistance, showing that the regulation of actin-modifying proteins during the innate immune response bolsters first-line defense against intracellular pathogens and has a sustained effect on virus production. Moreover, these data provide proof of principle for a concept in which the cell cytoskeleton could be targeted to elicit broad antiviral protection. PMID:22633459

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

    PubMed

    Dandekar, Abhaya M; Gouran, Hossein; Ibáñez, Ana María; Uratsu, Sandra L; Agüero, 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

  13. 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 protein–protein 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

  14. 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

  15. Neonatal Natural Killer Cell Function: Relevance to Antiviral Immune Defense

    PubMed Central

    Lee, Yen-Chang; Lin, Syh-Jae

    2013-01-01

    Neonates are particularly susceptible to various pathogens compared to adults, which is attributed in part to their immature innate and adaptive immunity. Natural killer cells provide first-line innate immune reactions against virus-infected cells without prior sensitization. This review updates phenotypic and functional deficiencies of neonatal cells compared to their adult counterparts and their clinical implications. PMID:24066005

  16. 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

  17. Optimal defensive coloration strategies during the growth period of prey.

    PubMed

    Higginson, Andrew D; Ruxton, Graeme D

    2010-01-01

    Defensive coloration that reduces the risk of predation is considered to be widespread in animals. Many closely related species adopt differing coloration strategies during the life cycle, including crypsis, conspicuousness, and ontogenic change between the two coloration types. Here, we use a dynamic state-dependent approach to use ecological and intrinsic factors to predict the proportion of the developmental period of immature animals that should be spent as cryptic or conspicuous, and when conspicuous coloration should be reliably associated with investment in defenses. The model predicts that animals should change color more than once during development only in specific circumstances. In contrast, change from crypsis to conspicuous can occur over a range of conditions related to the frequency of detection by predators, but may also depend on the opportunity costs of crypsis and the effect of size on the deterrent effect of conspicuous coloration. We also report the results of a survey of coloration strategies in lepidopteron larvae, and note a qualitative agreement with the predictions of our model in the relationship between body size and coloration strategy. Our results provide explanations for several widespread antipredator coloration phenomena in prey animals, and provide a comprehensive predictive framework for the types of coloration strategies that are employed in nature. PMID:19674097

  18. Mucosal Immunity: Its Role in Defense and Allergy

    Microsoft Academic Search

    Helena Tlaskalová-Hogenová; Bozena Cukrowska; David P. Funda; Hana Kozáková; Ilja Trebichavský; Dan Sokol; Petra Fundová; Dana Horáková; Lenka Jelínková; Daniel Sánchez

    2002-01-01

    The interface between the organism and the outside world, which is the site of exchange of nutrients, export of products and waste components, must be selectively permeable and at the same time, it must constitute a barrier equipped with local defense mechanisms against environmental threats (e.g. invading pathogens). The boundaries with the environment (mucosal and skin surfaces) are therefore covered

  19. An alternative to present United States defense strategy

    E-print Network

    Anthony, William Wallace

    1971-01-01

    country, as a site for a strong deterrence as a feature of nuclear strategy and defense policy. An evaluation of the advantages of such an area, relative to the joint installation and control oi fixed intercontinental missiles, is considered... OF THE U. S. AND NATO: 1HL" EVOLU1IQN OF S1RATEGY POLICY AN ALTERNATIVE STRATZGY FOR THE UNITED SlATZS The Survival Potential of Nations Involved in Conventional Military Action Rate of Growth of American and Russian Nuclear Missile Weapons Types...

  20. 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

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

    PubMed Central

    Fábián, Tibor Károly; Hermann, Péter; Beck, Anita; Fejérdy, Pál; Fábián, Gábor

    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. Innate immunity and antimicrobial defense systems in psoriasis

    Microsoft Academic Search

    Amanda S. Büchau; Richard L. Gallo

    2007-01-01

    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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Innate immune evasion strategies of influenza viruses

    PubMed Central

    Hale, Benjamin G; Albrecht, Randy A; García-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 virus–host 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

  9. An analysis of defensive strategies used by home and away basketball teams.

    PubMed

    Gómez, Miguel A; Lorenzo, Alberto; Ibáñez, Sergio J; Ortega, Enrique; Leite, Nuno; Sampaio, Jaime

    2010-02-01

    The aim of the present study was to identify differences in defensive strategies used during basketball games, to compare the defensive strategies used by home and away basketball teams, and to analyze the effectiveness of home and away ball possessions when playing against each defensive strategy. The sample was composed of 10 games of the Spanish men's 2005-2006 regular basketball season (N = 1,785 ball possessions). The analyzed variables were the number of types of defenses used, points per possession, foul percentage, and turnover percentage according to the type of defensive strategy and game location. The game location main effect was significant in points per possession, with home teams having lower values than away teams. The defensive strategy main effect was significant in number of types of defenses used, with man-to-man as the most frequently utilized defense, and foul percentages with higher values in zone defenses. There was a statistically significant interaction in turnover percentages, with significantly lower values for man-to-man defense and home games. Overall, it is suggested that team performance for the studied variables changed according to the factors and, thus, it may be beneficial to change defensive (and offensive) strategies according to game location. PMID:20391881

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

    PubMed Central

    Våge, 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

  11. Physiological integration of roots and shoots in plant defense strategies links above-and belowground

    E-print Network

    Ginzel, Matthew

    in the genus Nicotiana employ alkaloids (e.g. nicotine) as a constitutive and inducible defense against leaf Roots play a critical, but largely unappreciated, role in aboveground anti-herbivore plant defense (eLETTER Physiological integration of roots and shoots in plant defense strategies links above

  12. 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

  13. Oil and related toxicant effects on mallard immune defenses

    SciTech Connect

    Rocke, T.E.; Yuill, T.M.; Hinsdill, R.D.

    1984-04-01

    A crude oil, a petroleum distillate, and chemically dispersed oil were tested for their effects on resistance to bacterial infection and the immune response in waterfowl. Sublethal oral doses for mallards were determined for South Louisiana crude oil, Bunker C fuel oil a dispersant-Corexit 9527, and oil/Corexit combinations by gizzard intubation. Resistance to bacterial challange (Pasteurella multocida) was significantly lowered in mallards receiving 2.5 or 4.0 ml/kg of Bunker C fuel oil, 4.0 ml/kg of South Louisiana crude oil, and 4.0 ml/kg of a 50:1 Bunker C fuel oil/Corexit mixture daily for 28 days. Ingestion of oil or oil/Corexit mixtures had no effect on mallard antibody-producing capability as measured by the direct spleen plaque-forming assay.

  14. ECOLOGICAL IMMUNOLOGY Fitness consequences of immune responses

    E-print Network

    Obbard, Darren

    ECOLOGICAL IMMUNOLOGY Fitness consequences of immune responses: strengthening the empirical fitness consequences of different strategies for immune defense. 2. Measuring the fitness consequences of immune responses is difficult, partly because of com- plex relationships between host fitness

  15. Bacterial strategies for overcoming host innate and adaptive immune responses

    Microsoft Academic Search

    Mathias W. Hornef; Mary Jo Wick; Mikael Rhen; Staffan Normark

    2002-01-01

    In higher organisms a variety of host defense mechanisms control the resident microflora and, in most cases, effectively prevent invasive microbial disease. However, it appears that microbial organisms have coevolved with their hosts to overcome protective host barriers and, in selected cases, actually take advantage of innate host responses. Many microbial pathogens avoid host recognition or dampen the subsequent immune

  16. Nonsense-mediated mRNA decay modulates immune receptor levels to regulate plant antibacterial defense.

    PubMed

    Gloggnitzer, Jiradet; Akimcheva, Svetlana; Srinivasan, Arunkumar; Kusenda, Branislav; Riehs, Nina; Stampfl, Hansjörg; Bautor, Jaqueline; Dekrout, Bettina; Jonak, Claudia; Jiménez-Gómez, José M; Parker, Jane E; Riha, Karel

    2014-09-10

    Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic RNA surveillance mechanism that degrades aberrant mRNAs. NMD impairment in Arabidopsis is linked to constitutive immune response activation and enhanced antibacterial resistance, but the underlying mechanisms are unknown. Here we show that NMD contributes to innate immunity in Arabidopsis by controlling the turnover of numerous TIR domain-containing, nucleotide-binding, leucine-rich repeat (TNL) immune receptor-encoding mRNAs. Autoimmunity resulting from NMD impairment depends on TNL signaling pathway components and can be triggered through deregulation of a single TNL gene, RPS6. Bacterial infection of plants causes host-programmed inhibition of NMD, leading to stabilization of NMD-regulated TNL transcripts. Conversely, constitutive NMD activity prevents TNL stabilization and impairs plant defense, demonstrating that host-regulated NMD contributes to disease resistance. Thus, NMD shapes plant innate immunity by controlling the threshold for activation of TNL resistance pathways. PMID:25211079

  17. An Application Based on Spatial-Relationship to Basketball Defensive Strategies

    Microsoft Academic Search

    Su-li Chin; Chun-hong Huang; Chia-tong Tang; Jason C. Hung

    2005-01-01

    \\u000a This paper aims to develop a simulated system used for teaching and training basketball defensive strategies.  Respectively,\\u000a defensive strategies can be described within one method by editing video recorded from basketball games into desired clips\\u000a for analysis and storing them into the database. In this paper, we used Spatial-Temporal Relationships to describe the local\\u000a defensive movements by the basketball players

  18. An experimental heat wave changes immune defense and life history traits in a freshwater snail

    PubMed Central

    Leicht, Katja; Jokela, Jukka; Seppälä, Otto

    2013-01-01

    The predicted increase in frequency and severity of heat waves due to climate change is expected to alter disease dynamics by reducing hosts' ability to resist infections. This could take place via two different mechanisms: (1) through general reduction in hosts' performance under harsh environmental conditions and/or (2) through altered resource allocation that reduces expression of defense traits in order to maintain other traits. We tested these alternative hypotheses by measuring the effect of an experimental heat wave (25 vs. 15°C) on the constitutive level of immune defense (hemocyte concentration, phenoloxidase [PO]-like activity, antibacterial activity of hemolymph), and life history traits (growth and number of oviposited eggs) of the great pond snail Lymnaea stagnalis. We also manipulated the exposure time to high temperature (1, 3, 5, 7, 9, or 11 days). We found that if the exposure to high temperature lasted <1 week, immune function was not affected. However, when the exposure lasted longer than that, the level of snails' immune function (hemocyte concentration and PO-like activity) was reduced. Snails' growth and reproduction increased within the first week of exposure to high temperature. However, longer exposures did not lead to a further increase in cumulative reproductive output. Our results show that short experimental heat waves do not alter immune function but lead to plastic responses that increase snails' growth and reproduction. Thus, although the relative expression of traits changes, short experimental heat waves do not impair snails' defenses. Negative effects on performance get pronounced when the heat waves are prolonged suggesting that high performance cannot be maintained over long time periods. This ultimately reduces the levels of defense traits. PMID:24455121

  19. Community-based Immunization Strategies for Epidemic Control

    E-print Network

    Gupta, Naveen; Cherifi, Hocine

    2014-01-01

    Understanding the epidemic dynamics, and finding out efficient techniques to control it, is a challenging issue. A lot of research has been done on targeted immunization strategies, exploiting various global network topological properties. However, in practice, information about the global structure of the contact network may not be available. Therefore, immunization strategies that can deal with a limited knowledge of the network structure are required. In this paper, we propose targeted immunization strategies that require information only at the community level. Results of our investigations on the SIR epidemiological model, using a realistic synthetic benchmark with controlled community structure, show that the community structure plays an important role in the epidemic dynamics. An extensive comparative evaluation demonstrates that the proposed strategies are as efficient as the most influential global centrality based immunization strategies, despite the fact that they use a limited amount of informatio...

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

    PubMed

    Thomas, François; 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. Increased activity correlates with reduced ability to mount immune defenses to endotoxin in zebra finches.

    PubMed

    Lopes, Patricia C; Springthorpe, Dwight; Bentley, George E

    2014-10-01

    When suffering from infection, animals experience behavioral and physiological alterations that potentiate the immune system's ability to fight pathogens. The behavioral component of this response, termed "sickness behavior," is characterized by an overall reduction in physical activity. A growing number of reports demonstrate substantial flexibility in these sickness behaviors, which can be partially overcome in response to mates, intruders and parental duties. Since it is hypothesized that adopting sickness behaviors frees energetic resources for mounting an immune response, we tested whether diminished immune responses coincided with reduced sickness behaviors by housing male zebra finches (Taeniopygia guttata) in social conditions that alter their behavioral response to an endotoxin. To facilitate our data collection, we developed and built a miniaturized sensor capable of detecting changes in dorsoventral acceleration and categorizing them as different behaviors when attached to the finches. We found that the immune defenses (quantified as haptoglobin-like activity, ability to change body temperature and bacterial killing capacity) increased as a function of increased time spent resting. The findings indicate that when animals are sick attenuation of sickness behaviors may exact costs, such as reduced immune function. The extent of these costs depends on how relevant the affected components of immunity are for fighting a specific infection. PMID:24888267

  3. Immune regulatory activities of fowlicidin-1, a cathelicidin host defense peptide.

    PubMed

    Bommineni, Yugendar R; Pham, Giang H; Sunkara, Lakshmi T; Achanta, Mallika; Zhang, Guolong

    2014-05-01

    Appropriate modulation of immunity is beneficial in antimicrobial therapy and vaccine development. Host defense peptides (HDPs) constitute critically important components of innate immunity with both antimicrobial and immune regulatory activities. We previously showed that a chicken HDP, namely fowlicidin-1(6-26), has potent antibacterial activities in vitro and in vivo. Here we further revealed that fowl-1(6-26) possesses strong immunomodulatory properties. The peptide is chemotactic specifically to neutrophils, but not monocytes or lymphocytes, after injected into the mouse peritoneum. Fowl-1(6-26) also has the capacity to activate macrophages by inducing the expression of inflammatory mediators including IL-1?, CCL2, and CCL3. However, unlike bacterial lipopolysaccharide that triggers massive production of inflammatory cytokines and chemokines, fowl-1(6-26) only marginally increased their expression in mouse RAW264.7 macrophages. Additionally, fowl-1(6-26) enhanced the surface expression of MHC II and CD86 on RAW264.7 cells, suggesting that it may facilitate development of adaptive immune response. Indeed, co-immunization of mice with chicken ovalbumin (OVA) and fowl-1(6-26) augmented both OVA-specific IgG1 and IgG2a titers, relative to OVA alone. We further showed that fowl-1(6-26) is capable of preventing a methicillin-resistant Staphylococcus aureus (MRSA) infection due to its enhancement of host defense. All mice survived from an otherwise lethal infection when the peptide was administered 1-2 days prior to MRSA infection, and 50% mice were protected if receiving the peptide 4 days before infection. Taken together, with a strong capacity to stimulate innate and adaptive immunity, fowl-1(6-26) may have potential to be developed as a novel antimicrobial and a vaccine adjuvant. PMID:24491488

  4. Cell death and immunityApoptosis as an HIV strategy to escape immune attack

    Microsoft Academic Search

    Marie-Lise Gougeon

    2003-01-01

    Viruses have evolved numerous mechanisms to evade the host immune system and one of the strategies developed by HIV is to activate apoptotic programmes that destroy immune effectors. Not only does the HIV genome encode pro-apoptotic proteins, which kill both infected and uninfected lymphocytes through either members of the tumour-necrosis factor family or the mitochondrial pathway, but it also creates

  5. In defense of phage: viral suppressors of CRISPR-mediated adaptive immunity in bacteria.

    PubMed

    Wiedenheft, Blake

    2013-05-01

    Viruses that infect bacteria are the most abundant biological agents on the planet and bacteria have evolved diverse defense mechanisms to combat these genetic parasites. One of these bacterial defense systems relies on a repetitive locus, referred to as a CRISPR (clusters of regularly interspaced short palindromic repeats). Bacteria and archaea acquire resistance to invading viruses and plasmids by integrating short fragments of foreign nucleic acids at one end of the CRISPR locus. CRISPR loci are transcribed and the long primary CRISPR transcript is processed into a library of small RNAs that guide the immune system to invading nucleic acids, which are subsequently degraded by dedicated nucleases. However, the development of CRISPR-mediated immune systems has not eradicated phages, suggesting that viruses have evolved mechanisms to subvert CRISPR-mediated protection. Recently, Bondy-Denomy and colleagues discovered several phage-encoded anti-CRISPR proteins that offer new insight into the ongoing molecular arms race between viral parasites and the immune systems of their hosts. PMID:23392292

  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. 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

  8. Finding a Better Immunization Strategy Yiping Chen,1

    E-print Network

    Stanley, H. Eugene

    networks. We present a newly developed graph-partitioning strategy which requires 5% to 50% fewer [3,4]. In this Letter we propose a novel ``equal graph partition- ing (EGP)'' immunization strategy network structures have been studied, such as Erdos-Re´nyi (ER) networks [9,10] and random regular graphs

  9. Immune evasion strategies of molluscum contagiosum virus.

    PubMed

    Shisler, Joanna L

    2015-01-01

    Molluscum contagiosum virus (MCV) is the causative agent of molluscum contagiosum (MC), the third most common viral skin infection in children, and one of the five most prevalent skin diseases worldwide. No FDA-approved treatments, vaccines, or commercially available rapid diagnostics for MCV are available. This review discusses several aspects of this medically important virus including: physical properties of MCV, MCV pathogenesis, MCV replication, and immune responses to MCV infection. Sequencing of the MCV genome revealed novel immune evasion molecules which are highlighted here. Special attention is given to the MCV MC159 and MC160 proteins. These proteins are FLIPs with homologs in gamma herpesviruses and in the cell. They are of great interest because each protein regulates apoptosis, NF-?B, and IRF3. However, the mechanism that each protein uses to impart its effects is different. It is important to elucidate how MCV inhibits immune responses; this knowledge contributes to our understanding of viral pathogenesis and also provides new insights into how the immune system neutralizes virus infections. PMID:25701888

  10. Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection.

    PubMed

    Zaki, Md Hasan; Man, Si Ming; Vogel, Peter; Lamkanfi, Mohamed; Kanneganti, Thirumala-Devi

    2014-01-01

    The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 12 (NLRP12) plays a protective role in intestinal inflammation and carcinogenesis, but the physiological function of this NLR during microbial infection is largely unexplored. Salmonella enterica serovar Typhimurium (S. typhimurium) is a leading cause of food poisoning worldwide. Here, we show that NLRP12-deficient mice were highly resistant to S. typhimurium infection. Salmonella-infected macrophages induced NLRP12-dependent inhibition of NF-?B and ERK activation by suppressing phosphorylation of I?B? and ERK. NLRP12-mediated down-regulation of proinflammatory and antimicrobial molecules prevented efficient clearance of bacterial burden, highlighting a role for NLRP12 as a negative regulator of innate immune signaling during salmonellosis. These results underscore a signaling pathway defined by NLRP12-mediated dampening of host immune defenses that could be exploited by S. typhimurium to persist and survive in the host. PMID:24347638

  11. An efficient immunization strategy for community networks.

    PubMed

    Gong, Kai; Tang, Ming; Hui, Pak Ming; Zhang, Hai Feng; Younghae, Do; Lai, Ying-Cheng

    2013-01-01

    An efficient algorithm that can properly identify the targets to immunize or quarantine for preventing an epidemic in a population without knowing the global structural information is of obvious importance. Typically, a population is characterized by its community structure and the heterogeneity in the weak ties among nodes bridging over communities. We propose and study an effective algorithm that searches for bridge hubs, which are bridge nodes with a larger number of weak ties, as immunizing targets based on the idea of referencing to an expanding friendship circle as a self-avoiding walk proceeds. Applying the algorithm to simulated networks and empirical networks constructed from social network data of five US universities, we show that the algorithm is more effective than other existing local algorithms for a given immunization coverage, with a reduced final epidemic ratio, lower peak prevalence and fewer nodes that need to be visited before identifying the target nodes. The effectiveness stems from the breaking up of community networks by successful searches on target nodes with more weak ties. The effectiveness remains robust even when errors exist in the structure of the networks. PMID:24376708

  12. Immunization strategy for epidemic spreading on multilayer networks

    E-print Network

    Buono, C

    2014-01-01

    In many real-world complex systems, individuals have many kind 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 the 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...

  13. 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.

  14. Complex interplay of body condition, life history, and prevailing environment shapes immune defenses of garter snakes in the wild.

    PubMed

    Palacios, Maria G; Cunnick, Joan E; Bronikowski, Anne M

    2013-01-01

    The immunocompetence "pace-of-life" hypothesis proposes that fast-living organisms should invest more in innate immune defenses and less in adaptive defenses compared to slow-living ones. We found some support for this hypothesis in two life-history ecotypes of the snake Thamnophis elegans; fast-living individuals show higher levels of innate immunity compared to slow-living ones. Here, we optimized a lymphocyte proliferation assay to assess the complementary prediction that slow-living snakes should in turn show stronger adaptive defenses. We also assessed the "environmental" hypothesis that predicts that slow-living snakes should show lower levels of immune defenses (both innate and adaptive) given the harsher environment they live in. Proliferation of B- and T-lymphocytes of free-living individuals was on average higher in fast-living than slow-living snakes, opposing the pace-of-life hypothesis and supporting the environmental hypothesis. Bactericidal capacity of plasma, an index of innate immunity, did not differ between fast-living and slow-living snakes in this study, contrasting the previously documented pattern and highlighting the importance of annual environmental conditions as determinants of immune profiles of free-living animals. Our results do not negate a link between life history and immunity, as indicated by ecotype-specific relationships between lymphocyte proliferation and body condition, but suggest more subtle nuances than those currently proposed. PMID:23995485

  15. Arabidopsis systemic immunity uses conserved defense signaling pathways and is mediated by jasmonates

    PubMed Central

    Truman, William; Bennett, Mark H.; Kubigsteltig, Ines; Turnbull, Colin; Grant, Murray

    2007-01-01

    In the absence of adaptive immunity displayed by animals, plants respond locally to biotic challenge via inducible basal defense networks activated through recognition and response to conserved pathogen-associated molecular patterns. In addition, immunity can be induced in tissues remote from infection sites by systemic acquired resistance (SAR), initiated after gene-for-gene recognition between plant resistance proteins and microbial effectors. The nature of the mobile signal and remotely activated networks responsible for establishing SAR remain unclear. Salicylic acid (SA) participates in the local and systemic response, but SAR does not require long-distance translocation of SA. Here, we show that, despite the absence of pathogen-associated molecular pattern contact, systemically responding leaves rapidly activate a SAR transcriptional signature with strong similarity to local basal defense. We present several lines of evidence that suggest jasmonates are central to systemic defense, possibly acting as the initiating signal for classic SAR. Jasmonic acid (JA), but not SA, rapidly accumulates in phloem exudates of leaves challenged with an avirulent strain of Pseudomonas syringae. In systemically responding leaves, transcripts associated with jasmonate biosynthesis are up-regulated within 4 h, and JA increases transiently. SAR can be mimicked by foliar JA application and is abrogated in mutants impaired in jasmonate synthesis or response. We conclude that jasmonate signaling appears to mediate long-distance information transmission. Moreover, the systemic transcriptional response shares extraordinary overlap with local herbivory and wounding responses, indicating that jasmonates may be pivotal to an evolutionarily conserved signaling network that decodes multiple abiotic and biotic stress signals. PMID:17215350

  16. Microbial symbiosis with the innate immune defense system of the skin.

    PubMed

    Gallo, Richard L; Nakatsuji, Teruaki

    2011-10-01

    Skin protects itself against infection through a variety of mechanisms. Antimicrobial peptides (AMPs) are major contributors to cutaneous innate immunity, and this system, combined with the unique ionic, lipid, and physical barrier of the epidermis, is the first-line defense against invading pathogens. However, recent studies have revealed that our skin's innate immune system is not solely of human origin. Staphylococcus epidermidis, a major constituent of the normal microflora on healthy human skin, acts as a barrier against colonization of potentially pathogenic microbes and against overgrowth of already present opportunistic pathogens. Our resident commensal microbes produce their own AMPs, act to enhance the normal production of AMPs by keratinocytes, and are beneficial to maintaining inflammatory homeostasis by suppressing excess cytokine release after minor epidermal injury. These observations indicate that the normal human skin microflora protects skin by various modes of action, a conclusion supported by many lines of evidence associating diseases such as acne, atopic dermatitis, psoriasis, and rosacea with an imbalance of the microflora even in the absence of classical infection. This review highlights recent observations on the importance of innate immune systems and the relationship with the normal skin microflora to maintain healthy skin. PMID:21697881

  17. Optimal Treatment Strategy for a Tumor Model under Immune Suppression

    PubMed Central

    Kim, Kwang Su; Cho, Giphil; Jung, Il Hyo

    2014-01-01

    We propose a mathematical model describing tumor-immune interactions under immune suppression. These days evidences indicate that the immune suppression related to cancer contributes to its progression. The mathematical model for tumor-immune interactions would provide a new methodology for more sophisticated treatment options of cancer. To do this we have developed a system of 11 ordinary differential equations including the movement, interaction, and activation of NK cells, CD8+T-cells, CD4+T cells, regulatory T cells, and dendritic cells under the presence of tumor and cytokines and the immune interactions. In addition, we apply two control therapies, immunotherapy and chemotherapy to the model in order to control growth of tumor. Using optimal control theory and numerical simulations, we obtain appropriate treatment strategies according to the ratio of the cost for two therapies, which suggest an optimal timing of each administration for the two types of models, without and with immunosuppressive effects. These results mean that the immune suppression can have an influence on treatment strategies for cancer. PMID:25140193

  18. 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

  19. Natural History of Innate Host Defense Peptides

    Microsoft Academic Search

    A. Linde; B. Wachter; O. P. Höner; L. Dib; C. Ross; A. R. Tamayo; F. Blecha; T. Melgarejo

    2009-01-01

    Host defense peptides act on the forefront of innate immunity, thus playing a central role in the survival of animals and\\u000a plants. Despite vast morphological changes in species through evolutionary history, all animals examined to date share common\\u000a features in their innate immune defense strategies, hereunder expression of host defense peptides (HDPs). Most studies on\\u000a HDPs have focused on humans,

  20. Extraribosomal L13a Is a Specific Innate Immune Factor for Antiviral Defense

    PubMed Central

    Poddar, Darshana; Basu, Abhijit; Kour, Ravinder; Verbovetskaya, Valentina

    2014-01-01

    ABSTRACT We report a novel extraribosomal innate immune function of mammalian ribosomal protein L13a, whereby it acts as an antiviral agent. We found that L13a is released from the 60S ribosomal subunit in response to infection by respiratory syncytial virus (RSV), an RNA virus of the Pneumovirus genus and a serious lung pathogen. Unexpectedly, the growth of RSV was highly enhanced in L13a-knocked-down cells of various lineages as well as in L13a knockout macrophages from mice. In all L13a-deficient cells tested, translation of RSV matrix (M) protein was specifically stimulated, as judged by a greater abundance of M protein and greater association of the M mRNA with polyribosomes, while general translation was unaffected. In silico RNA folding analysis and translational reporter assays revealed a putative hairpin in the 3?untranslated region (UTR) of M mRNA with significant structural similarity to the cellular GAIT (gamma-activated inhibitor of translation) RNA hairpin, previously shown to be responsible for assembling a large, L13a-containing ribonucleoprotein complex that promoted translational silencing in gamma interferon (IFN-?)-activated myeloid cells. However, RNA-protein interaction studies revealed that this complex, which we named VAIT (respiratory syncytial virus-activated inhibitor of translation) is functionally different from the GAIT complex. VAIT is the first report of an extraribosomal L13a-mediated, IFN-?-independent innate antiviral complex triggered in response to virus infection. We provide a model in which the VAIT complex strongly hinders RSV replication by inhibiting the translation of the rate-limiting viral M protein, which is a new paradigm in antiviral defense. IMPORTANCE The innate immune mechanisms of host cells are diverse in nature and act as a broad-spectrum cellular defense against viruses. Here, we report a novel innate immune mechanism functioning against respiratory syncytial virus (RSV), in which the cellular ribosomal protein L13a is released from the large ribosomal subunit soon after infection and inhibits the translation of a specific viral mRNA, namely, that of the matrix protein M. Regarding its mechanism, we show that the recognition of a specific secondary structure in the 3? untranslated region of the M mRNA leads to translational arrest of the mRNA. We also show that the level of M protein in the infected cell is rate limiting for viral morphogenesis, providing a rationale for L13a to target the M mRNA for suppression of RSV growth. Translational silencing of a viral mRNA by a deployed ribosomal protein is a new paradigm in innate immunity. PMID:24899178

  1. Immune Evasion Strategies of Ranaviruses and Innate Immune Responses to These Emerging Pathogens

    PubMed Central

    Grayfer, Leon; Andino, Francisco De Jesús; Chen, Guangchun; Chinchar, Gregory V.; Robert, Jacques

    2012-01-01

    Ranaviruses (RV, Iridoviridae) are large double-stranded DNA viruses that infect fish, amphibians and reptiles. For ecological and commercial reasons, considerable attention has been drawn to the increasing prevalence of ranaviral infections of wild populations and in aquacultural settings. Importantly, RVs appear to be capable of crossing species barriers of numerous poikilotherms, suggesting that these pathogens possess a broad host range and potent immune evasion mechanisms. Indeed, while some of the 95–100 predicted ranavirus genes encode putative evasion proteins (e.g., vIF?, vCARD), roughly two-thirds of them do not share significant sequence identity with known viral or eukaryotic genes. Accordingly, the investigation of ranaviral virulence and immune evasion strategies is promising for elucidating potential antiviral targets. In this regard, recombination-based technologies are being employed to knock out gene candidates in the best-characterized RV member, Frog Virus (FV3). Concurrently, by using animal infection models with extensively characterized immune systems, such as the African clawed frog, Xenopus laevis, it is becoming evident that components of innate immunity are at the forefront of virus-host interactions. For example, cells of the macrophage lineage represent important combatants of RV infections while themselves serving as targets for viral infection, maintenance and possibly dissemination. This review focuses on the recent advances in the understanding of the RV immune evasion strategies with emphasis on the roles of the innate immune system in ranaviral infections. PMID:22852041

  2. 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

  3. 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

  4. Origin and diversification of the L-amino oxidase family in innate immune defenses of animals

    PubMed Central

    Hughes, Austin L.

    2010-01-01

    L-amino acid oxidases (LAOs), because they produce hydrogen peroxide as a by-product, function in innate immune defenses of both vertebrates and mollusks. Phylogenetic analysis revealed two major subfamilies of LAOs: (1) a subfamily including LAOs from vertebrates and mainly from Terrabacteria and (2) a subfamily including LAOs from mollusks and Hydrobacteria. These subfamilies thus originated early in the history of life, implying that their innate immune functions in vertebrates and mollusks have evolved separately. Mammalian LAOs were found to belong to three separate clades: (1) LAO1, (2) LAO2, and (3) IL4I1. Phylogenetic analysis supported the hypothesis that LAO1 and LAO2 arose by a gene duplication prior to the divergence of marsupials from placental mammals, while IL4I1 duplicated from the ancestor of the LAO1 and LAO2 prior to the divergence of tetrapods from bony fishes. Mammalian IL4I1 clustered with LAOs from bony fishes, and these molecules shared a number of unique sequence features, including both amino acid replacements and a unique two-codon deletion. It is certain such unique features may be functionally important, especially three unique amino acid replacements in close proximity to the putative active site. PMID:20878154

  5. Oxidative innate immune defenses by Nox/Duox family NADPH Oxidases

    PubMed Central

    Rada, Balázs; Leto, Thomas L.

    2009-01-01

    The importance of reactive oxygen species (ROS) in innate immunity was first recognized in professional phagocytes undergoing a “respiratory burst” upon activation. This robust oxygen consumption is related to a superoxide-generating enzyme, the phagocytic NADPH oxidase (Nox2 or phox). The oxidase is essential for microbial killing, since patients lacking a functional oxidase suffer from enhanced susceptibility to microbial infections. ROS derived from superoxide attack bacteria in the isolated niche of the neutrophil phagosome. The oxidase is electrogenic, alters ion currents across membranes, induces apoptosis, regulates cytokine production, influences gene expression, and promotes formation of extracellular traps. Recently, new homologues of Nox2 were discovered establishing the Nox family of NADPH oxidases that encompasses seven members. Nox1 is highly expressed in the colon epithelium, and can be induced by LPS or IFN-?. Nox4 was implicated in innate immunity since LPS induces Nox4-dependent ROS generation. Duox1 and Duox2 localize to the apical plasma membrane of epithelial cells in major airways, salivary glands, and the gastrointestinal tract, and provide extracellular hydrogen peroxide to lactoperoxidase to produce antimicrobial hypothiocyanite ions. Th1 and Th2 cytokines regulate expression of Dual oxidases in human airways and may thereby act in host defense or in proinflammatory responses. PMID:18511861

  6. Oxidative innate immune defenses by Nox/Duox family NADPH oxidases.

    PubMed

    Rada, Balázs; Leto, Thomas L

    2008-01-01

    The importance of reactive oxygen species (ROS) in innate immunity was first recognized in professional phagocytes undergoing a 'respiratory burst'upon activation. This robust oxygen consumption is related to a superoxide-generating enzyme, the phagocytic NADPH oxidase (Nox2-based or phox). The oxidase is essential for microbial killing, since patients lacking a functional oxidase suffer from enhanced susceptibility to microbial infections. ROS derived from superoxide attack bacteria in the isolated niche of the neutrophil phagosome. The oxidase is electrogenic, alters ion currents across membranes, induces apoptosis, regulates cytokine production, influences gene expression, and promotes formation of extracellular traps. Recently, new homologues of Nox2 were discovered establishing the Nox family of NADPH oxidases that encompasses seven members. Nox1 is highly expressed in the colon epithelium, and can be induced by LPS or IFN- gamma. Nox4 was implicated in innate immunity since LPS induces Nox4-dependent ROS generation. Duox1 and Duox2 localize to the apical plasma membrane of epithelial cells in major airways, salivary glands, and the gastrointestinal tract, and provide extracellular hydrogen peroxide to lactoperoxidase to produce antimicrobial hypothiocyanite ions. Th1 and Th2 cytokines regulate expression of dual oxidases in human airways and may thereby act in host defense or in proinflammatory responses. PMID:18511861

  7. Human macrophage SCN5A activates an innate immune signaling pathway for antiviral host defense.

    PubMed

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

    2014-12-19

    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

  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; Laurière, 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. Brain capillary pericytes contribute to the immune defense in response to cytokines or LPS in vitro.

    PubMed

    Pieper, Christian; Marek, Jasmin Jacqueline; Unterberg, Marlies; Schwerdtle, Tanja; Galla, Hans-Joachim

    2014-03-01

    The prevention of an inflammation in the brain is one of the most important goals the body has to achieve. As pericytes are located on the abluminal side of the capillaries in the brain, their role in fighting against invading pathogens has been investigated in some points, mostly in their ability to behave like macrophages. Here we studied the potential of pericytes to react as immune cells under inflammatory conditions, especially regarding the expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), major histocompatibility complex II (MHC II) molecules, CD68, as well as the generation of reactive oxygen and nitrogen species (RONS), and their ability in phagocytosis. Quantitative real time PCR and western blot analysis showed that pericytes are able to increase the expression of typical inflammatory marker proteins after the stimulation with tumor necrosis factor-alpha (TNF-?), interleukin-1beta (IL-1?), interferon-gamma (IFN-?), or lipopolysaccharides (LPS). Depending on the different specific pro-inflammatory factors pericytes changed the expression of alpha smooth muscle actin (?SMA), the most predominant pericyte marker. We conclude that the role of the pericytes within the immune system is regulated and fine-tuned by different cytokines strongly depending on the time when the cytokines are released and their concentration. The present results will help to understand the pericyte mediated defense mechanisms in the brain. PMID:24418464

  10. How to succeed as a virus: strategies for dealing with the immune system.

    PubMed

    Peterhans, E; Zanoni, R; Bertoni, G

    1999-12-15

    Viruses may be viewed as genetic information whose success depends on avoiding elimination from individual hosts, or, if this is not possible, in persisting in the population of their hosts. The immune system represents the crucial defense mechanism responsible for the elimination of viruses from individual hosts and for the establishment of immunity that prevents a recurring infection by the same virus. Herd immunity, i.e., immunity of the population against infection resulting from the immunity of a certain fraction of the individuals of the population, represents an important concept in the interaction of viruses with their hosts. Thus, if the number of susceptible hosts decreases below a critical threshold, viruses may risk extinction because they literally run out of substrate. This possibility is increased due to the viruses' low resistance to inactivation outside their hosts by physical influences, such as heat and ultraviolet radiation. Some viruses have adopted a strategy of dual host tropism, i.e., they may reside in reservoir hosts that permit them to survive for extended periods of times. Examples of such viruses are the large and taxonomically diverse group of arboviruses. Moreover, although not normally discussed under this aspect, influenza viruses can also be said to have adopted this strategy, in view of water fowl representing reservoir hosts from which complete viruses may directly cross over to mammals, as was the case with the equine Jilin (Guo et al., 1995) or, more recently, the H5 subtype of influenza virus in humans (Shortridge et al., 1998). In addition, influenza viruses of birds may be transmitted, albeit only partially, through genetic reassortment (Shu et al., 1996). PMID:10614500

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

    PubMed

    Wi?niewski, 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 ?-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

  12. New reservoirs of HLA alleles: pools of rare variants enhance immune defense.

    PubMed

    Klitz, William; Hedrick, Philip; Louis, Edward J

    2012-10-01

    Highly polymorphic exons of the major histocompatibility complex (MHC, or HLA in humans) encode critical amino acids that bind foreign peptides. Recognition of the peptide-MHC complexes by T cells initiates the adaptive immune response. The particular structure of these exons facilitates gene conversion(GC) events, leading to the generation of new alleles. Estimates for allele creation and loss indicate that more than 10000 such alleles are circulating at low frequencies in human populations. Empirical sampling has affirmed this expectation. This suggests that the MHC loci have a system for moving valuable and often complex variants into adaptive service. Here, we argue that HLA loci carry many new mutant alleles prepared to assume epidemiologically meaningful roles when called on by selection provoked by exposure to new and evolving pathogens. Because new mutant alleles appear in a population at the lowest possible frequency (i.e., a single copy), they have typically been thought of as having little consequence. However, this large population of rare yet potentially valuable new alleles may contribute to pathogen defense. PMID:22867968

  13. Adolescent Humor and its Relationship to Coping, Defense Strategies, Psychological Distress, and Well-Being

    Microsoft Academic Search

    Sarah J. Erickson; Sarah W. Feldstein

    2007-01-01

    Objective  This study investigated the psychometric properties of the Humor Styles Questionnaire (HSQ) in measuring adolescent humor,\\u000a including the relationship between humor and coping style, defense style, depressive symptoms, and adjustment in a non-clinical\\u000a sample of adolescents.\\u000a \\u000a \\u000a \\u000a Method  Humor, coping, defense strategies, depressive symptoms, and adjustment were investigated in 94 adolescents aged 12–15.\\u000a \\u000a \\u000a \\u000a Results  The HSQ demonstrated adequate internal consistency. Inter-scale correlational patterns

  14. Considerations for developing an immunization strategy with enterovirus 71 vaccine.

    PubMed

    Li, Li; Yin, Hongzhang; An, Zhijie; Feng, Zijian

    2015-02-25

    Enterovirus 71 (EV71) is a common pathogen for hand, foot, and mouth disease (HFMD), which has significant morbidity and mortality, and for which children aged 6-59 months age are at highest risk. Due to lack of effective treatment options, control of EV71 epidemics has mainly focused on development of EV71 vaccines. Clinical trials have been completed on 3 EV71 vaccines, with trial results demonstrating good vaccine efficacy and safety. When EV71 vaccine is approved by China's national regulatory authority, an evidence-based strategy should be developed to optimize impact and safety. An immunization strategy for EV71 vaccine should consider several factors, including the target population age group, the number of doses for primary immunization, the need for a booster dose, concomitant administration of other vaccines, economic value, program capacity and logistics, and public acceptance. Once EV71 vaccines are in use, vaccine effectiveness and safety must be monitored in large populations, and the epidemiology of HFMD must be evaluated to assure a match between vaccination strategy and epidemiology. Evaluation in China is especially important because there are no other EV71 vaccines globally. PMID:25444807

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

    PubMed

    Kögel, Susanne; Eben, Astrid; Hoffmann, Christoph; Gross, Jürgen

    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

  16. 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

  17. Molecular properties and immune defense of two ferritin subunits from freshwater pearl mussel, Hyriopsis schlegelii.

    PubMed

    He, Shuhao; Peng, Kou; Hong, Yijiang; Wang, Junhua; Sheng, Junqing; Gu, Qing

    2013-03-01

    Ferritin is a conserved iron-binding protein involved in cellular iron metabolism and host defense. In the present study, two distinct cDNAs for ferritins in the freshwater pearl mussel Hyriopsis schlegelii were identified (designated as HsFer-1 and HsFer-2) by SMART RACE approach and expressed sequence tag (EST) analysis. The full-length cDNAs of HsFer-1 and HsFer-2 were of 760 and 877 bp, respectively. Both of the two cDNAs contained an open reading frame (ORF) of 522 bp encoding for 174 amino acid residues. Sequence characterization and homology alignment indicated that HsFer-1 and HsFer-2 had higher similarity to H-type subunit of vertebrate ferritins than L-type subunit. Analysis of the HsFer-1 and HsFer-2 untranslated regions (UTR) showed that both of them had an iron response element (IRE) in the 5'-UTR, which was considered to be the binding site for iron regulatory protein (IRP). Quantitative real-time PCR (qPCR) assays were employed to examine the mRNA expression profiles. Under normal physiological conditions, the expression level of both HsFer-1 and HsFer-2 mRNA were the highest in hepatopancreas, moderate in gonad, axe foot, intestine, kidney, heart, gill, adductor muscle and mantle, the lowest in hemocytes. After stimulation with bacteria Aeromonas hydrophila, HsFer-1 mRNA experienced a different degree of increase in the tissues of hepatopancreas, gonad and hemocytes, the peak level was 2.47-fold, 9.59-fold and 1.37-fold, respectively. Comparatively, HsFer-2 showed up-regulation in gonad but down-regulation in hepatopancreas and hemocytes. Varying expression patterns indicate that two types of ferritins in H. schlegelii might play different roles in response to bacterial challenge. Further bacteriostatic analysis showed that both the purified recombinant ferritins inhibited the growth of A. hydrophila to a certain degree. Collectively, our results suggest that HsFer-1 and HsFer-2 are likely to be functional proteins involved in immune defense against bacterial infection. PMID:23339972

  18. Stimulatory effects of chitinase on growth and immune defense of orange-spotted grouper (Epinephelus coioides).

    PubMed

    Zhang, Yanhong; Feng, Shaozhen; Chen, Jun; Qin, Chaobin; Lin, Haoran; Li, Wensheng

    2012-05-01

    Chitinase, belonging to either family 18 or family 19 of the glycosylhydrolases, hydrolyze chitin into oligosaccharides. In the present study, the cDNA fragment encoding orange-spotted grouper (Epinephelus coioides) chitinase1 was subcloned into pPIC3.5K vector and expressed in Pichia pastoris GS115. The results showed that a band with the size of about 53 kDa could be detected by SDS-PAGE and Western blot. The recombinant protein of grouper chitinase1 (rgChi1) was added into the fish diet containing shrimp shell chitin for feeding experiment lasting 8 weeks. The weight of orange-spotted grouper, fed with diets containing rgChi1 at 0, 5, 10 and 20 ?g/g was calculated on the 2nd, 4th, 6th and 8th weeks, and difference in growth rates was first observed in the 6th week of the feeding period and it kept until the end of the feeding experiment. At the end of 8 weeks feeding trial, the percent weight gain (PWG), growth rate (GR) and specific growth rate (SGR) of fish fed with 10 and 20 ?g rgChi1/g feed were significantly higher compared to the control group. The neuropeptide Y (NPY), growth-hormone-releasing hormone (GHRH), growth-hormone (GH), interleukin-1beta (IL-1?), cyclooxygenase-2 (COX-2), superoxide dismutase (SOD) (Cu/Zn) and SOD (Mn) mRNA expression of fish fed with diet containing 10 ?g/g or/and 20 ?g/g rgChi1 were obviously higher than the control group. The lysozyme (LZM) and total SOD activity of fish fed with diet containing rgChi1 at 10 and 20 ?g/g were significantly higher than that of the control. The aspartate aminotransferase (AST)/glutamic oxalacetic transaminases (GOT) activity in 20 ?g/g group decreased compared to the control group. These results indicated that the grouper chitinase1 was successfully produced using the P. pastoris expression system and the recombinant protein had obvious effects on growth and immune defense. The mRNA expression and protein secretion of grouper chitinase1 and chitinase2 were significantly stimulated in spleen in response to bacterial lipopolysaccharide (LPS) challenge, strongly suggesting the existence of an innate pathway for local defense against chitin-containing organisms. Moreover, the pathogen such as Escherichia coli and Staphylococcus aureus could be inhibited by the recombinant protein of grouper chitinase1 to a certain extent. PMID:22365990

  19. Immune defense and eosinophilia in congenitally IgE-deficient SJA/9 mice infected with Angiostrongylus costaricensis.

    PubMed

    Watanabe, N; Ishiwata, K; Kaneko, S; Oku, Y; Kamiya, M; Katakura, K

    1993-01-01

    The roles of IgE in protective immunity and eosinophilia in Angiostrongylus costaricensis infection were examined by comparing IgE-deficient SJA/9 mice and IgE-producing SJL/J mice. In primary infection, mean total IgE levels increased to a maximum of 390 ng/ml, which was more than 10 times greater than the 29 ng/ml measured preinfection in SJL/J mice but less than the 10 ng/ml found in SJA/9 mice throughout the experiment. Immune defense as determined by recovery of adult worms and eosinophilia were similar in SJL/J and SJA/9 mice. Protective immunity was induced by infection with A. costaricensis followed by treatment with levamisole for 4-6 days postinfection. After the challenge infection, the numbers of adult worms and eosinophils in SJA/9 mice were not significantly different from those in SJL/J mice. Anti-A. costaricensis IgE antibody was not detected in either strain of mice during the experiment. These results indicate that A. costaricensis infection induced the production of IgE not specific for parasite antigens in IgE-producing mice. Potentiated nonspecific IgE played no significant role in immune defense and eosinophilia. PMID:8415551

  20. 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

  1. 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

  2. Paramyxovirus evasion of innate immunity: Diverse strategies for common targets

    PubMed Central

    Audsley, Michelle D; Moseley, Gregory W

    2013-01-01

    The paramyxoviruses are a family of > 30 viruses that variously infect humans, other mammals and fish to cause diverse outcomes, ranging from asymptomatic to lethal disease, with the zoonotic paramyxoviruses Nipah and Hendra showing up to 70% case-fatality rate in humans. The capacity to evade host immunity is central to viral infection, and paramyxoviruses have evolved multiple strategies to overcome the host interferon (IFN)-mediated innate immune response through the activity of their IFN-antagonist proteins. Although paramyxovirus IFN antagonists generally target common factors of the IFN system, including melanoma differentiation associated factor 5, retinoic acid-inducible gene-I, signal transducers and activators of transcription (STAT)1 and STAT2, and IFN regulatory factor 3, the mechanisms of antagonism show remarkable diversity between different genera and even individual members of the same genus; the reasons for this diversity, however, are not currently understood. Here, we review the IFN antagonism strategies of paramyxoviruses, highlighting mechanistic differences observed between individual species and genera. We also discuss potential sources of this diversity, including biological differences in the host and/or tissue specificity of different paramyxoviruses, and potential effects of experimental approaches that have largely relied on in vitro systems. Importantly, recent studies using recombinant virus systems and animal infection models are beginning to clarify the importance of certain mechanisms of IFN antagonism to in vivo infections, providing important indications not only of their critical importance to virulence, but also of their potential targeting for new therapeutic/vaccine approaches. PMID:24175230

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

    PubMed

    Sohn, Kee Hoon; Segonzac, Cécile; 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

  4. 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

  5. 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

  6. 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

  7. Loss of the innate immunity negative regulator IRAK-M leads to enhanced host immune defense against tumor growth

    PubMed Central

    Xie, Qifa; Gan, Lu; Wang, Jianxia; Wilson, Ingred; Li, Liwu

    2010-01-01

    IRAK-M is a negative regulator of innate immunity signaling processes. Although attenuation of innate immunity may help to prevent excessive inflammation, it may also lead to compromised immune surveillance of tumor cells and contribute to tumor formation and growth. Here, we demonstrate that IRAK-M?/? mice are resistant to tumor growth upon inoculation with transplantable tumor cells. Immune cells from IRAK-M?/? mice are responsible for the anti-tumor effect, since adoptive transfer of splenocytes from IRAK-M?/? mice to wild type mice can transfer the tumor-resistant phenotype. Upon tumor cell challenge, there are elevated populations of CD4+ and CD8+ T cells and a decreased population of CD4+ CD25+Foxp3+ regulatory T cells in IRAK-M ?/? splenocytes. Furthermore, we observe that IRAK-M deficiency leads to elevated proliferation and activation of T cells and B cells. Enhanced NF?B activation directly caused by IRAK-M deficiency may explain elevated activation of T and B cells. In addition, macrophages from IRAK-M?/? mice exhibit enhanced phagocytic function toward acetylated LDL and apoptotic thymocytes. Collectively, we demonstrate that IRAK-M is directly involved in the regulation of both innate and adaptive immune signaling processes, and deletion of IRAK-M enhances host anti-tumor immune response. PMID:17477969

  8. 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

  9. Immunization with PCEP microparticles containing pertussis toxoid, CpG ODN and a synthetic innate defense regulator peptide induces protective immunity against pertussis.

    PubMed

    Garlapati, Srinivas; Eng, Nelson F; Kiros, Tadele G; Kindrachuk, Jason; Mutwiri, George K; Hancock, Robert E W; Halperin, Scott A; Potter, Andrew A; Babiuk, Lorne A; Gerdts, Volker

    2011-09-01

    We investigated the efficacy of a novel microparticle (MP) based vaccine formulation consisting of pertussis toxoid (PTd), polyphosphazene (PCEP), CpG ODN 10101 and synthetic cationic innate defense regulator peptide 1002 (IDR) against Bordetella pertussis in mice. We studied whether encapsulation of these IDR-CpG ODN complexes into polyphosphazene-based microparticles further enhanced their immunomodulatory activity compared to soluble formulations containing PCEP (SOL), or without PCEP (AQ). In vitro stimulation of murine macrophages showed MP induced significantly higher levels of pro-inflammatory cytokines. When assessed in a B. pertussis infection challenge model, a single immunization with MP formulation led to significantly lower bacterial loads compared to other formulations and non-vaccinated animals. ELISPOT of splenocytes showed that MP group mice had significantly higher number of antigen-specific IL-17 secreting cells. The cytokine profile in lung homogenates of MP group mice after challenge showed significantly higher amounts of MCP-1, TNF-?, IFN-?, IL-12 and IL-17 and significantly lowered IL-10 levels suggesting a strong Th1 shift. Protection was observed against challenge infection with B. pertussis. On the other hand protective immune responses elicited in Quadracel(®) immunized mice were Th2 skewed. Hence, we conclude that formulation of PTd, PCEP, CpG ODN and IDR into MP generates a protective immune response in mice against pertussis emphasizing the potential of MP as a delivery vehicle for the potential development of single-shot vaccines. PMID:21771625

  10. Mucosal immunity and protection against HIV/SIV infection: strategies and challenges for vaccine design

    PubMed Central

    Demberg, Thorsten; Robert-Guroff, Marjorie

    2012-01-01

    To date most HIV vaccine strategies have focused on parenteral immunization and systemic immunity. These approaches have not yielded the efficacious HIV vaccine urgently needed to control the AIDS pandemic. As HIV is primarily mucosally transmitted, efforts are being refocused on mucosal vaccine strategies, in spite of complexities of immune response induction and evaluation. Here we outline issues in mucosal vaccine design and illustrate strategies with examples from the recent literature. Development of a successful HIV vaccine will require in depth understanding of the mucosal immune system, knowledge that ultimately will benefit vaccine design for all mucosally transmitted infectious agents. PMID:19241252

  11. Immune defense of ants is associated with changes in habitat characteristics.

    PubMed

    Sorvari, Jouni; Hakkarainen, Harri; Rantala, Markus J

    2008-02-01

    Although the immune functions of insects are known to correlate with body condition and food resources, the association between habitat structure and immune function is still largely unknown. We studied the effects of forest clear-cutting on encapsulation rate in gynes and workers in the forest-dwelling ant Formica aquilonia. Forest logging resulted in disturbed immunity in workers and gynes. Logging enhanced encapsulation reaction in gynes, whereas decreased that of workers. In gynes, there was a likely trade-off between growth and immune function that was apparent in terms of different investment in size and immune function in different habitats. In workers, however, such associations were not found. The results indicate that, because of disturbed immunity, environmental stress may increase susceptibility of wood ants to diseases and parasites in disturbed habitats. PMID:18348796

  12. Host defenses in experimental scrub typhus: role of cellular immunity in heterologous protection.

    PubMed

    Shirai, A; Catanzaro, P J; Phillips, S M; Osterman, J V

    1976-07-01

    The relative contributions of cellular and humoral immunity in scrub typhus infections were studied in inbred mice employing paired strains of Rickettsia tsutsugamushi differing in virulence. An infectious dose (100 MID50) of the less virulent Gilliam strain resulted in heterologous immune protection against an otherwise lethal challenge (1,000 MLD50) of the virulent Karp strain. Partial heterologous protection against lethal Karp challenge was observed in animals preimmunized with the Gilliam strain as early as 3 days prior to challenge, whereas complete protection against illness and death existed in animals immunized at least 7 days prior to challenge. In the heterologous protection provided by prior Gilliam infection, the role of humoral immunity was not of primary importance for the following reasons: (i) significant levels of complement-fixing antibody against R. tsutsugamushi were not detectable until long after animals were solidly immune; (ii) antibody eventually appearing after Gilliam immunization exhibited a consistently low complement-fixing titer against the immunizing homologous (Gilliam) strain and contained no detectable activity against the heterologous challenge (Karp) strain; and (iii) passive transfer of large quantities of serum from Gilliam immune mice, themselves immune to Karp challenge, failed to protect recipients against a similar challenge. However, protection was afforded by the passive transfer of serum containing antibody against Karp, suggesting a major role for antibody in protection against homologous infection. This heterologous challenge system was particularly useful because it minimized the role of humoral immunity, at least early in the course of infection, and allowed a definitive examination of the cellular response. Cell-mediated immunity played a major role in the heterologous protection observed after Gilliam immunization. This was evidenced by the significant protection against Karp challenge afforded by the passive transfer of spleen cells from animals immunized with Gilliam 7 to 63 days previously. Of the immune spleen cells, only those which were nonadherent, presumably lymphocytes, were capable of transferring passive heterologous protection. This protective effect of nonadherent cells could be ablated by depleting the cell population of thymus-derived or T cells with anti-theta serum and complement prior to transfer but not by use of anti-immunoglobulin serum and complement, which selectively removes bone marrow-derived or B cells. These results suggested that the cell in immune spleens capable of conferring heterologous protection was a T lymphocyte. PMID:820646

  13. 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.

  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; Kärkkäinen, 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. 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 parasite’s 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 mosquito’s innate immune system. This review will discuss our current understanding of the Anopheles mosquito’s innate immune responses against the malaria parasite Plasmodium and the influence of the insect’s intestinal microbiota on parasite infection. PMID:23988482

  17. 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

  18. Two fundamentals of mammalian defense in fungal infections: endothermy and innate antifungal immunity.

    PubMed

    Biega?ska, M J

    2014-01-01

    The environment of animals is inhabited by enormous fungal species, but only a few hundreds are pathogenic for mammals. Most of potentially pathogenic fungal species, excluding dermatophytes, seldom cause the disease in immunocompetent hosts. Data from literature indicate, that an immune system and endothermy are foundations for this mammalian relative resistance to fungal systemic infections. Stable and high temperature of the body restricts invasion and growth of potentially pathogenic fungi. Together with elevated metabolism it supports the effectiveness of mammalian immunity. The innate immunity is assigned to prevent the invasion of various microbes (including fungi) to the hosts' organism. It consists of cellular receptors and several humoral factors as the Antimicrobial Peptides. If the physical barriers fail in stopping the invader, it is recognized as "alien" by multiple Pattern Recognition Receptors (PRRs) like Toll Like Receptors (TLRs) expressed by cells of innate immunity and/or C-type lectins. At the same time innate inflammation begins and the complement cascade is activated. These mechanisms are able to stop and clear some fungal infections. During existing infection the adaptive immunity is induced. This review aims to show the role of mammalian endothermy and to point the most important elements of innate antifungal immunity. PMID:25286672

  19. 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

    Abstract 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

  20. Viral immune evasion strategies and the underlying cell biology.

    PubMed

    Lorenzo, M E; Ploegh, H L; Tirabassi, R S

    2001-02-01

    Evasion of the immune system by viruses is a well-studied field. It remains a challenge to understand how these viral tactics affect pathogenesis and the viral lifecycle. At the same time, the study of viral proteins involved in immune evasion has helped us to better understand a number of cellular processes at the molecular level. Here we review recent data on different viral tactics for immune evasion and highlight what these viral interventions might teach us about cell biology. PMID:11289794

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

    PubMed Central

    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

  2. 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

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

    PubMed Central

    Escalante-Pérez, María; Jaborsky, Mario; Lautner, Silke; Fromm, Jörg; Müller, 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

  4. Are there Economic Advantages for the Use of Immune Enhancer Strategies in Aquaculture?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper focuses on the perception that immune enhancer strategies provide reduced disease incidence, drug residues and increased growth performance. Disease control and growth performance results are inconsistent on the use of immune enhancers in both experimental and field trials. The uncertain...

  5. Leukotriene B4 enhances innate immune defense against the puerperal sepsis agent Streptococcus pyogenes

    PubMed Central

    Soares, Elyara M.; Mason, Katie L.; Rogers, Lisa M.; Serezani, Carlos H.; Faccioli, Lucia H.; Aronoff, David M.

    2012-01-01

    Puerperal sepsis is a leading cause of maternal mortality worldwide. Streptococcus pyogenes (Group A Streptococcus; GAS) is a major etiologic agent of severe postpartum sepsis yet little is known regarding the pathogenesis of these infections. Tissue macrophages provide innate defense against GAS and their actions are highly regulated. The intracellular second messenger cAMP can negatively regulate macrophage actions against GAS. Because leukotriene (LT) B4 has been shown to suppress intracellular cAMP in macrophages, we hypothesized that it could enhance innate defenses against GAS. We assessed the capacity of LTB4 to modulate anti-streptococcal actions of human macrophages, including placental and decidual macrophages and used a novel intrauterine infection model of GAS in mice lacking the 5-lipoxygenase (5LO) enzyme to determine the role of endogenous LTs in host defense against this pathogen. Animals lacking 5LO were significantly more vulnerable to intrauterine GAS infection than wild-type mice and showed enhanced dissemination of bacteria out of the uterus and a more robust inflammatory response compared to wild-type mice. Additionally, LTB4 reduced intracellular cAMP levels via the BLT1 receptor and was a potent stimulant of macrophage phagocytosis and NADPH oxidase-dependent intracellular killing of GAS. Importantly, interference was observed between the macrophage immunomodulatory actions of LTB4 and the cAMP-inducing lipid prostaglandin E2, suggesting that interplay between pro- and anti-inflammatory compounds may be important in vivo. This work underscores the potential for pharmacological targeting of lipid mediator signaling cascades in the treatment of invasive GAS infections. PMID:23325886

  6. West European and East Asian perspectives on defense, deterrence, and strategy. Volume 2. Western European perspectives on defense, deterrence, and strategy. Technical report, 1 December 1982-15 May 1984

    Microsoft Academic Search

    R. L. Pfaltzgraff; J. K. Davis; J. E. Dougherty; C. M. Perry

    1984-01-01

    A survey of contemporary West European perspectives on defense, deterrence, and strategy, with special emphasis on the role of nuclear weapons deployed in, or assigned to, the NATO area. Changes have occurred during the past decade in the relative military strength of NATO and the Warsaw Pact, particularly as a result of the substantial growth in Soviet nuclear-capable systems and

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

    Microsoft Academic Search

    W Strober; T Watanabe

    2011-01-01

    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

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

    PubMed Central

    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 Sjögren 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

  9. 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

  10. Supporting information for Evolution of suicide as a defense strategy against pathogens in a spatially structured environment

    E-print Network

    Supporting information for Evolution of suicide as a defense strategy against pathogens ( ), the evolution of altruistic suicide is given by: (A2) This equation shows that, in a well-mixed environment, altruistic suicide is never selected for. At best, when there is no cost of altruistic suicide, the evolution

  11. Strategies for defending a dribbler: categorisation of three defensive patterns in 1-on-1 basketball.

    PubMed

    Fujii, Keisuke; Yamashita, Daichi; Yoshioka, Shinsuke; Isaka, Tadao; Kouzaki, Motoki

    2014-09-01

    To clarify the defending-dribbler mechanism, the interaction between the dribbler and defender should be investigated. The purposes of this study were to identify variables that explain the outcome (i.e. 'penetrating' and 'guarding') and to understand how defenders stop dribblers by categorising defensive patterns. Ten basketball players participated as 24 dribbler-defender pairs, who played a real-time, 1-on-1 sub-phase of the basketball. The trials were categorised into penetrating trials, where a dribbler invaded the defended area behind the defender, and guarding trials, where the defender stopped the dribbler's advance. Our results demonstrated that defenders in guarding trials initiated their movements earlier and moved quicker than the defenders in penetrating trials. Moreover, linear discriminant analysis revealed that the differences in initiation time and medio-lateral peak velocity between the defenders and dribblers were critical parameters for explaining the difference between penetrating and guarding trials. Lastly, guarding trials were further categorised into three process patterns during 1-on-1 basketball (i.e. 'early initiation' trials, 'quick movement' trials, and 'dribbler's stop' trials). The results suggest that there are three defending strategies and that one strategy would be insufficient to explain the defending-dribbler mechanism, because both players' anticipation and reactive movement must be considered. PMID:25203390

  12. Defense Against Cannibalism: The SdpI Family of Bacterial Immunity/Signal Transduction Proteins

    PubMed Central

    Povolotsky, Tatyana Leonidovna; Orlova, Ekaterina; Tamang, Dorjee G.

    2010-01-01

    The SdpI family consists of putative bacterial toxin immunity and signal transduction proteins. One member of the family in Bacillus subtilis, SdpI, provides immunity to cells from cannibalism in times of nutrient limitation. SdpI family members are transmembrane proteins with 3, 4, 5, 6, 7, 8, or 12 putative transmembrane ?-helical segments (TMSs). These varied topologies appear to be genuine rather than artifacts due to sequencing or annotation errors. The basic and most frequently occurring element of the SdpI family has 6 TMSs. Homologues of all topological types were aligned to determine the homologous TMSs and loop regions, and the positive-inside rule was used to determine sidedness. The two most conserved motifs were identified between TMSs 1 and 2 and TMSs 4 and 5 of the 6 TMS proteins. These showed significant sequence similarity, leading us to suggest that the primordial precursor of these proteins was a 3 TMS–encoding genetic element that underwent intragenic duplication. Various deletional and fusional events, as well as intragenic duplications and inversions, may have yielded SdpI homologues with topologies of varying numbers and positions of TMSs. We propose a specific evolutionary pathway that could have given rise to these distantly related bacterial immunity proteins. We further show that genes encoding SdpI homologues often appear in operons with genes for homologues of SdpR, SdpI’s autorepressor. Our analyses allow us to propose structure–function relationships that may be applicable to most family members. Electronic supplementary material The online version of this article (doi:10.1007/s00232-010-9260-7) contains supplementary material, which is available to authorized users. PMID:20563570

  13. Defense against cannibalism: the SdpI family of bacterial immunity/signal transduction proteins.

    PubMed

    Povolotsky, Tatyana Leonidovna; Orlova, Ekaterina; Tamang, Dorjee G; Saier, Milton H

    2010-06-01

    The SdpI family consists of putative bacterial toxin immunity and signal transduction proteins. One member of the family in Bacillus subtilis, SdpI, provides immunity to cells from cannibalism in times of nutrient limitation. SdpI family members are transmembrane proteins with 3, 4, 5, 6, 7, 8, or 12 putative transmembrane alpha-helical segments (TMSs). These varied topologies appear to be genuine rather than artifacts due to sequencing or annotation errors. The basic and most frequently occurring element of the SdpI family has 6 TMSs. Homologues of all topological types were aligned to determine the homologous TMSs and loop regions, and the positive-inside rule was used to determine sidedness. The two most conserved motifs were identified between TMSs 1 and 2 and TMSs 4 and 5 of the 6 TMS proteins. These showed significant sequence similarity, leading us to suggest that the primordial precursor of these proteins was a 3 TMS-encoding genetic element that underwent intragenic duplication. Various deletional and fusional events, as well as intragenic duplications and inversions, may have yielded SdpI homologues with topologies of varying numbers and positions of TMSs. We propose a specific evolutionary pathway that could have given rise to these distantly related bacterial immunity proteins. We further show that genes encoding SdpI homologues often appear in operons with genes for homologues of SdpR, SdpI's autorepressor. Our analyses allow us to propose structure-function relationships that may be applicable to most family members. PMID:20563570

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

    PubMed Central

    Moné, Yves; Allienne, Jean François; Henri, Hélène; Delbecq, Stéphane; 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

  15. 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

  16. Chagas’ disease: an update on immune mechanisms and therapeutic strategies

    PubMed Central

    Boscardin, Silvia Beatriz; Torrecilhas, Ana Claudia Troccoli; Manarin, Romina; Revelli, Silvia; Rey, Elena Gonzalez; Tonelli, Renata Rosito; Silber, Ariel Mariano

    2010-01-01

    Abstract The final decade of the 20th century was marked by an alarming resurgence in infectious diseases caused by tropical parasites belonging to the kinetoplastid protozoan order. Among the pathogenic trypanosomatids, some species are of particular interest due to their medical importance. These species include the agent responsible for Chagas’ disease, Trypanosoma cruzi. Approximately 8 to 10 million people are infected in the Americas, and approximately 40 million are at risk. In the present review, we discuss in detail the immune mechanisms elicited during infection by T. cruzi and the effects of chemotherapy in controlling parasite proliferation and on the host immune system. PMID:20070438

  17. Immunization strategies for epidemic processes in time-varying contact networks

    E-print Network

    Starnini, Michele; Cattuto, Ciro; Barrat, Alain; Satorras, Romualdo Pastor

    2013-01-01

    Spreading processes represent a very efficient tool to investigate the structural properties of networks and the relative importance of their constituents, and have been widely used to this aim in static networks. Here we consider simple disease spreading processes on empirical time-varying networks of contacts between individuals, and compare the effect of several immunization strategies on these processes. An immunization strategy is defined as the choice of a set of nodes (individuals) who cannot catch nor transmit the disease. This choice is performed according to a certain ranking of the nodes of the contact network. We consider various ranking strategies, focusing in particular on the role of the training window during which the nodes' properties are measured in the time-varying network: longer training windows correspond to a larger amount of information collected and could be expected to result in better performances of the immunization strategies. We find instead an unexpected saturation in the effic...

  18. 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

  19. Selective Metabolism of Hypothiocyanous Acid by Mammalian Thioredoxin Reductase Promotes Lung Innate Immunity and Antioxidant Defense*

    PubMed Central

    Chandler, Joshua D.; Nichols, David P.; Nick, Jerry A.; Hondal, Robert J.; Day, Brian J.

    2013-01-01

    The endogenously produced oxidant hypothiocyanous acid (HOSCN) inhibits and kills pathogens but paradoxically is well tolerated by mammalian host tissue. Mammalian high molecular weight thioredoxin reductase (H-TrxR) is evolutionarily divergent from bacterial low molecular weight thioredoxin reductase (L-TrxR). Notably, mammalian H-TrxR contains a selenocysteine (Sec) and has wider substrate reactivity than L-TrxR. Recombinant rat cytosolic H-TrxR1, mouse mitochondrial H-TrxR2, and a purified mixture of both from rat selectively turned over HOSCN (kcat = 357 ± 16 min?1; Km = 31.9 ± 10.3 ?m) but were inactive against the related oxidant hypochlorous acid. Replacing Sec with Cys or deleting the final eight C-terminal peptides decreased affinity and turnover of HOSCN by H-TrxR. Similarly, glutathione reductase (an H-TrxR homologue lacking Sec) was less effective at HOSCN turnover. In contrast to H-TrxR and glutathione reductase, recombinant Escherichia coli L-TrxR was potently inhibited by HOSCN (IC50 = 2.75 ?m). Similarly, human bronchial epithelial cell (16HBE) lysates metabolized HOSCN, but E. coli and Pseudomonas aeruginosa lysates had little or no activity. HOSCN selectively produced toxicity in bacteria, whereas hypochlorous acid was nonselectively toxic to both bacteria and 16HBE. Treatment with the H-TrxR inhibitor auranofin inhibited HOSCN metabolism in 16HBE lysates and significantly increased HOSCN-mediated cytotoxicity. These findings demonstrate both the metabolism of HOSCN by mammalian H-TrxR resulting in resistance to HOSCN in mammalian cells and the potent inhibition of bacterial L-TrxR resulting in cytotoxicity in bacteria. These data support a novel selective mechanism of host defense in mammals wherein HOSCN formation simultaneously inhibits pathogens while sparing host tissue. PMID:23629660

  20. Selective metabolism of hypothiocyanous acid by mammalian thioredoxin reductase promotes lung innate immunity and antioxidant defense.

    PubMed

    Chandler, Joshua D; Nichols, David P; Nick, Jerry A; Hondal, Robert J; Day, Brian J

    2013-06-21

    The endogenously produced oxidant hypothiocyanous acid (HOSCN) inhibits and kills pathogens but paradoxically is well tolerated by mammalian host tissue. Mammalian high molecular weight thioredoxin reductase (H-TrxR) is evolutionarily divergent from bacterial low molecular weight thioredoxin reductase (L-TrxR). Notably, mammalian H-TrxR contains a selenocysteine (Sec) and has wider substrate reactivity than L-TrxR. Recombinant rat cytosolic H-TrxR1, mouse mitochondrial H-TrxR2, and a purified mixture of both from rat selectively turned over HOSCN (kcat = 357 ± 16 min(-1); Km = 31.9 ± 10.3 ?M) but were inactive against the related oxidant hypochlorous acid. Replacing Sec with Cys or deleting the final eight C-terminal peptides decreased affinity and turnover of HOSCN by H-TrxR. Similarly, glutathione reductase (an H-TrxR homologue lacking Sec) was less effective at HOSCN turnover. In contrast to H-TrxR and glutathione reductase, recombinant Escherichia coli L-TrxR was potently inhibited by HOSCN (IC50 = 2.75 ?M). Similarly, human bronchial epithelial cell (16HBE) lysates metabolized HOSCN, but E. coli and Pseudomonas aeruginosa lysates had little or no activity. HOSCN selectively produced toxicity in bacteria, whereas hypochlorous acid was nonselectively toxic to both bacteria and 16HBE. Treatment with the H-TrxR inhibitor auranofin inhibited HOSCN metabolism in 16HBE lysates and significantly increased HOSCN-mediated cytotoxicity. These findings demonstrate both the metabolism of HOSCN by mammalian H-TrxR resulting in resistance to HOSCN in mammalian cells and the potent inhibition of bacterial L-TrxR resulting in cytotoxicity in bacteria. These data support a novel selective mechanism of host defense in mammals wherein HOSCN formation simultaneously inhibits pathogens while sparing host tissue. PMID:23629660

  1. 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

  2. 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

  3. Characterizing immune repertoires by high throughput sequencing: strategies and applications.

    PubMed

    Calis, Jorg J A; Rosenberg, Brad R

    2014-10-01

    As the key cellular effectors of adaptive immunity, T and B lymphocytes utilize specialized receptors to recognize, respond to, and neutralize a diverse array of extrinsic threats. These receptors (immunoglobulins in B lymphocytes, T cell receptors in T lymphocytes) are incredibly variable, the products of specialized genetic diversification mechanisms that generate complex lymphocyte repertoires with extensive collections of antigen specificities. Recent advances in high throughput sequencing (HTS) technologies have transformed our ability to examine antigen receptor repertoires at single nucleotide, and more recently, single cell, resolution. Here we review current approaches to examining antigen receptor repertoires by HTS, and discuss inherent biological and technical challenges. We further describe emerging applications of this powerful methodology for exploring the adaptive immune system. PMID:25306219

  4. DNA methylation-associated colonic mucosal immune and defense responses in treatment-naïve pediatric ulcerative colitis.

    PubMed

    Harris, R Alan; Nagy-Szakal, Dorottya; Mir, Sabina A V; Frank, Eibe; Szigeti, Reka; Kaplan, Jess L; Bronsky, Jiri; Opekun, Antone; Ferry, George D; Winter, Harland; Kellermayer, Richard

    2014-08-01

    Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn's disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P<0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD. PMID:24937444

  5. Realization of cooperative strategies and swarm behavior in distributed autonomous robotic systems using artificial immune system

    Microsoft Academic Search

    Jin-Hyung Jun; Dong-Wook Lee; Kwee-Bo Sim

    1999-01-01

    In this paper, we propose a method of cooperative control (T-cell modeling) and selection of group behavior strategy (B-cell modeling) based on the immune system in a distributed autonomous robotic system (DARS). The immune system is a living body's self-protection and self-maintenance system. These features can be applied to decision making of optimal swarm behavior in a dynamically changing environment.

  6. Can investments in health systems strategies lead to changes in immunization coverage?

    PubMed

    Brenzel, Logan

    2014-04-01

    National immunization programs in developing countries have made major strides to immunize the world's children, increasing full coverage to 83% of children. However, the World Health Organization estimates that 22 million children less than five years of age are left unvaccinated, and coverage levels have been plateauing for nearly a decade. This paper describes the evidence on factors contributing to low vaccination uptake, and describes the connection between these factors and the documented strategies and interventions that can lead to changes in immunization outcomes. The author suggests that investments in these areas may contribute more effectively to immunization coverage and also have positive spill-over benefits for health systems. The paper concludes that while some good quality evidence exists of what works and may contribute to immunization outcomes, the quality of evidence needs to improve and major gaps need to be addressed. PMID:24588785

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

    PubMed Central

    Scheil, Alexandra E.; Hilsmann, Stefanie; Triebskorn, Rita; Köhler, 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

  8. 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

  9. 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.

  10. Clinical immune-monitoring strategies for predicting infection risk in solid organ transplantation

    PubMed Central

    Fernández-Ruiz, Mario; Kumar, Deepali; Humar, Atul

    2014-01-01

    Infectious complications remain a leading cause of morbidity and mortality after solid organ transplantation (SOT), and largely depend on the net state of immunosuppression achieved with current regimens. Cytomegalovirus (CMV) is a major opportunistic viral pathogen in this setting. The application of strategies of immunological monitoring in SOT recipients would allow tailoring of immunosuppression and prophylaxis practices according to the individual's actual risk of infection. Immune monitoring may be pathogen-specific or nonspecific. Nonspecific immune monitoring may rely on either the quantification of peripheral blood biomarkers that reflect the status of a given arm of the immune response (serum immunoglobulins and complement factors, lymphocyte sub-populations, soluble form of CD30), or on the functional assessment of T-cell responsiveness (release of intracellular adenosine triphosphate following a mitogenic stimulus). In addition, various methods are currently available for monitoring pathogen-specific responses, such as CMV-specific T-cell-mediated immune response, based on interferon-? release assays, intracellular cytokine staining or main histocompatibility complex-tetramer technology. This review summarizes the clinical evidence to date supporting the use of these approaches to the post-transplant immune status, as well as their potential limitations. Intervention studies based on validated strategies for immune monitoring still need to be performed. PMID:25505960

  11. Transcriptome Analysis Describing New Immunity and Defense Genes in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients

    PubMed Central

    Martin-Magniette, Marie-Laure; Lasbleiz, Sandra; Jacq, Laurent; Oliveira, Catarina Resende; Hilliquin, Pascal; Gut, Ivo; Cornelis, François; Petit-Teixeira, Elisabeth

    2009-01-01

    Background Large-scale gene expression profiling of peripheral blood mononuclear cells from Rheumatoid Arthritis (RA) patients could provide a molecular description that reflects the contribution of diverse cellular responses associated with this disease. The aim of our study was to identify peripheral blood gene expression profiles for RA patients, using Illumina technology, to gain insights into RA molecular mechanisms. Methodology/Principal Findings The Illumina Human-6v2 Expression BeadChips were used for a complete genome-wide transcript profiling of peripheral blood mononuclear cells (PBMCs) from 18 RA patients and 15 controls. Differential analysis per gene was performed with one-way analysis of variance (ANOVA) and P values were adjusted to control the False Discovery Rate (FDR<5%). Genes differentially expressed at significant level between patients and controls were analyzed using Gene Ontology (GO) in the PANTHER database to identify biological processes. A differentially expression of 339 Reference Sequence genes (238 down-regulated and 101 up-regulated) between the two groups was observed. We identified a remarkably elevated expression of a spectrum of genes involved in Immunity and Defense in PBMCs of RA patients compared to controls. This result is confirmed by GO analysis, suggesting that these genes could be activated systemically in RA. No significant down-regulated ontology groups were found. Microarray data were validated by real time PCR in a set of nine genes showing a high degree of correlation. Conclusions/Significance Our study highlighted several new genes that could contribute in the identification of innovative clinical biomarkers for diagnostic procedures and therapeutic interventions. PMID:19710928

  12. 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-13R?2) 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

  13. 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

  14. HDT701, a Histone H4 Deacetylase, Negatively Regulates Plant Innate Immunity by Modulating Histone H4 Acetylation of Defense-Related Genes in Rice[W][OA

    PubMed Central

    Ding, Bo; Bellizzi, Maria del Rosario; Ning, Yuese; Meyers, Blake C.; Wang, Guo-Liang

    2012-01-01

    Histone acetylation and deacetylation play an important role in the modification of chromatin structure and regulation of gene expression in eukaryotes. Chromatin acetylation status is modulated antagonistically by histone acetyltransferases and histone deacetylases (HDACs). In this study, we characterized the function of histone deacetylase701 (HDT701), a member of the plant-specific HD2 subfamily of HDACs, in rice (Oryza sativa) innate immunity. Transcription of HDT701 is increased in the compatible reaction and decreased in the incompatible reaction after infection by the fungal pathogen Magnaporthe oryzae. Overexpression of HDT701 in transgenic rice leads to decreased levels of histone H4 acetylation and enhanced susceptibility to the rice pathogens M. oryzae and Xanthomonas oryzae pv oryzae (Xoo). By contrast, silencing of HDT701 in transgenic rice causes elevated levels of histone H4 acetylation and elevated transcription of pattern recognition receptor (PRR) and defense-related genes, increased generation of reactive oxygen species after pathogen-associated molecular pattern elicitor treatment, as well as enhanced resistance to both M. oryzae and Xoo. We also found that HDT701 can bind to defense-related genes to regulate their expression. Taken together, these results demonstrate that HDT701 negatively regulates innate immunity by modulating the levels of histone H4 acetylation of PRR and defense-related genes in rice. PMID:22968716

  15. Immunization

    MedlinePLUS

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

  16. A tale of two tumours: Comparison of the immune escape strategies of contagious cancers?

    PubMed Central

    Siddle, Hannah V.; Kaufman, Jim

    2013-01-01

    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

  17. 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

  18. Strategies for Improving Influenza Immunization Rates among Hard-to-Reach Populations

    PubMed Central

    Coady, Micaela H.; Ompad, Danielle C.; Galea, Sandro

    2007-01-01

    Whereas considerable attention has been devoted to achieving high levels of influenza immunization, the importance of this issue is magnified by concern over pandemic influenza. Most recommendations for vaccine administration address high risk groups such as the elderly and those with chronic diseases, but coverage for hard-to-reach (HTR) populations has had less attention. HTR populations include minorities but also include other primarily urban groups such as undocumented immigrants, substance users, the homeless, and homebound elderly. Obstacles to the provision of immunization to HTR populations are present at the patient, provider, and structural levels. Strategies at the individual level for increasing immunization coverage include community-based educational campaigns to improve attitudes and increase motivation for receiving vaccine; at the provider level, education of providers to encourage immunizations, improving patient–provider interactions, broadening the provider base to include additional nurses and pharmacists, and adoption of standing orders for immunization administration; and at the structural level, promoting wider availability of and access to vaccine. The planning process for an influenza pandemic should include community engagement and extension of strategies beyond traditional providers to involve community-based organizations addressing HTR populations. PMID:17562184

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

    Microsoft Academic Search

    Niels Borregaard; Kim Theilgaard-Monch; Jack B. Cowland; Mona Ståhle; Ole E. Sørensen

    2004-01-01

    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 (1, 2). Like- wise, the skin and mucosal surfaces provide impor- tant barriers against infections. Traditionally, these major defense systems, the epithelial

  20. Addressing the Surveillance Goal in the National Strategy for Suicide Prevention: The Department of Defense Suicide Event Report

    PubMed Central

    Reger, Mark A.; Kinn, Julie T.; Luxton, David D.; Skopp, Nancy A.; Bush, Nigel E.

    2012-01-01

    The US National Strategy for Suicide Prevention (National Strategy) described 11 goals across multiple areas, including suicide surveillance. Consistent with these goals, the Department of Defense (DoD) has engaged aggressively in the area of suicide surveillance. The DoD's population-based surveillance system, the DoD Suicide Event Report (DoDSER) collects information on suicides and suicide attempts for all branches of the military. Data collected includes suicide event details, treatment history, military and psychosocial history, and psychosocial stressors at the time of the event. Lessons learned from the DoDSER program are shared to assist other public health professionals working to address the National Strategy objectives. PMID:22390595

  1. Body Defenses Immune System

    E-print Network

    Cochran-Stafira, D. Liane

    The Lymphatic System Consists of lymphatic vessels and the lymphatic organs Four main functions; Lymphatic of lipoproteins from the small intestines and transport them to the bloodstream; Lymphatic system produces Vessels & Organs Form a one-way system of capillaries, vessels, and ducts Lymphatic vessels take up

  2. 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

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

    PubMed

    Fedorka, Kenneth M; Copeland, Emily K; Winterhalter, Wade E

    2013-11-01

    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. PMID:23868839

  4. Targeting IL-6 by both passive or active immunization strategies prevents bleomycin-induced skin fibrosis

    PubMed Central

    2014-01-01

    Introduction Interleukin-6 (IL-6) is a pleiotropic cytokine for which preliminary data have suggested that it might contribute to systemic sclerosis (SSc). Our aims were to investigate, firstly, IL-6 expression in patients with SSc and, secondly, the efficacy of both passive and active immunization against IL-6 to reduce skin fibrosis in complementary mouse models of SSc. Methods Human serum levels and skin expression of IL-6 were determined by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. We first evaluated the antifibrotic properties of the monoclonal anti-IL-6R antibody, MR16-1, in the bleomycin-induced dermal fibrosis mouse model, reflecting early and inflammatory stages of SSc. Then, we assessed the efficacy of MR16-1 in tight skin-1 (Tsk-1) mice, an inflammation-independent model of skin fibrosis. Additionally, we have developed an innovative strategy using an anti-IL-6 peptide-based active immunization. Infiltrating leukocytes, T cells, and B cells were quantified, and IL-6 levels were measured in the serum and lesional skin of mice after passive or active immunization. Results Serum and skin levels of IL-6 were significantly increased in patients with early SSc. Treatment with MR16-1 led in the bleomycin mouse model to a 25% (P = 0.02) and 30% (P = 0.007) reduction of dermal thickness and hydroxyproline content, respectively. MR16-1 demonstrated no efficacy in Tsk-1 mice. Thereafter, mice were immunized against a small peptide derived from murine IL-6 and this strategy led in the bleomycin model to a 20% (P = 0.02) and 25% (P = 0.005) decrease of dermal thickness and hydroxyproline content, respectively. Passive and active immunization led to decreased T-cell infiltration in the lesional skin of mice challenged with bleomycin. Upon bleomycin injections, serum and skin IL-6 levels were increased after treatment with MR16-1 and were significantly reduced after anti-IL-6 active immunization. Conclusions Our results support the relevance of targeting IL-6 in patients with early SSc since IL-6 is overexpressed in early stages of the disease. Targeting IL-6 by both passive and active immunization strategies prevented the development of bleomycin-induced dermal fibrosis in mice. Our results highlight the therapeutic potential of active immunization against IL-6, which is a seductive alternative to passive immunization. PMID:25059342

  5. Annual Defense Report 2000

    NSDL National Science Digital Library

    Forwarded to the President and Congress annually, the Secretary of Defense's Annual Defense Report serves as "a basic reference document for those interested in national defense issues and programs." The 350-page 2000 edition is available in HTML and .pdf formats. It covers topics such as defense strategy, the current state of the armed forces, plans for transforming the armed forces and the Department of Defense, statutory reports from the individual secretaries, and a number of appendices.

  6. Defensive strategies of soft corals (Coelenterata: Octocorallia) of the Great Barrier Reef

    Microsoft Academic Search

    P. W. Sammarco; S. Barre; J. C. Coll

    1987-01-01

    The relationship between ichthyotoxicity and predation-related defensive functional morphology was examined in alcyonacean soft corals of the central and northern regions of the Great Barrier Reef (GBR), Australia. Approximately 170 specimens were assessed encompassing a number of genera within three families: 1) the Alcyoniidae (Lobophytum, Sarcophytum, Sinularia, Cladiella, Parerythropodium, and Alcyonium); 2) Neptheidae (Lemnalia, Paralemnalia, Capnella, Lithophyton, Nephthea, Dendronephthya, Scleronephthya,

  7. West European and East Asian perspectives on defense, deterrence, and strategy. Volume 2. Western European perspectives on defense, deterrence, and strategy. Technical report, 1 December 1982-15 May 1984

    SciTech Connect

    Pfaltzgraff, R.L.; Davis, J.K.; Dougherty, J.E.; Perry, C.M.

    1984-05-16

    A survey of contemporary West European perspectives on defense, deterrence, and strategy, with special emphasis on the role of nuclear weapons deployed in, or assigned to, the NATO area. Changes have occurred during the past decade in the relative military strength of NATO and the Warsaw Pact, particularly as a result of the substantial growth in Soviet nuclear-capable systems and conventional forces assigned to Europe, and the momentum manifested by the Soviet Union in its deployments of intercontinental ballistic missiles. There has also been a substantial shift in West European thinking and attitudes about security and strategy. Together, these trends have created a need to reassess the posture of NATO forces generally, and especially nuclear weapons, both in a broader Euro-strategic framework and on the Central Front in the 1980s. The survey is on such issues as the future of the British and French national strategic nuclear forces; the role of the U.S.-strategic nuclear forces in the deterrence of conflict in Europe; the prospects of raising the nuclear threshold by the deployment of new conventional technologies; the impact of strategic defense initiatives on U.S.-NATO security; and the modernization of NATO intermediate-range nuclear capabilities, especially in light of the continuing deployment of the Soviet Union of new generation Euro-strategic forces targeted against Western Europe.

  8. 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 Colombia’s 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 <5 years 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 Colombia’s EPI to inform the design of new communication strategies. PMID:24981729

  9. 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

  10. 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

  11. 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, ...

  12. Influence of immune-relevant genotype on the reproductive success of a salmonid alternative mating strategy.

    PubMed

    O'Malley, K G; Perales, B; Whitcomb, A C

    2015-03-01

    Major histocompatibility complex (MHC) and immune-relevant gene markers were used to evaluate differences in reproductive success (RS) among naturally spawning coho salmon Oncorhynchus kisutch mate pairs involving an alternative male reproductive phenotype, known as jacks. These mate pairs included both hatchery-reared and wild origin fish such that three classes were evaluated in two consecutive years (2005 and 2006) using a previously constructed multigenerational genetic pedigree: wild × wild (W × W), hatchery × hatchery (H × H) and wild × hatchery (W × H). Oncorhynchus kisutch jack mate pairs mated randomly based on immune-relevant genotype in both years; a result consistent with the opportunistic mating strategy of jacks. An association between greater number of alleles shared at three immune-relevant gene markers and increased RS was found for: W × H mate pairs in 2005 (BHMS429), W × H pairs in 2006 (SsalR016TKU) and W × W pairs in 2006 (OMM3085). No correlation between immune gene diversity and RS was found for H × H pairs in either year. The results suggest that the influence of immune-relevant genotype on mating success may be different for jacks when compared with previous studies of large adult male O. kisutch. PMID:25643937

  13. 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 1.05×106 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.

  14. Enhanced immune responses and protection by vaccination with respiratory syncytial virus fusion protein formulated with CpG oligodeoxynucleotide and innate defense regulator peptide in polyphosphazene microparticles.

    PubMed

    Garlapati, S; Garg, R; Brownlie, R; Latimer, L; Simko, E; Hancock, R E W; Babiuk, L A; Gerdts, V; Potter, A; van Drunen Littel-van den Hurk, S

    2012-07-27

    Although respiratory syncytial virus (RSV) is the leading cause of serious respiratory tract disease in children, to date no RSV vaccine is available. To produce an effective subunit vaccine, a truncated secreted version of the F protein (?F) was expressed in mammalian cells, purified and shown to form trimers. The ?F protein was then formulated with a CpG oligodeoxynucleotide (ODN) and an innate defense regulator (IDR) peptide in polyphosphazene microparticles (?F-MP). Mice immunized either intramuscularly (IM) or intranasally (IN) with ?F-MP developed significantly higher levels of virus-neutralizing antibodies in the sera and lungs, as well as higher numbers of IFN-? secreting cells than mice immunized with the ?F protein alone. In contrast, the IM delivered ?F induced high production of IL-5 while the IN delivered ?F did not elicit a measurable immune response. After RSV challenge, essentially no virus and no evidence of immunopathology were detected in mice immunized with ?F-MP regardless of the route of delivery. While the mice immunized IM with ?F alone also showed reduced virus replication, they developed enhanced levels of pulmonary IgE, IL-4, IL-5, IL-13 and eotaxin, as well as eosinophilia after challenge. The level of protection induced by the ?F-MP formulation was equivalent after IM and IN delivery. The efficacy and safety of the ?F-MP formulation was confirmed in cotton rats, which also developed enhanced immune responses and were fully protected from RSV challenge after vaccination with ?F-MP. In conclusion, formulation of recombinant ?F with CpG ODN and IDR peptide in polyphosphazene microparticles should be considered for further evaluation as a safe and effective vaccine against RSV. PMID:22713718

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

    E-print Network

    Allam, Bassem

    Effects of temperature on hard clam (Mercenaria mercenaria) immunity and QPX (Quahog Parasite Keywords: Hard clam Mercenaria mercenaria QPX Thraustochytrid Parasite Immune response Temperature Environment a b s t r a c t Quahog Parasite Unknown (QPX) is a protistan parasite affecting hard clams

  16. Immune Evasion, Immunopathology and the Regulation of the Immune System

    PubMed Central

    Sorci, Gabriele; Cornet, Stéphane; Faivre, Bruno

    2013-01-01

    Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths) that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response. PMID:25436882

  17. 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 ...

  18. The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity

    Microsoft Academic Search

    D. Yang; O. Chertov; J. J. Oppenheim

    2001-01-01

    Since we live in a dirty environment, we have developed many host defenses to contend with microor- ganisms. The epithelial lining of our skin, gastrointestinal tract and bronchial tree produces a number of antibacte- rial peptides, and our phagocytic neutrophils rapidly in- gest and enzymatically degrade invading organisms, as well as produce peptides and enzymes with antimicrobial activities. Some of

  19. 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

  20. An optimal defense strategy for phenolic glycoside production in Populus trichocarpa--isotope labeling demonstrates secondary metabolite production in growing leaves.

    PubMed

    Massad, Tara Joy; Trumbore, Susan E; Ganbat, Gantsetseg; Reichelt, Michael; Unsicker, Sybille; Boeckler, Andreas; Gleixner, Gerd; Gershenzon, Jonathan; Ruehlow, Steffen

    2014-07-01

    Large amounts of carbon are required for plant growth, but young, growing tissues often also have high concentrations of defensive secondary metabolites. Plants' capacity to allocate resources to growth and defense is addressed by the growth-differentiation balance hypothesis and the optimal defense hypothesis, which make contrasting predictions. Isotope labeling can demonstrate whether defense compounds are synthesized from stored or newly fixed carbon, allowing a detailed examination of these hypotheses. Populus trichocarpa saplings were pulse-labeled with 13CO2 at the beginning and end of a growing season, and the 13C signatures of phenolic glycosides (salicinoids), sugars, bulk tissue, and respired CO2 were traced over time. Half of the saplings were also subjected to mechanical damage. Populus trichocarpa followed an optimal defense strategy, investing 13C in salicinoids in expanding leaves directly after labeling. Salicinoids turned over quickly, and their production continued throughout the season. Salicin was induced by early-season damage, further demonstrating optimal defense. Salicinoids appear to be of great value to P. trichocarpa, as they command new C both early and late in the growing season, but their fitness benefits require further study. Export of salicinoids between tissues and biochemical pathways enabling induction also needs research. Nonetheless, the investigation of defense production afforded by isotope labeling lends new insights into plants' ability to grow and defend simultaneously. PMID:24739022

  1. 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.

  2. 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 Fc?-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

  3. 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-Escárate, 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

  4. Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune system

    Microsoft Academic Search

    Mihai G. Netea; Chantal van der Graaf; Bart Jan Kullberg

    2003-01-01

    Toll-like receptors (TLRs) have been identified as a major class of pattern-recognition receptors. Recognition of pathogen-associated mo- lecular patterns (PAMPs) by TLRs, alone or in heterodimerization with other TLR or non-TLR receptors, induces signals responsible for the acti- vation of genes important for an effective host defense, especially proinflammatory cytokines. Al- though a certain degree of redundancy exists be- tween

  5. BMD Agents: An Agent-Based Framework to Model Ballistic Missile Defense Strategies

    Microsoft Academic Search

    Duminda Wijesekera; James Bret Michael; Anil Nerode

    We introduce a model-based methodology for comparative eval- uation of the effectiveness of alternative ballistic missle de- fense strategies. The major new feature is that BMD is mod- elled as a distributed system of interacting agents in which some agents are physical (such as sensors and launch systems) and some are rule-based (such as decision makers and threat- evaluators). In

  6. Economics and Homeland Security Strategies: Issues regarding Carcass Disposal in Design of Animal Disease Defense Systems

    E-print Network

    McCarl, Bruce A.

    Economics and Homeland Security Strategies: Issues regarding Carcass Disposal in Design of Animal that involves the design of a disease management system in the face of a potential deliberate or accidental FMD, including burial, incineration, composting, rendering, lactic acid fermentation, alkaline hydrolysis

  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. Unraveling the Evolution of the Atlantic Cod’s (Gadus morhua L.) Alternative Immune Strategy

    PubMed Central

    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

  9. 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.

  10. 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

  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. Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection

    PubMed Central

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

    2011-01-01

    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

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

    PubMed

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

    2015-02-13

    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

  14. 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

  15. 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

  16. Immunizations.

    PubMed

    Middleton, D B

    1990-12-01

    The primary care physician has few tools as effective as immunization. Patients deserve to be advised about prophylaxis and appropriately treated when the need arises. Monitoring of the CDC's Morbidity and Mortality Weekly Report (MMWR) is the most efficient manner of keeping current. The Journal of the American Medical Association usually quotes the important advances from the MMWR. The local health department is generally helpful in covering local crises or giving travel advice. PMID:2290871

  17. Developmental timing of signals affects information content: song complexity but not consistency reflects innate immune strategy in male song sparrows.

    PubMed

    Kubli, Shawn P; MacDougall-Shackleton, Elizabeth A

    2014-05-01

    In short-lived animals, innate immunity is an important component of fitness and quality. Although receivers cannot generally assess a signaler's immune function directly, sexually selected displays such as birdsong may reflect past or current condition. We investigated the degree to which song complexity and consistency, thought to reflect condition over different developmental timescales, predict multiple aspects of innate immunity in male song sparrows (Melospiza melodia). We also investigated correlations among immune measures. Noncellular components of innate immunity (soluble blood proteins including natural antibody and other protective proteins) were negatively related to cellular (phagocytosis-based) components, suggesting trade-offs within innate immune protection. This pattern underscores the risk of inferring "immunocompetence" from a single metric. Song complexity, a permanent trait in this species, was positively related to noncellular relative to cellular immune components and may thus provide information as to the singer's innate immune strategy (investment in noncellular vs. cellular activity). Such a relationship could arise through shared timing of song learning and antibody repertoire development in early life. Singing consistency, thought to track variation in current condition and measured at both whole-song and syllable scales, did not predict any immune measures. Developmental timing of signals thus appears to influence their information content. PMID:24739198

  18. Estimating teh costs of achieving the WHO-UNICEF Global Immunization Vision and Strategy, 2006-2015

    Microsoft Academic Search

    Lara J Wolfson; François Gasse; Shook-Pui Lee-Martin; Patrick Lydon; Ahmed Magan; Abdelmajid Tibouti; Benjamin Johns; Raymond Hutubessy; Peter Salama; Jean-Marie Okwo-Bele

    2008-01-01

    Objective To estimate the cost of scaling up childhood immunization services required to reach the WHO-UNICEF 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

  19. West European and East Asian perspectives on defense, deterrence, and strategy. Volume 5. Chinese perspectives on defense, deterrence, and strategy. Technical report, 1 December 1982-15 May 1984

    SciTech Connect

    Pfaltzgraff, R.L.; Davis, J.K.; Dougherty, J.E.; Perry, C.M.

    1984-05-15

    This study assesses Chinese defense and foreign policy perspectives, especially as they influence, and are influenced by, China's strategic approach to international issues. Special emphasis is placed on China's recent perspectives on the Soviet Union, Japan, and the United States, together with other major countries, as well as the Third World. China's views on international and regional security issues are assessed with reference both to Marxist and more-traditional Chinese influences, including the perspective of Mao's Three Worlds and the revisions that have been made in this view - which might now be called a unified front strategy at the global level. This study also identified the principal members of the strategic and foreign-policy elite in the PRC and examines their perspectives on such key issues as the U.S.-Soviet strategic equation and its implications for the military balance in the Asian-Pacific region; arms control and disarmament schemes (especially with respect to nuclear weapons); the credibility of the U.S. protective guarantee for allies in East Asia; trends in the regional nuclear power balance (including the question of nuclear proliferation in Asia); and the prospects for future Sino-American cooperation.

  20. Macrophage defense mechanisms against intracellular bacteria.

    PubMed

    Weiss, Günter; 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

  1. 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

  2. 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

  3. 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, ?-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

  4. Strategies to Query and Display Allergy-Derived Epitope Data from the Immune Epitope Database

    PubMed Central

    Vaughan, Kerrie; Peters, Bjoern; Larche, Mark; Pomes, Anna; Broide, David; Sette, Alessandro

    2013-01-01

    The recognition of specific epitopes on allergens by antibodies and T cells is a key element in allergic processes. Analysis of epitope data may be of interest for basic immunopathology or for potential application in diagnostics or immunotherapy. The Immune Epitope Database (IEDB) is a freely available repository of epitope data from infectious disease agents, as well as epitopes defined for allergy, autoimmunity, and transplantation. The IEDB curates the experiments associated with each epitope and thus provides a variety of different ways to search the data. This review aims to demonstrate the utility of the IEDB and its query strategies, including searching by epitope structure (peptidic/nonpeptidic), by assay methodology, by host, by the allergen itself, or by the organism from which the allergen was derived. Links to tools for visualization of 3-D structures, epitope prediction, and analyses of B and T cell reactivity by host response frequency score are also highlighted. PMID:23172234

  5. 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

  6. 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

  7. 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 ?-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

  8. Human and Animal Isolates of Yersinia enterocolitica Show Significant Serotype-Specific Colonization and Host-Specific Immune Defense Properties

    PubMed Central

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

    2013-01-01

    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

  9. 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

  10. 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.…

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

    PubMed

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

    2015-02-01

    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

  12. Immune System

    MedlinePLUS

    ... scientists can use this information to develop new strategies for the prevention and treatment of infectious and immune-mediated diseases. Read more about Research Frontiers . What's New Media Availability: NIH Researchers Develop Database on Healthy Immune System — ...

  13. 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

  14. Tachylectin-2: crystal structure of a specific GlcNAc/GalNAc-binding lectin involved in the innate immunity host defense of the Japanese horseshoe crab Tachypleus tridentatus.

    PubMed Central

    Beisel, H G; Kawabata, S; Iwanaga, S; Huber, R; Bode, W

    1999-01-01

    Tachylectin-2, isolated from large granules of the hemocytes of the Japanese horseshoe crab (Tachypleus tridentatus), is a 236 amino acid protein belonging to the lectins. It binds specifically to N-acetylglucosamine and N-acetylgalactosamine and is a part of the innate immunity host defense system of the horseshoe crab. The X-ray structure of tachylectin-2 was solved at 2.0 A resolution by the multiple isomorphous replacement method and this molecular model was employed to solve the X-ray structure of the complex with N-acetylglucosamine. Tachylectin-2 is the first protein displaying a five-bladed beta-propeller structure. Five four-stranded antiparallel beta-sheets of W-like topology are arranged around a central water-filled tunnel, with the water molecules arranged as a pentagonal dodecahedron. Tachylectin-2 exhibits five virtually identical binding sites, one in each beta-sheet. The binding sites are located between adjacent beta-sheets and are made by a large loop between the outermost strands of the beta-sheets and the connecting segment from the previous beta-sheet. The high number of five binding sites within the single polypeptide chain strongly suggests the recognition of carbohydrate surface structures of pathogens with a fairly high ligand density. Thus, tachylectin-2 employs strict specificity for certain N-acetyl sugars as well as the surface ligand density for self/non-self recognition. PMID:10228146

  15. 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

  16. Innate immunity and pathogen-host interaction.

    PubMed

    Basset, Christelle; Holton, John; O'Mahony, Rachel; Roitt, Ivan

    2003-06-01

    The skin and contiguous mucosal surfaces define the primary locus of interaction between host and micro-organisms. In this review, we focus on the innate immune system in the mucosa, which manages to deal with invading pathogens, the mechanisms that organisms have evolved in order to circumvent this primary defensive barrier and, finally, potential therapeutic manipulation of the innate immune system that was the focus of meeting at a Euroconference/Workshop on "Novel Strategies of Mucosal Immunisation through Exploitation of Mechanisms of Innate Immunity in Pathogen-Host Interaction", which was held in Siena, Italy, November 2002. PMID:12763678

  17. 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

  18. 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.

  19. 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

  20. 78 FR 79469 - Strategies To Address Hemolytic Complications of Immune Globulin Infusions; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ...Hemolytic Complications of Immune Globulin Infusions; Public Workshop AGENCY: Food and Drug...Hemolytic Complications of Immune Globulin Infusions.'' The purpose of the public workshop...Globulin Intravenous (IGIV) (Human) infusion. Complications of hemolysis...

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

    PubMed

    Cueto, Juan A; Rodriguez, Cristian; 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. Prime-Boost Strategies in Mucosal Immunization Affect Local IgA Production and the Type of Th Response

    PubMed Central

    Fiorino, Fabio; Pettini, Elena; Pozzi, Gianni; Medaglini, Donata; Ciabattini, Annalisa

    2013-01-01

    Combinations of different delivery routes for priming and boosting represent vaccination strategies that can modulate magnitude, quality, and localization of the immune response. A murine model was used to study T cell clonal expansion following intranasal (IN) or subcutaneous (SC) priming, and secondary immune responses after boosting by either homologous or heterologous routes. T cell primary activation was studied by using the adoptive transfer model of ovalbumin-specific transgenic CD4+ T cells. Both IN and SC immunization efficiently elicited, in the respective draining lymph nodes, primary clonal expansion of antigen-specific CD4+ T cells that disseminated toward distal lymph nodes (mesenteric and iliac) and the spleen. After boosting, a significant serum IgG response was induced in all groups independent of the combination of immunization routes used, while significant levels of local IgA were detected only in mice boosted by the IN route. Mucosal priming drove a stronger Th1 polarization than the systemic route, as shown by serum IgG subclass analysis. IFN-gamma production was observed in splenocytes of all groups, while prime-boost vaccine combinations that included the mucosal route, yielded higher levels of IL-17. Memory lymphocytes were identified in both spleen and draining lymph nodes in all immunized mice, with the highest number of IL-2 producing cells detected in mice primed and boosted by the nasal route. This work shows the critical role of immunization routes in modulating quality and localization of immune responses in prime-boost vaccine strategies. PMID:23755051

  3. The politics of Soviet strategic defense: Political strategies, organization politics, and Soviet strategic thought. (Volumes I and II)

    Microsoft Academic Search

    1991-01-01

    This study formulates three different unitary rational-actor models and an organizational model that can be used to explain Soviet policy in strategic defense from 1966-1980, then tests the models to determine which most successfully explains Soviet behavior. The only rational-actor model that can explain the Soviet force posture for air defense relies on demonstrably false assumptions. A well-formulated organizational model

  4. Immunity in Fish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fish immune system has evolved with both non-specific (innate immunity) and acquired immune functions (humoral and cell mediated immunity) to eliminate invading foreign living and non-living agents. Fish possess a unique physical barrier (mucus and skin) that acts as the first line of defense a...

  5. A novel approach for the generation of Salmonella Gallinarum ghosts and evaluation of their vaccine potential using a prime-booster immunization strategy.

    PubMed

    Jawale, Chetan V; Lee, John Hwa

    2014-11-28

    A novel, regulatory E-lysis cassette was used in this study to avoid the untimely expression of lysis gene E and to achieve stable and improved production of Salmonella Gallinarum (SG) ghosts. A prime-booster immunization strategy using these ghosts was subsequently utilized with the aim of inducing a robust immune response for the prevention of acute fowl typhoid infection. In the first animal experiment, a total of 54 chickens were equally divided into three groups (n=18): group A (non-immunized control), group B (prime-boost immunized), and group C (singly immunized). Chickens from both immunized groups demonstrated significant increases in plasma IgG, intestinal secretory IgA, and antigen-specific lymphocyte proliferative responses. After virulent SG challenge, group B chickens immunized with the prime-boost regimen showed optimized protection. In the second animal experiment, total 20 chickens were equally divided into two groups (n=10): group A (non-immunized control), group B (prime-boost immunized) and the immunogenicity of the ghosts was further evaluated after a booster dose of the immunization. In the second animal experiment, the population of CD3+CD4+ positive T cells in the immunized chickens was significantly higher after booster immunization. In addition, increased gene expression levels of Th1 cytokines, IFN-?, and IL-2 were observed in SG-specific antigen stimulated peripheral blood mononuclear cells of prime-boost immunized chickens compared to non-immunized chickens. In summary, the current study describes a novel approach for stable production of a safety-enhanced SG ghost preparation, and demonstrates that utilization of a prime-boost immunization strategy has an advantage over single immunization because it induces a robust immune response for optimum protection against fowl typhoid. PMID:25454861

  6. 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.

  7. 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

  8. 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

  9. Modulating plant primary amino acid metabolism as a necrotrophic virulence strategy: the immune-regulatory role of asparagine synthetase in Botrytis cinerea-tomato interaction.

    PubMed

    Seifi, Hamed; De Vleesschauwer, David; Aziz, Aziz; Höfte, Monica

    2014-01-01

    The fungal plant pathogen Botrytis cinerea is the causal agent of the "gray mold" disease on a broad range of hosts. As an archetypal necrotroph, B. cinerea has evolved multiple virulence strategies for inducing cell death in its host. Moreover, progress of B. cinerea colonization is commonly associated with induction of senescence in the host tissue, even in non-invaded regions. In a recent study, we showed that abscisic acid deficiency in the sitiens tomato mutant culminates in an anti-senescence defense mechanism which effectively contributes to resistance against B. cinerea infection. Conversely, in susceptible wild-type tomato a strong induction of senescence could be observed following B. cinerea infection. Building upon this earlier work, we here discuss the immune-regulatory role of a key senescence-associated protein, asparagine synthetase. We found that infection of wild-type tomato leads to a strong transcriptional upregulation of asparagine synthetase, followed by a severe depletion of asparagine titers. In contrast, resistant sitiens plants displayed a strong induction of asparagine throughout the course of infection. We hypothesize that rapid activation of asparagine synthetase in susceptible tomato may play a dual role in promoting Botrytis cinerea pathogenesis by providing a rich source of N for the pathogen, on the one hand, and facilitating pathogen-induced host senescence, on the other. PMID:24521937

  10. 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

  11. ???T Lymphocytes as a First Line of Immune Defense: Old and New Ways of Antigen Recognition and Implications for Cancer Immunotherapy

    PubMed Central

    Poggi, Alessandro; Zocchi, Maria Raffaella

    2014-01-01

    Among ??T cells, the V?1 subset, resident in epithelial tissues, is implied in the defense against viruses, fungi, and certain hematological malignancies, while the circulating V?2 subpopulation mainly respond to mycobacteria and solid tumors. Both subsets can be activated by stress-induced molecules (MIC-A, MIC-B, ULBPs) to produce pro-inflammatory cytokines and lytic enzymes and destroy bacteria or damaged cells. ??T lymphocytes can also recognize lipids, as those associated to M. tuberculosis, presented by the CD1 molecule, or phosphoantigens (P-Ag), either autologous, which accumulates in virus-infected cells, or microbial produced by prokaryotes and parasites. In cancer cells, P-Ag accumulate due to alterations in the mevalonate pathway; recently, butyrophilin 3A1 has been shown to be the presenting molecule for P-Ag. Of interest, aminobisphosphonates indirectly activate V?2 T cells inducing the accumulation of P-Ag. Based on these data, ??T lymphocytes are attractive effectors for cancer immunotherapy. However, the results obtained in clinical trials so far have been disappointing: this review will focus on the possible reasons of this failure as well as on suggestions for implementation of the therapeutic strategies. PMID:25426121

  12. The politics of Soviet strategic defense: Political strategies, organization politics, and Soviet strategic thought. (Volumes I and II)

    SciTech Connect

    Kaufman, S.J.

    1991-01-01

    This study formulates three different unitary rational-actor models and an organizational model that can be used to explain Soviet policy in strategic defense from 1966-1980, then tests the models to determine which most successfully explains Soviet behavior. The only rational-actor model that can explain the Soviet force posture for air defense relies on demonstrably false assumptions. A well-formulated organizational model can explain these facts, as well as some organizational pathologies shown by the Soviet National Air Defense Forces. The findings suggest that military services, even when ostensibly closely directed by civilian and military superiors, often manage to pursue their own interests rather than the requirements of higher policy. Soviet civilian leaders generally had limited control over the formulation of military doctrine or over the force posture of Soviet military services, but arms control (especially the ABM Treaty) offered a policy handle which helped them to affect doctrine and force posture to a substantial degree.

  13. Oral immunization using alginate microparticles as a useful strategy for booster vaccination against fish lactoccocosis

    Microsoft Academic Search

    Jesús L Romalde; Asteria Luzardo-Alvárez; Carmen Ravelo; Alicia E Toranzo; José Blanco-Méndez

    2004-01-01

    In this work, oral vaccination with encapsulated and non-encapsulated antigens was preliminary evaluated as alternative immunization procedures against trout lacotococcosis. Fish were oral immunized with a variety of different Lactococcus garvieae vaccines including encapsulated and non-encapsulated bacterial cells. An aqueous-based bacterin administered by intraperitoneal injection (i.p.) was employed as positive control. The best protective rates by oral immunization were obtained

  14. 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

  15. Salmonella enterica induces and subverts the plant immune system

    PubMed Central

    García, Ana V.; Hirt, Heribert

    2014-01-01

    Infections with Salmonella enterica belong to the most prominent causes of food poisoning and infected fruits and vegetables represent important vectors for salmonellosis. Although it was shown that plants raise defense responses against Salmonella, these bacteria persist and proliferate in various plant tissues. Recent reports shed light into the molecular interaction between plants and Salmonella, highlighting the defense pathways induced and the means used by the bacteria to escape the plant immune system and accomplish colonization. It was recently shown that plants detect Salmonella pathogen-associated molecular patterns (PAMPs), such as the flagellin peptide flg22, and activate hallmarks of the defense program known as PAMP-triggered immunity (PTI). Interestingly, certain Salmonella strains carry mutations in the flg22 domain triggering PTI, suggesting that a strategy of Salmonella is to escape plant detection by mutating PAMP motifs. Another strategy may rely on the type III secretion system (T3SS) as T3SS mutants were found to induce stronger plant defense responses than wild type bacteria. Although Salmonella effector delivery into plant cells has not been shown, expression of Salmonella effectors in plant tissues shows that these bacteria also possess powerful means to manipulate the plant immune system. Altogether, these data suggest that Salmonella triggers PTI in plants and evolved strategies to avoid or subvert plant immunity. PMID:24772109

  16. Strategies of ROS regulation and antioxidant defense during transition from C? to C? photosynthesis in the genus Flaveria under PEG-induced osmotic stress.

    PubMed

    Uzilday, Baris; Turkan, Ismail; Ozgur, Rengin; Sekmen, Askim H

    2014-01-01

    In the present study, we aimed to elucidate how strategies of reactive oxygen species (ROS) regulation and the antioxidant defense system changed during transition from C? to C? photosynthesis, by using the model genus Flaveria, which contains species belonging to different steps in C? evolution. For this reason, four Flaveria species that have different carboxylation mechanisms, Flaveria robusta (C?), Flaveria anomala (C?-C?), Flaveria brownii (C?-like) and Flaveria bidentis (C?), were used. Physiological (growth, relative water content (RWC), osmotic potential), and photosynthetical parameters (stomatal conductance (g(s)), assimilation rate (A), electron transport rate (ETR)), antioxidant defense enzymes (superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX), glutathione reductases(GR)) and their isoenzymes, non-enzymatic antioxidant contents (ascorbate, glutathione), NADPH oxidase (NOX) activity, hydrogen peroxide (H?O?) content and lipid peroxidation levels (TBARS) were measured comparatively under polyethylene glycol (PEG 6000) induced osmotic stress. Under non-stressed conditions, there was a correlation only between CAT (decreasing), APX and GR (both increasing) and the type of carboxylation pathways through C? to C? in Flaveria species. However, they responded differently to PEG-induced osmotic stress in regards to antioxidant defense. The greatest increase in H?O? and TBARS content was observed in C? F. robusta, while the least substantial increase was detected in C?-like F. brownii and C? F. bidentis, suggesting that oxidative stress is more effectively countered in C?-like and C? species. This was achieved by a better induced enzymatic defense in F. bidentis (increased SOD, CAT, POX, and APX activity) and non-enzymatic antioxidants in F. brownii. As a response to PEG-induced oxidative stress, changes in activities of isoenzymes and also isoenzymatic patterns were observed in all Flaveria species, which might be related to ROS produced in different compartments of cells. PMID:23920414

  17. 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

  18. Is crypsis a common defensive strategy in plants? Speculation on signal deception in the New Zealand flora.

    PubMed

    Burns, Kevin C

    2010-01-01

    Color is a common feature of animal defense. Herbivorous insects are often colored in shades of green similar to their preferred food plants, making them difficult for predators to locate. Other insects advertise their presence with bright colors after they sequester enough toxins from their food plants to make them unpalatable. Some insects even switch between cryptic and aposomatic coloration during development. Although common in animals, quantitative evidence for color-based defense in plants is rare. After all, the primary function of plant leaves is to absorb light for photosynthesis, rather than reflect light in ways that alter their appearance to herbivores. However, recent research is beginning to challenge the notion that color-based defence is restricted to animals. PMID:20592801

  19. 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.

  20. 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, Héctor

    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 cell–cell 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

  1. Estimating the costs of achieving the WHO–UNICEF Global Immunization Vision and Strategy, 2006–2015

    PubMed Central

    Gasse, François; 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 WHO–UNICEF 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$ 1.8–4.2) billion on immunization in 2005, an increase from US$ 1.1 (range: US$ 0.9–1.6) billion in 2000. By 2015 annual immunization costs will on average increase to about US$ 4.0 (range US$ 2.9–6.7) billion. Total immunization costs for 2006–2015 are estimated at US$ 35 (range US$ 13–40) 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 2006–2015 are estimated at US$ 76 (range: US$ 23–110) billion, with US$ 49 billion for maintaining current systems and $27 billion for scaling-up. Conclusion In the 72 poorest countries, US$ 11–15 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

  2. Quadrennial Defense Review, 2001

    NSDL National Science Digital Library

    2001-01-01

    Every four years, the military issues the Quadrennial Defense Review (QDR) Report, a document that is key in setting military goals and priorities. This 79-page report, issued September 30, 2001, is divided into seven main sections (e.g., Defense Strategy, Revitalizing the DoD Establishment) and includes a statement by the Chairman of the Joint Chiefs of Staff. The report explains that, "Even before the attack of September 11, 2001, the senior leaders of the Defense Department set out to establish a new strategy for America's defense that would embrace uncertainty and contend with surprise, a strategy premised on the idea that to be effective abroad, America must be safe at home." In the service of that new strategy, the QDR outlines DoD's four main policy objectives: to assure allies and friends of the US' steadfastness and military capability, to dissuade adversaries from undertaking programs potentially threatening to the US, to deter threats by increasing "the capacity to swiftly defeat attacks and impose severe penalties for aggression," and when deterrence fails, to decisively defeat any adversary. A central objective of this review was to shift the basis of defense planning. The report explains that overall the strategy seeks to move the US military "from a 'threat-based' model that has dominated thinking in the past to a 'capabilities-based' model for the future."

  3. 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

  4. Parasite Exposure Drives Selective Evolution of Constitutive versus Inducible Defense.

    PubMed

    Westra, Edze R; van Houte, Stineke; Oyesiku-Blakemore, Sam; Makin, Ben; Broniewski, Jenny M; Best, Alex; Bondy-Denomy, Joseph; Davidson, Alan; Boots, Mike; Buckling, Angus

    2015-04-20

    In the face of infectious disease, organisms evolved a range of defense mechanisms, with a clear distinction between those that are constitutive (always active) and those that are inducible (elicited by parasites) [1]. Both defense strategies have evolved from each other [2], but we lack an understanding of the conditions that favor one strategy over the other. While it is hard to generalize about their degree of protection, it is possible to make generalizations about their associated fitness costs, which are commonly detected [3-5]. By definition, constitutive defenses are always "on," and are therefore associated with a fixed cost, independent of parasite exposure [4, 5]. Inducible defenses, on the other hand, may lack costs in the absence of parasites but become costly when defense is elicited [6] through processes such as immunopathology [7]. Bacteria can evolve constitutive defense against phage by modification/masking of surface receptors [8, 9], which is often associated with reduced fitness in the absence of phage [10]. Bacteria can also evolve inducible defense using the CRISPR-Cas (clustered regularly interspaced short palindromic repeat, CRISPR associated) immune system [11], which is typically elicited upon infection [12-14]. CRISPR-Cas functions by integrating phage sequences into CRISPR loci on the host genome [15]. Upon re-infection, CRISPR transcripts guide cleavage of phage genomes [16-20]. In nature, both mechanisms are important [21, 22]. Using a general theoretical model and experimental evolution, we tease apart the mechanism that drives their evolution and show that infection risk determines the relative investment in the two arms of defense. PMID:25772450

  5. West European and East Asian perspectives on defense, deterrence, and strategy. Volume 6. South Korean perspectives on defense, deterrence, and strategy. Technical report, 1 December 1981-30 November 1982

    SciTech Connect

    Pfaltzgraff, R.L.; Dougherty, J.E.; Davis, J.K.; Perry, C.M.

    1984-04-11

    This study addresses the international security perspectives of the Republic of Korea (South Korea). Particular emphasis is placed on the way in which American, Soviet, Chinese and Japanese interests intersect on the Korean Peninsula and on their impact upon the military balance between North and South Korea. A major portion of this analysis is devoted as well to an examination of inter-Korean relations, spotlighting the varying security implications of the continued partition, as opposed to the eventual reunification of the two Koreas. The importance to South Korea of the Seoul-Washington-Tokyo relationship is discussed, as well as the effect of the Sino-Soviet dispute on South Korean defense and foreign policies. In order to clarify further the strategic perspectives of key decision makers in Seoul, the study reviewed and assessed South Korean views on such controversial issues as the expansion of Japan's self-defense forces, the withdrawal of the U.S. ground troops from the Korean peninsula, Sino-Soviet moves toward rapprochement, and the proliferation of nuclear weapons in Northeast Asia.

  6. Antibody-Mediated Immunity against Tuberculosis: Implications for Vaccine Development

    PubMed Central

    Achkar, Jacqueline M.; Casadevall, Arturo

    2013-01-01

    There is an urgent need for new and better vaccines against tuberculosis (TB). Current vaccine design strategies are generally focused on the enhancement of cell-mediated immunity. Antibody-based approaches are not being considered, mostly due to the paradigm that humoral immunity plays little role in the protection against intracellular pathogens. Here, we reappraise and update the increasing evidence for antibody-mediated immunity against Mycobacterium tuberculosis, discuss the complexity of antibody responses to mycobacteria, and address mechanism of protection. Based on these findings and discussions, we challenge the common belief that immunity against M. tuberculosis relies solely on cellular defense mechanisms, and posit that induction of antibody-mediated immunity should be included in TB vaccine development strategies. PMID:23498951

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Immune checkpoint blockade in malignant mesothelioma: A novel therapeutic strategy against a deadly disease?

    PubMed

    Calabrò, Luana; Maio, Michele

    2014-01-01

    Monoclonal antibodies that target immune checkpoints are undoubtedly changing the therapeutic landscape of different human malignancies. Here we comment on the effects of blocking cytotoxic T lymphocyte-associated protein 4 (CTLA4) by means of the monoclonal antibody tremelimumab in patients with refractory malignant mesothelioma, a deadly disease with no effective therapeutic options. PMID:24734215

  13. 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...

  14. Intranasal Immunization Strategy To Impede Pilin-Mediated Binding of Pseudomonas aeruginosa to Airway Epithelial Cells

    Microsoft Academic Search

    Jennifer C. Hsieh; Doris M. Tham; Weijun Feng; Fan Huang; Selamawit Embaie; Keyi Liu; Deborah Dean; Ralf Hertle; David J. FitzGerald; Randall J. Mrsny

    2005-01-01

    Prevention of pulmonary Pseudomonas aeruginosa infections represents a critical unmet medical need for cystic fibrosis (CF) patients. We have examined the tenet that a mucosal immunization approach can reduce interactions of a piliated form of this opportunistic pathogen with respiratory epithelial cells. Vaccinations were performed using ntPEpilinPAK, a protein chimera composed of a nontoxic form of P. aeruginosa exotoxin A

  15. Defensive strategies in Geranium sylvaticum. Part 1: organ-specific distribution of water-soluble tannins, flavonoids and phenolic acids.

    PubMed

    Tuominen, Anu; Toivonen, Eija; Mutikainen, Pia; Salminen, Juha-Pekka

    2013-11-01

    A combination of high-resolution mass spectrometry and modern HPLC column technology, assisted by diode array detection, was used for accurate characterization of water-soluble polyphenolic compounds in the pistils, stamens, petals, sepals, stems, leaves, roots and seeds of Geranium sylvaticum. The organs contained a large variety of polyphenols, five types of tannins (ellagitannins, proanthocyanidins, gallotannins, galloyl glucoses and galloyl quinic acids) as well as flavonoids and simple phenolic acids. In all, 59 compounds were identified. Geraniin and other ellagitannins dominated in all the green photosynthetic organs. The other organs seem to produce distinctive polyphenol groups: pistils accumulated gallotannins; petals acetylglucose derivatives of galloylglucoses; stamens kaempferol glycosides, and seeds and roots accumulated proanthocyanidins. The intra-plant distribution of the different polyphenol groups may reflect the different functions and importance of various types of tannins as the defensive chemicals against herbivory. PMID:23790750

  16. Captive and free-living red knots Calidris canutus exhibit differences in non-induced immunity that suggest different immune strategies in different environments

    Microsoft Academic Search

    Deborah M. Buehler; Theunis Piersma; B. Irene Tieleman

    2008-01-01

    Experiments on captive animals, in which conditions can be controlled, are useful for examining complex biological phenomena such as immune function. Such experiments have increased our understanding of immune responses in the context of trade-offs and pathogen pressure. However, few studies have examined how captivity itself affects immune function. We used microbial killing, leukocyte concentrations and complement-natural antibody assays to

  17. Immunodulation and Helminths: Towards New Strategies for Treatment of Immune-Mediated Diseases?

    Microsoft Academic Search

    Fabrizio Bruschi; Lorena Chiumiento; Gianfranco Del Prete

    \\u000a Parasitic helminths, and other persistent pathogens are able to produce molecules modulating the host immune response; hookworm\\u000a for example produce the so-called neutrophil inhibitory factor (NIF), a protein which is the ligand of the integrin CD11b\\/CD18\\u000a present on the surface of neutrophil granulocytes, blocking the adherence of inflammatory cells to the endothelium. The cDNA\\u000a for this protein derived from Ancylostoma

  18. Base modification strategies to modulate immune stimulation by an siRNA.

    PubMed

    Valenzuela, Rachel Anne P; Suter, Scott R; Ball-Jones, Alexi A; Ibarra-Soza, José M; Zheng, Yuxuan; Beal, Peter A

    2015-01-19

    Immune stimulation triggered by siRNAs is one of the major challenges in the development of safe RNAi-based therapeutics. Within an immunostimulatory siRNA sequence, this hurdle is commonly addressed by using ribose modifications (e.g., 2'-OMe or 2'-F), which results in decreased cytokine production. However, as immune stimulation by siRNAs is a sequence-dependent phenomenon, recognition of the nucleobases by the trigger receptor(s) is also likely. Here, we use the recently published crystal structures of Toll-like receptor 8 (TLR8) bound to small-molecule agonists to generate computational models for ribonucleotide binding by this immune receptor. Our modeling suggested that modification of either the Watson-Crick or Hoogsteen face of adenosine would disrupt nucleotide/TLR8 interactions. We employed chemical synthesis to alter either the Watson-Crick or Hoogsteen face of adenosine and evaluated the effect of these modifications in an siRNA guide strand by measuring the immunostimulatory and RNA interference properties. For the siRNA guide strand tested, we found that modifying the Watson-Crick face is generally more effective at blocking TNF? production in human peripheral blood mononuclear cells (PBMCs) than modification at the Hoogsteen edge. We also observed that modifications near the 5'-end were more effective at blocking cytokine production than those placed at the 3'-end. This work advances our understanding of how chemical modifications can be used to optimize siRNA performance. PMID:25487859

  19. Base Modification Strategies to Modulate Immune Stimulation by an siRNA

    PubMed Central

    Valenzuela, Rachel Anne P.; Suter, Scott R.; Ball-Jones, Alexi A.; Ibarra-Soza, José M.; Zheng, Yuxuan

    2015-01-01

    Immune stimulation triggered by siRNAs is one of the major challenges in the development of safe RNAi-based therapeutics. Within an immunostimulatory siRNA sequence, this hurdle is commonly addressed by using ribose modifications (e.g. 2?-OMe or 2?-F) which results in decreased cytokine production. However, since immune stimulation by siRNAs is a sequence-dependent phenomenon, recognition of the nucleobases by the trigger receptor(s) is also likely. Here, we use the recently published crystal structures of Toll-like receptor 8 (TLR8) bound to small molecule agonists to generate computational models for ribonucleotide binding by this immune receptor. Our modeling suggested that modification of either the Watson-Crick or Hoogsteen face of adenosine would disrupt nucleotide/TLR8 interactions. We employed chemical synthesis to alter either the Watson-Crick or Hoogsteen face of adenosine and evaluated the effect of these modifications in an siRNA guide strand by measuring the immunostimulatory and RNA interference properties. For the siRNA guide strand tested, we found that modifying the Watson-Crick face is generally more effective at blocking TNF? production in human peripheral blood mononuclear cells (PBMCs) than modification at the Hoogsteen edge. We also observed that modifications near the 5? end were more effective at blocking cytokine production than those placed at the 3? end. This work advances our understanding of how chemical modifications can be used to optimize siRNA performance. PMID:25487859

  20. The Effect of Various Probiotic Strains or Avilamycin Feed Additive on Immune Defense Markers and Acute-Phase Response to Salmonella Infection in Chickens

    Microsoft Academic Search

    Maria Bielecka; Wanda Smoragiewicz; Andrzej K. Siwicki; Roman Wójcik; El?bieta Biedrzycka; Andrzej Or?owski; Signe Kask; Jan Jankowski; Barbara Karska-Wysocki; Daniela Ham

    2010-01-01

    Probiotics are a nutritional tool for disease prevention. It has been proposed that stimulation of immune response could affect\\u000a the growth-promoting properties of antimicrobial growth promoters as well as the control of foodborne pathogens. The current\\u000a study compares immune response in the blood of 280 non-infected and Salmonella-infected chickens fed either with the growth promoter avilamycin or with one of

  1. Pharmacy-based Immunization in Rural Communities Strategy (PhICS)

    PubMed Central

    Kaczorowski, Janusz; Gastonguay, Louise; Marra, Carlo A.; Lynd, Larry D.; Kendall, Perry

    2014-01-01

    Background: Influenza is a major cause of morbidity and mortality in Canada, with up to 7000 influenza-related deaths occurring every year. The elderly and individuals with chronic diseases are at increased risk for influenza-related morbidity and mortality. Methods: We conducted a 2-year, community cluster-randomized trial targeting elderly people and at-risk groups to assess the effectiveness of pharmacy-based influenza vaccination clinics on influenza vaccination rates. Small rural communities in interior and northern British Columbia were randomly allocated to the intervention or control. In the intervention communities, pharmacy-based influenza vaccination clinics were held and were promoted to eligible patients using personalized invitations from the pharmacists, invitations distributed opportunistically by a pharmacist to eligible patients presenting to pharmacies during the flu season and community-wide promotion using posters and the local media. The main outcome measure was a difference in the mean influenza vaccination rates. The immunization rates were calculated using the number of immunizations given in each community divided by the population size estimated from the census data. Results: Baseline influenza immunization rates in the population ?65 years of age were the same in the control (n = 10, mean 85.6% [SD 16.6]) and intervention (n = 14, mean 83.8% [SD 16.3]) communities in 2009 (p = 0.79). In 2010, the mean influenza immunization rate was 56.9% (SD 28.0) in the control communities (n = 15) and 80.1% (SD 18.4) in the intervention communities (n = 14) (p = 0.01) for those ?65 years of age. However, in 2010, for those 2 to 64 years with chronic medical conditions, the immunization rates were lower in the intervention communities (mean 16.3% [SD 7.1]) compared with the control communities (mean 21.2% [SD 5.8]) (p = 0.04). Conclusion Clinics were feasible and well attended and they resulted in increased vaccination rates for elderly residents. In contrast, vaccination rates in the younger population with comorbidities remained low and unchanged. PMID:24494014

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

    E-print Network

    Raman, Rahul

    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 ...

  3. Innate Immunity in the Lungs

    Microsoft Academic Search

    Thomas R. Martin; Charles W. Frevert

    2005-01-01

    Innate immunity is a primordial system that has a primary role in lung antimicrobial defenses. Recent advances in understanding the recognition systems by which cells of the innate immune system recognize and respond to microbial products have revolutionized the understanding of host defenses in the lungs and other tissues. Theinnateimmunesystemincludeslungleukocytesandalsoepithe- lial cells lining the alveolar surface and the conducting airways.

  4. 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

  5. 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

  6. 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

  7. Stability of microbiota facilitated by host immune regulation: informing probiotic strategies to manage amphibian disease.

    PubMed

    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

  8. 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

  9. Toll-like receptors in antiviral innate immunity

    PubMed Central

    Lester, Sandra N.; Li, Kui

    2014-01-01

    Toll-like receptors (TLRs) are fundamental sensor molecules of the host innate immune system, which detect conserved molecular signatures of a wide range of microbial pathogens and initiate innate immune responses via distinct signaling pathways. Various TLRs are implicated in the early interplay of host cells with invading viruses, which regulates viral replication and/or host responses, ultimately impacting on viral pathogenesis. To survive the host innate defense mechanisms, many viruses have developed strategies to evade or counteract signaling through the TLR pathways, creating an advantageous environment for their propagation. Here we review the current knowledge of the roles TLRs play in antiviral innate immune responses, discuss examples of TLR-mediated viral recognition, and describe strategies used by viruses to antagonize the host antiviral innate immune responses. PMID:24316048

  10. Survival Strategy of Obligately Intracellular Ehrlichia chaffeensis: Novel Modulation of Immune Response and Host Cell Cycles

    PubMed Central

    Zhang, Jian-zhi; Sinha, Mala; Luxon, Bruce A.; Yu, Xue-jie

    2004-01-01

    Ehrlichia chaffeensis is an obligatory intracellular bacterium which resides in an early endosome in monocytes. E. chaffeensis infection in a human monocyte cell line (THP1) significantly altered the transcriptional levels of 4.5% of host genes, including those coding for apoptosis inhibitors, proteins regulating cell differentiation, signal transduction, proinflammatory cytokines, biosynthetic and metabolic proteins, and membrane trafficking proteins. The transcriptional profile of the host cell revealed key themes in the pathogenesis of Ehrlichia. First, E. chaffeensis avoided stimulation of or repressed the transcription of cytokines involved in the early innate immune response and cell-mediated immune response to intracellular microbes, such as the interleukin-12 (IL-12), IL-15, and IL-18 genes, which might make Ehrlichia a stealth organism for the macrophage. Second, E. chaffeensis up-regulated NF-?B and apoptosis inhibitors and differentially regulated cell cyclins and CDK expression, which may enhance host cell survival. Third, E. chaffeensis also inhibited the gene transcription of RAB5A, SNAP23, and STX16, which are involved in membrane trafficking. By comparing the transcriptional response of macrophages infected with other bacteria and that of macrophages infected with E. chaffeensis, we have identified few genes that are commonly induced and no commonly repressed genes. These results illustrate the stereotyped macrophage response to other pathogens, in contrast with the novel host response to obligate intracellular Ehrlichia, whose survival depends entirely on a long evolutionary process of outmaneuvering macrophages. PMID:14688131

  11. 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

  12. A new strategy of immune evasion by influenza A virus: inhibition of monocyte differentiation into dendritic cells.

    PubMed

    Boliar, Saikat; Chambers, Thomas M

    2010-08-15

    Dendritic cells (DC) play a versatile role in orchestrating immune responses against influenza virus. During inflammation or infection, monocytes preferentially differentiate to generate DCs. Here, we demonstrate that in vitro infection of monocytes with influenza virus impairs their development into DCs. Influenza infection of monocytes, pre-treated with GM-CSF and IL-4 for DC differentiation, was minimally productive and non-cytopathic. In spite of successful viral genome transcription, viral protein synthesis was restricted at an early stage. However, despite the limited replication, influenza infected monocytes failed to develop distinctive DC-like morphologies. Infected cells expressed reduced amounts of CD11c, CD172a, CD1w2 and CCR5. Antigen endocytosis by infected monocytes was also affected. Cytokine expression profiles were also modified which was conducive for arresting DC differentiation. At least limited viral replication was necessary for complete inhibition of differentiation. This identifies a new strategy by influenza virus to interfere with DC differentiation and evade virus specific immune responses. PMID:20356633

  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. Insect Defenses

    NSDL National Science Digital Library

    0000-00-00

    A page from Dr. John Meyer's General Entomology course at NC State University detailing how insects defend themselves. Topics covered include speed, playing-dead, urticating hairs, chemical defenses, protective coloration and more.

  15. 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).

  16. 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 (Scripps); (UCSD)

    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.

  17. 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

  18. 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

  19. 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

  20. Improved Antimicrobial Host Defense in Mice following Poly-(1,6)-?-d-Glucopyranosyl-(1,3)-?-d-Glucopyranose Glucan Treatment by a Gender-Dependent Immune Mechanism ?

    PubMed Central

    Newsome, Courtni T.; Flores, Estefany; Ayala, Alfred; Gregory, Stephen; Reichner, Jonathan S.

    2011-01-01

    Clinical trials with biological modifiers targeting specific inflammatory mediators associated with severe sepsis have shown no or limited survival benefit. The approach taken in studies reported here was to limit the point source of intra-abdominal infection by potentiating innate immune function, thereby lessening the severity of sepsis and improving survival. Soluble beta-glucans, glucose polymers of the fungal cell wall, have been shown to stimulate innate immune host defense in animal and human studies when administered prior to an infectious challenge. We evaluated the effects of poly-(1,6)-?-d-glucopyranosyl-(1,3)-?-d-glucopyranose glucan (PGG glucan) on overall survival when administered intraperitoneally after the onset of polymicrobial infection by cecal ligation and puncture (CLP). Since gender-dependent differences in host immune response to infection have been reported, male and female mice were prospectively stratified for PGG glucan treatment. Outbred CD-1 mice were administered 10 mg/kg of body weight PGG glucan or the polysaccharide control, dextran, 1 h after CLP. Six hours after CLP, blood samples were obtained for cytokine measurements. Surprisingly, a gender-dependent effect on the response to PGG glucan was revealed. PGG glucan enhanced survival in female mice over a 10-day period, but survival in males was improved for only 24 h. In female mice, PGG glucan reduced interleukin-6 (IL-6) and IL-10 levels and reduced the bacterial burden in the liver. Ovariectomy abrogated the response to PGG glucan. Together, the translational potential of these findings is the indicated use of PGG glucan given locally, rather than intravenously, for improved source control during the management of sepsis. This therapy does not require prophylactic beta-glucan administration. PMID:21976224

  1. 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 ...

  2. 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

  3. 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

  4. Induction of antitumor immunity through xenoplacental immunization

    Microsoft Academic Search

    Zhaohui Zhong; Kornel P Kusznieruk; Igor A Popov; Neil H Riordan; Hamid Izadi; Li Yijian; Salman Sher; Orest M Szczurko; Michael G Agadjanyan; Richard H Tullis; Amir Harandi; Boris N Reznik; Grigor V Mamikonyan; Thomas E Ichim

    2006-01-01

    Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic

  5. 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

  6. Transcriptional networks in plant immunity.

    PubMed

    Tsuda, Kenichi; Somssich, Imre E

    2015-05-01

    932 I. 932 II. 933 III. 934 IV. 938 V. 941 943 References 943 SUMMARY: Next to numerous abiotic stresses, plants are constantly exposed to a variety of pathogens within their environment. Thus, their ability to survive and prosper during the course of evolution was strongly dependent on adapting efficient strategies to perceive and to respond to such potential threats. It is therefore not surprising that modern plants have a highly sophisticated immune repertoire consisting of diverse signal perception and intracellular signaling pathways. This signaling network is intricate and deeply interconnected, probably reflecting the diverse lifestyles and infection strategies used by the multitude of invading phytopathogens. Moreover it allows signal communication between developmental and defense programs thereby ensuring that plant growth and fitness are not significantly retarded. How plants integrate and prioritize the incoming signals and how this information is transduced to enable appropriate immune responses is currently a major research area. An important finding has been that pathogen-triggered cellular responses involve massive transcriptional reprogramming within the host. Additional key observations emerging from such studies are that transcription factors (TFs) are often sites of signal convergence and that signal-regulated TFs act in concert with other context-specific TFs and transcriptional co-regulators to establish sensory transcription regulatory networks required for plant immunity. PMID:25623163

  7. Are risk evaluation and mitigation strategies associated with less off-label use of medications? The case of immune thrombocytopenia.

    PubMed

    Sarpatwari, A; Franklin, J M; Avorn, J; Seeger, J D; Landon, J E; Kesselheim, A S

    2015-02-01

    Using data from a large commercial health insurer, we studied prescribing of romiplostim (Nplate) and eltrombopag (Promacta), two drugs for primary immune thrombocytopenia (ITP) for which risk evaluation and mitigation strategies (REMS) with elements to assure safe use were initially imposed and then removed. We identified 103 and 117 new users of romiplostim and eltrombopag, respectively. Use was almost exclusively for FDA-approved indications ("on-label") while the REMS with elements to assure safe use were in place. After these elements were lifted, off-label use of eltrombopag among patients with hepatitis C virus (HCV), a subsequently approved indication, increased. The ratio of incidence rate ratios of off-label/HCV to on-label initiation of eltrombopag between the two time periods was significant (13.41; P < 0.001). Our finding of an association with reduced off-label prescribing suggests that REMS with elements to assure safe use can help promote patient safety but may also prevent promising off-label drug uses. PMID:25670524

  8. 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

  9. Inhibition of the TRAIL Death Receptor by CMV Reveals Its Importance in NK Cell-Mediated Antiviral Defense

    PubMed Central

    Wang, Qiao; McDonald, Bryan; Redwood, Alec; Benedict, Chris A.

    2014-01-01

    TNF-related apoptosis inducing ligand (TRAIL) death receptors (DR) regulate apoptosis and inflammation, but their role in antiviral defense is poorly understood. Cytomegaloviruses (CMV) encode many immune-modulatory genes that shape host immunity, and they utilize multiple strategies to target the TNF-family cytokines. Here we show that the m166 open reading frame (orf) of mouse CMV (MCMV) is strictly required to inhibit expression of TRAIL-DR in infected cells. An MCMV mutant lacking m166 expression (m166stop) is severely compromised for replication in vivo, most notably in the liver, and depleting natural killer (NK) cells, or infecting TRAIL-DR?/? mice, restored MCMV-m166stop replication completely. These results highlight the critical importance for CMV to have evolved a strategy to inhibit TRAIL-DR signaling to thwart NK-mediated defenses. PMID:25122141

  10. Recommendations of the Advisory Committee on Immunization Practices: programmatic strategies to increase vaccination coverage by age 2 years--linkage of vaccination and WIC services.

    PubMed

    1996-03-15

    This statement by the Advisory Committee on Immunization Practices (ACIP), in collaboration with the U.S. Department of Agriculture's (USDA's) Food and Consumer Service (FCS), presents programmatic strategies to increase vaccination rates among preschool-aged children. This is the first statement to recommend assessment of vaccination status and referral for needed vaccinations of children receiving services from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). PMID:8609878

  11. 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.

  12. Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus.

    PubMed

    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

  13. 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

  14. 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

  15. 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

  16. A Rapid Immunization Strategy with a Live-Attenuated Tetravalent Dengue Vaccine Elicits Protective Neutralizing Antibody Responses in Non-Human Primates

    PubMed Central

    Ambuel, Yuping; Young, Ginger; Brewoo, Joseph N.; Paykel, Joanna; Weisgrau, Kim L.; Rakasz, Eva G.; Haller, Aurelia A.; Royals, Michael; Huang, Claire Y.-H.; Capuano, Saverio; Stinchcomb, Dan T.; Partidos, Charalambos D.; Osorio, Jorge E.

    2014-01-01

    Dengue viruses (DENVs) cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine tetravalent dengue vaccine (TDV) that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3, and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS) is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0) at two different anatomical locations with a needle-free disposable syringe jet injection delivery devices (PharmaJet) in non-human primates. This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (2?months later) vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-?, IL-2, and TNF-?, and targeting the DENV-2 NS1, NS3, and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post-challenge). RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas. PMID:24926294

  17. Hormonal crosstalk in plant immunity

    Microsoft Academic Search

    A. van der Does

    2012-01-01

    The plant hormones salicylic acid (SA), also known as plant aspirin, and jasmonic acid (JA) play major roles in the regulation of the plant immune system. In general, SA is important for defense against pathogens with a biotrophic lifestyle, whereas JA is essential for defense against insect herbivores and pathogens with a necrotrophic lifestyle. Antagonistic and synergistic interactions between the

  18. Epithelial Cells and Innate Antifungal Defense

    PubMed Central

    Weindl, G.; Wagener, J.; Schaller, M.

    2010-01-01

    The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. Clinical observations indicate that mucocutaneous Candida infections are commonly associated with defective cell-mediated immune responses. The importance of the innate immune system as a first-line defense against pathogenic challenge has long been recognized. Over the last decade, many key molecules mediating innate host defense have been identified. Central to these developments is the discovery of pattern recognition receptors such as Toll-like receptors and C-type lectin-receptors that induce innate immune responses and also modulate cellular and humoral adaptive immunity during Candida infections. Although a large amount of information is now available in systemic infections, little is known about localized infections. We address the most relevant pattern recognition receptors and their signaling mechanisms in oral epithelial cells, to gain a better understanding of their contributions to antifungal innate immunity. PMID:20395411

  19. Rapid deletion of antigen-specific CD4+ T cells following infection represents a strategy of immune evasion and persistence for Anaplasma marginale1

    PubMed Central

    Han, Sushan; Norimine, Junzo; Palmer, Guy H.; Mwangi, Waithaka; Lahmers, Kevin K.; Brown, Wendy C.

    2009-01-01

    Acquired T-cell immunity is central for protection against infection. However, the immunological consequences of exposing memory T cells to high antigen loads during acute and persistent infection with systemic pathogens are poorly understood. We investigated this using infection with Anaplasma marginale, a ruminant pathogen that replicates to levels of 109 bacteria per ml of blood during acute infection and maintains mean bacteremia levels of 106 per ml during long-term persistent infection. We established that immunization-induced antigen-specific peripheral blood CD4+ T cell responses were rapidly and permanently lost following infection. To determine whether these T cells were anergic, sequestered in the spleen, or physically deleted from peripheral blood, CD4+ T lymphocytes from the peripheral blood specific for major surface protein (MSP)1a T-cell epitope were enumerated by DRB3*1101 tetramer staining and FACS analysis throughout the course of immunization and challenge. Immunization induced significant epitope-specific T lymphocyte responses that rapidly declined near peak bacteremia to background levels. Concomitantly, the mean frequency of tetramer+ CD4+ cells decreased rapidly from 0.025% before challenge to a pre-immunization level of 0.0003% of CD4+ T cells. Low frequencies of tetramer+ CD4+ T cells in spleen, liver, and inguinal lymph nodes sampled 9-12 weeks post-challenge were consistent with undetectable or unsustainable antigen-specific responses and the lack of T-cell sequestration. Thus, infection of cattle with A. marginale leads to the rapid loss of antigen-specific T cells and immunologic memory, which may be a strategy for this pathogen to modulate the immune response and persist. PMID:19017965

  20. Symbiotes and defensive Mutualism: Moving Target Defense

    E-print Network

    Yang, Junfeng

    Chapter 5 Symbiotes and defensive Mutualism: Moving Target Defense Ang Cui and Salvatore J. Stolfo on perpetual mutation and diversity, driven by symbiotic defensive mutualism can fundamentally change the `cat malware. 5.1 Introduction We propose a host-based defense mechanism that we call Symbiotic Embedded

  1. Community Immunity (Herd Immunity)

    MedlinePLUS

    ... Skip Content Marketing Share this: Main Content Area Community Immunity ("Herd" Immunity) Vaccines can prevent outbreaks of ... save lives. When a critical portion of a community is immunized against a contagious disease, most members ...

  2. M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

    PubMed

    Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

    2014-07-31

    Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 ?g pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. PMID:24958702

  3. Immune System Defender

    NSDL National Science Digital Library

    2012-06-18

    This interactive unit demonstrates the immune system's defense mechanisms. Users will defend the human body against an infection using a "team" of white blood cells called granulocytes. The white blood cells will be used to destroy the bacteria via a fun interactive game. In the "Information Terminal" section of the interactive unit, students can read more about the immune system and its cells as well as the Nobel Prize awarded for the discovery of the phagocyte cell.

  4. 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

  5. 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

  6. Effector-triggered post-translational modifications and their role in suppression of plant immunity

    PubMed Central

    Howden, Andrew J. M.; Huitema, Edgar

    2012-01-01

    Plant–pathogen interactions feature complex signaling exchanges between host and microbes that ultimately determine association outcomes. Plants deploy pattern recognition receptors to perceive pathogen-associated molecular patterns, mount pattern-triggered immunity (PTI), and fend off potential pathogens. In recent years an increasing number of defense-signaling components have been identified along with a mechanistic understanding of their regulation during immune responses. Post-translational modifications (PTMs) are now thought to play a crucial role in regulating defense signaling. In a bid to suppress PTI and infect their host, pathogens have evolved large repertoires of effectors that trigger susceptibility and allow colonization of host tissues. While great progress has been made in elucidating defense-signaling networks in plants and the activities of effectors in immune suppression, a critical gap exists in our understanding of effector mechanism-of-action. Given the importance of PTMs in the regulation of defense signaling, we will explore the question: how do effectors modify the post-translational status of host proteins and thus interfere with host processes required for immunity? We will consider how emerging proteomics-based experimental strategies may help us answer this important question and ultimately open the pathogens’ effector black box. PMID:22811685

  7. Food-Induced Immune Responses as Origin of Bowel Disease?

    Microsoft Academic Search

    Frank Seibold

    2005-01-01

    Food-induced immune responses cause or influence a number of intestinal diseases. Food antigens may either directly affect the mucosal immune system, or food modulate the intestinal flora, which may alter the immune response. The system preventing food-induced immune responses is complex: The mucosal barrier is the primary mechanism of host defense. Secondly, the innate immune system can neutralize some of

  8. West European and East Asian perspectives on defense, deterrence, and strategy. Volume 1. Main report. Technical report, 1 December 1982-15 May 1984

    SciTech Connect

    Pfaltzgraff, R.L.; Davis, J.K.; Dougherty, J.E.; Perry, C.M.

    1984-05-16

    This report provides a summary, analysis and categorization of the perspectives of defense elites in Western Europe, together with an examination of such perspective in the People's Republic of China, with special emphasis on nuclear capabilities and directly related security issues. In Europe, attention is focused on Great Britain, France, the Federal Republic of Germany, Belgium, The Netherlands, Portugal, and Spain. As a distinctive feature of this report, four schools of strategic thought have been developed for each of the European countries under study. Based upon a comprehensive assessment of the defense views held by strategic theoreticians, prominent government policymakers, political party leaders, and others active in the defense debates of Western Europe, these schools of thought provide a unique tool for identifying and evaluating key issues and spokesmen in the West European security debate of the 1980s. The overall objective of this study is to identify and assess the continuities and discontinuities of security perspectives among West European countries (especially concerning NATO's nuclear weapons options) and, on the basis of this analysis, to examine the prospects for maintaining, or strengthening, the consensus upon which European security is based. In its assessment of Chinese security perspectives, this report focuses on the evaluation of the PRC's strategic approach to international affairs and on the effects of recent personnel and organizational changes in the Chinese hierarchy on the PRC's foreign and defense policies.

  9. Small RNAs in plant defense responses during viral and bacterial interactions: similarities and differences

    PubMed Central

    Peláez, 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 plant–microbe 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 plant–bacteria 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

  10. 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

  11. Celecoxib Improves Host Defense through Prostaglandin Inhibition during Histoplasma capsulatum Infection

    PubMed Central

    Pereira, Priscilla Aparecida Tartari; Trindade, Bruno Caetano; Secatto, Adriana; Nicolete, Roberto; Peres-Buzalaf, Camila; Ramos, Simone Gusmão; Sadikot, Ruxana; Bitencourt, Claudia da Silva

    2013-01-01

    Prostaglandins act as mediators of inflammation and, similar to cytokines, function as immune modulators during innate and adaptive immune responses. Therefore, using a pharmacological inhibitor, celecoxib, we investigated the role of prostaglandins in host defense against Histoplasma capsulatum infection in C57BL/6 mice. Our results showed that treatment with celecoxib inhibited cyclooxygenase 2, reduced the total fungal burden, and reduced the concentration of PGE2, cytokines, lymphocytes, neutrophils, and mononuclear cells in the bronchoalveolar space and lung parenchyma. In addition, celecoxib treatment increased the synthesis of nitric oxide, IFN-?, LTB4, and the phagocytic capacity of alveolar macrophages. Moreover, celecoxib treatment increased the survival of mice after infection with a lethal inoculum of H. capsulatum. These results suggest that prostaglandins alter the host immune response and play an important role in the pathogenesis of histoplasmosis. Thus, the inhibition of prostaglandins could be a valuable immunomodulatory strategy and antifungal therapy for histoplasmosis treatment. PMID:23818746

  12. Celecoxib improves host defense through prostaglandin inhibition during Histoplasma capsulatum infection.

    PubMed

    Pereira, Priscilla Aparecida Tartari; Trindade, Bruno Caetano; Secatto, Adriana; Nicolete, Roberto; Peres-Buzalaf, Camila; Ramos, Simone Gusmão; Sadikot, Ruxana; Bitencourt, Claudia da Silva; Faccioli, Lúcia Helena

    2013-01-01

    Prostaglandins act as mediators of inflammation and, similar to cytokines, function as immune modulators during innate and adaptive immune responses. Therefore, using a pharmacological inhibitor, celecoxib, we investigated the role of prostaglandins in host defense against Histoplasma capsulatum infection in C57BL/6 mice. Our results showed that treatment with celecoxib inhibited cyclooxygenase 2, reduced the total fungal burden, and reduced the concentration of PGE2, cytokines, lymphocytes, neutrophils, and mononuclear cells in the bronchoalveolar space and lung parenchyma. In addition, celecoxib treatment increased the synthesis of nitric oxide, IFN- ?, LTB4, and the phagocytic capacity of alveolar macrophages. Moreover, celecoxib treatment increased the survival of mice after infection with a lethal inoculum of H. capsulatum. These results suggest that prostaglandins alter the host immune response and play an important role in the pathogenesis of histoplasmosis. Thus, the inhibition of prostaglandins could be a valuable immunomodulatory strategy and antifungal therapy for histoplasmosis treatment. PMID:23818746

  13. Defense Data Network an Overview

    Microsoft Academic Search

    F. Lee Maybaum; Howard C. Duffield

    1986-01-01

    The paper provides the genesis of the Defense Data Network (DDN), its scope and implementation strategy. This is followed by a description of the DDN today in terms of its hardware elements, protocols, architecture and topology. The paper concludes with a discussion of the planned and projected improvements needed for the evolution of the DDN in the 1980s and its

  14. 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.

  15. MAIT cells and pathogen defense.

    PubMed

    Cowley, Siobhán C

    2014-12-01

    Mucosa-associated invariant T (MAIT) cells are a unique population of innate T cells that are abundant in humans. These cells possess an evolutionarily conserved invariant T cell receptor ? chain restricted by the nonpolymorphic class Ib major histocompatibility (MHC) molecule, MHC class I-related protein (MR1). The recent discovery that MAIT cells are activated by MR1-bound riboflavin metabolite derivatives distinguishes MAIT cells from all other ?? T cells in the immune system. Since mammals lack the capacity to synthesize riboflavin, intermediates from the riboflavin biosynthetic pathway are distinct microbial molecular patterns that provide a unique signal to the immune system. Multiple lines of evidence suggest that MAIT cells, which produce important cytokines such as IFN-?, TNF, and IL-17A, have the potential to influence immune responses to a broad range of pathogens. Here we will discuss our current understanding of MAIT cell biology and their role in pathogen defense. PMID:25164578

  16. Antiviral innate immune response of RNA interference.

    PubMed

    Sidahmed, Abubaker; Abdalla, Shaza; Mahmud, Salahedin; Wilkie, Bruce

    2014-07-01

    RNA interference (RNAi) is an ancient, natural process conserved among species from different kingdoms. RNAi is a transcriptional and post-transcriptional gene silencing mechanism in which, double-stranded RNA or hairpin RNA is cleaved by an RNase III-type enzyme called Dicer into small interfering RNA duplex. This subsequently directs sequence-specific, homology dependent, Watson-Crick base-pairing post-transcriptional gene silencing by binding to its complementary RNA and initiating its elimination through degradation or by persuading translational inhibition. In plants, worms, and insects, RNAi is the main and strong antiviral defense mechanism. It is clear that RNAi silencing, contributes in restriction of viral infection in vertebrates. In a short period, RNAi has progressed to become a significant experimental tool for the analysis of gene function and target validation in mammalian systems. In addition, RNA silencing has then been found to be involved in translational repression, transcriptional inhibition, and DNA degradation. RNAi machinery required for robust RNAi-mediated antiviral response are conserved throughout evolution in mammals and plays a crucial role in antiviral defense of invertebrates, but despite these important functions RNAi contribution to mammalian antiviral innate immune defense has been underestimated and disputed. In this article, we review the literature concerning the roles of RNAi as components of innate immune system in mammals and how, the RNAi is currently one of the most hopeful new advances toward disease therapy. This review highlights the potential of RNAi as a therapeutic strategy for viral infection and gene regulation to modulate host immune response to viral infection. PMID:25022288

  17. Human Metapneumovirus Antagonism of Innate Immune Responses

    PubMed Central

    Kolli, Deepthi; Bao, Xiaoyong; Casola, Antonella

    2012-01-01

    Human metapneumovirus (hMPV) is a recently identified RNA virus belonging to the Paramyxoviridae family, which includes several major human and animal pathogens. Epidemiological studies indicate that hMPV is a significant human respiratory pathogen with worldwide distribution. It is associated with respiratory illnesses in children, adults, and immunocompromised patients, ranging from upper respiratory tract infections to severe bronchiolitis and pneumonia. Interferon (IFN) represents a major line of defense against virus infection, and in response, viruses have evolved countermeasures to inhibit IFN production as well as IFN signaling. Although the strategies of IFN evasion are similar, the specific mechanisms by which paramyxoviruses inhibit IFN responses are quite diverse. In this review, we will present an overview of the strategies that hMPV uses to subvert cellular signaling in airway epithelial cells, the major target of infection, as well as in primary immune cells. PMID:23223197

  18. Innate immune recognition of HIV-1.

    PubMed

    Iwasaki, Akiko

    2012-09-21

    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

  19. COMPETING HIV STRAINS AND IMMUNE SYSTEM RESPONSE

    E-print Network

    Paris-Sud XI, Université de

    COMPETING HIV STRAINS AND IMMUNE SYSTEM RESPONSE THIERRY GOBRON1 , MARIO SANTORO2 , AND LIVIO between an immune system with a specific and powerful response, and a virus with a broad toxicity and fast on the cells which are the keystone of the immune defense system. A number of theoretical papers have studied

  20. InCVAX - A novel strategy for treatment of late-stage, metastatic cancers through photoimmunotherapy induced tumor-specific immunity.

    PubMed

    Zhou, Feifan; Li, Xiaosong; Naylor, Mark F; Hode, Tomas; Nordquist, Robert E; Alleruzzo, Luciano; Raker, Joseph; Lam, Samuel S K; Du, Nan; Shi, Lei; Wang, Xiuli; Chen, Wei R

    2015-04-10

    A novel, promising potential cancer vaccine strategy was proposed to use a two-injection procedure for solid tumors to prompt the immune system to identify and systemically eliminate primary and metastatic cancers. The two-injection procedure consists of local photothermal application on a selected tumor intended to liberate whole cell tumor antigens, followed by a local injection of an immunoadjuvant that consists of a semi-synthetic functionalized glucosamine polymer, N-dihydro-galacto-chitosan (GC), which is intended to activate antigen presenting cells and facilitate an increased uptake of tumor antigens. This strategy is thus proposed as an in situ autologous cancer vaccine (inCVAX) that may activate antigen presenting cells and expose them to tumor antigens in situ, with the intention of inducing a systemic tumor specific T-cell response. Here, the development of inCVAX for the treatment of metastatic cancers in the past decades is systematically reviewed. The antitumor immune responses of local photothermal treatment and immunological stimulation with GC are also discussed. This treatment approach is also commonly referred to as laser immunotherapy (LIT). PMID:25633839

  1. Comparative genomics of defense systems in archaea and bacteria.

    PubMed

    Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V

    2013-04-01

    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

  2. Single-cell technologies for monitoring interactions between immune cells

    E-print Network

    Yamanaka, Yvonne J. (Yvonne Joy)

    2014-01-01

    Immune cells participate in dynamic cellular interactions that play a critical role in the defense against pathogens and the destruction of malignant cells. The vast heterogeneity of immune cells motivates the study of ...

  3. 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

  4. A new strategy of immune evasion by influenza A virus: Inhibition of monocyte differentiation into dendritic cells

    Microsoft Academic Search

    Saikat Boliar; Thomas M. Chambers

    2010-01-01

    Dendritic cells (DC) play a versatile role in orchestrating immune responses against influenza virus. During inflammation or infection, monocytes preferentially differentiate to generate DCs. Here, we demonstrate that in vitro infection of monocytes with influenza virus impairs their development into DCs. Influenza infection of monocytes, pre-treated with GM-CSF and IL-4 for DC differentiation, was minimally productive and non-cytopathic. In spite

  5. 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 newborn’s 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

  6. [Targeting the PD-1/PD-L1 immune checkpoint signal - a new treatment strategy for cancer].

    PubMed

    Hamanishi, Junzo; Konishi, Ikuo

    2014-09-01

    Recent studies have revealed that tumor cells can acquire several mechanisms to evade host immunity in the tumor microenvironment, called cancer immune escape. One of the most important mechanisms in this system is an immunosuppressive co- signal, called immune checkpoint, in the programmed cell death-1(PD-1)/programmed death-ligand 1(PD-L1)pathway. PD-1 is mainly expressed on activated T cells, while PD-L1 is frequently expressed on tumor cells. Inhibition of the interaction between PD-1 and PD-L1 enhances T-cell response and mediates antitumor activity. Several clinical trials by several institutions and pharmaceutical companies in the world have shown the antitumor efficacy of PD-1/PD-L1 signal blockade in patients with some solid and hematological malignancies. Production of some drugs for use in anti-PD-1 therapies are on the verge of completion. Herein, we provide a background about the PD-1/PD-L1 signal and describe some previously performed foreign clinical trials, including a trial in our department. PMID:25248890

  7. The innate immune system of the perinatal lung and responses to respiratory syncytial virus infection.

    PubMed

    Derscheid, R J; Ackermann, M R

    2013-09-01

    The response of the preterm and newborn lung to airborne pathogens, particles, and other insults is initially dependent on innate immune responses since adaptive responses may not fully mature and require weeks for sufficient responses to antigenic stimuli. Foreign material and microbial agents trigger soluble, cell surface, and cytoplasmic receptors that activate signaling cascades that invoke release of surfactant proteins, defensins, interferons, lactoferrin, oxidative products, and other innate immune substances that have antimicrobial activity, which can also influence adaptive responses. For viral infections such as respiratory syncytial virus (RSV), the pulmonary innate immune responses has an essential role in defense as there are no fully effective vaccines or therapies for RSV infections of humans and reinfections are common. Understanding the innate immune response by the preterm and newborn lung may lead to preventive strategies and more effective therapeutic regimens. PMID:23528938

  8. Molecular Mechanisms of Aging and Immune System Regulation in Drosophila

    PubMed Central

    Eleftherianos, Ioannis; Castillo, Julio Cesar

    2012-01-01

    Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span. PMID:22949833

  9. The effects of attachment avoidance and the defensive regulation of emotional faces: Brain potentials examining the role of preemptive and postemptive strategies.

    PubMed

    Zheng, Minsi; Zhang, Youxin; Zheng, Yong

    2015-02-01

    Deactivating strategies, including preemptive and postemptive strategies, are effective methods used by avoidant adults to regulate emotional processing. In the present study, we examined the mechanisms of preemptive and postemptive strategies used by highly avoidant participants to defend against emotional faces. Event-related potentials were recorded while participants performed a face version of a study-test task that comprised emotional and neutral faces. Emotional faces elicited larger N170 amplitude than did neutral faces in highly avoidant individuals. In addition, early and parietal old/new effects were observed in highly avoidant participants in response to neutral but not emotional faces. Less-avoidant participants exhibited an extensive old/new effect in response to negative and neutral faces. These results suggest that highly avoidant individuals allocate more cognitive resources when encoding emotional faces at an early stage, which contributes to the use of postemptive strategies to suppress the accessibility of previously encoded emotional information in recognition. PMID:25666553

  10. Regulation of adaptive immunity by the innate immune system.

    PubMed

    Iwasaki, Akiko; Medzhitov, Ruslan

    2010-01-15

    Twenty years after the proposal that pattern recognition receptors detect invasion by microbial pathogens, the field of immunology has witnessed several discoveries that have elucidated receptors and signaling pathways of microbial recognition systems and how they control the generation of T and B lymphocyte-mediated immune responses. However, there are still many fundamental questions that remain poorly understood, even though sometimes the answers are assumed to be known. Here, we discuss some of these questions, including the mechanisms by which pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune recognition in host defense from infection and injury. PMID:20075244

  11. Survival for Immunity: The Price of Immune System Activation for Bumblebee Workers

    Microsoft Academic Search

    Yannick Moret; Paul Schmid-Hempel

    2000-01-01

    Parasites do not always harm their hosts because the immune system keeps an infection at bay. Ironically, the cost of using immune defenses could itself reduce host fitness. This indirect cost of parasitism is often not visible because of compensatory resource intake. Here, workers of the bumblebee, Bombus terrestris, were challenged with lipopolysaccharides and micro-latex beads to induce their immune

  12. Resistance to chytridiomycosis varies among amphibian species and is correlated with skin peptide defenses

    Microsoft Academic Search

    D. C. Woodhams; K. Ardipradja; R. A. Alford; G. Marantelli; L. K. Reinert; L. A. Rollins-Smith

    2007-01-01

    Innate immune mechanisms of defense are especially important to ectothermic vertebrates in which adaptive immune responses may be slow to develop. One innate defense in amphibian skin is the release of abundant quantities of antimicrobial peptides. Chytridiomycosis is an emerging infectious disease of amphibians caused by the skin fungus, Batrachochytrium dendrobatidis. Suscept- ibility to chytridiomycosis varies among species, and mechanisms

  13. A sophisticated network of signaling pathways regulates stomatal defenses to bacterial pathogens.

    PubMed

    Arnaud, Dominique; Hwang, Ildoo

    2014-11-01

    Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. A decade ago, stomata have been shown to play an important role in plant defense as a part of the innate immune response. Indeed, plants actively close their stomata upon contact with microbes thereby preventing pathogen entry into the leaves and the subsequent colonization of host tissues. In this review, we will present current knowledges of molecular mechanisms and signaling pathways implicated in stomatal defenses with a particular attention on plant-bacteria interactions. Stomatal defense responses begin from the perception of pathogen-associated molecular patterns (PAMPs) and activate a signaling cascade involving the production of secondary messengers such as reactive oxygen species (ROS), nitric oxide (NO) and calcium for the regulation of plasma membrane ion channels. The analyses on downstream molecular mechanisms implicated in PAMP-triggered stomatal closure have revealed extensive interplays with components regulating hormonal signaling pathways. We will also discuss on strategies deployed by pathogenic bacteria to counteract stomatal immunity through the example of the phytotoxin coronatine. PMID:25366179

  14. Prevalence of Local Immune Response against Oral Infection in a Drosophila/Pseudomonas Infection Model

    PubMed Central

    Liehl, Peter; Blight, Mark; Vodovar, Nicolas; Boccard, Frédéric; Lemaitre, Bruno

    2006-01-01

    Pathogens have developed multiple strategies that allow them to exploit host resources and resist the immune response. To study how Drosophila flies deal with infectious diseases in a natural context, we investigated the interactions between Drosophila and a newly identified entomopathogen, Pseudomonas entomophila. Flies orally infected with P. entomophila rapidly succumb despite the induction of both local and systemic immune responses, indicating that this bacterium has developed specific strategies to escape the fly immune response. Using a combined genetic approach on both host and pathogen, we showed that P. entomophila virulence is multi-factorial with a clear differentiation between factors that trigger the immune response and those that promote pathogenicity. We demonstrate that AprA, an abundant secreted metalloprotease produced by P. entomophila, is an important virulence factor. Inactivation of aprA attenuated both the capacity to persist in the host and pathogenicity. Interestingly, aprA mutants were able to survive to wild-type levels in immune-deficient Relish flies, indicating that the protease plays an important role in protection against the Drosophila immune response. Our study also reveals that the major contribution to the fly defense against P. entomophila is provided by the local, rather than the systemic immune response. More precisely, our data points to an important role for the antimicrobial peptide Diptericin against orally infectious Gram-negative bacteria, emphasizing the critical role of local antimicrobial peptide expression against food-borne pathogens. PMID:16789834

  15. Small molecule perimeter defense in entomopathogenic bacteria.

    PubMed

    Crawford, Jason M; Portmann, Cyril; Zhang, Xu; Roeffaers, Maarten B J; Clardy, Jon

    2012-07-01

    Two gram-negative insect pathogens, Xenorhabdus nematophila and Photorhabdus luminescens, produce rhabduscin, an amidoglycosyl- and vinyl-isonitrile-functionalized tyrosine derivative. Heterologous expression of the rhabduscin pathway in Escherichia coli, precursor-directed biosynthesis of rhabduscin analogs, biochemical assays, and visualization using both stimulated Raman scattering and confocal fluorescence microscopy established rhabduscin's role as a potent nanomolar-level inhibitor of phenoloxidase, a key component of the insect's innate immune system, as well as rhabduscin's localization at the bacterial cell surface. Stimulated Raman scattering microscopy visualized rhabduscin at the periphery of wild-type X. nematophila cells and E. coli cells heterologously expressing the rhabduscin pathway. Precursor-directed biosynthesis created rhabduscin mimics in X. nematophila pathway mutants that could be accessed at the bacterial cell surface by an extracellular bioorthogonal probe, as judged by confocal fluorescence microscopy. Biochemical assays using both wild-type and mutant X. nematophila cells showed that rhabduscin was necessary and sufficient for potent inhibition (low nM) of phenoloxidases, the enzymes responsible for producing melanin (the hard black polymer insects generate to seal off microbial pathogens). These observations suggest a model in which rhabduscin's physical association at the bacterial cell surface provides a highly effective inhibitor concentration directly at the site of phenoloxidase contact. This class of molecules is not limited to insect pathogens, as the human pathogen Vibrio cholerae also encodes rhabduscin's aglycone, and bacterial cell-coated immunosuppressants could be a general strategy to combat host defenses. PMID:22711807

  16. A comparative approach to strategies for cloning, expression, and purification of Mycobacterium tuberculosis mycolyl transferase 85B and evaluation of immune responses in BALB/c mice.

    PubMed

    Aghababa, Haniyeh; Mohabati Mobarez, Ashraf; Khoramabadi, Nima; Behmanesh, Mehrdad; Mahdavi, Mehdi; Tebianian, Majid; Nejati, Mehdi

    2014-06-01

    Protein antigens have drawn a lot of attention from investigators working on tuberculosis vaccines. These proteins can be used to improve the immunogenicity of the new generation BCG vaccines or even replace them completely. Recombinant technology is used to insure the production of pure mycobacterial antigens in high quantities. Mycolyl transferase 85B (Ag85B) is a potent, mycobacterial antigen that significantly stimulates immune responses. Since Ag85B is an apolar protein, production of the water-soluble antigen is of interest. In this work, we report a systematic optimization strategy concerning cloning systems and purification methods, aiming at increasing the yield of recombinant Ag85B. Our optimized method resulted in a yield of 8 mg of recombinant Ag85B from 1 liter of induced culture (400 ?g/ml) by using pET32a(+), Escherichia coli Rosseta-gami™(DE3) pLysS and a Ni-NTA agarose-based procedure and on-column re-solubilization. The purified recombinant Ag85B showed strong immunostimulating properties by inducing high levels of TNF-?, IFN-?, IL-12, and IgG2a in immunized mice, therefore it can effectively be applied in TB vaccine researches. PMID:24619477

  17. Immune Reactions Among Marine and Other Invertebrates

    ERIC Educational Resources Information Center

    Bang, Frederik B.

    1973-01-01

    Discusses the defense mechanisms and immune reaction found in invertebrates, and examines the wealth of related biological problems that need study and many of the leads that have recently been developed. (JR)

  18. Interactions between the cellular and humoral immune responses in Drosophila

    Microsoft Academic Search

    Monicia Elrod-Erickson; Smita Mishra; David Schneider

    2000-01-01

    Drosophila has highly efficient defenses againstinfection. These include both cellular immune responses, such as the phagocytosis of invading microorganisms, and humoral immune responses, such as the secretion of antimicrobial peptides into the hemolymph [1,2]. These defense systems are thought to interact, but the nature and extent of these interactions is not known. Here we describe a method for inhibiting phagocytosis

  19. Novel HIV IL-4R antagonist vaccine strategy can induce both high avidity CD8 T and B cell immunity with greater protective efficacy.

    PubMed

    Jackson, Ronald J; Worley, Matthew; Trivedi, Shubhanshi; Ranasinghe, Charani

    2014-09-29

    We have established that the efficacy of a heterologous poxvirus vectored HIV vaccine, fowlpox virus (FPV)-HIV gag/pol prime followed by attenuated vaccinia virus (VV)-HIV gag/pol booster immunisation, is strongly influenced by the cytokine milieu at the priming vaccination site, with endogenous IL-13 detrimental to the quality of the HIV specific CD8+ T cell response induced. We have now developed a novel HIV vaccine that co-expresses a C-terminal deletion mutant of the mouse IL-4, deleted for the essential tyrosine (Y119) required for signalling. In our vaccine system, the mutant IL-4C118 can bind to IL-4 type I and II receptors with high affinity, and transiently prevent the signalling of both IL-4 and IL-13 at the vaccination site. When this IL-4C118 adjuvanted vaccine was used in an intranasal rFPV/intramuscular rVV prime-boost immunisation strategy, greatly enhanced mucosal/systemic HIV specific CD8+ T cells with higher functional avidity, expressing IFN-?, TNF-? and IL-2 and greater protective efficacy were detected. Surprisingly, the IL-4C118 adjuvanted vaccines also induced robust long-lived HIV gag-specific serum antibody responses, specifically IgG1 and IgG2a. The p55-gag IgG2a responses induced were of a higher magnitude relative to the IL-13R?2 adjuvant vaccine. More interestingly, our recently tested IL-13R?2 adjuvanted vaccine which only inhibited IL-13 activity, even though induced excellent high avidity HIV-specific CD8+ T cells, had a detrimental impact on the induction of gag-specific IgG2a antibody immunity. Our observations suggest that (i) IL-4 cell-signalling in the absence of IL-13 retarded gag-specific antibody isotype class switching, or (ii) IL-13R?2 signalling was involved in inducing good gag-specific B cell immunity. Thus, we believe our novel IL-4R antagonist adjuvant strategy offers great promise not only for HIV-1 vaccines, but also against a range of chronic infections where sustained high quality mucosal and systemic T and B cell immunity are required for protection. PMID:25151041

  20. Bench-to-bedside review: Functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis

    PubMed Central

    Opal, Steven M; Esmon, Charles T

    2003-01-01

    The innate immune response system is designed to alert the host rapidly to the presence of an invasive microbial pathogen that has breached the integument of multicellular eukaryotic organisms. Microbial invasion poses an immediate threat to survival, and a vigorous defense response ensues in an effort to clear the pathogen from the internal milieu of the host. The innate immune system is able to eradicate many microbial pathogens directly, or innate immunity may indirectly facilitate the removal of pathogens by activation of specific elements of the adaptive immune response (cell-mediated and humoral immunity by T cells and B cells). The coagulation system has traditionally been viewed as an entirely separate system that has arisen to prevent or limit loss of blood volume and blood components following mechanical injury to the circulatory system. It is becoming increasingly clear that coagulation and innate immunity have coevolved from a common ancestral substrate early in eukaryotic development, and that these systems continue to function as a highly integrated unit for survival defense following tissue injury. The mechanisms by which these highly complex and coregulated defense strategies are linked together are the focus of the present review. PMID:12617738

  1. Toll-like receptor control of the adaptive immune responses

    Microsoft Academic Search

    Akiko Iwasaki; Ruslan Medzhitov

    2004-01-01

    Recognition of microbial infection and initiation of host defense responses is controlled by multiple mechanisms. Toll-like receptors (TLRs) have recently emerged as a key component of the innate immune system that detect microbial infection and trigger antimicrobial host defense responses. TLRs activate multiple steps in the inflammatory reactions that help to eliminate the invading pathogens and coordinate systemic defenses. In

  2. Budgeting For Defense: Maintaining Today's Forces

    NSDL National Science Digital Library

    This report from the Congressional Budget Office provides excellent background research for the current debate between the two major Presidential candidates over the American military's state of readiness. In keeping with its nonpartisan mandate, the report makes no recommendations, but it does summarize the current threats to US security, current military strategy, and the factors that drive Defense Department budgetary requests. In addition, the report offers estimates for budgetary requirements for sustaining defense capabilities at their current levels (as well as a discussion of the limitations to these estimates) and reviews alternative budget approaches, including reducing or raising defense funding.

  3. A Common Origin for Immunity and Digestion

    PubMed Central

    Broderick, Nichole A.

    2015-01-01

    Historically, the digestive and immune systems were viewed and studied as separate entities. However, there are remarkable similarities and shared functions in both nutrient acquisition and host defense. Here, I propose a common origin for both systems. This association provides a new prism for viewing the emergence and evolution of host defense mechanisms. PMID:25745424

  4. Can plants use an entomopathogenic virus as a defense against herbivores?

    Microsoft Academic Search

    Manuela van Munster; Arne Janssen; Alain Clérivet; Johannes van den Heuvel

    2005-01-01

    It is by now well established that plants use various strategies to defend themselves against herbivores. Besides conventional weapons such as spines and stinging hairs and sophisticated chemical defenses, plants can also involve the enemies of the herbivores in their defense. It has been suggested that plants could even use entomopathogens as part of their defense strategies. In this paper,

  5. COMICR-947; NO. OF PAGES 8 Please cite this article in press as: Kim HK, et al. Recurrent infections and immune evasion strategies of Staphylococcus aureus, Curr Opin Microbiol (2011), doi:10.1016/j.mib.2011.10.012

    E-print Network

    2011-01-01

    infections and immune evasion strategies of Staphylococcus aureus, Curr Opin Microbiol (2011), doi:10.1016/j.mib.2011.10.012 Recurrent infections and immune evasion strategies of Staphylococcus aureus Hwan Keun Kim, Vilasack Thammavongsa, Olaf Schneewind and Dominique Missiakas Staphylococcus aureus causes purulent skin

  6. Role of innate immunity in the pathogenesis of otitis media.

    PubMed

    Mittal, Rahul; Kodiyan, Joyson; Gerring, Robert; Mathee, Kalai; Li, Jian-Dong; Grati, M'hamed; Liu, Xue Zhong

    2014-12-01

    Otitis media (OM) is a public health problem in both developed and developing countries. It is the leading cause of hearing loss and represents a significant healthcare burden. In some cases, acute OM progresses to chronic suppurative OM (CSOM), characterized by effusion and discharge, despite antimicrobial therapy. The emergence of antibiotic resistance and potential ototoxicity of antibiotics has created an urgent need to design non-conventional therapeutic strategies against OM based on modern insights into its pathophysiology. In this article, we review the role of innate immunity as it pertains to OM and discuss recent advances in understanding the role of innate immune cells in protecting the middle ear. We also discuss the mechanisms utilized by pathogens to subvert innate immunity and thereby overcome defensive responses. A better knowledge about bacterial virulence and host resistance promises to reveal novel targets to design effective treatment strategies against OM. The identification and characterization of small natural compounds that can boost innate immunity may provide new avenues for the treatment of OM. There is also a need to design novel methods for targeted delivery of these compounds into the middle ear, allowing higher therapeutic doses and minimizing systemic side effects. PMID:25447732

  7. Mumps: immune status of adults and epidemiology as a necessary background for choice of vaccination strategy in Jordan.

    PubMed

    Batayneh, Naji; Bdour, Salwa

    2002-08-01

    The prevalence of antibodies against mumps in 333 students at Jordan University was assessed using the ELISA technique. Most of the students (93.7%) were seropositive for mumps. About 50% of unvaccinated students and students vaccinated using the optional single-dose MMR vaccine had mumps. The incidence rate of mumps in different age groups and sexes, the geographic distribution and the seasonality of mumps infection prior to the adoption of compulsory MMR vaccination were investigated during the period from 1988 to 2000. Mumps occurred in all age groups in both sexes and the incidence rate was higher in children aged 5-14 years than in adults. There was a higher frequency in winter and spring with epidemic peaks in 1988, 1993 and 2000. Southern Jordan had the highest incidence rate due to low vaccination coverage by the private clinics. The data support the introduction of compulsory MMR vaccination in Jordan for all susceptible individuals. Evaluation of the effectiveness of the compulsory single-dose vaccine and, based on the outcome, a second dose of this vaccine is also recommended in order to achieve and maintain a high level of immunization. PMID:12390410

  8. 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…

  9. Alphacoronavirus Protein 7 Modulates Host Innate Immune Response

    PubMed Central

    Cruz, Jazmina L. G.; Becares, Martina; Sola, Isabel; Oliveros, Juan Carlos; Zúñiga, Sonia

    2013-01-01

    Innate immune response is the first line of antiviral defense resulting, in most cases, in pathogen clearance with minimal clinical consequences. Viruses have developed diverse strategies to subvert host defense mechanisms and increase their survival. In the transmissible gastroenteritis virus (TGEV) as a model, we previously reported that accessory gene 7 counteracts the host antiviral response by associating with the catalytic subunit of protein phosphatase 1 (PP1c). In the present work, the effect of the absence of gene 7 on the host cell, during infection, was further analyzed by transcriptomic analysis. The pattern of gene expression of cells infected with a recombinant mutant TGEV, lacking gene 7 expression (rTGEV-?7), was compared to that of cells infected with the parental virus (rTGEV-wt). Genes involved in the immune response, the interferon response, and inflammation were upregulated during TGEV infection in the absence of gene 7. An exacerbated innate immune response during infection with rTGEV-?7 virus was observed both in vitro and in vivo. An increase in macrophage recruitment and activation in lung tissues infected with rTGEV-?7 virus was observed compared to cells infected with the parental virus. In summary, the absence of protein 7 both in vitro and in vivo led to increased proinflammatory responses and acute tissue damage after infection. In a porcine animal model, which is immunologically similar to humans, we present a novel example of how viral proteins counteract host antiviral pathways to determine the infection outcome and pathogenesis. PMID:23824792

  10. Immune Effector Mechanisms Implicated in Atherosclerosis: From Mice to Humans

    PubMed Central

    Libby, Peter; Lichtman, Andrew H.; Hansson, Göran K.

    2013-01-01

    According to the traditional view, atherosclerosis results from a passive buildup of cholesterol in the artery wall. Yet, burgeoning evidence implicates inflammation and immune effector mechanisms in the pathogenesis of this disease. Both innate and adaptive immunity operate during atherogenesis and link many traditional risk factors to altered arterial functions. Inflammatory pathways have become targets in the quest for novel preventive and therapeutic strategies against cardiovascular disease, a growing contributor to morbidity and mortality worldwide. Here we review current experimental and clinical knowledge of the pathogenesis of atherosclerosis through an immunological lens and how host defense mechanisms essential for survival of the species actually contribute to this chronic disease but also present new opportunities for its mitigation. PMID:23809160

  11. Strategis

    NSDL National Science Digital Library

    1998-01-01

    Strategis is a web site developed by Industry Canada to provide business information resources to Canadian businesses. Resources available include a searchable database of Canadian companies, business information for each sector, a list of business support services, and a guide to business laws and regulation. The International Business Information Network offers information about business opportunities abroad; Trade Data Online provides Canadian and US trade data. A collection of research publications by Industry Canada and monthly economic indicators on the economy are additional economic resources found at this site. Users can view this site in French or English.

  12. Innate immunity and chronic obstructive pulmonary disease: a mini-review.

    PubMed

    Shaykhiev, Renat; Crystal, Ronald G

    2013-01-01

    Chronic obstructive pulmonary disease (COPD), a major smoking-associated lung disorder characterized by progressive irreversible airflow limitation, affects >200 million people worldwide. Individuals with COPD have increased susceptibility to respiratory infections, resulting in exacerbations of the disease. A growing body of evidence indicates that multiple host defense mechanisms, such as those provided by the airway epithelial barrier and innate immune cells, including alveolar macrophages, neutrophils, dendritic cells and natural killer cells, are broadly suppressed in COPD in a smoking-dependent manner. Inactivation of the innate immune system observed in COPD smokers is remarkably similar to the immunosenescence phenotype associated with aging. As a consequence of defective innate immune defense, the lungs of COPD smokers are frequently colonized with pathogens and commonly develop bacterial and viral infections, which cause secondary inflammation, a major driver of the disease progression. In this review, we summarize the evidence from human studies related to disordering of the innate immune system in COPD, discuss possible relationships between those changes and aging, and provide insights into potential therapeutic strategies aimed at the prevention of COPD progression via normalization of the disordered innate immune mechanisms. PMID:24008598

  13. Immunity to Francisella

    PubMed Central

    Cowley, Siobhán C.; Elkins, Karen L.

    2011-01-01

    In recent years, studies on the intracellular pathogen Francisella tularensis have greatly intensified, generating a wealth of new information on the interaction of this organism with the immune system. Here we review the basic elements of the innate and adaptive immune responses that contribute to protective immunity against Francisella species, with special emphasis on new data that has emerged in the last 5?years. Most studies have utilized the mouse model of infection, although there has been an expansion of work on human cells and other new animal models. In mice, basic immune parameters that operate in defense against other intracellular pathogen infections, such as interferon gamma, TNF-?, and reactive nitrogen intermediates, are central for control of Francisella infection. However, new important immune mediators have been revealed, including IL-17A, Toll-like receptor 2, and the inflammasome. Further, a variety of cell types in addition to macrophages are now recognized to support Francisella growth, including epithelial cells and dendritic cells. CD4+ and CD8+ T cells are clearly important for control of primary infection and vaccine-induced protection, but new T cell subpopulations and the mechanisms employed by T cells are only beginning to be defined. A significant role for B cells and specific antibodies has been established, although their contribution varies greatly between bacterial strains of lower and higher virulence. Overall, recent data profile a pathogen that is adept at subverting host immune responses, but susceptible to many elements of the immune system's antimicrobial arsenal. PMID:21687418

  14. Innate Immunity in Atopic Dermatitis

    Microsoft Academic Search

    Andreas Wollenberg; Helen-Caroline Räwer; Jürgen Schauber

    Atopic dermatitis (AD) is a clinically defined, highly pruritic, chronic inflammatory skin disease. In AD patients, the combination\\u000a of a genetic predisposition for skin barrier dysfunction and dysfunctional innate and adaptive immune responses leads to a\\u000a higher frequency of bacterial and viral skin infections. The innate immune system quickly mobilizes an unspecific, standardized\\u000a first-line defense against different pathogens. Defects in

  15. Vitamin D and Innate Immunity

    Microsoft Academic Search

    Philip Liu; Martin Hewison; John S. Adams

    2009-01-01

    This chapter will examine the role of vitamin D in the innate immune system as a mediator of human host defense mechanisms\\u000a microbial disease, focusing on tuberculosis. The first section will examine tuberculosis and the innate immune response to\\u000a the intracellular pathogen, Mycobacterium tuberculosis (M.\\u000a tuberculosis), the causative agent of tuberculosis. This is followed by a discussion of the known

  16. Cytokines, Immunity and Disordered Sleep

    Microsoft Academic Search

    Michael Irwin

    \\u000a Sleep is hypothesized to have a restorative function on immune processes (1). In turn, disordered sleep and sleep loss are thought to impair host defense mechanisms and impact susceptibility to viral-\\u000a and bacterial pathogens (2,3). Few studies have evaluated the association between disordered sleep and immunity in psychiatric patient populations, even\\u000a though depressed- and alcoholic patients show prominent disturbances of

  17. Combined active and passive immunization against nicotine: Minimizing monoclonal antibody requirements using a target antibody concentration strategy

    PubMed Central

    Cornish, Katherine E.; Harris, Andrew C.; LeSage, Mark G.; Keyler, Dan E.; Burroughs, Danielle; Earley, Cathy; Pentel, Paul R.

    2011-01-01

    Nicotine vaccines have shown preliminary evidence of efficacy for enhancing smoking cessation rates, but the serum nicotine-specific antibody (NicAb) concentrations produced are highly variable and many subjects do not develop effective levels. As an alternative to vaccination, passive immunization with nicotine-specific monoclonal antibodies could produce more uniform serum NicAb concentrations, but its use is limited by their high cost and shorter elimination half-life. This study investigated supplementing vaccination with monoclonal antibodies in a targeted fashion to increase vaccine efficacy while minimizing the required monoclonal antibody dose. Rats were vaccinated and then given individualized supplemental doses of the nicotine-specific monoclonal antibody Nic311 to achieve a target total serum NicAb concentration known to be effective for blocking locomotor sensitization (LMS) to nicotine. Rats received vaccine, Nic311, both, or neither, followed by 0.3 mg/kg nicotine s.c. for 10 days to produce LMS. Combination immunotherapy completely blocked the development of LMS, while monotherapy with vaccine or Nic311 alone were only minimally effective. Lower brain nicotine levels were associated with reduced locomotor activity averaged over days 7-10. Despite its greater efficacy, combination immunotherapy did not reduce the variability in the resulting total serum NicAb concentrations. Variability in total serum NicAb concentrations was contributed to by both vaccine-generated antibody and by Nic311. These data show that combination immunotherapy, using a Nic311 dose that is by itself only minimally effective, can substantially enhance nicotine vaccine efficacy. However, variability in serum NicAb levels with combination immunotherapy may make translation of this approach challenging. PMID:21802529

  18. Immunity and immune suppression in human ovarian cancer

    PubMed Central

    Preston, Claudia C; Goode, Ellen L; Hartmann, Lynn C; Kalli, Kimberly R; Knutson, Keith L

    2011-01-01

    Clinical outcomes in ovarian cancer are heterogeneous, independent of common features such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling issue is the response of the patient’s immune system to her ovarian cancer. Several studies have confirmed a prominent role for the immune system in modifying disease course. This has led to the identification and evaluation of novel immune-modulating therapeutic approaches such as vaccination and antibody therapy. Antitumor immunity, however, is often negated by immune suppression mechanisms present in the tumor microenvironment. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological issues that could influence ovarian cancer outcome, including tumor antigens, endogenous immune responses, immune escape and new and developing immunotherapeutic strategies. PMID:21463194

  19. Synergy of local, regional, and systemic non-specific stressors for host defense against pathogens.

    PubMed

    Day, J D; LeGrand, E K

    2015-02-21

    The immune brinksmanship conceptual model postulates that many of the non-specific stressful components of the acute-phase response (e.g. fever, loss of appetite, iron and zinc sequestration) are host-derived systemic stressors used with the "hope" that pathogens will be harmed relatively more than the host. The concept proposes that pathogens, needing to grow and replicate in order to invade their host, should be relatively more vulnerable to non-specific systemic stress than the host and its cells. However, the conceptual model acknowledges the risk to the host in that the gamble to induce systemic self-harming stress to harm pathogens may not pay off in the end. We developed an agent-based model of a simplified host having a local infection to evaluate the utility of non-specific stress, harming host and pathogen alike, for host defense. With our model, we explore the benefits and risks of self-harming strategies and confirm the immune brinksmanship concept of the potential of systemic stressors to be an effective but costly host defense. Further, we extend the concept by including in our model the effects of local and regional non-specific stressors at sites of infection as additional defenses. These include the locally hostile inflammatory environment and the stress of reduced perfusion in the infected region due to coagulation and vascular leakage. In our model, we found that completely non-specific stressors at the local, regional, and systemic levels can act synergistically in host defense. PMID:25457230

  20. [Innate immunity, Toll receptor and sepsis].

    PubMed

    Carrillo-Esper, Raúl

    2003-01-01

    The innate immune response is the first line of defense against infection. Toll-like receptors (TLRs) recognize bacterial lipopolysaccharide and other pathogen-associated molecular patterns (PAMPs). Intracellular signals initiated by interaction between Toll receptors and specific PAMPs results in inflammatory response. Sepsis and septic shock are the result of an exaggerated inflammatory systemic response induced by innate immune dysregulation. PMID:14617415

  1. The Immune System - Nobel Prize Educational Game

    NSDL National Science Digital Library

    2009-01-01

    The Immune System Defender educational game, with three related readings, are based on the 1908 Nobel Prize in Physiology or Medicine, which was awarded for key discoveries about the immune defense system Â? for identifying certain body cells that engulfe bacteria and for work on trying to explain how antibodies are formed in the body.

  2. Evasion of innate immunity by parasitic protozoa

    Microsoft Academic Search

    Alan Sher; David Sacks

    2002-01-01

    Parasitic protozoa are a major cause of global infectious disease. These eukaryotic pathogens have evolved with the vertebrate immune system and typically produce long-lasting chronic infections. A critical step in their host interaction is the evasion of innate immune defenses. The ability to avoid attack by humoral effector mechanisms, such as complement lysis, is of particular importance to extracellular parasites,

  3. Immune System Branden & Tooze, Chapter 15

    E-print Network

    Park, Sheldon

    Immune System Branden & Tooze, Chapter 15 Protects complex multicellular organisms from pathogens, e.g. virus, bacteria, yeast, parasites, worms, etc Innate immunity ­ first line of defense past physical barriers, e.g. skin ­ comprises molecules that recognize pathogen-associated molecular pattern

  4. Exchange of computable patient data between the Department of Veterans Affairs (VA) and the Department of Defense (DoD): terminology mediation strategy.

    PubMed

    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

  5. Mechanisms of immune resolution

    PubMed Central

    Ayala, Alfred; Chung, Chun-Shiang; Grutkoski, Patricia S.; Song, Grace Y.

    2008-01-01

    Initially after injury, the innate/proinflammatory and some aspects of the acquired immune response are up-regulated to maintain a defense against foreign pathogens, clear tissue debris present at the wound site, and orchestrate aspects of tissue remodeling, cell proliferation and angiogenic process, associated with the wound response. However, for proper wound healing to progress, this initial inflammatory response has to be regulated or shut down so as to allow for the reestablishment of matrix, recellularization, and tissue remodeling. Inability to properly resolve the extent of innate/acquired response at a site of injury can lead to poor wound healing, immune suppression, and recurrent infectious episodes. This review attempts to summarize information on regulatory mechanisms that are thought to be involved in controlling/resolving innate or acquired immune responses so as to provide a framework for use in thinking about the impact these processes and their manipulation may have on wound healing and its potential management. PMID:12907886

  6. Intracellular immunity: finding the enemy within—how cells recognize and respond to intracellular pathogens

    PubMed Central

    Tam, Jerry C. H.; Jacques, David A.

    2014-01-01

    Historically, once a cell became infected, it was considered to be beyond all help. By this stage, the invading pathogen had breached the innate defenses and was beyond the reach of the humoral arm of the adaptive immune response. The pathogen could still be removed by cell-mediated immunity (e.g., by NK cells or cytotoxic T lymphocytes), but these mechanisms necessitated the destruction of the infected cell. However, in recent years, it has become increasingly clear that many cells possess sensor and effector mechanisms for dealing with intracellular pathogens. Most of these mechanisms are not restricted to professional immune cells nor do they all necessitate the destruction of the host. In this review, we examine the strategies that cells use to detect and destroy pathogens once the cell membrane has been penetrated. PMID:24899588

  7. Priming in Systemic Plant Immunity

    SciTech Connect

    Jung, Ho Won [University of Chicago; Tschaplinski, Timothy J [ORNL; Wang, Lin [University of Minnesota; Glazebrook, Jane [University of Minnesota; Greenberg, Jean T. [University of Chicago

    2009-01-01

    Upon local infection, plants possess inducible systemic defense responses against their natural enemies. Bacterial infection results in the accumulation to high levels of the mobile metabolite C9-dicarboxylic acid azelaic acid in the vascular sap of Arabidopsis. Azelaic acid confers local and systemic resistance against Pseudomonas syringae. The compound primes plants to strongly accumulate salicylic acid (SA), a known defense signal, upon infection. Mutation of a gene induced by azelaic acid (AZI1) results in the specific loss in plants of systemic immunity triggered by pathogen or azelaic acid and of the priming of SA induction. AZI1, a predicted secreted protein, is also important for generating vascular sap that confers disease resistance. Thus, azelaic acid and AZI1 comprise novel components of plant systemic immunity involved in priming defenses.

  8. Immune Thrombocytopenia

    MedlinePLUS

    ... page from the NHLBI on Twitter. What Is Immune Thrombocytopenia? Immune thrombocytopenia (THROM-bo-si-toe-PE-ne- ... passed from one person to another. Types of Immune Thrombocytopenia The two types of ITP are acute (temporary ...

  9. Immune Restoration

    MedlinePLUS

    ... marrow cells immune to HIV infection. Letting the immune system repair itself: CD4 counts have increased for many ... have taken ART. Some scientists believe that the immune system might be able to heal and repair itself ...

  10. A DNA Microarray-based Analysis of the Host Response to a Nonviral Gene Carrier: A Strategy for Improving the Immune Response

    PubMed Central

    Hatakeyama, Hiroto; Ito, Erika; Yamamoto, Momoko; Akita, Hidetaka; Hayashi, Yasuhiro; Kajimoto, Kazuaki; Kaji, Noritada; Baba, Yoshinobu; Harashima, Hideyoshi

    2011-01-01

    The purpose of this study was to investigate the host response to systemically administered lipid nanoparticles (NPs) encapsulating plasmid DNA (pDNA) in the spleen using a DNA microarray. As a model for NPs, we used a multifunctional envelope-type nano device (MEND). Microarray analysis revealed that 1,581 of the differentially expressed genes could be identified by polyethylene glycol (PEG)-unmodified NP using a threefold change relative to the control. As the result of PEGylation, the NP treatment resulted in the reduction in the expression of most of the genes. However, the expression of type I interferon (IFN) was specifically increased by PEGylation. Based on the microarray and a pathway analysis, we hypothesize that PEGylation inhibited the endosomal escape of NP, and extended the interaction of toll-like receptor-9 (TLR9) with CpG-DNA accompanied by the production of type I IFN. This hypothesis was tested by introducing a pH-sensitive fusogenic peptide, GALA, which enhances the endosomal escape of PEGylated NP. As expected, type I IFN was reduced and interleukin-6 (IL-6) remained at the baseline. These findings indicate that a carrier design based on microarray analysis and the manipulation of intracellular trafficking constitutes a rational strategy for reducing the host immune response to NPs. PMID:21386823

  11. Induction of antitumor immunity through xenoplacental immunization

    PubMed Central

    Zhong, Zhaohui; Kusznieruk, Kornel P; Popov, Igor A; Riordan, Neil H; Izadi, Hamid; Yijian, Li; Sher, Salman; Szczurko, Orest M; Agadjanyan, Michael G; Tullis, Richard H; Harandi, Amir; Reznik, Boris N; Mamikonyan, Grigor V; Ichim, Thomas E

    2006-01-01

    Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential. PMID:16725035

  12. The hnRNP-Q Protein LIF2 Participates in the Plant Immune Response

    PubMed Central

    Le Roux, Clémentine; Del Prete, Stefania; Boutet-Mercey, Stéphanie; Perreau, François; Balagué, Claudine; Roby, Dominique; Fagard, Mathilde; Gaudin, Valérie

    2014-01-01

    Eukaryotes have evolved complex defense pathways to combat invading pathogens. Here, we investigated the role of the Arabidopsis thaliana heterogeneous nuclear ribonucleoprotein (hnRNP-Q) LIF2 in the plant innate immune response. We show that LIF2 loss-of-function in A. thaliana leads to changes in the basal expression of the salicylic acid (SA)- and jasmonic acid (JA)- dependent defense marker genes PR1 and PDF1.2, respectively. Whereas the expression of genes involved in SA and JA biosynthesis and signaling was also affected in the lif2-1 mutant, no change in SA and JA hormonal contents was detected. In addition, the composition of glucosinolates, a class of defense-related secondary metabolites, was altered in the lif2-1 mutant in the absence of pathogen challenge. The lif2-1 mutant exhibited reduced susceptibility to the hemi-biotrophic pathogen Pseudomonas syringae and the necrotrophic ascomycete Botrytis cinerea. Furthermore, the lif2-1 sid2-2 double mutant was less susceptible than the wild type to P. syringae infection, suggesting that the lif2 response to pathogens was independent of SA accumulation. Together, our data suggest that lif2-1 exhibits a basal primed defense state, resulting from complex deregulation of gene expression, which leads to increased resistance to pathogens with various infection strategies. Therefore, LIF2 may function as a suppressor of cell-autonomous immunity. Similar to its human homolog, NSAP1/SYNCRIP, a trans-acting factor involved in both cellular processes and the viral life cycle, LIF2 may regulate the conflicting aspects of development and defense programs, suggesting that a conserved evolutionary trade-off between growth and defense pathways exists in eukaryotes. PMID:24914891

  13. Strategic Power Infrastructure Defense

    Microsoft Academic Search

    Hao Li; GARY W. ROSENWALD; JUHWAN JUNG; Chen-ching Liu

    2005-01-01

    This paper provides a comprehensive state-of-the-art overview on power infrastructure defense systems. A review of the literature on the subjects of critical infrastructures, threats to the power grids, defense system concepts, and the special protection systems is reported. The proposed Strategic Power Infrastructure Defense (SPID) system methodology is a real-time, wide-area, adaptive protection and control system involving the power, communication,

  14. The defense message system

    Microsoft Academic Search

    Robert W. Shirey; INTRODUCTIO N

    1990-01-01

    The U.S. Department of Defense (DoD) plans to modernize the Defense Message System (DMS) to reduce costs and improve services. DMS includes all hardware, software, procedures, standards, facilities, and personnel used to exchange messages electronically in DoD. DMS today has two separate parts. The AUTODIN system handles formal messages between organizations, and the Defense Data Network's electronic mail system handles

  15. Parentage of Overlapping Offspring of an Arboreal-Breeding Frog with No Nest Defense: Implications for Nest Site Selection and Reproductive Strategy

    PubMed Central

    Tung, Wan-Ping; Chen, Yi-Huey; Cheng, Wei-Chun; Chuang, Ming-Feng; Hsu, Wan-Tso; Kam, Yeong-Choy; Lehtinen, Richard M.

    2015-01-01

    Overlapping offspring occurs when eggs are laid in a nest containing offspring from earlier reproduction. Earlier studies showed that the parentage is not always obvious due to difficulties in field observation and/or alternative breeding tactics. To unveil the parentage between overlapping offspring and parents is critical in understanding oviposition site selection and the reproductive strategies of parents. Amplectant pairs of an arboreal-breeding frog, Kurixalus eiffingeri, lay eggs in tadpole-occupied nests where offspring of different life stages (embryos and tadpoles) coexist. We used five microsatellite DNA markers to assess the parentage between parents and overlapping offspring. We also tested the hypothesis that the male or female frog would breed in the same breeding site because of the scarcity of nest sites. Results showed varied parentage patterns, which may differ from the phenomenon of overlapping egg clutches reported earlier. Parentage analyses showed that only 58 and 25% of the tadpole-occupied stumps were reused by the same male and female respectively, partially confirming our prediction. Re-nesting by the same individual was more common in males than females, which is most likely related to the cost of tadpole feeding and/or feeding schemes of females. On the other hand, results of parentage analyses showed that about 42 and 75% of male and female respectively bred in tadpole-occupied stumps where tadpoles were genetically unrelated. Results of a nest-choice experiment revealed that 40% of frogs chose tadpole-occupied bamboo cups when we presented identical stumps, without or with tadpoles, suggesting that the habitat saturation hypothesis does not fully explain why frogs used the tadpole-occupied stumps. Several possible benefits of overlapping offspring with different life stages were proposed. Our study highlights the importance of integrating molecular data with field observations to better understand the reproductive biology and nest site selection of anuran amphibians. PMID:25835716

  16. Interaction between Yersinia pestis and the Host Immune System

    Microsoft Academic Search

    B. Li; R. Yang

    2008-01-01

    The mammalian immune system comprises multiple physi- cal, chemical, and cellular components that are traditionally classified as innate and adaptive immunity. The innate immune response is the first line of host defense against pathogens, depending on barrier structures, phagocytic cells (neutrophils, macrophages, and dendritic cells (DCs)), natural killer (NK) cells, and molecules such as complement proteins, cytokines, and antimicrobial peptides.

  17. Immunity: plants as effective mediators.

    PubMed

    Sultan, M Tauseef; Butt, Masood Sadiq; Qayyum, Mir M Nasir; Suleria, Hafiz Ansar Rasul

    2014-01-01

    In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders. PMID:24564587

  18. Technologies for distributed defense

    NASA Astrophysics Data System (ADS)

    Seiders, Barbara; Rybka, Anthony

    2002-07-01

    For Americans, the nature of warfare changed on September 11, 2001. Our national security henceforth will require distributed defense. One extreme of distributed defense is represented by fully deployed military troops responding to a threat from a hostile nation state. At the other extreme is a country of 'citizen soldiers', with families and communities securing their common defense through heightened awareness, engagement as good neighbors, and local support of and cooperation with local law enforcement, emergency and health care providers. Technologies - for information exploitation, biological agent detection, health care surveillance, and security - will be critical to ensuring success in distributed defense.

  19. Technologies for Distributed Defense

    SciTech Connect

    Seiders, Barbara AB; Rybka, Anthony J.

    2002-07-01

    For Americans, the nature of warfare changed on September 11, 2001. Our national security henceforth will require distributed defense. One extreme of distributed defense is represented by fully deployed military troops responding to a threat from a hostile nation state. At the other extreme is a country of "citizen soldiers," with families and communities securing their common defense through heightened awareness, engagement as good neighbors, and local support of and cooperation with local law enforcement, emergency and health care providers. Technologies - for information exploitation, biological agent detection, health care surveillance, and security - will be critical to ensuring success in distributed defense.

  20. Immunization of epidemics in multiplex networks.

    PubMed

    Zhao, Dawei; Wang, Lianhai; Li, Shudong; Wang, Zhen; Wang, Lin; Gao, Bo

    2014-01-01

    Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted) immunization and layer node-based random (targeted) immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER) random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF) networks. PMID:25401755

  1. Immunization of Epidemics in Multiplex Networks

    PubMed Central

    Zhao, Dawei; Wang, Lianhai; Li, Shudong; Wang, Zhen; Wang, Lin; Gao, Bo

    2014-01-01

    Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted) immunization and layer node-based random (targeted) immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER) random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF) networks. PMID:25401755

  2. Innate Immunity to Aspergillus Species

    PubMed Central

    Park, Stacy J.; Mehrad, Borna

    2009-01-01

    Summary: All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused by Aspergillus species, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses to Aspergillus species is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses against Aspergillus species that dictate the outcome of this host-microbe interaction. PMID:19822887

  3. Innate immunity to Aspergillus species.

    PubMed

    Park, Stacy J; Mehrad, Borna

    2009-10-01

    All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused by Aspergillus species, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses to Aspergillus species is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses against Aspergillus species that dictate the outcome of this host-microbe interaction. PMID:19822887

  4. SDI (Strategic Defense Initiative): a policy analysis

    SciTech Connect

    Fought, S.O.

    1987-01-01

    Contents include -- Foundations of Deterrence; A Model for Stability; Analysis of SDI/Stability; Related Issues; Treatment of Implementation Factors; Historical Evolution and Trends; The Strategic Choices and Flexible Response; The Planners' Perspective; The Impact of Strategic Defense on a Strategy of Flexible Response; Synthesis.

  5. Earthworm immune responses.

    PubMed

    Jarosz, J; Gli?ski, Z

    1997-01-01

    The knowledge of the immunity in annelids started with the use of earthworms as biomarkers indicating changes caused by environmental pollution. Defence strategies effectively protect earthworms against bacterial infections and parasitic invasion. A natural immunity formed by anatomical and chemical protective barriers prevents damage of the underlying tissues, body fluid losses, and microbial infections of the body cavity. The internal defence mechanisms of annelids involve phagocytosis, nodule formation and encapsulation, blood coagulation and wound repair, and antibacterial immune proteins. The antibacterial activity of coelomic fluid associated with lysozyme-like substances and inducible humoral molecules support haemocytic reactions in the annelid defence system. PMID:9557138

  6. Dynamic Imaging of the Effector Immune Response to Listeria Infection In Vivo

    E-print Network

    Waite, Janelle C.

    Host defense against the intracellular pathogen Listeria monocytogenes (Lm) requires innate and adaptive immunity. Here, we directly imaged immune cell dynamics at Lm foci established by dendritic cells in the subcapsular ...

  7. Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP).

    PubMed

    Watson, J C; Hadler, S C; Dykewicz, C A; Reef, S; Phillips, L

    1998-05-22

    These revised recommendations of the Advisory Committee on Immunization Practices (ACIP) on measles, mumps, and rubella prevention supersede recommendations published in 1989 and 1990. This statement summarizes the goals and current strategies for measles, rubella, and congenital rubella syndrome (CRS) elimination and for mumps reduction in the United States. Changes from previous recommendations include: Emphasis on the use of combined MMR vaccine for most indications; A change in the recommended age for routine vaccination to 12-15 months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A recommendation that all states take immediate steps to implement a two dose MMR requirement for school entry and any additional measures needed to ensure that all school-aged children are vaccinated with two doses of MMR by 2001; A clarification of the role of serologic screening to determine immunity; A change in the criteria for determining acceptable evidence of rubella immunity; A recommendation that all persons who work in health-care facilities have acceptable evidence of measles and rubella immunity; Changes in the recommended interval between administration of immune globulin and measles vaccination; and Updated information on adverse events and contraindications, particularly for persons with severe HIV infection, persons with a history of egg allergy or gelatin allergy, persons with a history of thrombocytopenia, and persons receiving steroid therapy. PMID:9639369

  8. Ethnic appeal: A self-defense tool for Kenyan politicians

    Microsoft Academic Search

    Dane Kiambi

    So far, analyses of apologetic rhetoric strategies as used by individuals or organizations to respond to accusations of wrongdoing have been concentrated in the West. An analysis of political apologia in an African setting – in this case Kenya – reveals that while Kenyan politicians have used denial, victimization, mortification, and counterattacking among other self-defense strategies, one particular strategy emerges

  9. Active and passive immunization strategies based on the SDPM1 peptide demonstrate pre-clinical efficacy in the APPswePSEN1dE9 mouse model for Alzheimer’s disease

    PubMed Central

    Camboni, Marybeth; Wang, Chiou-Miin; Miranda, Carlos; Yoon, Jung Hae; Xu, Rui; Zygmunt, Deborah; Kaspar, Brian K.; Martin, Paul T.

    2013-01-01

    Recent clinical and pre-clinical studies suggest that both active and passive immunization strategies targeting A? amyloid may have clinical benefit in Alzheimer’s disease. Here, we demonstrate that vaccination of APPswePSEN1dE9 mice with SDPM1, an engineered non-native A? amyloid-specific binding peptide, lowers brain A? amyloid plaque burden and brain A?1-40 and A?1-42 peptide levels, improves cognitive learning and memory in Morris Water maze tests and increases the expression of synaptic brain proteins. This was the case in young mice immunized prior to development of significant brain amyloid burden, and in older mice, where brain amyloid was already present. Active immunization was optimized using ALUM as an adjuvant to stimulate production of anti-SDPM1 and anti-A? amyloid antibodies. Intracerebral injection of P4D6, an SDPM1 peptide-mimotope antibody, also lowered brain amyloid plaque burden in APPswePSEN1dE9 mice. Additionally, P4D6 inhibited A? amyloid-mediated toxicity in cultured neuronal cells. The protein sequence of the variable domain within the P4D6 heavy chain was found to mimic a multimer of the SDPM1 peptide motif. These data demonstrate the efficacy of active and passive vaccine strategies to target specific A? amyloid oligomers using an engineered peptide-mimotope strategy. PMID:24021662

  10. Extreme Resistance as a Host Counter-counter Defense against Viral Suppression of RNA Silencing

    PubMed Central

    Sansregret, Raphaël; Dufour, Vanessa; Langlois, Mathieu; Daayf, Fouad; Dunoyer, Patrice; Voinnet, Olivier; Bouarab, Kamal

    2013-01-01

    RNA silencing mediated by small RNAs (sRNAs) is a conserved regulatory process with key antiviral and antimicrobial roles in eukaryotes. A widespread counter-defensive strategy of viruses against RNA silencing is to deploy viral suppressors of RNA silencing (VSRs), epitomized by the P19 protein of tombusviruses, which sequesters sRNAs and compromises their downstream action. Here, we provide evidence that specific Nicotiana species are able to sense and, in turn, antagonize the effects of P19 by activating a highly potent immune response that protects tissues against Tomato bushy stunt virus infection. This immunity is salicylate- and ethylene-dependent, and occurs without microscopic cell death, providing an example of “extreme resistance” (ER). We show that the capacity of P19 to bind sRNA, which is mandatory for its VSR function, is also necessary to induce ER, and that effects downstream of P19-sRNA complex formation are the likely determinants of the induced resistance. Accordingly, VSRs unrelated to P19 that also bind sRNA compromise the onset of P19-elicited defense, but do not alter a resistance phenotype conferred by a viral protein without VSR activity. These results show that plants have evolved specific responses against the damages incurred by VSRs to the cellular silencing machinery, a likely necessary step in the never-ending molecular arms race opposing pathogens to their hosts. PMID:23785291

  11. Skunk Defensive Secretion

    NSDL National Science Digital Library

    Wood, William F.

    1999-01-01

    Skunk Defensive Secretion is a interesting site maintained by William F. Wood from the Department of Chemistry at Humboldt State University. He explains how to remove skunk odor, the chemistry of skunk spray, the history of skunk defensive secretion research, skunk pictures, and even how to happily coexist with skunks. This is a fun, informative, and potentially olfactory friendly site.

  12. Defense Mechanisms: A Bibliography.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    This bibliography includes studies of defense mechanisms, in general, and studies of multiple mechanisms. Defense mechanisms, briefly and simply defined, are the unconscious ego defendants against unpleasure, threat, or anxiety. Sigmund Freud deserves the clinical credit for studying many mechanisms and introducing them in professional literature.…

  13. Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination

    NASA Astrophysics Data System (ADS)

    de Santo, Carmela; Serafini, Paolo; Marigo, Ilaria; Dolcetti, Luigi; Bolla, Manlio; del Soldato, Piero; Melani, Cecilia; Guiducci, Cristiana; Colombo, Mario P.; Iezzi, Manuela; Musiani, Piero; Zanovello, Paola; Bronte, Vincenzo

    2005-03-01

    Active suppression of tumor-specific T lymphocytes can limit the immune-mediated destruction of cancer cells. Of the various strategies used by tumors to counteract immune attacks, myeloid suppressors recruited by growing cancers are particularly efficient, often resulting in the induction of systemic T lymphocyte dysfunction. We have previously shown that the mechanism by which myeloid cells from tumor-bearing hosts block immune defense strategies involves two enzymes that metabolize L-arginine: arginase and nitric oxide (NO) synthase. NO-releasing aspirin is a classic aspirin molecule covalently linked to a NO donor group. NO aspirin does not possess direct antitumor activity. However, by interfering with the inhibitory enzymatic activities of myeloid cells, orally administered NO aspirin normalized the immune status of tumor-bearing hosts, increased the number and function of tumor-antigen-specific T lymphocytes, and enhanced the preventive and therapeutic effectiveness of the antitumor immunity elicited by cancer vaccination. Because cancer vaccines and NO aspirin are currently being investigated in independent phase I/II clinical trials, these findings offer a rationale to combine these treatments in subjects with advanced neoplastic diseases. arginase | immunosuppression | myeloid cells | nitric oxide | immunotherapy

  14. Glutamate Utilization Couples Oxidative Stress Defense and the Tricarboxylic Acid Cycle in Francisella Phagosomal Escape

    PubMed Central

    Ramond, Elodie; Gesbert, Gael; Rigard, Mélanie; Dairou, Julien; Dupuis, Marion; Dubail, Iharilalao; Meibom, Karin; Henry, Thomas; Barel, Monique; Charbit, Alain

    2014-01-01

    Intracellular bacterial pathogens have developed a variety of strategies to avoid degradation by the host innate immune defense mechanisms triggered upon phagocytocis. Upon infection of mammalian host cells, the intracellular pathogen Francisella replicates exclusively in the cytosolic compartment. Hence, its ability to escape rapidly from the phagosomal compartment is critical for its pathogenicity. Here, we show for the first time that a glutamate transporter of Francisella (here designated GadC) is critical for oxidative stress defense in the phagosome, thus impairing intra-macrophage multiplication and virulence in the mouse model. The gadC mutant failed to efficiently neutralize the production of reactive oxygen species. Remarkably, virulence of the gadC mutant was partially restored in mice defective in NADPH oxidase activity. The data presented highlight links between glutamate uptake, oxidative stress defense, the tricarboxylic acid cycle and phagosomal escape. This is the first report establishing the role of an amino acid transporter in the early stage of the Francisella intracellular lifecycle. PMID:24453979

  15. Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.

    PubMed

    Ramond, Elodie; Gesbert, Gael; Rigard, Mélanie; Dairou, Julien; Dupuis, Marion; Dubail, Iharilalao; Meibom, Karin; Henry, Thomas; Barel, Monique; Charbit, Alain

    2014-01-01

    Intracellular bacterial pathogens have developed a variety of strategies to avoid degradation by the host innate immune defense mechanisms triggered upon phagocytocis. Upon infection of mammalian host cells, the intracellular pathogen Francisella replicates exclusively in the cytosolic compartment. Hence, its ability to escape rapidly from the phagosomal compartment is critical for its pathogenicity. Here, we show for the first time that a glutamate transporter of Francisella (here designated GadC) is critical for oxidative stress defense in the phagosome, thus impairing intra-macrophage multiplication and virulence in the mouse model. The gadC mutant failed to efficiently neutralize the production of reactive oxygen species. Remarkably, virulence of the gadC mutant was partially restored in mice defective in NADPH oxidase activity. The data presented highlight links between glutamate uptake, oxidative stress defense, the tricarboxylic acid cycle and phagosomal escape. This is the first report establishing the role of an amino acid transporter in the early stage of the Francisella intracellular lifecycle. PMID:24453979

  16. Mechanisms of plant defense against insect herbivores

    PubMed Central

    War, Abdul Rashid; Paulraj, Michael Gabriel; Ahmad, Tariq; Buhroo, Abdul Ahad; Hussain, Barkat; Ignacimuthu, Savarimuthu; Sharma, Hari Chand

    2012-01-01

    Plants respond to herbivory through various morphological, biochemicals, and molecular mechanisms to counter/offset the effects of herbivore attack. The biochemical mechanisms of defense against the herbivores are wide-ranging, highly dynamic, and are mediated both by direct and indirect defenses. The defensive compounds are either produced constitutively or in response to plant damage, and affect feeding, growth, and survival of herbivores. In addition, plants also release volatile organic compounds that attract the natural enemies of the herbivores. These strategies either act independently or in conjunction with each other. However, our understanding of these defensive mechanisms is still limited. Induced resistance could be exploited as an important tool for the pest management to minimize the amounts of insecticides used for pest control. Host plant resistance to insects, particularly, induced resistance, can also be manipulated with the use of chemical elicitors of secondary metabolites, which confer resistance to insects. By understanding the mechanisms of induced resistance, we can predict the herbivores that are likely to be affected by induced responses. The elicitors of induced responses can be sprayed on crop plants to build up the natural defense system against damage caused by herbivores. The induced responses can also be engineered genetically, so that the defensive compounds are constitutively produced in plants against are challenged by the herbivory. Induced resistance can be exploited for developing crop cultivars, which readily produce the inducible response upon mild infestation, and can act as one of components of integrated pest management for sustainable crop production. PMID:22895106

  17. Mechanisms of plant defense against insect herbivores.

    PubMed

    War, Abdul Rashid; Paulraj, Michael Gabriel; Ahmad, Tariq; Buhroo, Abdul Ahad; Hussain, Barkat; Ignacimuthu, Savarimuthu; Sharma, Hari Chand

    2012-10-01

    Plants respond to herbivory through various morphological, biochemicals, and molecular mechanisms to counter/offset the effects of herbivore attack. The biochemical mechanisms of defense against the herbivores are wide-ranging, highly dynamic, and are mediated both by direct and indirect defenses. The defensive compounds are either produced constitutively or in response to plant damage, and affect feeding, growth, and survival of herbivores. In addition, plants also release volatile organic compounds that attract the natural enemies of the herbivores. These strategies either act independently or in conjunction with each other. However, our understanding of these defensive mechanisms is still limited. Induced resistance could be exploited as an important tool for the pest management to minimize the amounts of insecticides used for pest control. Host plant resistance to insects, particularly, induced resistance, can also be manipulated with the use of chemical elicitors of secondary metabolites, which confer resistance to insects. By understanding the mechanisms of induced resistance, we can predict the herbivores that are likely to be affected by induced responses. The elicitors of induced responses can be sprayed on crop plants to build up the natural defense system against damage caused by herbivores. The induced responses can also be engineered genetically, so that the defensive compounds are constitutively produced in plants against are challenged by the herbivory. Induced resistance can be exploited for developing crop cultivars, which readily produce the inducible response upon mild infestation, and can act as one of components of integrated pest management for sustainable crop production. PMID:22895106

  18. Immune suppression in cancer: Effects on immune cells, mechanisms and future therapeutic intervention

    Microsoft Academic Search

    Theresa L. Whiteside

    2006-01-01

    Evidence indicates that the healthy immune system is necessary for control of malignant disease and that immune suppression associated with cancer contributes to its progression. Tumors have developed strategies to successfully evade the host immune system, and various molecular and cellular mechanisms responsible for tumor evasion have been identified. Certain of these mechanisms target immune anti-tumor effector cells. Dysfunction and

  19. Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms.

    PubMed

    Goldberg, Emily L; Romero-Aleshire, Melissa J; Renkema, Kristin R; Ventevogel, Melissa S; Chew, Wade M; Uhrlaub, Jennifer L; Smithey, Megan J; Limesand, Kirsten H; Sempowski, Gregory D; Brooks, Heddwen L; Nikolich-Žugich, Janko

    2015-02-01

    Aging of the world population and a concomitant increase in age-related diseases and disabilities mandates the search for strategies to increase healthspan, the length of time an individual lives healthy and productively. Due to the age-related decline of the immune system, infectious diseases remain among the top 5-10 causes of mortality and morbidity in the elderly, and improving immune function during aging remains an important aspect of healthspan extension. Calorie restriction (CR) and more recently rapamycin (rapa) feeding have both been used to extend lifespan in mice. Preciously few studies have actually investigated the impact of each of these interventions upon in vivo immune defense against relevant microbial challenge in old organisms. We tested how rapa and CR each impacted the immune system in adult and old mice. We report that each intervention differentially altered T-cell development in the thymus, peripheral T-cell maintenance, T-cell function and host survival after West Nile virus infection, inducing distinct but deleterious consequences to the aging immune system. We conclude that neither rapa feeding nor CR, in the current form/administration regimen, may be optimal strategies for extending healthy immune function and, with it, lifespan. PMID:25424641

  20. Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms

    PubMed Central

    Goldberg, Emily L; Romero-Aleshire, Melissa J; Renkema, Kristin R; Ventevogel, Melissa S; Chew, Wade M; Uhrlaub, Jennifer L; Smithey, Megan J; Limesand, Kirsten H; Sempowski, Gregory D; Brooks, Heddwen L; Nikolich-Žugich, Janko

    2015-01-01

    Aging of the world population and a concomitant increase in age-related diseases and disabilities mandates the search for strategies to increase healthspan, the length of time an individual lives healthy and productively. Due to the age-related decline of the immune system, infectious diseases remain among the top 5–10 causes of mortality and morbidity in the elderly, and improving immune function during aging remains an important aspect of healthspan extension. Calorie restriction (CR) and more recently rapamycin (rapa) feeding have both been used to extend lifespan in mice. Preciously few studies have actually investigated the impact of each of these interventions upon in vivo immune defense against relevant microbial challenge in old organisms. We tested how rapa and CR each impacted the immune system in adult and old mice. We report that each intervention differentially altered T-cell development in the thymus, peripheral T-cell maintenance, T-cell function and host survival after West Nile virus infection, inducing distinct but deleterious consequences to the aging immune system. We conclude that neither rapa feeding nor CR, in the current form/administration regimen, may be optimal strategies for extending healthy immune function and, with it, lifespan. PMID:25424641

  1. DIVERGENCE IN STRUCTURE AND ACTIVITY OF PHENOLIC DEFENSES IN YOUNG LEAVES

    E-print Network

    Coley, Phyllis

    DIVERGENCE IN STRUCTURE AND ACTIVITY OF PHENOLIC DEFENSES IN YOUNG LEAVES OF TWO CO-OCCURRING Inga selection on young leaves has given rise to a variety of leaf developmental strategies and age-specific chemical defense modes. We are studying correlations between leaf developmental types and chemical defenses

  2. Garland Science 2009 ! The evolution of the immune system can be studied

    E-print Network

    Utrecht, Universiteit

    © Garland Science 2009 #12;·! The evolution of the immune system can be studied by comparing the genes expressed by different species! !- Evolution of the innate immune system! !- Evolution of the adaptive immune system! !"#$%&'() © Garland Science 2009 #12;·! The concept of an immune system-the defense

  3. 76 FR 6637 - Assumption Buster Workshop: Defense-in-Depth Is a Smart Investment for Cyber Security

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-07

    ...Defense-in-Depth Is a Smart Investment for Cyber Security AGENCY: The National Coordination...working group that coordinates cyber security research activities in support...Defense-in-Depth strategy for cyber security. The workshop will be held...

  4. 76 FR 2151 - Assumption Buster Workshop: Defense-in-Depth is a Smart Investment for Cyber Security

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ...Defense-in-Depth is a Smart Investment for Cyber Security AGENCY: The National Coordination...working group that coordinates cyber security research activities in support...defense-in-depth strategy for cyber security. The workshop will be held...

  5. Segmenting consumers for food defense communication strategies

    Microsoft Academic Search

    Dennis Degeneffe; Jean Kinsey; Thomas Stinson; Koel Ghosh

    2009-01-01

    Purpose – In the light of lessons learned from recent disasters (The London subway bombings, and Hurricane Katrina), it has become increasingly clear that supply chain partners as well as government agencies need to be prepared to communicate effectively to consumers and customers before, during and after a disaster. Effective communication can minimize confusion and harm to company reputations, to

  6. A family of conserved bacterial effectors inhibits salicylic acid-mediated basal immunity and promotes disease necrosis in plants

    PubMed Central

    DebRoy, Sruti; Thilmony, Roger; Kwack, Yong-Bum; Nomura, Kinya; He, Sheng Yang

    2004-01-01

    Salicylic acid (SA)-mediated host immunity plays a central role in combating microbial pathogens in plants. Inactivation of SA-mediated immunity, therefore, would be a critical step in the evolution of a successful plant pathogen. It is known that mutations in conserved effector loci (CEL) in the plant pathogens Pseudomonas syringae (the ?CEL mutation), Erwinia amylovora (the dspA/E mutation), and Pantoea stewartii subsp. stewartii (the wtsE mutation) exert particularly strong negative effects on bacterial virulence in their host plants by unknown mechanisms. We found that the loss of virulence in ?CEL and dspA/E mutants was linked to their inability to suppress cell wall-based defenses and to cause normal disease necrosis in Arabidopsis and apple host plants. The ?CEL mutant activated SA-dependent callose deposition in wild-type Arabidopsis but failed to elicit high levels of callose-associated defense in Arabidopsis plants blocked in SA accumulation or synthesis. This mutant also multiplied more aggressively in SA-deficient plants than in wild-type plants. The hopPtoM and avrE genes in the CEL of P. syringae were found to encode suppressors of this SA-dependent basal defense. The widespread conservation of the HopPtoM and AvrE families of effectors in various bacteria suggests that suppression of SA-dependent basal immunity and promotion of host cell death are important virulence strategies for bacterial infection of plants. PMID:15210989

  7. Defense Health Program DEPARTMENT OF DEFENSE MULTIPLE SCLEROSIS RESEARCH PROGRAM

    E-print Network

    von der Heydt, Rüdiger

    Defense Health Program DEPARTMENT OF DEFENSE MULTIPLE SCLEROSIS RESEARCH PROGRAM FISCAL YEAR 2013) to the Department of Defense Multiple Sclerosis Research Program (MSRP). The Department of Defense Multiple to critical discoveries in understanding the causes and progression of multiple sclerosis (MS) and

  8. Mother-derived trans-generational immune priming in the red palm weevil, Rhynchophorus ferrugineus Olivier (Coleoptera, Dryophthoridae).

    PubMed

    Shi, Z H; Lin, Y T; Hou, Y M

    2014-12-01

    Rhynchophorus ferrugineus (Coleoptera, Curculionidae) is the most destructive pest of palm trees worldwide containing it invasive areas, such as the southern part of China. It is always emphasized to develop integrated pest management based on biological agents, but their success is not very exciting. Presently, the immune defenses of this pest against biological agents attract scarce attention. It is still unclear whether immune priming also generally occurs in insect pests and in response to different pathogens. Our results indicated that previous challenge of bacteria pathogen enhanced the magnitude of phenoloxidase activity and antibacterial activity in R. ferrugineus larvae against the secondary infection. Furthermore, trans-generational immune priming was also determined in this pest, and only challenged R. ferrugineus mothers transferred the immune protection to their offspring which suggested males and females of this pest might have evolved different strategies on the investment of delivering immune protection to their offspring. Importantly, our data provide the evidence to suggest that different kinds of biological control agents might be used alternatively or in combination to fight against R. ferrugineus because of the existence of immune priming with low species-specific level. On the other hand, for this invasive pest, the immune priming may also facilitate its adaptation and dispersal in the new regions. PMID:25208627

  9. Exploring the Pharmacological Potential of Promiscuous Host-Defense Peptides: From Natural Screenings to Biotechnological Applications

    PubMed Central

    Silva, Osmar N.; Mulder, Kelly C. L.; Barbosa, Aulus E. A. D.; Otero-Gonzalez, Anselmo J.; Lopez-Abarrategui, Carlos; Rezende, Taia M. B.; Dias, Simoni C.; Franco, Octávio L.

    2011-01-01

    In the last few years, the number of bacteria with enhanced resistance to conventional antibiotics has dramatically increased. Most of such bacteria belong to regular microbial flora, becoming a real challenge, especially for immune-depressed patients. Since the treatment is sometimes extremely expensive, and in some circumstances completely inefficient for the most severe cases, researchers are still determined to discover novel compounds. Among them, host-defense peptides (HDPs) have been found as the first natural barrier against microorganisms in nearly all living groups. This molecular class has been gaining attention every day for multiple reasons. For decades, it was believed that these defense peptides had been involved only with the permeation of the lipid bilayer in pathogen membranes, their main target. Currently, it is known that these peptides can bind to numerous targets, as well as lipids including proteins and carbohydrates, from the surface to deep within the cell. Moreover, by using in vivo models, it was shown that HDPs could act both in pathogens and cognate hosts, improving immunological functions as well as acting through multiple pathways to control infections. This review focuses on structural and functional properties of HDP peptides and the additional strategies used to select them. Furthermore, strategies to avoid problems in large-scale manufacture by using molecular and biochemical techniques will also be explored. In summary, this review intends to construct a bridge between academic research and pharmaceutical industry, providing novel insights into the utilization of HDPs against resistant bacterial strains that cause infections in humans. PMID:22125552

  10. Nonoffensive defense is overrated

    SciTech Connect

    Flanagan, S.J. (National Defense Univ., Washingtion, DC (USA))

    1988-09-01

    Some Western analysts argue that European security would stabilize if nations shifted to forces and doctrines that left them structurally incapable of conducting offensive military actions. Some, including American scholar Gene Sharp, have even called for replacing traditional military forces with plans for civilian-based resistance. Purely defensive postures would be reassuring to neighboring states, all of these theorists say, but such defenses would still be strong enough to defeat an attack if deterrence failed. This defensive-only stance, according to its advocates, is a purer form of deterrence by denial than now exists, since it removes even the possibility of inflicting punishment in retaliation for an attack: it deters only be denying victory. But Mr. Flanagan questions whether such defense actually would serve as a credible deterrent. In addition, the various proposed schemes share some serious weaknesses, which he proceeds to discuss. 5 refs.

  11. Jane's Internet Defense Glossary

    NSDL National Science Digital Library

    Jane's Information Group, well-known publisher of defense and aerospace information, provides this handy, no-nonsense glossary of over 20,000 pertinent acronyms and abbreviations. The glossary is both browseable and searchable by acronym or definition.

  12. Department of Defense INSTRUCTION

    E-print Network

    April 16, 2009 USD(P&R) SUBJECT: DoD Civilian Personnel Management System: Injury Compensation regarding civilian personnel management within the Department of Defense. b. Volume. This Volume ......................................................................................................................7 CIVILIAN PERSONNEL MANAGEMENT SERVICE (CPMS)............................................7

  13. Immunization Coverage

    MedlinePLUS

    ... based on local priorities and needs. World Immunization Week The last week of April each year is marked by WHO and partners as World Immunization Week. It aims to raise public awareness of how ...

  14. Immune response

    MedlinePLUS

    ... antigens. These include a group of antigens called HLA antigens . Your immune system learns to see these ... disappear between ages 6 and 12 months. Passive immunization may also be due to injection of antiserum, ...

  15. 14 CFR 297.23 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    14 Aeronautics and Space 4 2012-01-01 2012-01-01...23 Section 297.23 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  16. 14 CFR 375.26 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    14 Aeronautics and Space 4 2010-01-01 2010-01-01...26 Section 375.26 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  17. 14 CFR 297.23 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    14 Aeronautics and Space 4 2011-01-01 2011-01-01...23 Section 297.23 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  18. 14 CFR 375.26 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    14 Aeronautics and Space 4 2013-01-01 2013-01-01...26 Section 375.26 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  19. 14 CFR 297.23 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    14 Aeronautics and Space 4 2010-01-01 2010-01-01...23 Section 297.23 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  20. 14 CFR 297.23 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    14 Aeronautics and Space 4 2014-01-01 2014-01-01...23 Section 297.23 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  1. 14 CFR 375.26 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    14 Aeronautics and Space 4 2011-01-01 2011-01-01...26 Section 375.26 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  2. 14 CFR 297.23 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    14 Aeronautics and Space 4 2013-01-01 2013-01-01...23 Section 297.23 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  3. 14 CFR 375.26 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    14 Aeronautics and Space 4 2014-01-01 2014-01-01...26 Section 375.26 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  4. 14 CFR 375.26 - Waiver of sovereign immunity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    14 Aeronautics and Space 4 2012-01-01 2012-01-01...26 Section 375.26 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT...any defense of sovereign immunity from suit in any action or proceeding...

  5. Recent advances in the innate immunity of invertebrate animals.

    PubMed

    Iwanaga, Sadaaki; Lee, Bok Luel

    2005-03-31

    Invertebrate animals, which lack adaptive immune systems, have developed other systems of biological host defense, so called innate immunity, that respond to common antigens on the cell surfaces of potential pathogens. During the past two decades, the molecular structures and functions of various defense components that participated in innate immune systems have been established in Arthropoda, such as, insects, the horseshoe crab, freshwater crayfish, and the protochordata ascidian. These defense molecules include phenoloxidases, clotting factors, complement factors, lectins, protease inhibitors, antimicrobial peptides, Toll receptors, and other humoral factors found mainly in hemolymph plasma and hemocytes. These components, which together compose the innate immune system, defend invertebrate from invading bacterial, fungal, and viral pathogens. This review describes the present status of our knowledge concerning such defensive molecules in invertebrates. PMID:15826490

  6. Vaccine strategies against Babesia bovis based on prime-boost immunizations in mice with modified vaccinia Ankara vector and recombinant proteins.

    PubMed

    Jaramillo Ortiz, José Manuel; Del Médico Zajac, María Paula; Zanetti, Flavia Adriana; Molinari, María Paula; Gravisaco, María José; Calamante, Gabriela; Wilkowsky, Silvina Elizabeth

    2014-08-01

    In this study, a recombinant modified vaccinia virus Ankara vector expressing a chimeric multi-antigen was obtained and evaluated as a candidate vaccine in homologous and heterologous prime-boost immunizations with a recombinant protein cocktail. The chimeric multi-antigen comprises immunodominant B and T cell regions of three Babesia bovis proteins. Humoral and cellular immune responses were evaluated in mice to compare the immunogenicity induced by different immunization schemes. The best vaccination scheme was achieved with a prime of protein cocktail and a boost with the recombinant virus. This scheme induced high level of specific IgG antibodies and secreted IFN and a high degree of activation of IFN?(+) CD4(+) and CD8(+) specific T cells. This is the first report in which a novel vaccine candidate was constructed based on a rationally designed multi-antigen and evaluated in a prime-boost regime, optimizing the immune response necessary for protection against bovine babesiosis. PMID:24968152

  7. INTERACTIVE IMMUNITY

    NSDL National Science Digital Library

    European Federation of Immunological Societies, EFIS

    2012-07-19

    The resource is an interactive on-line book based upon the book “Your Amazing Immune System” which brings students to an exploration on how our immune system protects our body from infectious diseases. In addition, it gives students background on autoimmune diseases, immune reactions, and how immunology can be used in fighting cancer.

  8. Plant defense activators: applications and prospects in cereal crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review addresses the current understanding of the plant immune response and the molecular mechanisms responsible for systemic acquired resistance as well as the phenomenon of "priming" in plant defense. A detailed discussion of the role of salicylic acid in activating the plant transcription c...

  9. Interleukin17 and Lung Host Defense against Klebsiella pneumoniae Infection

    Microsoft Academic Search

    Peng Ye; Patrick B. Garvey; Ping Zhang; Steve Nelson; Greg Bagby; Warren R. Summer; Paul Schwarzenberger; Judd E. Shellito; Jay K. Kolls

    Bacterial pneumonia remains an important cause of morbidity and mortality worldwide, especially in immune-compromised patients. Cytokines and chemokines are critical molecules ex- pressed in response to invading pathogens and are necessary for normal lung bacterial host defenses. Here we show that in- terleukin (IL)-17, a novel cytokine produced largely by CD4 ? T cells, is produced in a compartmentalized fashion

  10. Disease resistance or growth: the role of plant hormones in balancing immune responses and fitness costs

    PubMed Central

    Denancé, Nicolas; Sánchez-Vallet, Andrea; Goffner, Deborah; Molina, Antonio

    2013-01-01

    Plant growth and response to environmental cues are largely governed by phytohormones. The plant hormones ethylene, jasmonic acid, and salicylic acid (SA) play a central role in the regulation of plant immune responses. In addition, other plant hormones, such as auxins, abscisic acid (ABA), cytokinins, gibberellins, and brassinosteroids, that have been thoroughly described to regulate plant development and growth, have recently emerged as key regulators of plant immunity. Plant hormones interact in complex networks to balance the response to developmental and environmental cues and thus limiting defense-associated fitness costs. The molecular mechanisms that govern these hormonal networks are largely unknown. Moreover, hormone signaling pathways are targeted by pathogens to disturb and evade plant defense responses. In this review, we address novel insights on the regulatory roles of the ABA, SA, and auxin in plant resistance to pathogens and we describe the complex interactions among their signal transduction pathways. The strategies developed by pathogens to evade hormone-mediated defensive responses are also described. Based on these data we discuss how hormone signaling could be manipulated to improve the resistance of crops to pathogens. PMID:23745126

  11. Phytophthora infestans effector AVRblb2 prevents secretion of a plant immune protease at the haustorial interface.

    PubMed

    Bozkurt, Tolga O; Schornack, Sebastian; Win, Joe; Shindo, Takayuki; Ilyas, Muhammad; Oliva, Ricardo; Cano, Liliana M; Jones, Alexandra M E; Huitema, Edgar; van der Hoorn, Renier A L; Kamoun, Sophien

    2011-12-20

    In response to pathogen attack, plant cells secrete antimicrobial molecules at the site of infection. However, how plant pathogens interfere with defense-related focal secretion remains poorly known. Here we show that the host-translocated RXLR-type effector protein AVRblb2 of the Irish potato famine pathogen Phytophthora infestans focally accumulates around haustoria, specialized infection structures that form inside plant cells, and promotes virulence by interfering with the execution of host defenses. AVRblb2 significantly enhances susceptibility of host plants to P. infestans by targeting the host papain-like cysteine protease C14 and specifically preventing its secretion into the apoplast. Plants altered in C14 expression were significantly affected in susceptibility to P. infestans in a manner consistent with a positive role of C14 in plant immunity. Our findings point to a unique counterdefense strategy that plant pathogens use to neutralize secreted host defense proteases. Effectors, such as AVRblb2, can be used as molecular probes to dissect focal immune responses at pathogen penetration sites. PMID:22143776

  12. Essays on strategy VII

    SciTech Connect

    Gill, T.C.

    1990-01-01

    Revolutionary developments in Europe and their global reverberations since 1989 have affected certain aspects of our national strategy. This volume presents nine essays dealing imaginatively with the issues of the post-Cold War period. One of them addresses general US strategy for the 1990s. Three focus on high-level strategic matters: the future of flexible response, antisatellite weapons, and forward, mobile defenses. The others address US chemical weapons policy, use of civilian aircraft for defense airlift, neutrality of the Panama Canal after 1999, arms sales by China, and strategic defense at reduced cost.

  13. HPV: immune response to infection and vaccination

    E-print Network

    Stanley, Margaret A

    2010-10-20

    coat protein L1 is protective suggesting that this would be an effective prophylactic vaccine strategy. The current prophylactic HPV VLP vaccines are delivered i.m. circumventing the intra-epithelial immune evasion strategies. These vaccines generate...

  14. The Immune System, the Skin, and Childhood Rheumatic Disease

    Microsoft Academic Search

    Robert C. Fuhlbrigge; Rafka Chaiban

    2011-01-01

    As the body’s largest organ and first line of defense against the environment, the skin plays a vital role in host immune\\u000a defense. In addition to its function as a physical barrier, the skin contains an active immune surveillance network and can\\u000a mount highly specific responses to eliminate invading organisms. In this review, we discuss the functions of adhesion molecules

  15. Brucella melitensis, B. neotomae and B. ovis Elicit Common and Distinctive Macrophage Defense Transcriptional Responses

    PubMed Central

    Covert, Jill; Mathison, Angela J.; Eskra, Linda; Banai, Menachem; Splitter, Gary

    2010-01-01

    Brucella spp. establish an intracellular replicative niche in macrophages, while macrophages attempt to eliminate the bacteria by innate defense mechanisms. Brucella spp. possess similar genomes yet exhibit different macrophage infections. Few B. melitensis and B. neotomae enter macrophages with intracellular adaptation occurring over 4–8 hr. Conversely, B. ovis are readily ingested by macrophages and exhibit a persistent plateau of infection. Evaluating early macrophage interaction with Brucella spp. allows discovery of host entry and intracellular translocation mechanisms. Microarray analysis of macrophage transcriptional response following a 4 hr infection by different Brucella spp. revealed common macrophage genes altered in expression compared to uninfected macrophages. Macrophage infection with three different Brucella spp. provokes a common innate immune theme with increased transcript levels of chemokines and defense response genes and decreased transcript levels of GTPase signaling and cytoskeletal function that may affect trafficking of Brucella containing vesicles. For example, transcript levels of genes associated with chemotaxis (IL-1?, MIP-1?), cytokine regulation (Socs3) and defense (Fas, Tnf) were increased, while transcript levels of genes associated with vesicular trafficking (Rab3d) and lysosomal associated enzymes (prosaposin) were decreased. Genes with altered macrophage transcript levels among Brucella spp. infections may correlate with species specific host defenses and intracellular survival strategies. Depending on the infecting Brucella species, gene ontology categorization identified genes differentially involved in cell growth and maintenance, endopeptidase inhibitor activity and G-protein mediated signaling. Examples of decreased gene expression in B. melitensis infection but not other Brucella spp. were growth arrest (Gas2), immunoglobulin receptor (Fc?rI) and chemokine receptor (Cxcr4) genes, suggesting opposing effects on intracellular functions. PMID:19934366

  16. Obesity and respiratory infections: Does excess adiposity weigh down host defense?

    PubMed Central

    Mancuso, Peter

    2012-01-01

    The number of overweight and obese individuals has dramatically increased in the US and other developed nations during the past 30 years. While type II diabetes and cardiovascular disease are well recognized co-morbid conditions associated with obesity, recent reports have demonstrated a greater severity of illness in obese patients due to influenza during the 2009 H1N1 pandemic. Consistent with these reports, diet-induced obesity has been shown to impair anti-viral host defense in murine models of influenza infection. However, the impact of obesity on the risk of community-acquired and nosocomial pneumonia in human patients is not clear. Relatively few studies have evaluated the influence of diet-induced obesity in murine models of bacterial infections of the respiratory tract. Obese leptin deficient humans and leptin and leptin-receptor deficient mice exhibit greater susceptibility to respiratory infections suggesting a requirement for leptin in the pulmonary innate and adaptive immune response to infection. In contrast to these studies, we have observed that obese leptin receptor signaling mutant mice are resistant to pneumococcal pneumonia highlighting the complex interaction between leptin receptor signaling and immune function. Given the increased prevalence of obesity and poor responsiveness of obese individuals to vaccination against influenza, the development of novel immunization strategies for this population is warranted. Additional clinical and animal studies are needed to clarify the relationship between increased adiposity and susceptibility to community-acquired and nosocomial pneumonia. PMID:22634305

  17. Inflammasomes: Caspase-1-Activating Platforms with Critical Roles in Host Defense

    PubMed Central

    Vande Walle, Lieselotte; Lamkanfi, Mohamed

    2010-01-01

    Activation of the inflammatory cysteine protease caspase-1 in inflammasome complexes plays a critical role in the host response to microbial infections. Inflammasome activation induces inflammation through secretion of the pro-inflammatory cytokines interleukin (IL)-1? and IL-18 and through extracellular release of the alarmin high mobility group box 1. Moreover, caspase-1 activation by inflammasomes counters bacterial replication and induces pyroptosis, a specialized cell death program that removes infected immune cells as part of the host defense system. It is thus not surprising that bacterial and viral pathogens evolved virulence factors targeting inflammasome activation and activity. Here, we provide an overview of the distinct inflammasome complexes that are activated in a pathogen-specific manner and discuss the diverse strategies employed by viruses and bacteria to modulate inflammasome function. PMID:21687402

  18. Review of defense display research programs

    NASA Astrophysics Data System (ADS)

    Tulis, Robert W.; Hopper, Darrel G.; Morton, David C.; Shashidhar, Ranganathan

    2001-09-01

    Display research has comprised a substantial portion of the defense investment in new technology for national security for the past 13 years. These investments have been made by the separate service departments and, especially, via several Defense Research Projects Agency (DARPA) programs, known collectively as the High Definition Systems (HDS) Program (which ended in 2001) and via the Office of the Secretary of Defense (OSD) Defense Production Act (DPA) Title III Program (efforts ended in 2000). Using input from the Army, Navy, and Air Force to focus research and identify insertion opportunities, DARPA and the Title III Program Office have made investments to develop the national technology base and manufacturing infrastructure necessary to meet the twin challenge of providing affordable displays in current systems and enabling the DoD strategy of winning future conflicts by getting more information to all participants during the battle. These completed DARPA and DPA research and infrastructure programs are reviewed. Service investments have been and are being made to transition display technology; examples are described. Display science and technology (S&T) visions are documented for each service to assist the identification of areas meriting consideration for future defense research.

  19. Chemerin regulation and role in host defense

    PubMed Central

    Zabel, Brian A; Kwitniewski, Mateusz; Banas, Magdalena; Zabieglo, Katarzyna; Murzyn, Krzysztof; Cichy, Joanna

    2014-01-01

    Chemerin is a widely distributed multifunctional secreted protein implicated in immune cell migration, adipogenesis, osteoblastogenesis, angiogenesis, myogenesis, and glucose homeostasis. Chemerin message is regulated by nuclear receptor agonists, metabolic signaling proteins and intermediates, and proinflammatory cytokines. Following translation chemerin is secreted as an inactive pro-protein, and its secretion can be regulated depending on cell type. Chemerin bioactivity is largely dependent on carboxyl-terminal proteolytic processing and removal of inhibitory residues. Chemerin is abundant in human epidermis where it is well-placed to provide barrier protection. In host defense, chemerin plays dual roles as a broad spectrum antimicrobial protein and as a leukocyte attractant for macrophages, dendritic cells, and NK cells. Here we review the mechanisms underlying chemerin regulation and its function in host defense. PMID:24660117

  20. Echinoderm immunity.

    PubMed

    Smith, L Courtney; Ghosh, Julie; Buckley, Katherine M; Clow, Lori A; Dheilly, Nolwenn M; Haug, Tor; Henson, John H; Li, Chun; Lun, Cheng Man; Majeske, Audrey J; Matranga, Valeria; Nair, Sham V; Rast, Jonathan P; Raftos, David A; Roth, Mattias; Sacchi, Sandro; Schrankel, Catherine S; Stensvåg, Klara

    2010-01-01

    A survey for immune genes in the genome for the purple sea urchin has shown that the immune system is complex and sophisticated. By inference, immune responses of all echinoderms maybe similar. The immune system is mediated by several types of coelomocytes that are also useful as sensors of environmental stresses. There are a number of large gene families in the purple sea urchin genome that function in immunity and of which at least one appears to employ novel approaches for sequence diversification. Echinoderms have a simpler complement system, a large set of lectin genes and a number of antimicrobial peptides. Profiling the immune genes expressed by coelomocytes and the proteins in the coelomic fluid provide detailed information about immune functions in the sea urchin. The importance of echinoderms in maintaining marine ecosystem stability and the disastrous effects of their removal due to disease will require future collaborations between ecologists and immunologists working towards understanding and preserving marine habitats. PMID:21528703

  1. The Role of Nutrition in Enhancing Immunity in Aging

    PubMed Central

    Pae, Munkyong; Meydani, Simin Nikbin; Wu, Dayong

    2011-01-01

    Aging is associated with declined immune function, particularly T cell-mediated activity, which contributes to increased morbidity and mortality from infectious disease and cancer in the elderly. Studies have shown that nutritional intervention may be a promising approach to reversing impaired immune function and diminished resistance to infection with aging. However, controversy exists concerning every nutritional regimen tested to date. In this article, we will review the progress of research in this field with a focus on nutrition factor information that is relatively abundant in the literature. While vitamin E deficiency is rare, intake above recommended levels can enhance T cell function in aged animals and humans. This effect is believed to contribute toward increased resistance to influenza infection in animals and reduced incidence of upper respiratory infection in the elderly. Zinc deficiency, common in the elderly, is linked to impaired immune function and increased risk for acquiring infection, which can be rectified by zinc supplementation. However, higher than recommended upper limits of zinc may adversely affect immune function. Probiotics are increasingly being recognized as an effective, immune-modulating nutritional factor. However, to be effective, they require an adequate supplementation period; additionally, their effects are strain-specific and among certain strains, a synergistic effect is observed. Increased intake of fish or n-3 PUFA may be beneficial to inflammatory and autoimmune disorders as well as to several age-related diseases. Conversely, the immunosuppressive effect of fish oils on T cell-mediated function has raised concerns regarding their impact on resistance to infection. Caloric restriction (CR) is shown to delay immunosenescence in animals, but this effect needs to be verified in humans. Timing for CR initiation may be important to determine whether CR is effective or even beneficial at all. Recent studies have suggested that CR, which is effective at improving the immune response of unchallenged animals, might compromise the host’s defense against pathogenic infection and result in higher morbidity and mortality. The studies published thus far describe a critical role for nutrition in maintaining the immune response of the aged, but they also indicate the need for a more in-depth, wholestic approach to determining the optimal nutritional strategies that would maintain a healthy immune system in the elderly and promote their resistance to infection and other immune-related diseases PMID:22500273

  2. Innate Immunity: A Cutaneous Perspective

    Microsoft Academic Search

    Heidi Goodarzi; Janet Trowbridge; Richard L. Gallo

    2007-01-01

    The first responsibility for protection against microbial infection rests on the normal function of the innate immune system.\\u000a This system establishes an antimicrobial barrier, recognizes attempts to breach this barrier, and responds rapidly to danger,\\u000a all based on an innate defense system. Here, we review this system as it applies to mammalian skin, highlighting how a physical,\\u000a cellular, and chemical

  3. Plant immunity in plant–aphid interactions

    PubMed Central

    Jaouannet, Maëlle; Rodriguez, Patricia A.; Lenoir, Camille J. G.; MacLeod, Ruari; Escudero-Martinez, Carmen; Bos, Jorunn I.B.

    2014-01-01

    Aphids are economically important pests that cause extensive feeding damage and transmit viruses. While some species have a broad host range and cause damage to a variety of crops, others are restricted to only closely related plant species. While probing and feeding aphids secrete saliva, containing effectors, into their hosts to manipulate host cell processes and promote infestation. Aphid effector discovery studies pointed out parallels between infection and infestation strategies of plant pathogens and aphids. Interestingly, resistance to some aphid species is known to involve plant resistance proteins with a typical NB-LRR domain structure. Whether these resistance proteins indeed recognize aphid effectors to trigger ETI remains to be elucidated. In addition, it was recently shown that unknown aphid derived elicitors can initiate reactive oxygen species (ROS) production and callose deposition and that these responses were dependent on BAK1 (BRASSINOSTERIOD INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1) which is a key component of the plant immune system. In addition, BAK-1 contributes to non-host resistance to aphids pointing to another parallel between plant-pathogen and – aphid interactions. Understanding the role of plant immunity and non-host resistance to aphids is essential to generate durable and sustainable aphid control strategies. Although insect behavior plays a role in host selection and non-host resistance, an important observation is that aphids interact with non-host plants by probing the leaf surface, but are unable to feed or establish colonization. Therefore, we hypothesize that aphids interact with non-host plants at the molecular level, but are potentially not successful in suppressing plant defenses and/or releasing nutrients. PMID:25520727

  4. Moscow's defense intellectuals

    SciTech Connect

    Lambeth, B.S.

    1990-01-01

    This essay was originally written two decades ago as a seminar paper. A substantial portion of it addresses what were then only the first steps toward the establishment of a community of professional civilian defense analysts in the Soviet Union. Throughout most of the intervening period, that community found itself mired in immobilism as jurisdiction over such key Soviet national security inputs as military doctrine, force requirements, resource needs, and to a considerable degree, arms negotiating positions remained an exclusive prerogative of the Defense Ministry and the General Staff. Today, this former military monopoly has come to be challenged with increasing success by a host of newcomers to the Soviet defense scene, including the Foreign Ministry, the Supreme Soviet, and an ambitious cadre of civilian analysts attached to the social science research institutes of the Academy of Sciences. These individuals are making a determined bid for greater influence over Soviet defense policy, with the express encouragement of President Gorbachev and his supporters. The result has been an unprecedented infusion of pluralism into Soviet defense politics and a significant change in the content and goals of Soviet military policy.

  5. Inflammatory Monocytes Orchestrate Innate Antifungal Immunity in the Lung

    PubMed Central

    Dutta, Orchi; Kasahara, Shinji; Donnelly, Robert; Du, Peicheng; Rosenfeld, Jeffrey; Leiner, Ingrid; Chen, Chiann-Chyi; Ron, Yacov; Hohl, Tobias M.; Rivera, Amariliz

    2014-01-01

    Aspergillus fumigatus is an environmental fungus that causes invasive aspergillosis (IA) in immunocompromised patients. Although -CC-chemokine receptor-2 (CCR2) and Ly6C-expressing inflammatory monocytes (CCR2+Mo) and their derivatives initiate adaptive pulmonary immune responses, their role in coordinating innate immune responses in the lung remain poorly defined. Using conditional and antibody-mediated cell ablation strategies, we found that CCR2+Mo and monocyte-derived dendritic cells (Mo-DCs) are essential for innate defense against inhaled conidia. By harnessing fluorescent Aspergillus reporter (FLARE) conidia that report fungal cell association and viability in vivo, we identify two mechanisms by which CCR2+Mo and Mo-DCs exert innate antifungal activity. First, CCR2+Mo and Mo-DCs condition the lung inflammatory milieu to augment neutrophil conidiacidal activity. Second, conidial uptake by CCR2+Mo temporally coincided with their differentiation into Mo-DCs, a process that resulted in direct conidial killing. Our findings illustrate both indirect and direct functions for CCR2+Mo and their derivatives in innate antifungal immunity in the lung. PMID:24586155

  6. Modulation of immune responses of Rhynchophorus ferrugineus (Insecta: Coleoptera) induced by the entomopathogenic nematode Steinernema carpocapsae (Nematoda: Rhabditida).

    PubMed

    Mastore, Maristella; Arizza, Vincenzo; Manachini, Barbara; Brivio, Maurizio F

    2014-05-20

    Aim of this study was to investigate relationships between the red palm weevil (RPW) Rhynchophorus ferrugineus (Olivier) and the entomopathogenic nematode Steinernema carpocapsae (EPN); particularly, the work was focused on the immune response of the insect host in naive larvae and after infection with the EPN. Two main immunological processes have been addressed: the activity and modulation of host prophenoloxidase-phenoloxidase (proPO) system, involved in melanization of not-self and hemocytes recognition processes responsible for not-self encapsulation. Moreover, immune depressive and immune evasive strategies of the parasite have been investigated. Our results suggest that RPW possess an efficient immune system, however in the early phase of infection, S. carpocapsae induces a strong inhibition of the host proPO system. In addition, host cell-mediated mechanisms of encapsulation, are completely avoided by the parasite, the elusive strategies of S. carpocapsae seem to be related to the structure of its body-surface, since induced alterations of the parasite cuticle resulted in the loss of its mimetic properties. S. carpocapsae before the release of its symbiotic bacteria, depress and elude RPW immune defenses, with the aim to arrange a favorable environment for its bacteria responsible of the septicemic death of the insect target. PMID:24846780

  7. A cross-disciplinary perspective on the innate immune responses to bacterial lipopolysaccharide.

    PubMed

    Tan, Yunhao; Kagan, Jonathan C

    2014-04-24

    The study of innate immunity to bacteria has focused heavily on the mechanisms by which mammalian cells detect lipopolysaccharide (LPS), the conserved surface component of Gram-negative bacteria. While Toll-like receptor 4 (TLR4) is responsible for all the host transcriptional responses to LPS, recent discoveries have revealed the existence of several TLR4-independent responses to LPS. These discoveries not only broaden our view of the means by which mammalian cells interact with bacteria, but they also highlight new selective pressures that may have promoted the evolution of bacterial immune evasion strategies. In this review, we highlight past and recent discoveries on host LPS sensing mechanisms and discuss bacterial countermeasures that promote infection. By looking at both sides of the host-pathogen interaction equation, we hope to provide comprehensive insights into host defense mechanisms and bacterial pathogenesis. PMID:24766885

  8. Nutrition, The Infant and the Immune System

    Microsoft Academic Search

    Ger T. Rijkers; Laetitia Niers; Marianne Stasse-Wolthuis; Frans M. Rombouts

    \\u000a The human newborn possesses a functional but immature immune system in order to provide defense against a world teeming with\\u000a microorganisms. Breast milk contains a number of biological active compounds which support the infant’s immune system. These\\u000a include secretory IgAs, which confer specific protection against enteric pathogens, as well as many other immunological active\\u000a ingredients. A number of these ingredients

  9. Platelet, not endothelial, P-selectin expression contributes to generation of immunity in cutaneous contact hypersensitivity.

    PubMed

    Ludwig, Ralf J; Bergmann, Peri; Garbaraviciene, Jurate; von Stebut, Esther; Radeke, Heinfried H; Gille, Jens; Diehl, Sandra; Hardt, Katja; Henschler, Reinhard; Kaufmann, Roland; Pfeilschifter, Josef M; Boehncke, Wolf-Henning

    2010-03-01

    Leukocyte extravasation is a prerequisite for host defense and autoimmunity alike. Detailed understanding of the tightly controlled and overlapping sequences of leukocyte extravasation might aid development of novel therapeutic strategies. Leukocyte extravasation is initiated by interaction of selectins with appropriate carbohydrate ligands. Lack of P-selectin expression leads to decreased contact hypersensitivity responses. Yet, it remains unclear if this is due to inhibition of leukocyte extravasation to the skin or due to interference with initial immune activation in lymph nodes. In line with previous data, we here report a decreased contact hypersensitivity response, induced by 2,4,-dinitrofluorobenzene (DNFB), in P-selectin-deficient mice. Eliciting an immune reaction towards DNFB in wild-type mice, followed by adoptive transfer to P-selectin-deficient mice, had no impact on inflammatory response in recipients. This was significantly reduced in wild-type recipient mice adoptively transferred with DNFB immunity generated in P-selectin-deficient mice. To investigate if platelet or endothelial P-selectin was involved, mice solely lacking platelet P-selectin expression generated by bone marrow transplantation were used. Adoptive transfer of immunity from wild-type mice reconstituted with P-selectin-deficient bone marrow led to a decrease of inflammatory response. Comparing this decrease to the one observed using P-selectin-deficient mice, no differences were observed. Our observations indicate that platelet, not endothelial, P-selectin contributes to generation of immunity in DNFB-induced contact hypersensitivity. PMID:20056837

  10. Platelet, Not Endothelial, P-Selectin Expression Contributes to Generation of Immunity in Cutaneous Contact Hypersensitivity

    PubMed Central

    Ludwig, Ralf J.; Bergmann, Peri; Garbaraviciene, Jurate; Stebut, Esther von; Radeke, Heinfried H.; Gille, Jens; Diehl, Sandra; Hardt, Katja; Henschler, Reinhard; Kaufmann, Roland; Pfeilschifter, Josef M.; Boehncke, Wolf-Henning

    2010-01-01

    Leukocyte extravasation is a prerequisite for host defense and autoimmunity alike. Detailed understanding of the tightly controlled and overlapping sequences of leukocyte extravasation might aid development of novel therapeutic strategies. Leukocyte extravasation is initiated by interaction of selectins with appropriate carbohydrate ligands. Lack of P-selectin expression leads to decreased contact hypersensitivity responses. Yet, it remains unclear if this is due to inhibition of leukocyte extravasation to the skin or due to interference with initial immune activation in lymph nodes. In line with previous data, we here report a decreased contact hypersensitivity response, induced by 2,4,-dinitrofluorobenzene (DNFB), in P-selectin-deficient mice. Eliciting an immune reaction towards DNFB in wild-type mice, followed by adoptive transfer to P-selectin-deficient mice, had no impact on inflammatory response in recipients. This was significantly reduced in wild-type recipient mice adoptively transferred with DNFB immunity generated in P-selectin-deficient mice. To investigate if platelet or endothelial P-selectin was involved, mice solely lacking platelet P-selectin expression generated by bone marrow transplantation were used. Adoptive transfer of immunity from wild-type mice reconstituted with P-selectin-deficient bone marrow led to a decrease of inflammatory response. Comparing this decrease to the one observed using P-selectin-deficient mice, no differences were observed. Our observations indicate that platelet, not endothelial, P-selectin contributes to generation of immunity in DNFB-induced contact hypersensitivity. PMID:20056837

  11. Immune surveillance of the central nervous system in multiple sclerosis– Relevance for therapy and experimental models

    PubMed Central

    Hussain, Rehana Z.; Hayardeny, Liat; Cravens, Petra C.; Yarovinsky, Felix; Eagar, Todd N.; Arellano, Benjamine; Deason, Krystin; Castro-Rojas, Cyd; Stüve, Olaf

    2015-01-01

    Treatment of central nervous system (CNS) autoimmune disorders frequently involves the reduction, or depletion of immune-competent cells. Alternatively, immune cells are being sequestered away from the target organ by interfering with their movement from secondary lymphoid organs, or their migration into tissues. These therapeutic strategies have been successful in multiple sclerosis (MS), the most prevalent autoimmune inflammatory disorder of the CNS. However, many of the agents that are currently approved or in clinical development also have severe potential adverse effects that stem from the very mechanisms that mediate their beneficial effects by interfering with CNS immune surveillance. This review will outline the main cellular components of the innate and adaptive immune system that participate in host defense and maintain immune surveillance of the CNS. Their pathogenic role in MS and its animal model experimental autoimmune encephalomyelitis (EAE) is also discussed. Furthermore, an experimental model is introduced that may assist in evaluating the effect of therapeutic interventions on leukocyte homeostasis and function within the CNS. This model or similar models may become a useful tool in the repertoire of pre-clinical tests of pharmacological agents to better explore their potential for adverse events. PMID:25282087

  12. The spiderweb defense

    SciTech Connect

    Grin, J.; Unterseher, L. (Free Univ., Amsterdam (Netherlands))

    1988-09-01

    The study group on Alternative Security Policy (SAS) has laid out the most detailed plan to date for making West German military forces strictly defensive. This group includes active soldiers, politicians, and scientific and military experts. The authors shows there that these concepts are based on sound military thinking and therefore can deter aggression. The SAS defense concept proposes a structural change in air, naval, and land forces. This article deals only with land forces, which have three components in this concept: static light infantry, light and heavy armored formations, and troops for rear area defense. The third component is not considered here because it is only of secondary importance for the military rationale of the SAS proposal. It is the interaction between the other two elements that inspired Egbert Boeker to term the SAS concept spider in the web. 6 refs.

  13. Interaction and Cellular Localization of the Human Host Defense Peptide LL37 with Lung Epithelial Cells

    Microsoft Academic Search

    Y. Elaine Lau; Annett Rozek; Monisha G. Scott; Danika L. Goosney; Donald J. Davidson; Robert E. W. Hancock

    2005-01-01

    LL-37 is a human cationic host defense peptide that is an essential component of innate immunity. In addition to its modest antimicrobial activity, LL-37 affects the gene expression and behavior of effector cells involved in the innate immune response, although its mode of interaction with eukaryotic cells remains unclear. The interaction of LL-37 with epithelial cells was characterized in tissue

  14. Augmentation of Innate Host Defense by Expression of a Cathelicidin Antimicrobial Peptide

    Microsoft Academic Search

    ROBERT BALS; DANIEL J. WEINER; A. DAVID MOSCIONI; RUPALIE L. MEEGALLA; JAMES M. WILSON

    1999-01-01

    Antimicrobial peptides, such as defensins or cathelicidins, are effector substances of the innate immune system and are thought to have antimicrobial properties that contribute to host defense. The evidence that vertebrate antimicrobial peptides contribute to innate immunity in vivo is based on their expression pattern and in vitro activity against microorganisms. The goal of this study was to investigate whether

  15. Density-dependent effects of prey defenses and predator offenses.

    PubMed

    Jeschke, Jonathan M

    2006-10-21

    Defenses protect prey, while offenses arm predators. Some defenses and offenses are constitutive (e.g. tortoise shells), while others are phenotypically plastic and not always expressed (e.g. neckteeth in water fleas). All of them are costly and only adaptive at certain prey densities. Here, I analyse such density-dependent effects, applying a functional response model to categorize defenses and offenses and qualitatively predict at which prey densities each category should evolve (if it is constitutive) or be expressed (if it is phenotypically plastic). The categories refer to the step of the predation cycle that a defense or offense affects: (1) search, (2) encounter, (3) detection, (4) attack, or (5) meal. For example, prey warning signals such as red coloration prevent predator attacks and are hence step 4 defenses, while sharp predator eyes enhance detection and are step 3 offenses. My theoretical analyses predict that step 1 defenses, which prevent predators from searching for their next meal (e.g. toxic substances), evolve or are expressed at intermediate prey densities. Other defenses, however, should be most beneficial at low prey densities. Regarding predators, step 1 offenses (e.g. immunity against prey toxins) are predicted to evolve or be expressed at high prey densities, other offenses at intermediate densities. I provide evidence from the literature that supports these predictions. PMID:16842823

  16. Value of space defenses

    SciTech Connect

    Canavan, G.H.

    1992-10-29

    This report discusses the economic value of defenses against Near-Earth Object (NEO) impacts is bounded by calculating expected losses in their absence, which illustrates the contributions from NEOs of different sizes and the sensitivity of total expected losses to impact frequencies. For typical size distributions and damage of only a few decades duration, losses are most sensitive to small NEOs, and lead to defenses worth a few $M/yr. When the persistence of damage with NEO size is taken into account, that shifts the loss to the largest NEOs and greatly increases expected loss and values.

  17. Reactive Immunization

    NASA Astrophysics Data System (ADS)

    Wirsching, Peter; Ashley, Jon A.; Lo, Chih-Hung L.; Janda, Kim D.; Lerner, Richard A.

    1995-12-01

    For almost 200 years inert antigens have been used for initiating the process of immunization. A procedure is now described in which the antigen used is so highly reactive that a chemical reaction occurs in the antibody combining site during immunization. An organophosphorus diester hapten was used to illustrate this concept coined "reactive immunization." The organophosphonate recruited chemical potential from the immune response that resembled the way these compounds recruit the catalytic power of the serine hydrolases. During this recruitment, a large proportion of the isolated antibodies catalyzed the formation and cleavage of phosphonylated intermediates and subsequent ester hydrolysis. Reactive immunization can augment traditional immunization and enhance the scope of catalytic antibody chemistry. Among the compounds anticipated to be effective are those that contain appropriate reactive functionalities or those that are latently reactive, as in the mechanism-based inhibitors of enzymes.

  18. Rationality Validation of a Layered Decision Model for Network Defense

    SciTech Connect

    Wei, Huaqiang; Alves-Foss, James; Zhang, Du; Frincke, Deb

    2007-08-31

    We propose a cost-effective network defense strategy built on three key: three decision layers: security policies, defense strategies, and real-time defense tactics for countering immediate threats. A layered decision model (LDM) can be used to capture this decision process. The LDM helps decision-makers gain insight into the hierarchical relationships among inter-connected entities and decision types, and supports the selection of cost-effective defense mechanisms to safeguard computer networks. To be effective as a business tool, it is first necessary to validate the rationality of model before applying it to real-world business cases. This paper describes our efforts in validating the LDM rationality through simulation.

  19. Defense styles of pedophilic offenders.

    PubMed

    Drapeau, Martin; Beretta, Véronique; de Roten, Yves; Koerner, Annett; Despland, Jean-Nicolas

    2008-04-01

    This pilot study investigated the defense styles of pedophile sexual offenders. Interviews with 20 pedophiles and 20 controls were scored using the Defense Mechanisms Rating Scales. Results showed that pedophiles had a significantly lower overall defensive functioning score than the controls. Pedophiles used significantly fewer obsessional-level defenses but more major image-distorting and action-level defenses. Results also suggested differences in the prevalence of individual defenses where pedophiles used more dissociation, displacement, denial, autistic fantasy, splitting of object, projective identification, acting out, and passive aggressive behavior but less intellectualization and rationalization. PMID:17875603

  20. HIV-1 Gag-virus-like particles induce natural killer cell immune responses via activation and maturation of dendritic cells.

    PubMed

    Chang, Myint Oo; Suzuki, Tomoyuki; Suzuki, Hitoshi; Takaku, Hiroshi

    2012-01-01

    Despite the extensive efforts that have been made to combat acquired immune deficiency syndrome (AIDS), the number of people infected each year with human immunodeficiency virus type 1 (HIV-1) is still increasing worldwide, and a safe and effective vaccine to control HIV infection is urgently needed. Recently, the natural killer (NK) cell-mediated innate immune response, which represents the first line of defense against infections, has attracted attention for its role in combating HIV infection and disease progression. In the present study, we investigated the immunogenic ability of HIV-1 Gag-virus-like particles (Gag-VLPs) to induce NK cell immune responses in vitro and in vivo. Gag-VLPs efficiently activated human monocyte-derived dendritic cells (MDDCs), eliciting MDDC maturation with an associated increase in the surface expression of CD80, CD86 and MHC classes I and II, MDDC proliferation and proinflammatory cytokine production. Gag-VLP-treated MDDCs subsequently activated autologous NK cells, leading to their proliferation and production of interferon-? and to the upregulation of NK cell cytotoxicity against YAC-1 cells and HIV-1-infected CD4(+) T cells. In addition, we introduced a 2-phase immunization strategy in BALB/c mice to assess the role of DCs in the induction of NK cell immune responses by Gag-VLPs in vivo. Our findings reveal that Gag-VLPs efficiently activate DCs, which in turn induce innate and Gag-specific immune responses in NK cells. PMID:21778700

  1. Immune dysfunction in cirrhosis

    PubMed Central

    Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

  2. Brain Innate Immunity in the Regulation of Neuroinflammation: Therapeutic Strategies by Modulating CD200-CD200R Interaction Involve the Cannabinoid System

    PubMed Central

    Hernangómez, Miriam; Carrillo-Salinas, Francisco J; Mecha, Miriam; Correa, Fernando; Mestre, Leyre; Loría, Frida; Feliú, Ana; Docagne, Fabian; Guaza, Carmen

    2014-01-01

    The central nervous system (CNS) innate immune response includes an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons that is involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the CNS are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple sclerosis (MS) Alzheimer's disease (AD) being primary examples. Hence, it is important to identify the key regulatory mechanisms involved in the control of CNS innate immunity and which could be harnessed to explore novel therapeutic avenues. Neuroimmune regulatory proteins (NIReg) such as CD95L, CD200, CD47, sialic acid, complement regulatory proteins (CD55, CD46, fH, C3a), HMGB1, may control the adverse immune responses in health and diseases. In the absence of these regulators, when neurons die by apoptosis, become infected or damaged, microglia and infiltrating immune cells are free to cause injury as well as an adverse inflammatory response in acute and chronic settings. We will herein provide new emphasis on the role of the pair CD200-CD200R in MS and its experimental models: experimental autoimmune encephalomyelitis (EAE) and Theiler’s virus induced demyelinating disease (TMEV-IDD). The interest of the cannabinoid system as inhibitor of inflammation prompt us to introduce our findings about the role of endocannabinoids (eCBs) in promoting CD200-CD200 receptor (CD200R) interaction and the benefits caused in TMEV-IDD. Finally, we also review the current data on CD200-CD200R interaction in AD, as well as, in the aging brain. PMID:24588829

  3. Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells.

    PubMed

    Liao, Hsin-Kai; Gu, Ying; Diaz, Arturo; Marlett, John; Takahashi, Yuta; Li, Mo; Suzuki, Keiichiro; Xu, Ruo; Hishida, Tomoaki; Chang, Chan-Jung; Esteban, Concepcion Rodriguez; Young, John; Izpisua Belmonte, Juan Carlos

    2015-01-01

    To combat hostile viruses, bacteria and archaea have evolved a unique antiviral defense system composed of clustered regularly interspaced short palindromic repeats (CRISPRs), together with CRISPR-associated genes (Cas). The CRISPR/Cas9 system develops an adaptive immune resistance to foreign plasmids and viruses by creating site-specific DNA double-stranded breaks (DSBs). Here we adapt the CRISPR/Cas9 system to human cells for intracellular defense against foreign DNA and viruses. Using HIV-1 infection as a model, our results demonstrate that the CRISPR/Cas9 system disrupts latently integrated viral genome and provides long-term adaptive defense against new viral infection, expression and replication in human cells. We show that engineered human-induced pluripotent stem cells stably expressing HIV-targeted CRISPR/Cas9 can be efficiently differentiated into HIV reservoir cell types and maintain their resistance to HIV-1 challenge. These results unveil the potential of the CRISPR/Cas9 system as a new therapeutic strategy against viral infections. PMID:25752527

  4. RIP1 and FADD's Role in Innate Immunity

    Microsoft Academic Search

    Jinhee Hyun

    2011-01-01

    Rapid production of type I Interferon is pivotal to initiate cellular antiviral host defense and adaptive immunity. In order to facilitate innate immune processes, a cell harbors pattern recognition receptors (PRRs) which sense distinctive forms of pathogen associated molecular patterns (PAMPs). For example, Toll like receptors (TLRs) and RIG-I like receptors (RLRs) were discovered as PRRs for pathogen derived molecules

  5. Immunology 101 at poxvirus U: Immune evasion genes

    Microsoft Academic Search

    Bernard Moss; Joanna L. Shisler

    2001-01-01

    Poxviruses, unlike some other large DNA viruses, do not undergo a latent stage but rely on the expression of viral proteins to evade host immune responses. Of the many poxviral evasion genes identified, most target cytokines or other innate immune defenses. Resistance to interferons appears to be a priority as there are viral proteins that prevent their induction, receptor binding,

  6. Aerospace & Defense Collaboratory

    E-print Network

    McGraw, Kevin J.

    flight, air traffic control). Fast Facts ADRC Contact Suzanne M. Benoît, president of Aero Montréal to transform research discoveries into practical, real-world use and enterprise. From energy to intelligent and Defense (A&D) industry, nationally and internationally. The Collaboratory focuses on increasing

  7. Radiological Defense Manual.

    ERIC Educational Resources Information Center

    Defense Civil Preparedness Agency (DOD), Washington, DC.

    Originally prepared for use as a student textbook in Radiological Defense (RADEF) courses, this manual provides the basic technical information necessary for an understanding of RADEF. It also briefly discusses the need for RADEF planning and expected postattack emergency operations. There are 14 chapters covering these major topics: introduction…

  8. The Weekly Defense Monitor

    NSDL National Science Digital Library

    This new free electronic publication by the Center for Defense Information will bring readers a few short articles on various military and foreign affairs issues each week. Recent topics included an arms trade code of conduct introduced in the Senate, US base closures and the military force structure, and the cost of defending Western Europe.

  9. Weakened Immune Systems

    MedlinePLUS

    ... Immunizations > Weakened Immune Systems Safety & Prevention Listen Weakened Immune Systems Article Body Some children have weakened immune systems because of chronic diseases or medications they’re ...

  10. 76 FR 13297 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-11

    ...DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 215 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations System, Department of Defense...

  11. Polyphenol oxidase as a biochemical seed defense mechanism

    PubMed Central

    Fuerst, E. Patrick; Okubara, Patricia A.; Anderson, James V.; Morris, Craig F.

    2014-01-01

    Seed dormancy and resistance to decay are fundamental survival strategies, which allow a population of seeds to germinate over long periods of time. Seeds have physical, chemical, and biological defense mechanisms that protect their food reserves from decay-inducing organisms and herbivores. Here, we hypothesize that seeds also possess enzyme-based biochemical defenses, based on induction of the plant defense enzyme, polyphenol oxidase (PPO), when wild oat (Avena fatua L.) caryopses and seeds were challenged with seed-decaying Fusarium fungi. These studies suggest that dormant seeds are capable of mounting a defense response to pathogens. The pathogen-induced PPO activity from wild oat was attributed to a soluble isoform of the enzyme that appeared to result, at least in part, from proteolytic activation of a latent PPO isoform. PPO activity was also induced in wild oat hulls (lemma and palea), non-living tissues that cover and protect the caryopsis. These results are consistent with the hypothesis that seeds possess inducible enzyme-based biochemical defenses arrayed on the exterior of seeds and these defenses represent a fundamental mechanism of seed survival and longevity in the soil. Enzyme-based biochemical defenses may have broader implications since they may apply to other defense enzymes as well as to a diversity of plant species and ecosystems. PMID:25540647

  12. Polyphenol oxidase as a biochemical seed defense mechanism.

    PubMed

    Fuerst, E Patrick; Okubara, Patricia A; Anderson, James V; Morris, Craig F

    2014-01-01

    Seed dormancy and resistance to decay are fundamental survival strategies, which allow a population of seeds to germinate over long periods of time. Seeds have physical, chemical, and biological defense mechanisms that protect their food reserves from decay-inducing organisms and herbivores. Here, we hypothesize that seeds also possess enzyme-based biochemical defenses, based on induction of the plant defense enzyme, polyphenol oxidase (PPO), when wild oat (Avena fatua L.) caryopses and seeds were challenged with seed-decaying Fusarium fungi. These studies suggest that dormant seeds are capable of mounting a defense response to pathogens. The pathogen-induced PPO activity from wild oat was attributed to a soluble isoform of the enzyme that appeared to result, at least in part, from proteolytic activation of a latent PPO isoform. PPO activity was also induced in wild oat hulls (lemma and palea), non-living tissues that cover and protect the caryopsis. These results are consistent with the hypothesis that seeds possess inducible enzyme-based biochemical defenses arrayed on the exterior of seeds and these defenses represent a fundamental mechanism of seed survival and longevity in the soil. Enzyme-based biochemical defenses may have broader implications since they may apply to other defense enzymes as well as to a diversity of plant species and ecosystems. PMID:25540647

  13. MICROBIOLOGY: Rogue Insect Immunity

    NSDL National Science Digital Library

    David S. Schneider (Stanford University; Department of Microbiology and Immunology)

    2008-11-21

    Access to the article is free, however registration and sign-in are required. Insects use a variety of strategies to fight pathogens at different stages of infection, which may guide antimicrobial development for human use.Two recent studies have quietly and subversively broken the models we've used to describe insect immunity. Impressively, they've accomplished this by using gross observational studies rather than mechanistic approaches. Haine et al. suggest that what we've considered the central pillar of insect immunity--antimicrobial peptides--may perform a "mopping up" role in clearing pathogens. Hedges et al. show that heritable epigenetic properties can have as large an impact on insect immunity as any genetically encoded pathway yet tested. Both studies teach us important lessons about the way a host organism interacts with microbes and may have immediate practical applications.

  14. Skin immunity.

    PubMed

    Schwarz, T

    2003-11-01

    As the major barrier of the body to the outside, the skin is constantly confronted with microbial, chemical and physical insults. However, the skin does not only function as a mechanical barrier but also uses the immune system for protection. Therefore, the skin is endowed with the capacity to generate immune responses of the innate as well as of the adaptive type. PMID:14616336

  15. Immune System

    EPA Science Inventory

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

  16. Chitin Modulates Innate Immune Responses of Keratinocytes

    Microsoft Academic Search

    Barbara Koller; Alisa Sophie Müller-Wiefel; Rudolph Rupec; Hans Christian Korting; Thomas Ruzicka; Jürgen Schauber

    2011-01-01

    BackgroundChitin, after cellulose the second most abundant polysaccharide in nature, is an essential component of exoskeletons of crabs, shrimps and insects and protects these organisms from harsh conditions in their environment. Unexpectedly, chitin has been found to activate innate immune cells and to elicit murine airway inflammation. The skin represents the outer barrier of the human host defense and is

  17. Joint stabilizing projects in defense

    SciTech Connect

    Canavan, G.H.; Browne, J.C.; Joseph, R.J.

    1992-06-01

    Joint defensive projects could increase stability and decrease the alert rates of strategic forces. Areas include the defense of the US, Commonwealth of Independent States (CIS), and their allies against third world threats; protection against each other's accidental or unauthorized launches; and defense against intentional attacks. The most promising area appears to be defining interfaces for the handover of satellite warning and trajectory information, which applies to most phases of theater defense and mutual protection. 19 refs.

  18. Novel Plant Immune-Priming Compounds Identified via High-Throughput Chemical Screening Target Salicylic Acid Glucosyltransferases in Arabidopsis[W][OA

    PubMed Central

    Noutoshi, Yoshiteru; Okazaki, Masateru; Kida, Tatsuya; Nishina, Yuta; Morishita, Yoshihiko; Ogawa, Takumi; Suzuki, Hideyuki; Shibata, Daisuke; Jikumaru, Yusuke; Hanada, Atsushi; Kamiya, Yuji

    2012-01-01

    Plant activators are compounds, such as analogs of the defense hormone salicylic acid (SA), that protect plants from pathogens by activating the plant immune system. Although some plant activators have been widely used in agriculture, the molecular mechanisms of immune induction are largely unknown. Using a newly established high-throughput screening procedure that screens for compounds that specifically potentiate pathogen-activated cell death in Arabidopsis thaliana cultured suspension cells, we identified five compounds that prime the immune response. These compounds enhanced disease resistance against pathogenic Pseudomonas bacteria in Arabidopsis plants. Pretreatments increased the accumulation of endogenous SA, but reduced its metabolite, SA-O-?-d-glucoside. Inducing compounds inhibited two SA glucosyltransferases (SAGTs) in vitro. Double knockout plants that lack both SAGTs consistently exhibited enhanced disease resistance. Our results demonstrate that manipulation of the active free SA pool via SA-inactivating enzymes can be a useful strategy for fortifying plant disease resistance and may identify useful crop protectants. PMID:22960909

  19. Autophagy as an innate defense against mycobacteria.

    PubMed

    Jo, Eun-Kyeong

    2013-03-01

    Over the past several years, much has been revealed about the roles of autophagy and the mechanisms by which the autophagic pathway activates the host innate effector response against Mycobacterium tuberculosis (Mtb) infection. In response to invading mycobacteria, the host innate immune system not only recognizes pathogen motifs through innate receptors, it also produces appropriate effector proteins, including cytokines. These innate signals activate or regulate autophagic pathways during infection. It is now clear that vitamin D and functional vitamin D receptor signaling are critical in the activation of autophagic defenses against Mtb in human cells. Immunity-related GTPase family M proteins, including the cationic antimicrobial protein cathelicidin and autophagic receptor p62, participate in autophagic pathways that enhance antimicrobial activity against mycobacteria. Moreover, reactive oxygen species mediate antibacterial autophagy and successful antimicrobial responses during antibiotic chemotherapy. Recent work has also shown that pathogenic Mtb can be targeted by selective autophagy through an ESX-1 type VII secretion system. Here, we review the triggers, host factors, and intracellular pathways that regulate host autophagy and its impact on antimicrobial host defenses during mycobacterial infection. PMID:23620156

  20. 76 FR 28960 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ...DEPARTMENT OF DEFENSE Office of the Secretary Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting AGENCY: National Defense Intelligence College, Defense Intelligence Agency, Department of...