Sample records for immune defense strategies

  1. 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

  2. Lymphoma: Immune Evasion Strategies

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Testicular defense systems: immune privilege and innate immunity.

    PubMed

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

    2014-09-01

    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

  5. 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

  6. 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.

  7. Immunization Strategies Against Henipaviruses

    PubMed Central

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

    2015-01-01

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

  8. Cutaneous Immune Defenses Against Staphylococcus aureus Infections

    PubMed Central

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

    2014-01-01

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

  9. Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium

    PubMed Central

    Pukkila-Worley, Read; Ausubel, Frederick M

    2013-01-01

    Intestinal epithelial cells provide an essential line of defense for Caenorhabditis elegans against ingested pathogens. Because nematodes consume microorganisms as their food source, there has presumably been selection pressure to evolve and maintain immune defense mechanisms within the intestinal epithelium. Here we review recent advances that further define the immune signaling network within these cells and suggest mechanisms used by the nematode to monitor for infection. In reviewing studies of pathogenesis that use this simple model system, we hope to illustrate some of the basic principles of epithelial immunity that may also be of relevance in higher order hosts. PMID:22236697

  10. 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

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

    PubMed

    Suresh, Rahul; Mosser, David M

    2013-12-01

    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

  12. 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

  13. 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

  14. Immune defense and biological responses induced by toxics in Annelida

    Microsoft Academic Search

    André Dhainaut; Patrick Scaps

    2001-01-01

    The phylum Annelida comprises primitive coelomates that possess specially developed cellular immunity against pathogens. Active phagocytosis by coelomocytes occurs in the struggle against bacteria in Polychaeta and Oligochaeta. Encapsulation plays an important role in defense against parasites, and experimental studies have demon- strated that cooperation between different coelomocyte populations occurs in this process. Spontaneous cytotoxicity of coelomocytes against xenogenic or

  15. T Cell–Mediated Host Immune Defenses in the Lung

    PubMed Central

    Chen, Kong; Kolls, Jay K.

    2014-01-01

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

  16. Stealth Proteins: In Silico Identification of a Novel Protein Family Rendering Bacterial Pathogens Invisible to Host Immune Defense

    Microsoft Academic Search

    Peter Sperisen; Christoph D. Schmid; Philipp Bucher; Olav Zilian

    2005-01-01

    There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is

  17. Efficient immunization strategies to prevent financial contagion

    PubMed Central

    Kobayashi, Teruyoshi; Hasui, Kohei

    2014-01-01

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

  18. Phylogenetic escalation and decline of plant defense strategies

    E-print Network

    Agrawal, Anurag

    Phylogenetic escalation and decline of plant defense strategies Anurag A. Agrawal* and Mark 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

  19. Candida albicans Infection of Caenorhabditis elegans Induces Antifungal Immune Defenses

    PubMed Central

    Pukkila-Worley, Read

    2011-01-01

    Candida albicans yeast cells are found in the intestine of most humans, yet this opportunist can invade host tissues and cause life-threatening infections in susceptible individuals. To better understand the host factors that underlie susceptibility to candidiasis, we developed a new model to study antifungal innate immunity. We demonstrate that the yeast form of C. albicans establishes an intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected with C. albicans yeast showed that exposure to C. albicans stimulated a rapid host response involving 313 genes (124 upregulated and 189 downregulated, ?1.6% of the genome) many of which encode antimicrobial, secreted or detoxification proteins. Interestingly, the host genes affected by C. albicans exposure overlapped only to a small extent with the distinct transcriptional responses to the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus, indicating that there is a high degree of immune specificity toward different bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa and S. aureus were strongly over-represented among the genes downregulated during C. albicans infection, suggesting that in response to fungal pathogens, nematodes selectively repress the transcription of antibacterial immune effectors. A similar phenomenon is well known in the plant immune response, but has not been described previously in metazoans. Finally, 56% of the genes induced by live C. albicans were also upregulated by heat-killed yeast. These data suggest that a large part of the transcriptional response to C. albicans is mediated through “pattern recognition,” an ancient immune surveillance mechanism able to detect conserved microbial molecules (so-called pathogen-associated molecular patterns or PAMPs). This study provides new information on the evolution and regulation of the innate immune response to divergent pathogens and demonstrates that nematodes selectively mount specific antifungal defenses at the expense of antibacterial responses. PMID:21731485

  20. Degree-based attacks and defense strategies in complex networks

    NASA Astrophysics Data System (ADS)

    Yehezkel, Aviv; Cohen, Reuven

    2012-12-01

    We study the stability of random scale-free networks to degree-dependent attacks. We present analytical and numerical results to compute the critical fraction pc of nodes that need to be removed for destroying the network under this attack for different attack parameters. We study the effect of different defense strategies, based on the addition of a constant number of links on network robustness. We test defense strategies based on adding links to either low degree, middegree or high degree nodes. We find using analytical results and simulations that the middegree nodes defense strategy leads to the largest improvement to the network robustness against degree-based attacks. We also test these defense strategies on an internet autonomous systems map and obtain similar results.

  1. Stealthy attacks and defense strategies in competing sensor networks 

    E-print Network

    Czarlinska, Aleksandra

    2009-05-15

    for Cluster Size n and Probability of Event p ... 57 II Comparison of Stealth Condition for Strategy Types ......... 101 III Comparison of the Expected Power of Attack E[P a ] for Strategy Types ................................... 104 IV Output of Algorithm 4... Processing (LIP) Organized in Order of Decreasing Detection Performance P D .... 158 xi LIST OF FIGURES FIGURE Page 1 Dual stealthy attack and defense problem. ............... 2 2 Applications of the stealthy attack mechanism and the dual attack defense...

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

    PubMed

    Carmona, Diego; Fornoni, Juan

    2013-01-01

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

  3. Ontogeny of innate and adaptive immune defense components in free-living tree swallows, Tachycineta bicolor.

    PubMed

    Palacios, Maria G; Cunnick, Joan E; Vleck, David; Vleck, Carol M

    2009-04-01

    Little is known about the development of immune function in wild animals. We investigated the ontogeny of immune defense in a free-living bird, the tree swallow. We assessed total and differential leukocyte counts, natural antibodies, complement activity, in vivo skin swelling response, and in vitro lymphocyte proliferation and compared the levels of development between nestlings and young adults. We also assessed whether body condition explained variation in these immune components. We found some support for the prediction that innate defenses, which do not need to generate a broad repertoire of specific receptors, would reach adult levels earlier than adaptive defenses. In contrast, we found limited support for the prediction that adaptive defenses, which are thought to be more costly to develop, would be more related to body condition than innate defenses. We discuss our findings in the context of other studies on the ontogeny of immune function. PMID:18848578

  4. 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

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

    PubMed

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

    2013-04-01

    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

  6. 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

  7. Immune evasion strategies used by Helicobacter pylori.

    PubMed

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

    2014-09-28

    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

  8. 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

  9. Immune Defense Mechanisms of Culex quinquefasciatus (Diptera: Culicidae) against Candida albicans Infection

    Microsoft Academic Search

    José B Da Silva; Cleide M. R De Albuquerque; Eva Cristina De Araújo; Christina A Peixoto; Hilary Hurd

    2000-01-01

    Mosquitoes have an efficient defense system against infection. The cellular immune defense mechanism initiated by the mosquito Culex quinquefasciatus infected with the fungus Candida albicans was investigated in this study. Differences in the hemocyte counts in hemolymph perfused from uninoculated, saline-inoculated, and C. albicans-infected mosquitoes were compared using a light microscope. Phagocytosis was also investigated using electron microscopy. Four types

  10. Restraining Epidemics by Improving Immunization Strategies

    E-print Network

    Schneider, Christian M; Havlin, Shlomo; Herrmann, Hans J

    2011-01-01

    The way diseases spread through social and global transportation networks is crucially determining their risk for humanity. Based on percolation theory we quantitatively analyze the effect of immunization strategies on the spreading of diseases through networks and propose a novel approach to improve their effectiveness. We find that the network's vulnerability to epidemics can be significantly reduced by implementing improved immunization strategies based on high betweenness centrality. We demonstrate this on two real networks, the global flight network, which is known as the most important source of pandemic spreading and a school friendship network. In theses networks, the average probability for a node to get infected is reduced by more than 10% compared to the betweenness centrality method believed to be the most efficient strategy to prevent epidemic spreading.

  11. 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

  12. Ontogeny of innate and adaptive immune defense components in free-living tree swallows, Tachycineta bicolor

    Microsoft Academic Search

    Maria G. Palacios; Joan E. Cunnick; David Vleck; Carol M. Vleck

    2009-01-01

    Little is known about the development of immune function in wild animals. We investigated the ontogeny of immune defense in a free-living bird, the tree swallow. We assessed total and differential leukocyte counts, natural antibodies, complement activity, in vivo skin swelling response, and in vitro lymphocyte proliferation and compared the levels of development between nestlings and young adults. We also

  13. 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

  14. An alternative to present United States defense strategy 

    E-print Network

    Anthony, William Wallace

    1971-01-01

    J BSTRACT An Alternative to Present United States Defense Strategy. (Nay 1971) william 1:. 'allace Anthony, B. A. , Tarleton State College; Directed by: Dr. N. Z. Benton 'he purpose of tnis study is to explore the policy relative to a nuclear... strategic capability that wo ld enhance the defensive nuclear posture of tne United States and its allies in the North Atlantic Treaty Organization (NATO). The thesis postulates the employment of a land mass, that is a possession of a N"TO alliance...

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

    PubMed Central

    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

    2012-01-01

    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

  16. 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

  17. Probing the unknowns in cytokinin-mediated immune defense in Arabidopsis with systems biology approaches.

    PubMed

    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

  18. Insights how monocytes and dendritic cells contribute and regulate immune defense against microbial pathogens.

    PubMed

    Bieber, Kristin; Autenrieth, Stella E

    2015-02-01

    The immune system protects from infections primarily by detecting and eliminating invading pathogens. Beside neutrophils, monocytes and dendritic cells (DCs) have been recently identified as important sentinels and effectors in combating microbial pathogens. In the steady state mononuclear phagocytes like monocytes and DCs patrol the blood and the tissues. Mammalian monocytes contribute to antimicrobial defense by supplying tissues with macrophage and DC precursors. DCs recognize pathogens and are essential in presenting antigens to initiate antigen-specific adaptive immune responses, thereby bridging the innate and adaptive immune systems. Both, monocytes and DCs play distinct roles in the shaping of immune response. In this review we will focus on the contributions of monocytes and lymphoid organ DCs to immune defense against microbial pathogens in the mouse and their dynamic regulation from steady state to infection. PMID:25468558

  19. Beijing’s defense strategy and the Korean peninsula

    Microsoft Academic Search

    Weixing Hu

    1995-01-01

    The Korean peninsula has been one of the key regions for China’s security. With a strong interest in maintaining peace and\\u000a stability on the peninsula, Beijing is readjusting its foreign policy toward two Koreas in the post-cold war era. This article\\u000a examines the recent changes in Beijing’s defense strategy and their implications for the Korean peninsula. It is argued that

  20. 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

  1. 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

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

    Microsoft Academic Search

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

    2007-01-01

    In the absence of adaptive immunity displayed by animals, palnts 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

  3. DIVERGENT DEFENSIVE STRATEGIES OF YOUNG LEAVES IN TWO SPECIES OF INGA

    Microsoft Academic Search

    Phyllis D. Coley; John Lokvam; Kathleen Rudolph; Keryn Bromberg; Tara E. Sackett; Leslie Wright; Tania Brenes-Arguedas; Dan Dvorett; Seth Ring; Alex Clark; Caroline Baptiste; R. Toby Pennington; Thomas A. Kursar

    2005-01-01

    In the recently radiated genus Inga (Fabaceae), few nucleotide substitutions have accumulated among species, yet large divergences have occurred in defensive phe- notypes, suggesting strong selection by herbivores. We compared herbivory and defenses of young leaves for I. goldmanii, a more derived species that follows a ''defense'' strategy, and I. umbellifera, a more basal species that follows an ''escape'' strategy.

  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. 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

  6. Oil and related toxicant effects on mallard immune defenses

    Microsoft Academic Search

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

    1984-01-01

    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

  7. Extending the Computer Defense Immune System: Network Intrusion Detection with a Multiobjective Evolutionary Programming Approach

    Microsoft Academic Search

    Kevin P. Anchor; Jesse B. Zydallis; Gregg H. Gunsch; Gary B. Lamont

    Attacks against computer networks are becom- ing more sophisticated, with adversaries using new attacks or modifying existing attacks. The research uses two types of multiobjective ap- proaches, lexicographic and Pareto-based, in an evolutionary programming algorithm to develop a new method for detecting such attacks. This development extends the Computer Defense Im- mune System, an artificial immune system for virus and

  8. 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

  9. Anthrax toxins: A weapon to systematically dismantle the host immune defenses

    Microsoft Academic Search

    Jean-Nicolas Tournier; Silvia Rossi Paccani; Anne Quesnel-Hellmann; Cosima T. Baldari

    2009-01-01

    Successful colonization of the host by bacterial pathogens relies on their capacity to evade the complex and powerful defenses opposed by the host immune system, at least in the initial phases of infection. The two toxins of Bacillus anthracis, lethal toxin and edema toxin, appear to have been shaped by evolution to assist the microorganism in this crucial function, in

  10. 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.

  11. 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.

  12. 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

  13. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    2015-01-01

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

  16. Two novel secreted ferritins involved in immune defense of Chinese mitten crab Eriocheir sinensis.

    PubMed

    Kong, Pengfei; Wang, Lingling; Zhang, Huan; Zhou, Zhi; Qiu, Limei; Gai, Yunchao; Song, Linsheng

    2010-04-01

    As a principal extracellular iron storage molecule, secreted ferritin plays an important role in the iron-withholding strategy of innate immunity. In this study, two novel secreted ferritins were identified from Chinese mitten crab Eriocheir sinensis (designated as EsFer-1 and EsFer-2) by rapid amplification of cDNA ends (RACE) approaches and expressed sequence tag (EST) analysis. The full-length cDNAs of EsFer-1 and EsFer-2 were of 1278 and 1595 bp, respectively, both containing a putative iron response element (IRE) in their 5' UTRs and multiple A + U-destabilizing elements (TATT or ATTTA) in their 3' UTRs. The ORFs of these two crab ferritin cDNAs were of 639 and 663 bp, respectively, encoding two peptides of 212 and 220 amino acid residues each with a signal peptide and typical structures of ferritins such as four long alpha-helices, one short alpha-helix and an L-loop. EsFer-2 exhibited higher similarity with the H-ferritins from both invertebrates and vertebrates, while EsFer-1 was closer matched to L-ferritins. The eight amino acid residues identified as metal binding sites in vertebrate H-ferritins were conserved in EsFer-2 (Glu53, Tyr60, Glu87, Glu88, His91, Glu146, Glu177 and Gln178), but none of them was observed in EsFer-1. By fluorescent quantitative real-time PCR, mRNA transcripts of EsFer-1 and EsFer-2 were mainly detected in muscle, hepatopancreas and gill, and also marginally detectable in gonad, heart and hemocytes. After the crabs were challenged by bacteria Listonella anguillarum, the transcriptional levels of both EsFer-1 and EsFer-2 in hemocytes were up-regulated twice. In the first up-regulation, the mRNA relative expression levels of both EsFer-1 and EsFer-2 reached peak at 3 h post-challenge, while in the second up-regulation, they did not reach the highest point within the experiment duration. After the fungi Pichia pastoris GS115 challenge, there was only one transcriptional level peak of both the two ferritins, appearing at 6 h post-challenge. These results suggest that secreted EsFer-1 and EsFer-2 are crucial proteins in the iron-withholding defense system, and play important roles in the innate immune responses in crabs. PMID:20045469

  17. Recognition strategies in the innate immune system of ancestral chordates

    Microsoft Academic Search

    Konstantin Khalturin; Zeev Panzer; Max D. Cooper; Thomas C. G. Bosch

    2004-01-01

    Many components of the innate immune system in vertebrates can be reliably traced to urochordates and successful strategies for the detection and elimination of pathogens are present at that level of animal evolution, but the issue of where and how the adaptive immune system emerged is still obscure. There is a paucity of evidence for a gradual transition from the

  18. The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous Candidiasis in Humans.

    PubMed

    Soltész, Beáta; Tóth, Beáta; Sarkadi, Adrien Katalin; Erd?s, Melinda; Maródi, László

    2015-05-01

    The discovery of interleukin (IL)-17-mediated immunity has provided a robust framework upon which our current understanding of the mechanism involved in host defense against mucocutaneous candidiasis (CMC) has been built. Studies have shed light on how pattern recognition receptors expressed by innate immune cells recognize various components of Candida cell wall. Inborn errors of immunity affecting IL-17+ T cell differentiation have recently been defined, such as deficiencies of signal transducer and activator of transcription (STAT)3, STAT1, IL-12R?1 and IL-12p40, and caspase recruitment domain 9. Impaired receptor-ligand coupling was identified in patients with IL-17F and IL-17 receptor A (IL17RA) deficiency and autoimmune polyendocrine syndrome (APS) type 1. Mutation in the nuclear factor kappa B activator (ACT) 1 was described as a cause of impaired IL-17R-mediated signaling. CMC may be part of a complex clinical phenotype like in patients with deficiencies of STAT3, IL-12R?1/IL-12p40 and APS-1 or may be the only or dominant phenotypic manifestation of disease which is referred to as CMC disease. CMCD may result from deficiencies of STAT1, IL-17F, IL-17RA and ACT1. In this review we discuss how recent research on IL-17-mediated immunity shed light on host defense against mucocutaneous infection by Candida and how the discovery of various germ-line mutations and the characterization of associated clinical phenotypes have provided insights into the role of CD4+IL-17+ lymphocytes in the regulation of anticandidal defense of body surfaces. PMID:26154078

  19. Prime-Boost Immunization Strategies against Chikungunya Virus

    PubMed Central

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

    2014-01-01

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

  20. Anthrax toxins: a weapon to systematically dismantle the host immune defenses.

    PubMed

    Tournier, Jean-Nicolas; Rossi Paccani, Silvia; Quesnel-Hellmann, Anne; Baldari, Cosima T

    2009-12-01

    Successful colonization of the host by bacterial pathogens relies on their capacity to evade the complex and powerful defenses opposed by the host immune system, at least in the initial phases of infection. The two toxins of Bacillus anthracis, lethal toxin and edema toxin, appear to have been shaped by evolution to assist the microorganism in this crucial function, in addition to act as general toxins acting on almost all cell types. Edema toxin causes a consistent elevation of cAMP, an important second messenger the production of which is normally strictly controlled in mammalian cells, whereas lethal toxin cleaves most isoforms of mitogen-activated protein kinase kinases. By disrupting or subverting central modules common to all the principal signaling networks which control immune cell activation, effector function and migration, the anthrax toxins effectively and systematically dismantle both the innate and the adaptive immune defenses of the host. Here, we review the specific effects of the lethal and edema toxins of B. anthracis on the activation and function of phagocytes, dendritic cells and lymphocytes. We also discuss some open issues which should be addressed to gain a comprehensive insight into the complex relationship that B. anthracis establishes with the host. PMID:19560486

  1. Psychological Defense Strategies According to the Defense Mechanism Test Among Patients with Severe Conversion Disorder

    Microsoft Academic Search

    Elisabet Sundbom; Michael Binzer; Gunnar Kullgren

    1999-01-01

    Nineteen patients with a diagnosis of conversion disorder (according to DSM-IV criteria), and 32 healthy nonpatients, were assessed using the Defense Mechanism Test (DMT), which is a projective perception test that examines psychodynamic defense operations according to psychoanalytical theory. The conversion group was significantly separated from the non-patient group. The nonpatients showed better reality testing and the ability to perceive

  2. 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

  3. Formally Specifying Design Goals of Worm Defense Strategies EXTENDED ABSTRACT

    E-print Network

    Briesemeister, Linda

    and Phillip A. Porras firstname.lastname@sri.com Computer Science Laboratory, SRI International 333 Ravenswood we consider how to more rigor- ously express design goals regarding the local impact of a defensive on assessing growth rate impact on an abstracted topology of global population. Current worm defense

  4. Sugaring the Pill: Assessing Rhetorical Strategies Designed to Minimize Defensive Reactions to Group Criticism

    ERIC Educational Resources Information Center

    Hornsey, Matthew J.; Robson, Erin; Smith, Joanne; Esposo, Sarah; Sutton, Robbie M.

    2008-01-01

    People are considerably more defensive in the face of group criticism when the criticism comes from an out-group rather than an in-group member (the intergroup sensitivity effect). We tested three strategies that out-group critics can use to reduce this heightened defensiveness. In all studies, Australians received criticism of their country…

  5. 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,…

  6. 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

  7. 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.

  8. An Efficient Immunization Strategy for Community Networks

    PubMed Central

    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

  9. Neisseria gonorrhoeae Modulates Iron-Limiting Innate Immune Defenses in Macrophages

    PubMed Central

    Zughaier, Susu M.; Kandler, Justin L.; Shafer, William M.

    2014-01-01

    Neisseria gonorrhoeae is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. The gonococcus can survive extracellularly and intracellularly, but in both environments the bacteria must acquire iron from host proteins for survival. However, upon infection the host uses a defensive response by limiting the bioavailability of iron by a number of mechanisms including the enhanced expression of hepcidin, the master iron-regulating hormone, which reduces iron uptake from the gut and retains iron in macrophages. The host also secretes the antibacterial protein NGAL, which sequesters bacterial siderophores and therefore inhibits bacterial growth. To learn whether intracellular gonococci can subvert this defensive response, we examined expression of host genes that encode proteins involved in modulating levels of intracellular iron. We found that N. gonorrhoeae can survive in association (tightly adherent and intracellular) with monocytes and macrophages and upregulates a panel of its iron-responsive genes in this environment. We also found that gonococcal infection of human monocytes or murine macrophages resulted in the upregulation of hepcidin, NGAL, and NRAMP1 as well as downregulation of the expression of the gene encoding the short chain 3-hydroxybutyrate dehydrogenase (BDH2); BDH2 catalyzes the production of the mammalian siderophore 2,5-DHBA involved in chelating and detoxifying iron. Based on these findings, we propose that N. gonorrhoeae can subvert the iron-limiting innate immune defenses to facilitate iron acquisition and intracellular survival. PMID:24489950

  10. How to leverage an endogenous immune defense mechanism: the example of granulocyte colony-stimulating factor.

    PubMed

    Hartung, Thomas; Von Aulock, Sonja; Schneider, Christian; Faist, Eugen

    2003-01-01

    Our understanding of host defense has exploded during the past two decades. It is temping to take advantage of this knowledge by considering the modulation and control of these mechanisms as therapeutic options. In intensive care medicine, the aim is usually to block an overwhelming inflammatory response, which represents the "bad" side of the double-edged sword of host defense. The obvious danger of such treatment strategies is that impairing the inflammatory reaction means impairing host defense in patients exposed to infectious agents. The alternative approach, i.e., strengthening or supplementing favorable host defense mechanism, has so far been little explored clinically. Granulocyte colony-stimulating factor, the granulocyte colony-stimulating factor, combines the unique properties of an anti-infectious and an anti-inflammatory factor. This attractive profile has led us to various approaches to exploit these immunomodulatory activities. In a recently terminated, placebo-controlled, randomized study, we investigated if prophylactic treatment with rh granulocyte colony-stimulating factor (Filgrastim), at the time a risk can be anticipated such as before an operation, may offer protection from immunoinflammatory dyshomeostasis and thus lower the incidence of postoperative sepsis. Perioperative rh granulocyte colony-stimulating factor administration, compared with placebo treatment, resulted in the prevention of postoperative monocyte deactivation, conservation of an adequate Th1/Th2 ratio, as well as a considerable alleviation of the acute phase response. In parallel, there was a clear tendency toward lowering the rate of postoperative septic complications under the administration of Filgrastim. PMID:12544979

  11. A proteomics perspective on viral DNA sensors in host defense and viral immune evasion mechanisms.

    PubMed

    Crow, Marni S; Javitt, Aaron; Cristea, Ileana M

    2015-06-01

    The sensing of viral DNA is an essential step of cellular immune response to infections with DNA viruses. These human pathogens are spread worldwide, triggering a wide range of virus-induced diseases, and are associated with high levels of morbidity and mortality. Despite similarities between DNA molecules, mammalian cells have the remarkable ability to distinguish viral DNA from their own DNA. This detection is carried out by specialized antiviral proteins, called DNA sensors. These sensors bind to foreign DNA to activate downstream immune signaling pathways and alert neighboring cells by eliciting the expression of antiviral cytokines. The sensing of viral DNA was shown to occur both in the cytoplasm and in the nucleus of infected cells, disproving the notion that sensing occurred by simple spatial separation of viral and host DNA. A number of omic approaches, in particular, mass-spectrometry-based proteomic methods, have significantly contributed to the constantly evolving field of viral DNA sensing. Here, we review the impact of omic methods on the identification of viral DNA sensors, as well as on the characterization of mechanisms involved in host defense or viral immune evasion. PMID:25728651

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

    PubMed

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

    2015-03-01

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

  13. 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

  14. 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,

  15. Immune evasion strategies of Porphyromonas gingivalis

    PubMed Central

    Hajishengallis, George

    2011-01-01

    Porphyromonas gingivalis is strongly correlated with chronic periodontitis. Its chronic persistence in the periodontium depends on its ability to evade host immunity without inhibiting the overall inflammatory response, which is actually beneficial for this and other periodontal bacteria. Indeed, the inflammatory exudate (gingival crevicular fluid) is a source of essential nutrients, such as peptides and hemin-derived iron. In this review, I discuss how P. gingivalis can promote its adaptive fitness through instigation of subversive crosstalk signaling. These interactions involve Toll-like receptor-2, complement receptor 3, C5a anaphylatoxin receptor, and CXC-chemokine receptor 4. Their exploitation by P. gingivalis allows the pathogen to escape elimination, obtain nutrients, and collaterally inflict periodontal tissue injury. PMID:22162663

  16. Possible new antiaging strategies related to neuroendocrine-immune interactions.

    PubMed

    Mocchegiani, Eugenio; Malavolta, Marco

    2008-01-01

    The aging process demonstrates gradual and spontaneous changes, resulting in maturation through childhood, puberty and young adulthood, and then decline through middle and late age. However, animals and humans are capable of reaching the extreme limit of life span characteristic for the species with a very efficient network of antiaging mechanisms. Among them, neuroendocrine-immune interactions play a pivotal role. The loss of the capacity of the organism in remodeling the neuroendocrine-immune response leads to the appearance of age-associated pathologies. We herein report some substances which can be proposed as new antiaging strategies because of their capacity to remodel some biological functions in old animals and humans. These substances are: L-deprenyl, leptin, ghrelin, carnosine and NO donors. Their role as possible antiaging strategies in healthy people in relation to neuroendocrine-immune responses and zinc ion bioavailability is reported and discussed. PMID:19047810

  17. Plant Lectins: Wheat Defense Strategy Against Hessian Fly

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Latitudinal variation of immune defense and sickness behavior in the white-crowned sparrow (Zonotrichia leucophrys).

    PubMed

    Owen-Ashley, Noah T; Hasselquist, Dennis; Råberg, Lars; Wingfield, John C

    2008-05-01

    There is a general trend that parasitism risk declines as latitude increases. Host populations breeding at high latitudes should therefore invest less in costly immune defenses than populations breeding in temperate or tropical zones, although it is unknown if such an effect is mediated by environmental (photoperiodic) or genetic factors or both. Acquired immune function (humoral, cell-mediated) and behavioral sickness responses to lipopolysaccharide (LPS; mimics bacterial infection) were assessed in two subspecies of white-crowned sparrow (Zonotrichia leucophrys) that breed at different latitudes in western North America. Zonotrichia l. gambelii (GWCS) is a high-latitude breeder (47-68 degrees N) while Z. l. pugetensis (PWCS) breeds at temperate latitudes (40-49 degrees N). Captive males of each subspecies were acclimated to (1) a short day (non-breeding) photoperiod (8L:16D), (2) the breeding photoperiod of PWCS (16L:8D), or (3) the breeding photoperiod of GWCS (20L:4D). Photoperiod was manipulated because shorter day lengths may enhance immune function. In support of a genetic effect, humoral responses to diphtheria-tetanus vaccination were significantly higher in PWCS compared to GWCS, regardless of photoperiod. There were no differences in cell-mediated responses to phytohemagglutinin (PHA) between subspecies or among photoperiods. For sickness responses to LPS, a significant interaction between photoperiod and subspecies was found, with long day GWCS producing stronger sickness responses (losing more weight, eating less) than short day GWCS and PWCS on all day lengths. However, these effects were influenced by photoperiodic changes in body condition. In conclusion, we find evidence for genetic control of immune responses across latitude, but no support for environmental (photoperiodic) regulation. PMID:18255257

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

    NASA Astrophysics Data System (ADS)

    Szolnoki, Attila; Perc, Matjaž

    2015-05-01

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

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

    E-print Network

    Szolnoki, Attila

    2015-01-01

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

  1. Drosophila Immune Deficiency (IMD) Is a Death Domain Protein that Activates Antibacterial Defense and Can Promote Apoptosis

    Microsoft Academic Search

    Philippe Georgel; Silvia Naitza; Christine Kappler; Dominique Ferrandon; Daniel Zachary; Candace Swimmer; Casey Kopczynski; Geoffrey Duyk; Jean-Marc Reichhart; Jules A. Hoffmann

    2001-01-01

    We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila. imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-?B activation and apoptosis. We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD

  2. A Role for Host Activation-Induced Cytidine Deaminase in Innate Immune Defense against KSHV

    PubMed Central

    Bekerman, Elena; Jeon, Diana; Ardolino, Michele; Coscoy, Laurent

    2013-01-01

    Activation-induced cytidine deaminase (AID) is specifically induced in germinal center B cells to carry out somatic hypermutation and class-switch recombination, two processes responsible for antibody diversification. Because of its mutagenic potential, AID expression and activity are tightly regulated to minimize unwanted DNA damage. Surprisingly, AID expression has been observed ectopically during pathogenic infections. However, the function of AID outside of the germinal centers remains largely uncharacterized. In this study, we demonstrate that infection of human primary naïve B cells with Kaposi's sarcoma-associated herpesvirus (KSHV) rapidly induces AID expression in a cell intrinsic manner. We find that infected cells are marked for elimination by Natural Killer cells through upregulation of NKG2D ligands via the DNA damage pathway, a pathway triggered by AID. Moreover, without having a measurable effect on KSHV latency, AID impinges directly on the viral fitness by inhibiting lytic reactivation and reducing infectivity of KSHV virions. Importantly, we uncover two KSHV-encoded microRNAs that directly regulate AID abundance, further reinforcing the role for AID in the antiviral response. Together our findings reveal additional functions for AID in innate immune defense against KSHV with implications for a broader involvement in innate immunity to other pathogens. PMID:24244169

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

    PubMed

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

    2003-12-01

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

  4. Defense strategy of old and modern spring wheat varieties during soil drying.

    PubMed

    Fan, Xian-Wei; Li, Feng-Min; Song, Lei; Xiong, You-Cai; An, Li-zhe; Jia, Yu; Fang, Xiang-Wen

    2009-07-01

    Different defense mechanisms of three spring wheat (Triticum aestivum L.) varieties were studied by withholding watering in well-watered pots to gradually increase water deficit of plants grown in containers. The strategies of plant adaptation were divided into three phases according to the severity of drought: first, a positive defense phase that started from commencement of non-hydraulic root-sourced signals (nHRS) and ended at onset of hydraulic root-sourced signals (HRS)--the plant responded to imminent drought by decreasing stomatal aperture to lessen water loss and no membrane injury occurred. The second defense phase occurred between the onset of HRS and temporary wilting (TW), characterized by enhancement of reactive oxygen species (ROS), marked enzyme activity and increased MDA content. Mild lipid membrane peroxidation came mainly from a dynamic imbalance between free radical production and enzymatic defense reaction, which indicated that injury by ROS had not been completely repaired by increasing enzymatic activity. The third defense phase was from TW to permanent wilting (PW), the synthesis of SOD and CAT during TW could not deal with the collapse of antioxidant enzymes, and SOD and CAT activities began to decrease, which caused the excessive ROS production and thus serious membrane lipid peroxidation. The defense strategies to drought are similar among the varieties, but modern varieties LC8275 and GY602 bred after 1975 had relatively higher defense levels at all three defense phases, which suggest that modern varieties are more resistant than old ones, and artificial selection would lead to a different direction in evolution from natural selection. PMID:19453498

  5. Stability and topology of scale-free networks under attack and defense strategies Lazaros K. Gallos1

    E-print Network

    Cohen, Reuven

    Stability and topology of scale-free networks under attack and defense strategies Lazaros K. Gallos and topology of random scale-free networks under attack and defense strategies that depend on the degree k properties, as compared to lattice models or even to small-world networks [1]. One important fea- ture

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

    Microsoft Academic Search

    Mark Fabro

    2007-01-01

    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

  7. Adenoviral Vector Immunity: Its Implications and circumvention strategies

    PubMed Central

    Ahi, Yadvinder S.; Bangari, Dinesh S.; Mittal, Suresh K.

    2014-01-01

    Adenoviral (Ad) vectors have emerged as a promising gene delivery platform for a variety of therapeutic and vaccine purposes during last two decades. However, the presence of preexisting Ad immunity and the rapid development of Ad vector immunity still pose significant challenges to the clinical use of these vectors. Innate inflammatory response following Ad vector administration may lead to systemic toxicity, drastically limit vector transduction efficiency and significantly abbreviate the duration of transgene expression. Currently, a number of approaches are being extensively pursued to overcome these drawbacks by strategies that target either the host or the Ad vector. In addition, significant progress has been made in the development of novel Ad vectors based on less prevalent human Ad serotypes and nonhuman Ad. This review provides an update on our current understanding of immune responses to Ad vectors and delineates various approaches for eluding Ad vector immunity. Approaches targeting the host and those targeting the vector are discussed in light of their promises and limitations. PMID:21453277

  8. 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

  9. An alternative to present United States defense strategy

    E-print Network

    Anthony, William Wallace

    1971-01-01

    can weather massive nuclear attacl?, even witn li. tie or no warning, in sufficient sarong-. n to strike a decisive counter-blow. Tnis force ". ust be of a. character which will per, 't its use, in t!. e event of etta. ck, in a cool and deliberate..., force, coercion, and perception have a special meaning as regards nuclear strategy as a deterrent and the various plans that have 12 "Deterrence as an Influence Process" (excerpt from Teqh Pub TP 5879, US Naval Ordinance Test Station, China Lake...

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

    PubMed Central

    Rosenzweig, Jason A.; Chopra, Ashok K.

    2013-01-01

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

  11. 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

  12. 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

  13. 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

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

    PubMed Central

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

    2014-01-01

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

  15. Production and release of antimicrobial and immune defense proteins by mammary epithelial cells following Streptococcus uberis infection of sheep.

    PubMed

    Addis, Maria Filippa; Pisanu, Salvatore; Marogna, Gavino; Cubeddu, Tiziana; Pagnozzi, Daniela; Cacciotto, Carla; Campesi, Franca; Schianchi, Giuseppe; Rocca, Stefano; Uzzau, Sergio

    2013-09-01

    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

  16. Electronic Warfare: Comprehensive Strategy Still Needed for Suppressing Enemy Air Defenses

    NASA Astrophysics Data System (ADS)

    2002-11-01

    U.S. military aircraft are often at great risk from enemy air defenses, and the services use specialized aircraft to neutralize or destroy them. In January 2001, GAO reported that a gap existed between the services' suppression capabilities and their needs and recommended that a comprehensive strategy was needed to fix the situation. In response to GAO's report, DOD emphasized that a major study underway at the time would provide the basis for a Department-wide strategy and lead to a balanced set of acquisition programs between the services. This report updates our previous work and assesses actions that DOD has taken to improve its suppression capabilities.

  17. 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

  18. A Recessive Mutation, Immune Deficiency (imd), Defines Two Distinct Control Pathways in the Drosophila Host Defense

    Microsoft Academic Search

    Bruno Lemaitre; Elisabeth Kromer-Metzger; Lydia Michaut; Emmanuelle Nicolas; Marie Meister; Philippe Georgel; Jean-Marc Reichhart; Jules A. Hoffmann

    1995-01-01

    In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila. When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies. We also report that, in contrast to the anti-bacterial peptides, the antifungal peptide drosomycin remains inducible in

  19. 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

  20. 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.

  1. A Novel Strategy Involved Anti-Oxidative Defense: The Conversion of NADH into NADPH by a Metabolic

    E-print Network

    Appanna, Vasu

    A Novel Strategy Involved Anti-Oxidative Defense: The Conversion of NADH into NADPH by a Metabolic dinucleotide phosphate (NADPH) is pivotal to the cellular anti-oxidative defence strategies in most organisms oxidative stress as the increase of an anti-oxidant is coupled to the decrease of a pro-oxidant. Citation

  2. Ironing out the wrinkles in host defense: interactions between iron homeostasis and innate immunity.

    PubMed

    Wang, Lijian; Cherayil, Bobby J

    2009-01-01

    Iron is an essential micronutrient for both microbial pathogens and their mammalian hosts. Changes in iron availability and distribution have significant effects on pathogen virulence and on the immune response to infection. Recent advances in our understanding of the molecular regulation of iron metabolism have shed new light on how alterations in iron homeostasis both contribute to and influence innate immunity. In this article, we review what is currently known about the role of iron in the response to infection. PMID:20375603

  3. Oxygen Toxicity, Biological Defense Systems and Immunity—A Historical Perspective

    Microsoft Academic Search

    C. R. Kang; S. Sweetser; L. M. Boylan; J. E. Spallholz

    1994-01-01

    Oxygen, the diradical byproduct of photosynthesis from algae and plants, made possible the emergence of aerobic life beginning about 4 billion years ago. Along with the evolution of aerobic life processes came the consequence of oxygen toxicity and the necessity of the development of an antioxidant defense system by aerobic prokaryotes. Eukaryotes, both by inheriting and improving upon the first

  4. 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

  5. Ironing Out the Wrinkles in Host Defense: Interactions between Iron Homeostasis and Innate Immunity

    Microsoft Academic Search

    Lijian Wang; Bobby J. Cherayil

    2009-01-01

    Iron is an essential micronutrient for both microbial pathogens and their mammalian hosts. Changes in iron availability and distribution have significant effects on pathogen virulence and on the immune response to infection. Recent advances in our understanding of the molecular regulation of iron metabolism have shed new light on how alterations in iron homeostasis both contribute to and influence innate

  6. Transgenerational Effects of Heavy Metal Pollution on Immune Defense of the Blow Fly Protophormia terraenovae

    PubMed Central

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

    2012-01-01

    Recently environmental conditions during early parental development have been found to have transgenerational effects on immunity and other condition-dependent traits. However, potential transgenerational effects of heavy metal pollution have not previously been studied. Here we show that direct exposure to heavy metal (copper) upregulates the immune system of the blow fly, Protophormia terraenovae, reared in copper contaminated food. In the second experiment, to test transgenerational effects of heavy metal, the parental generation of the P. terraenovae was reared in food supplemented with copper, and the immunocompetence of their offspring, reared on uncontaminated food, was measured. Copper concentration used in this study was, in the preliminary test, found to have no effect on mortality of the flies. Immunity was tested on the imago stage by measuring encapsulation response against an artificial antigen, nylon monofilament. We found that exposure to copper during the parental development stages through the larval diet resulted in immune responses that were still apparent in the next generation that was not exposed to the heavy metal. We found that individuals reared on copper-contaminated food developed more slowly compared with those reared on uncontaminated food. The treatment groups did not differ in their dry body mass. However, parental exposure to copper did not have an effect on the development time or body mass of their offspring. Our study suggests that heavy metal pollution has positive feedback effect on encapsulation response through generations which multiplies the harmful effects of heavy metal pollution in following generations. PMID:22719959

  7. Adapting a transforming growth factor -related tumor protection strategy to enhance antitumor immunity

    Microsoft Academic Search

    Catherine M. Bollard; Claudia Rossig; M. Julia Calonge; M. Helen; Hans-Joachim Wagner Huls; Joan Massague; Malcolm K. Brenner; Helen E. Heslop; Cliona M. Rooney

    2002-01-01

    Transforming growth factor (TGF-), a pleiotropic cytokine that regulates cell growth and differentiation, is secreted by many human tumors and markedly inhib- its tumor-specific cellular immunity. Tu- mors can avoid the differentiating and apoptotic effects of TGF- by expressing a nonfunctional TGF- receptor. We have determined whether this immune evasion strategy can be manipulated to shield tumor-specific cytotoxic T lymphocytes

  8. 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...

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

    PubMed Central

    Tan, Demeng; Svenningsen, Sine Lo

    2015-01-01

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

  10. 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

  11. Directing traffic: IL-17 and IL-22 coordinate pulmonary immune defense.

    PubMed

    McAleer, Jeremy P; Kolls, Jay K

    2014-07-01

    Respiratory infections and diseases are among the leading causes of death worldwide, and effective treatments probably require manipulating the inflammatory response to pathogenic microbes or allergens. Here, we review mechanisms controlling the production and functions of interleukin-17 (IL-17) and IL-22, cytokines that direct several aspects of lung immunity. Innate lymphocytes (?? T cells, natural killer cells, innate lymphoid cells) are the major source of IL-17 and IL-22 during acute infections, while CD4(+) T-helper 17 (Th17) cells contribute to vaccine-induced immunity. The characterization of dendritic cell (DC) subsets has revealed their central roles in T-cell activation. CD11b(+) DCs stimulated with bacteria or fungi secrete IL-1? and IL-23, potent inducers of IL-17 and IL-22. On the other hand, recognition of viruses by plasmacytoid DCs inhibits IL-1? and IL-23 release, increasing susceptibility to bacterial superinfections. IL-17 and IL-22 primarily act on the lung epithelium, inducing antimicrobial proteins and neutrophil chemoattractants. Recent studies found that stimulation of macrophages and DCs with IL-17 also contributes to antibacterial immunity, while IL-22 promotes epithelial proliferation and repair following injury. Chronic diseases such as asthma and chronic obstructive pulmonary disease have been associated with IL-17 and IL-22 responses directed against innocuous antigens. Future studies will evaluate the therapeutic efficacy of targeting the IL-17/IL-22 pathway in pulmonary inflammation. PMID:24942687

  12. Directing traffic: IL-17 and IL-22 coordinate pulmonary immune defense

    PubMed Central

    McAleer, Jeremy P.; Kolls, Jay K.

    2014-01-01

    Summary Respiratory infections and diseases are among the leading causes of death worldwide, and effective treatments likely require manipulating the inflammatory response to pathogenic microbes or allergens. Here we review mechanisms controlling the production and functions of interleukin-17 (IL-17) and IL-22, cytokines that direct several aspects of lung immunity. Innate lymphocytes (??T cells, natural killer cells, innate lymphoid cells) are the major source of IL-17 and IL-22 during acute infections, while CD4+ T-helper 17 (Th17) cells contribute to vaccine-induced immunity. The characterization of dendritic cell (DC) subsets has revealed their central roles in T-cell activation. CD11b+ DCs stimulated with bacteria or fungi secrete IL-1? and IL-23, potent inducers of IL-17 and IL-22. On the other hand, recognition of viruses by plasmacytoid DCs inhibits IL-1? and IL-23 release, increasing susceptibility to bacterial superinfections. IL-17 and IL-22 primarily act on the lung epithelium, inducing antimicrobial proteins and neutrophil chemoattractants. Recent studies found that stimulation of macrophages and DCs with IL-17 also contributes to anti-bacterial immunity, while IL-22 promotes epithelial proliferation and repair following injury. Chronic diseases such as asthma and chronic obstructive pulmonary disease have been associated with IL-17 and IL-22 responses directed against innocuous antigens. Future studies will evaluate the therapeutic efficacy of targeting the IL-17/IL-22 pathway in pulmonary inflammation. PMID:24942687

  13. 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

  14. Poplar extrafloral nectaries: two types, two strategies of indirect defenses against herbivores.

    PubMed

    Escalante-Pérez, María; Jaborsky, Mario; Lautner, Silke; Fromm, Jörg; Müller, Tobias; Dittrich, Marcus; Kunert, Maritta; Boland, Wilhelm; Hedrich, Rainer; Ache, Peter

    2012-07-01

    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

  15. 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

  16. 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

  17. 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

  18. A mid-term assessment of progress towards the immunization coverage goal of the Global Immunization Vision and Strategy (GIVS)

    PubMed Central

    2011-01-01

    Background The Global Immunization Vision and Strategy (GIVS) (2006-2015) aims to reach and sustain high levels of vaccine coverage, provide immunization services to age groups beyond infancy and to those currently not reached, and to ensure that immunization activities are linked with other health interventions and contribute to the overall development of the health sector. Objective To examine mid-term progress (through 2010) of the immunization coverage goal of the GIVS for 194 countries or territories with special attention to data from 68 countries which account for more than 95% of all maternal and child deaths. Methods We present national immunization coverage estimates for the third dose of diphtheria and tetanus toxoid with pertussis (DTP3) vaccine and the first dose of measles containing vaccine (MCV) during 2000, 2005 and 2010 and report the average annual relative percent change during 2000-2005 and 2005-2010. Data are taken from the WHO and UNICEF estimates of national immunization coverage, which refer to immunizations given during routine immunization services to children less than 12 months of age where immunization services are recorded. Results Globally DTP3 coverage increased from 74% during 2000 to 85% during 2010, and MCV coverage increased from 72% during 2000 to 85% during 2010. A total of 149 countries attained or were on track to achieve the 90% coverage goal for DTP3 (147 countries for MCV coverage). DTP3 coverage ? 90% was sustained between 2005 and 2010 by 99 countries (98 countries for MCV). Among 68 priority countries, 28 countries were identified as having made either insufficient or no progress towards reaching the GIVS goal of 90% coverage by 2015 for DTP3 or MCV. DTP3 and MCV coverage remained < 70% during 2010 for 16 and 21 priority countries, respectively. Conclusion Progress towards GIVS goals highlights improvements in routine immunization coverage, yet it is troubling to observe priority countries with little or no progress during the past five years. These results highlight that further efforts are needed to achieve and maintain the global immunization coverage goals. PMID:21999521

  19. Stability and topology of scalefree networks under attack and defense strategies Lazaros K. Gallos 1 , Reuven Cohen 2 , Panos Argyrakis 1 , Armin Bunde 3 , and Shlomo Havlin 2

    E-print Network

    Cohen, Reuven

    Stability and topology of scale­free networks under attack and defense strategies Lazaros K. Gallos and topology of random scale­free networks under attack and defense strategies that depend on the degree k properties, as compared to lattice models or even to small­world networks [1]. One important fea­ ture

  20. 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

  1. Biomphalysin, a new ? pore-forming toxin involved in Biomphalaria glabrata immune defense against Schistosoma mansoni.

    PubMed

    Galinier, Richard; Portela, Julien; Moné, Yves; Allienne, Jean François; Henri, Hélène; Delbecq, Stéphane; Mitta, Guillaume; Gourbal, Benjamin; Duval, David

    2013-03-01

    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

  2. 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

  3. Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense.

    PubMed

    Loof, Torsten G; Mörgelin, Matthias; Johansson, Linda; Oehmcke, Sonja; Olin, Anders I; Dickneite, Gerhard; Norrby-Teglund, Anna; Theopold, Ulrich; Herwald, Heiko

    2011-09-01

    Phylogenetically conserved serine protease cascades play an important role in invertebrate and vertebrate immunity. The mammalian coagulation system can be traced back some 400 million years and shares homology with ancestral serine proteinase cascades that are involved in, for example, Toll receptor signaling in insects and release of antimicrobial peptides during hemolymph clotting. In the present study, we show that the induction of coagulation by bacteria leads to immobilization and killing of Streptococcus pyogenes bacteria inside the clot. The entrapment is mediated via cross-linking of bacteria to fibrin fibers by the action of coagulation factor XIII (fXIII), an evolutionarily conserved transglutaminase. In a streptococcal skin infection model, fXIII(-/-) mice developed severe signs of pathologic inflammation at the local site of infection, and fXIII treatment of wild-type animals dampened bacterial dissemination during early infection. Bacterial killing and cross-linking to fibrin networks was also detected in tissue biopsies from patients with streptococcal necrotizing fasciitis, supporting the concept that coagulation is part of the early innate immune system. PMID:21613262

  4. Coping strategies and immune neglect in affective forecasting: Direct evidence and key moderators

    PubMed Central

    Hoerger, Michael

    2012-01-01

    Affective forecasting skills have important implications for decision making. However, recent research suggests that immune neglect – the tendency to overlook coping strategies that reduce future distress – may lead to affective forecasting problems. Prior evidence for immune neglect has been indirect. More direct evidence and a deeper understanding of immune neglect are vital to informing the design of future decision-support interventions. In the current study, young adults (N = 325) supplied predicted, actual, and recollected reactions to an emotionally-evocative interpersonal event, Valentine’s Day. Based on participants’ qualitative descriptions of the holiday, a team of raters reliably coded the effectiveness of their coping strategies. Supporting the immune neglect hypothesis, participants overlooked the powerful role of coping strategies when predicting their emotional reactions. Immune neglect was present not only for those experiencing the holiday negatively (non-daters) but also for those experiencing it positively (daters), suggesting that the bias may be more robust than originally theorized. Immune neglect was greater for immediate emotional reactions than more enduring reactions. Further, immune neglect was conspicuously absent from recollected emotional reactions. Implications for decision-support interventions are discussed. PMID:22375161

  5. CsCCL17, a CC chemokine of Cynoglossus semilaevis, induces leukocyte trafficking and promotes immune defense against viral infection.

    PubMed

    Hu, Yong-Hua; Zhang, Jian

    2015-08-01

    CC chemokines are the largest subfamily of chemokines, which are important components of the innate immune system. To date, sequences of several CC chemokines have been identified in half-smooth tongue sole (Cynoglossus semilaevis); however, the activities and functions of these putative chemokines remain unknown. Herein, we characterized a CC chemokine, CsCCL17, from tongue sole, and examined its activity. CsCCL17 contains a 303 bp open reading frame, which encodes a polypeptide of 100 amino acids with a molecular mass of 12 kDa CsCCL17 is phylogenetically related to the CCL17/22 group of CC chemokines and possesses the typical arrangement of four cysteines and an SCCR motif found in known CC chemokines. Under normal physiological conditions, CsCCL17 expression was detected in spleen, liver, heart, gill, head kidney, muscle, brain, and intestine. When the fish were infected by bacterial and viral pathogens, CsCCL17 expression was significantly up-regulated in a time-dependent manner. Chemotactic analysis showed that recombinant CsCCL17 (rCsCCL17) induced migration of peripheral blood leukocytes. A mutagenesis study showed that when the two cysteine residues in the SCCR motif were replaced by serine, no apparent chemotactic activity was observed in the mutant protein rCsCCL17M. rCsCCL17 enhanced the resistance of tongue sole against viral infection, but rCsCCL17M lacked this antiviral effect. Taken together, these findings indicate that CsCCL17 is a functional CC chemokine with the ability to recruit leukocytes and enhance host immune defense in a manner that requires the conserved SCCR motif. PMID:26052018

  6. Strategies to potentiate immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.

    2015-03-01

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

  7. Possible New Antiaging Strategies Related to Neuroendocrine-Immune Interactions

    Microsoft Academic Search

    Eugenio Mocchegiani; Marco Malavolta

    2008-01-01

    The aging process demonstrates gradual and spontaneous changes, resulting in maturation through childhood, puberty and young adulthood, and then decline through middle and late age. However, animals and humans are capable of reaching the extreme limit of life span characteristic for the species with a very efficient network of antiaging mechanisms. Among them, neuroendocrine-immune interactions play a pivotal role. The

  8. Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection.

    PubMed

    Abt, Michael C; Lewis, Brittany B; Caballero, Silvia; Xiong, Huizhong; Carter, Rebecca A; Sušac, Bože; Ling, Lilan; Leiner, Ingrid; Pamer, Eric G

    2015-07-01

    Infection with the opportunistic enteric pathogen Clostridium difficile is an increasingly common clinical complication that follows antibiotic treatment-induced gut microbiota perturbation. Innate lymphoid cells (ILCs) are early responders to enteric pathogens; however, their role during C. difficile infection is undefined. To identify immune pathways that mediate recovery from C. difficile infection, we challenged C57BL/6, Rag1(-/-) (which lack T and B cells), and Rag2(-/-)Il2rg(-/-) (Rag?c(-/-)) mice (which additionally lack ILCs) with C. difficile. In contrast to Rag1(-/-) mice, ILC-deficient Rag?c(-/-) mice rapidly succumbed to infection. Rag1(-/-) but not Rag?c(-/-) mice upregulate expression of ILC1- or ILC3-associated proteins following C. difficile infection. Protection against infection was restored by transferring ILCs into Rag?c(-/-) mice. While ILC3s made a minor contribution to resistance, loss of IFN-? or T-bet-expressing ILC1s in Rag1(-/-) mice increased susceptibility to C. difficile. These data demonstrate a critical role for ILC1s in defense against C. difficile. PMID:26159718

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

    PubMed

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

    2014-01-01

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

  10. Nuclear pore complex component MOS7/Nup88 is required for innate immunity and nuclear accumulation of defense regulators in Arabidopsis.

    PubMed

    Cheng, Yu Ti; Germain, Hugo; Wiermer, Marcel; Bi, Dongling; Xu, Fang; García, Ana V; Wirthmueller, Lennart; Després, Charles; Parker, Jane E; Zhang, Yuelin; Li, Xin

    2009-08-01

    Plant immune responses depend on dynamic signaling events across the nuclear envelope through nuclear pores. Nuclear accumulation of certain resistance (R) proteins and downstream signal transducers are critical for their functions, but it is not understood how these processes are controlled. Here, we report the identification, cloning, and analysis of Arabidopsis thaliana modifier of snc1,7 (mos7-1), a partial loss-of-function mutation that suppresses immune responses conditioned by the autoactivated R protein snc1 (for suppressor of npr1-1, constitutive 1). mos7-1 single mutant plants exhibit defects in basal and R protein-mediated immunity and in systemic acquired resistance but do not display obvious pleiotropic defects in development, salt tolerance, or plant hormone responses. MOS7 is homologous to human and Drosophila melanogaster nucleoporin Nup88 and resides at the nuclear envelope. In animals, Nup88 attenuates nuclear export of activated NF-kappaB transcription factors, resulting in nuclear accumulation of NF-kappaB. Our analysis shows that nuclear accumulation of snc1 and the defense signaling components Enhanced Disease Susceptibility 1 and Nonexpresser of PR genes 1 is significantly reduced in mos7-1 plants, while nuclear retention of other tested proteins is unaffected. The data suggest that specifically modulating the nuclear concentrations of certain defense proteins regulates defense outputs. PMID:19700630

  11. Immune System (For Parents)

    MedlinePLUS

    ... can lead to illness and infection. About the Immune System The immune system is the body's defense against ... that cause colds. Back Continue Problems of the Immune System Disorders of the immune system fall into four ...

  12. [Immunization delay determinants: a study in a place attended by Family Health Strategy].

    PubMed

    Tertuliano, Gisele Cristina; Stein, Airton Tetelbom

    2011-02-01

    It is relevant to understand every aspect, regarding to strategies that will determine immunization coverage. Thus the main objective in this research is to identify the prevalence of depressive symptoms as well as low immunization uptake, identifying the caretakers' profile, considering his/her level of education, social-demographic character, marital status and also knowledge about immunization in which a Beck Inventory questionnaire was applied to the children's caretakers. Children's age ranged from 0 to 5 years and the number of subjects was 339 enrolled in a group of Family Health Strategy at the city of Cachoeirinha, in the state of Rio Grande do Sul, Brazil. The depression symptoms prevalence was 38.6%. The association between depression symptoms and the low immunization uptake was not statistical significant (OR=1.0, CI 95%, 0.62-1.73). The low immunization uptake rate was 23.3%. The high prevalence of depressive symptoms between mothers and the high percentage of immunization delay means the need of social help and the search of better effectivity of primary attention in health. PMID:21340327

  13. The cutaneous biochemical redox barrier: a component of the innate immune defenses against sensitization by highly reactive environmental xenobiotics.

    PubMed

    Pickard, Chris; Louafi, Fethi; McGuire, Carolann; Lowings, Kelly; Kumar, Pawan; Cooper, Hywel; Dearman, Rebecca J; Cumberbatch, Marie; Kimber, Ian; Healy, Eugene; Friedmann, Peter S

    2009-12-01

    Contact allergy to environmental xenobiotics is a common and important problem, but it is unclear why some chemicals are potent sensitizers and others weak/nonsensitizers. We explored this by investigating why similar chemicals, 2,4-dinitrochlorobenzene (DNCB) and 2,4-dinitrothiocyanobenzene (DNTB), differ in their ability to induce contact hypersensitivity (CHS). DNCB induced CHS in humans, whereas at similar doses DNTB did not. However, following DNCB sensitization, DNTB elicited CHS in vivo and stimulated DNCB-responsive T cells in vitro, suggesting that differences in response to these compounds lie in the sensitization phase. In contrast to DNCB, DNTB failed to induce emigration of epidermal Langerhans cells in naive individuals. Examination for protein dinitrophenylation in skin revealed that DNCB penetrated into the epidermis, whereas DNTB remained bound to a thiol-rich band within the stratum corneum. DNTB reacted rapidly with reduced glutathione in vitro and was associated with a decrease in the free thiol layer in the stratum corneum, but not in the nucleated epidermis. By contrast, DNCB required GST facilitation to react with gluthathione and, following penetration through the stratum corneum, depleted thiols in the viable epidermis. Chemical depletion of the thiol-rich band or removing it by tape stripping allowed increased penetration of DNTB into the epidermis. Our results suggest that the dissimilar sensitizing potencies of DNCB and DNTB in humans are determined by a previously undescribed outer epidermal biochemical redox barrier, a chemical component of the innate immune defense mechanisms that defend against sensitization by highly reactive environmental chemicals. PMID:19890059

  14. 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.

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

    PubMed

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

    2014-05-20

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

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

    PubMed Central

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

    2014-01-01

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

  17. Counterproliferation strategy: The influence of technology, budget, and arms control on theater missile defenses. Strategic research project

    SciTech Connect

    Parlier, G.H.

    1996-05-20

    This paper describes the historical evolution of the theater missile threat during World War II and the Persian Gulf War, and analyzes current technological challenges, budgetary pressures, and arms control restraints which constrain the development and deployment of effective theater missile defenses. The impact of these trends on strategic concepts as outlined in the National Military Strategy and their implications for attaining national policy objectives is assessed. A systems approach is used to described analyze, and evaluate the effectiveness of emerging counterproliferation strategy within the framework of an ends-ways-means strategy formulation paradigm. I conclude that current trends will lead to a self-deterring strategy: resources are inadequate to support the ways we intend to achieve our national objectives. Recommendations are made to eliminate unacceptable risk and enhance the concept of `extended conventional deterrence` consistent with U.S. national values and security interests for our role in a new world order.

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

    PubMed Central

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

    2012-01-01

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

  19. 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

  20. The involvement of suppressors of cytokine signaling 2 (SOCS2) in immune defense responses of Chinese mitten crab Eriocheir sinensis.

    PubMed

    Zhang, Ying; Zhao, Jianmin; Zhang, Huan; Gai, Yunchao; Wang, Lingling; Li, Fengmei; Yang, Jialong; Qiu, Limei; Song, Linsheng

    2010-01-01

    The suppressors of cytokine signaling 2 (SOCS2) has been identified as negative feedback inhibitors for various cytokines signaling via the JAK/STAT pathway. In the present studies, the cDNA of Eriocheir sinensis SOCS2 (designated as EsSOCS2) was cloned by expressed sequence tag (EST) and rapid amplification of cDNA ends (RACE) approaches. The full-length cDNA of EsSOCS2 was of 2535bp, consisting of an open reading frame (a ORF) of 1071bp encoding a polypeptide of 357 amino acids. The deduced amino acid sequence of EsSOCS2 shared 55-62% similarity with other SOCS2 family members. There were three typical conserved SOCS family domains in EsSOCS2, including an N-terminal ESS formed from a single amphipathic helix, a central SH2 domain with a classic phosphotyrosine (pY) site and a C-terminal SOCS box. The sequence and structural similarity of EsSOCS2 with SOCS2 proteins from other organisms indicated that EsSOCS2 should be a new member of the SOCS2 family. Phylogenetic analysis revealed that EsSOCS2 was clustered with SOCS2 from the other invertebrates, and fell into the group of type II SOCS subfamily as a sister branch to CIS and SOCS2 from vertebrate, suggesting the great divergence of SOCS2 of vertebrate from invertebrate and complex evolution of SOCS2 family members. The mRNA transcript of EsSOCS2 could be detected by semi-quantitative RT-PCR in all examined tissues of healthy crabs, including haemocytes, hepatopancreas, gill, muscle, heart and gonad. The mRNA expression of EsSOCS2 in haemocytes was up-regulated to 3.5-fold at 8h after Listonella anguillarum challenge, 3-fold and 3.5-fold at 4 and 6h, respectively, after Micrococcus luteus challenge. These results collectively suggested that EsSOCS2 could be induced by bacteria challenge, and it was involved in the immune defense responses in E. sinensis. PMID:19686773

  1. 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

  2. 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

  3. 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, ...

  4. 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.

  5. 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

  6. Inhibition of the interleukin-6 signaling pathway: a strategy to induce immune tolerance.

    PubMed

    Zhang, Cheng; Zhang, Xi; Chen, Xing-Hua

    2014-10-01

    Interleukin-6 (IL-6) is a proinflammatory cytokine that is multifunctional, with multifaceted effects. IL-6 signaling plays a vital role in the control of the differentiation and activation of T lymphocytes by inducing different pathways. In particular, IL-6 controls the balance between Th17 cells and regulatory T (Treg) cells. An imbalance between Treg and Th17 cells is thought to play a pathological role in various immune-mediated diseases. Deregulated IL-6 production and signaling are associated with immune tolerance. Therefore, methods of inhibiting IL-6 production, receptors, and signaling pathways are strategies that are currently being widely pursued to develop novel therapies that induce immune tolerance. This survey aims to provide an updated account of why IL-6 inhibitors are becoming a vital class of drugs that are potentially useful for inducing immune tolerance as a treatment for autoimmune diseases and transplant rejection. In addition, we discuss the effect of targeting IL-6 in recent experimental and clinical studies on autoimmune diseases and transplant rejection. PMID:24647663

  7. 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 ...

  8. 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

  9. 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

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

    PubMed

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

    2015-05-01

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

  11. 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

  12. 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

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

    PubMed Central

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

    2012-01-01

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

  14. Women's use of physical and nonphysical self-defense strategies during incidents of partner violence.

    PubMed

    Downs, William R; Rindels, Barb; Atkinson, Christine

    2007-01-01

    Two incidents of partner violence are investigated using qualitative methodology to discover strategies women use to protect themselves and examine women's use of violence. Data were collected from 447 women (age 18 or older) from 7 domestic violence programs and 5 substance use disorder treatment programs in a midwestern state. Women were found to have developed numerous self-protection strategies, some using nonphysical means only, others using physical means only, and others combining nonphysical and physical means. Women often used a variety of strategies in the same incident. Few women initiated violence against partners. Implications for theory and research are discussed. PMID:17179403

  15. 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

  16. Social defense: an evolutionary-developmental model of children's strategies for coping with threat in the peer group.

    PubMed

    Martin, Meredith J; Davies, Patrick T; MacNeill, Leigha A

    2014-01-01

    Navigating the ubiquitous conflict, competition, and complex group dynamics of the peer group is a pivotal developmental task of childhood. Difficulty negotiating these challenges represents a substantial source of risk for psychopathology. Evolutionary developmental psychology offers a unique perspective with the potential to reorganize the way we think about the role of peer relationships in shaping how children cope with the everyday challenges of establishing a social niche. To address this gap, we utilize the ethological reformulation of the emotional security theory as a guide to developing an evolutionary framework for advancing an understanding of the defense strategies children use to manage antagonistic peer relationships and protect themselves from interpersonal threat (Davies and Sturge-Apple, 2007). In this way, we hope to illustrate the value of an evolutionary developmental lens in generating unique theoretical insight and novel research directions into the role of peer relationships in the development of psychopathology. PMID:25299884

  17. 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

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

    PubMed

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

    2011-12-01

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

  19. 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

  20. 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

  1. Multilevel Coalition Formation Strategy for Suppression of Enemy Air Defenses Missions

    E-print Network

    Egerstedt, Magnus

    support/ coverage for other team members. For example, combat vehicles responsible for destroying targets, and reconnaissance teams; I I J 1 = J1 J 1, ordered set of all combat pairs J 2 = J2 J 2, ordered set of all to form coalitions in teams of heterogeneous vehicles. In particular, a coordination strategy is designed

  2. 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

  3. Balancing Terrorism and Natural Disasters - Defensive Strategy with Endogenous Attacker Effort

    Microsoft Academic Search

    Jun Zhuang; Vicki M. Bier

    2007-01-01

    In this paper, we apply game theory to identify equilibrium strategies for both attacker and defender in a fully endogenous model of resource allocation for countering terrorism and natural disasters. The key features of our model include balancing protection from terrorism and natural disasters, and describing the attacker choice by a continuous level of effort rather than a discrete choice

  4. Characterization of a honey bee Toll related receptor gene Am18w and its potential involvement in antimicrobial immune defense

    Microsoft Academic Search

    Katherine Aronstein; Eduardo Saldivar

    2005-01-01

    Toll receptors are involved in intracellular signal transduction and initiation of insect antimicrobial immune responses. Here we report the isolation and characterization of a novel gene (Am18w) from honey bee Apis mellifera, which encodes for the Toll-like receptor and shares a striking 51.4% similarity with Bombyx mori 18-wheeler, 46.6% with Drosophila Toll-7 receptor and 42.5% with Drosophila 18-wheeler. The sequence

  5. 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

  6. 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

  7. Community-based strategies for immunizing the "hard-to-reach" child: the New York State immunization and primary health care initiative.

    PubMed

    Rosenberg, Z; Findley, S; McPhillips, S; Penachio, M; Silver, P

    1995-01-01

    The 1989-1991 measles epidemic in New York City drew attention to the low immunization coverage rates found in urban neighborhoods. This article describes a joint initiative of the New York State Department of Health and the Columbia University School of Public Health to mobilize parents to fully immunize their children. Eleven community-based organizations (CBOs) used a variety of outreach strategies to identify and enroll underimmunized children in primary care. They enrolled 4,555 children, of whom 75% needed at least one basic vaccine dose to be up-to-date for their age. Enrolled children were followed by CBOs to ensure compliance with appointments. After nine months of program operation, 73% of children in an evaluation sample were up-to-date for age for their immunizations. Immunization coverage increases were greatest for the youngest children, for whom coverage rates more than doubled in the first nine months of program operation. Ninety-one percent of these "hard to reach" children were tracked successfully by CBOs. This article compares the strategies used by the community organizations and concludes with suggestions for improvements of future community-based mobilization programs. PMID:7669356

  8. 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

  9. A novel therapeutic strategy to rescue the immune effector function of proteolytically inactivated cancer therapeutic antibodies.

    PubMed

    Fan, Xuejun; Brezski, Randall J; Deng, Hui; Dhupkar, Pooja M; Shi, Yun; Gonzalez, Anneliese; Zhang, Songlin; Rycyzyn, Michael; Strohl, William R; Jordan, Robert E; Zhang, Ningyan; An, Zhiqiang

    2015-03-01

    Primary and acquired resistance to anticancer antibody immunotherapies presents significant clinical challenges. Here, we demonstrate that proteolytic inactivation of cancer-targeting antibodies is an unappreciated contributor to cancer immune evasion, and the finding presents novel opportunities for therapeutic intervention. A single peptide bond cleavage in the IgG1 hinge impairs cancer cell killing due to structural derangement of the Fc region. Hinge-cleaved trastuzumab gradually accumulated on the surfaces of HER2-expressing cancer cell lines in vitro, and was greatly accelerated when the cells were engineered to express the potent bacterial IgG-degrading proteinase (IdeS). Similar to cancer-related matrix metalloproteinases (MMP), IdeS exposes a hinge neoepitope that we have developed an antibody, mAb2095-2, to specifically target the epitope. In in vitro studies, mAb2095-2 restored the lost antibody-dependent cell-mediated cytotoxicity functionality of cell-bound single-cleaved trastuzumab (scIgG-T). In vivo, mAb2095-2 rescued the impaired Fc-dependent tumor-suppressive activity of scIgG-T in a xenograft tumor model and restored the recruitment of immune effector cells into the tumor microenvironment. More importantly, an Fc-engineered proteinase-resistant version of mAb2095-2 rescued trastuzumab antitumor efficacy in a mouse tumor model with human cancer cells secreting IdeS, whereas trastuzumab alone showed significantly reduced antitumor activity in the same model. Consistently, an Fc-engineered proteinase-resistant version of trastuzumab also greatly improved antitumor efficacy in the xenograft tumor model. Taken together, these findings point to a novel cancer therapeutic strategy to rescue proteolytic damage of antibody effector function by an Fc-engineered mAb against the hinge neoepitope and to overcome cancer evasion of antibody immunity. Mol Cancer Ther; 14(3); 681-91. ©2014 AACR. PMID:25552368

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

    PubMed

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

    2014-09-01

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

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

    PubMed

    Anders, Sherry; Kinney, Dennis K

    2015-08-18

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

  12. A neonatal Fc receptor-targeted mucosal vaccine strategy effectively induces HIV-1 antigen-specific immunity to genital infection.

    PubMed

    Lu, Li; Palaniyandi, Senthilkumar; Zeng, Rongyu; Bai, Yu; Liu, Xindong; Wang, Yunsheng; Pauza, C David; Roopenian, Derry C; Zhu, Xiaoping

    2011-10-01

    Strategies to prevent the sexual transmission of HIV include vaccines that elicit durable, protective mucosal immune responses. A key to effective mucosal immunity is the capacity for antigens administered locally to cross epithelial barriers. Given the role of neonatal Fc receptor (FcRn) in transferring IgG across polarized epithelial cells which line mucosal surfaces, FcRn might be useful for delivering HIV vaccine antigens across mucosal epithelial barriers to the underlying antigen-presenting cells. Chimeric proteins composed of HIV Gag (p24) fused to the Fc region of IgG (Gag-Fc) bind efficiently to airway mucosa and are transported across this epithelial surface. Mice immunized intranasally with Gag-Fc plus CpG adjuvant developed local and systemic immunity, including durable B and T cell memory. Gag-specific immunity was sufficiently potent to protect against an intravaginal challenge with recombinant vaccinia virus expressing the HIV Gag protein. Intranasal administration of a Gag-Fc/CpG vaccine protected at a distal mucosal site. Our data suggest that targeting of FcRn with chimeric immunogens may be an important strategy for mucosal immunization and should be considered a new approach for preventive HIV vaccines. PMID:21849464

  13. RabGAP22 is required for defense to the vascular pathogen Verticillium longisporum and contributes to stomata immunity.

    PubMed

    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

  14. 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

  15. A neuroendocrine-immune network based control strategy for single-phase photovoltaic grid-connected inverter

    Microsoft Academic Search

    Lei Wang; Yongsheng Ding; Xiao Liang; Kuangrong Hao; Yize Sun

    2011-01-01

    The technique of photovoltaic grid-connected inverter has become the leading method for solar generator system. However, it is urgent and very significant to develop new control strategy for photovoltaic grid-connected inverter to improve its stability. In this paper, a new control strategy based on neuroendocrine-immune (NEI) network is proposed for single-phase photovoltaic grid-connected inverter. Two-way hormone regulating mechanism of human

  16. 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

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

    PubMed Central

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

    2014-01-01

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is a major etiologic agent of nontyphoid salmonellosis in the United States. S. Enteritidis persistently and silently colonizes the intestinal and reproductive tract of laying hens, resulting in contaminated poultry products. The consumption of contaminated poultry products has been identified as a significant risk factor for human salmonellosis. To understand the mechanisms S. Enteritidis utilizes to colonize and persist in laying hens, we used selective capture of transcribed sequences to identify genes overexpressed in the HD11 chicken macrophage cell line and in primary chicken oviduct epithelial cells. From the 15 genes found to be overexpressed in both cell types, we characterized the antimicrobial peptide resistance (AMPR) genes, virK and ybjX, in vitro and in vivo. In vitro, AMPR genes were required for natural morphology, motility, secretion, defense against detergents such as EDTA and bile salts, and resistance to antimicrobial peptides polymyxin B and avian ?-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

  18. A metabolic profiling strategy for the dissection of plant defense against fungal pathogens.

    PubMed

    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

  19. 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.…

  20. 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.

  1. Pneumonia immunization in older adults: review of vaccine effectiveness and strategies

    PubMed Central

    Assaad, Usama; El-Masri, Ibrahim; Porhomayon, Jahan; El-Solh, Ali A

    2012-01-01

    Vaccination remains the primary preventive strategy in the elderly against Streptococcus pneumoniae and influenza infections. The effectiveness of this strategy in preventing pneumonia has been in doubt despite the increase in vaccination coverage among older adults. Randomized controlled trials (RCTs) and observational studies aimed at determining clinical outcomes and immune response following pneumococcal vaccination have yielded conflicting results. The protective efficacy of pneumococcal vaccination against pneumonia in older adults has not been firmly established due to a lack of RCTs specifically examining patients ? 65 years of age. Similarly, the reported benefits of influenza vaccination have been derived from observational data. The assessment of clinical benefit from influenza vaccination in the elderly population is complicated by varying cohorts, virulence of the influenza strain, and matching of vaccine and circulating viral strains. The presence of selection bias and use of nonspecific end points in these studies make the current evidence inconclusive in terms of overall benefit. The development of more immunogenic vaccines through new formulations or addition of adjuvants holds the promise of revolutionizing delivery and improving efficacy. Dismantling existing barriers through education, providing technology assistance predominantly to developing countries, and establishing clear regulatory guidance on pathways for approval are necessary to ensure timely production and equitable distribution. PMID:23152675

  2. The Role of Dietary Long-Chain N-3 Fatty Acids in Anti-Cancer Immune Defense and R3230AC Mammary Tumor Growth in Rats: Influence of Diet Fat Composition

    Microsoft Academic Search

    Lindsay E. Robinson; M. Thomas Clandinin; Catherine J. Field

    2002-01-01

    We determined if long-chain n-3 fatty acids fed as part of a: (1) high polyunsaturated fat diet (currently recommended by several health agencies) or (2) low polyunsaturated fat diet (representative of that consumed by a large segment of the North American population) improved antitumor immune defense and inhibited tumor growth. Rats were fed one of four semi-purified diets (20% w\\/w

  3. Anthrax Lethal Toxin-Mediated Killing of Human and Murine Dendritic Cells Impairs the Adaptive Immune Response

    Microsoft Academic Search

    Abdelkrim Alileche; Evan R. Serfass; Stefan M. Muehlbauer; Steven A. Porcelli; Jürgen Brojatsch

    2005-01-01

    Many pathogens have acquired strategies to combat the immune response. Bacillus anthracis interferes with host defenses by releasing anthrax lethal toxin (LT), which inactivates mitogen-activated protein kinase pathways, rendering dendritic cells (DCs) and T lymphocytes nonresponsive to immune stimulation. However, these cell types are considered resistant to killing by LT. Here we show that LT kills primary human DCs in

  4. 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...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  7. 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

  8. Lipids in salicylic acid-mediated defense in plants: focusing on the roles of phosphatidic acid and phosphatidylinositol 4-phosphate

    PubMed Central

    Zhang, Qiong; Xiao, Shunyuan

    2015-01-01

    Plants have evolved effective defense strategies to protect themselves from various pathogens. Salicylic acid (SA) is an essential signaling molecule that mediates pathogen-triggered signals perceived by different immune receptors to induce downstream defense responses. While many proteins play essential roles in regulating SA signaling, increasing evidence also supports important roles for signaling phospholipids in this process. In this review, we collate the experimental evidence in support of the regulatory roles of two phospholipids, phosphatidic acid (PA), and phosphatidylinositol 4-phosphate (PI4P), and their metabolizing enzymes in plant defense, and examine the possible mechanistic interaction between phospholipid signaling and SA-dependent immunity with a particular focus on the immunity-stimulated biphasic PA production that is reminiscent of and perhaps mechanistically connected to the biphasic reactive oxygen species (ROS) generation and SA accumulation during defense activation. PMID:26074946

  9. Is B-cell depletion still a good strategy for treating immune thrombocytopenia?

    PubMed

    Godeau, Bertrand; Stasi, Roberto

    2014-04-01

    B cells play an important role in the pathophysiology of immune thrombocytopenia (ITP). Thus, a rational approach to ITP treatment involves B-cell depletion such as with rituximab. More than 10 years after the first reports of data suggesting that anti-CD20 MoAbs could be effective treatment for ITP, we have now a clear view of its efficacy, with an overall response in about 60% of patients. The report of fatal opportunistic infections was initially a matter of concern, but to date, reassuring data have been reported and rituximab appears well tolerated with an acceptable risk of infection. In view of these data, rituximab may always be a valid option for ITP. However, relapses are frequent, and the long-term response appears modest. Therefore, strategies to ameliorate the long-term efficacy of the treatment must be developed. Several options may be tested including giving rituximab upfront or early on after ITP diagnosis, maintenance treatment with repeated infusions, and combining rituximab with other treatments able to modulate T-cell compartment to achieve a synergistic effect. New generations of B-cell targeted treatment, including new-generations anti-CD20 MoAbs, may be also tested. PMID:24636845

  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. 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

  13. Iron in Infection and Immunity

    PubMed Central

    Cassat, James E.; Skaar, Eric P.

    2013-01-01

    Iron is an essential nutrient for both humans and pathogenic microbes. Because of its ability to exist in one of two oxidation states, iron is an ideal redox catalyst for diverse cellular processes including respiration and DNA replication. However, the redox potential of iron also contributes to its toxicity, thus iron concentration and distribution must be carefully controlled. Given the absolute requirement for iron by virtually all human pathogens, an important facet of the innate immune system is to limit iron availability to invading microbes in a process termed nutritional immunity. Successful human pathogens must therefore possess mechanisms to circumvent nutritional immunity in order to cause disease. In this review, we discuss regulation of iron metabolism in the setting of infection and delineate strategies used by human pathogens to overcome iron-withholding defenses. PMID:23684303

  14. 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

  15. Mimicking microbial 'education' of the immune system: a strategy to revert the epidemic trend of atopy and allergic asthma?

    PubMed Central

    Matricardi, Paolo Maria; Bonini, Sergio

    2000-01-01

    Deficient microbial stimulation of the immune system, caused by hygiene, may underly the atopy and allergic asthma epidemic we are currently experiencing. Consistent with this 'hygiene hypothesis', research on immunotherapy of allergic diseases also centres on bacteria-derived molecules (eg DNA immunostimulatory sequences) as adjuvants for allergen-specific type 1 immune responses. If we understood how certain microbes physiologically 'educate' our immune system to interact safely with environmental nonmicrobial antigens, we might be able to learn to mimic their beneficial actions. Programmed 'immunoeducation' would consist of safe administration, by the correct route, dose and timing, of those microbial stimuli that are necessary to 'train' the developing mucosal immune system and to maintain an appropriate homeostatic equilibrium between its components. Overall, this would result in a prevention of atopy that is not limited to certain specific allergens. Although such a strategy is far beyond our present potential, it may in principle revert the epidemic trend of atopy and allergic asthma without jeopardizing the fight against infectious diseases. PMID:11667975

  16. Clinical and pharmacodynamic analysis of pomalidomide dosing strategies in myeloma: impact of immune activation and cereblon targets.

    PubMed

    Sehgal, Kartik; Das, Rituparna; Zhang, Lin; Verma, Rakesh; Deng, Yanhong; Kocoglu, Mehmet; Vasquez, Juan; Koduru, Srinivas; Ren, Yan; Wang, Maria; Couto, Suzana; Breider, Mike; Hansel, Donna; Seropian, Stuart; Cooper, Dennis; Thakurta, Anjan; Yao, Xiaopan; Dhodapkar, Kavita M; Dhodapkar, Madhav V

    2015-06-25

    In preclinical studies, pomalidomide mediated both direct antitumor effects and immune activation by binding cereblon. However, the impact of drug-induced immune activation and cereblon/ikaros in antitumor effects of pomalidomide in vivo is unknown. Here we evaluated the clinical and pharmacodynamic effects of continuous or intermittent dosing strategies of pomalidomide/dexamethasone in lenalidomide-refractory myeloma in a randomized trial. Intermittent dosing led to greater tumor reduction at the cost of more frequent adverse events. Both cohorts experienced similar event-free and overall survival. Both regimens led to a distinct pattern but similar degree of mid-cycle immune activation, manifested as increased expression of cytokines and lytic genes in T and natural killer (NK) cells. Pomalidomide induced poly-functional T-cell activation, with increased proportion of coinhibitory receptor BTLA(+) T cells and Tim-3(+) NK cells. Baseline levels of ikaros and aiolos protein in tumor cells did not correlate with response or survival. Pomalidomide led to rapid decline in Ikaros in T and NK cells in vivo, and therapy-induced activation of CD8(+) T cells correlated with clinical response. These data demonstrate that pomalidomide leads to strong and rapid immunomodulatory effects involving both innate and adaptive immunity, even in heavily pretreated multiple myeloma, which correlates with clinical antitumor effects. This trial was registered at www.clinicaltrials.gov as #NCT01319422. PMID:25869284

  17. JASMONATE-TRIGGERED PLANT IMMUNITY

    PubMed Central

    Campos, Marcelo L.; Kang, Jin-Ho; Howe, Gregg A.

    2014-01-01

    The plant hormone jasmonate (JA) exerts direct control over the production of chemical defense compounds that confer resistance to a remarkable spectrum of plant-associated organisms, ranging from microbial pathogens to vertebrate herbivores. The underlying mechanism of JA-triggered immunity (JATI) can be conceptualized as a multi-stage signal transduction cascade involving: i) pattern recognition receptors (PRRs) that couple the perception of danger signals to rapid synthesis of bioactive JA; ii) an evolutionarily conserved JA signaling module that links fluctuating JA levels to changes in the abundance of transcriptional repressor proteins; and iii) activation (de-repression) of transcription factors that orchestrate the expression of myriad chemical and morphological defense traits. Multiple negative feedback loops act in concert to restrain the duration and amplitude of defense responses, presumably to mitigate potential fitness costs of JATI. The convergence of diverse plant- and non-plant-derived signals on the core JA module indicates that JATI is a general response to perceived danger. However, the modular structure of JATI may accommodate attacker-specific defense responses through evolutionary innovation of PRRs (inputs) and defense traits (outputs). The efficacy of JATI as a defense strategy is highlighted by its capacity to shape natural populations of plant attackers, as well as the propensity of plant-associated organisms to subvert or otherwise manipulate JA signaling. As both a cellular hub for integrating informational cues from the environment and a common target of pathogen effectors, the core JA module provides a focal point for understanding immune system networks and the evolution of chemical diversity in the plant kingdom. PMID:24973116

  18. Phage Anti-Immune complex Assay (PHAIA): a general strategy for noncompetitive immunodetection of small molecules

    PubMed Central

    González-Techera, A; Vanrell, L; Last, J.; Hammock, B.D; González-Sapienza, G.

    2008-01-01

    Due to their size, small molecules can not be simultaneously bound by two antibodies precluding their detection by noncompetitive two-site immunoassays, which are superior to competitive ones in terms of sensitivity, kinetics, and working range. This has prompted the development of anti-immune complex antibodies, but these are difficult to produce, and often exhibit high cross-reactivity with the unliganded primary antibody. This work demonstrates that anti-immune complex antibodies can be substituted by phage particles isolated from phage display peptide libraries. Phages bearing specific small peptide loops allowed to focus the recognition to changes in the binding area of the immune complex. The concept was tested using environmental and drug analytes; with improved sensitivity and ready adaptation into onsite formats. Peptides specific for different immune complexes can be isolated from different peptide libraries in a simple and systematic fashion allowing the rapid development of noncompetitive assays for small molecules PMID:17845007

  19. Variation in immune parameters and disease prevalence among Lesser Black-backed Gulls (Larus fuscus sp.) with different migratory strategies.

    PubMed

    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

  20. The cell wall in plant cell response to trace metals: polysaccharide remodeling and its role in defense strategy

    Microsoft Academic Search

    Magdalena Krzes?owska

    2011-01-01

    This review paper is focused predominantly on the role of the cell wall in the defense response of plants to trace metals.\\u000a It is generally known that this compartment accumulates toxic divalent and trivalent metal cations both during their uptake\\u000a by the cell from the environment and at the final stage of their sequestration from the protoplast. However, from results

  1. Immune defence, parasite evasion strategies and their relevance for ‘macroscopic phenomena’ such as virulence

    PubMed Central

    Schmid-Hempel, Paul

    2008-01-01

    The discussion of host–parasite interactions, and of parasite virulence more specifically, has so far, with a few exceptions, not focused much attention on the accumulating evidence that immune evasion by parasites is not only almost universal but also often linked to pathogenesis, i.e. the appearance of virulence. Now, the immune evasion hypothesis offers a deeper insight into the evolution of virulence than previous hypotheses. Sensitivity analysis for parasite fitness and life-history theory shows promise to generate a more general evolutionary theory of virulence by including a major element, immune evasion to prevent parasite clearance from the host. Also, the study of dose–response relationships and multiple infections should be particularly illuminating to understand the evolution of virulence. Taking into account immune evasion brings immunological processes to the core of understanding the evolution of parasite virulence and for a range of related issues such as dose, host specificity or immunopathology. The aim of this review is to highlight the mechanism underlying immune evasion and to discuss possible consequences for the evolutionary ecology analysis of host–parasite interactions. PMID:18930879

  2. MicroRNA-mediated immune modulation as a therapeutic strategy in host-implant integration.

    PubMed

    Ong, Siew-Min; Biswas, Subhra K; Wong, Siew-Cheng

    2015-07-01

    The concept of implanting an artificial device into the human body was once the preserve of science fiction, yet this approach is now often used to replace lost or damaged biological structures in human patients. However, assimilation of medical devices into host tissues is a complex process, and successful implant integration into patients is far from certain. The body's immediate response to a foreign object is immune-mediated reaction, hence there has been extensive research into biomaterials that can reduce or even ablate anti-implant immune responses. There have also been attempts to embed or coat anti-inflammatory drugs and pro-regulatory molecules onto medical devices with the aim of preventing implant rejection by the host. In this review, we summarize the key immune mediators of medical implant reaction, and we evaluate the potential of microRNAs to regulate these processes to promote wound healing, and prolong host-implant integration. PMID:26024977

  3. The Validity of the Foreign Sovereign Immunity Defense in Suits Under the Convention on the Recognition and Enforcement of Foreign Arbitral Awards

    Microsoft Academic Search

    Tara A. OBrien

    1983-01-01

    This Note examines the interrelationship between the Convention and the FISA, specifically, whether a sovereign's ratification of the Convention constitutes a waiver of immunity under section 1605(a)(1) of the FISA in actions to enforce arbitration agreements and awards. The development of sovereign immunity law in arbitration enforcement actions, pre-FISA and under the FISA's \\

  4. 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.

  5. 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...

  6. Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy?

    PubMed Central

    Behar, Samuel M.; Divangahi, Maziar; Remold, Heinz G.

    2011-01-01

    Virulent Mycobacterium tuberculosis inhibits apoptosis and triggers necrosis of host macrophages to evade innate immunity and delay the initiation of adaptive immunity. By contrast, attenuated M. tuberculosis induces macrophage apoptosis, an innate defence mechanism that reduces bacterial viability. In this Opinion article, we describe how virulent M. tuberculosis blocks production of the eicosanoid lipid mediator prostaglandin E2 (PGE2). PGE2 production by infected macrophages prevents mitochondrial damage and initiates plasma membrane repair, two processes that are crucial for preventing necrosis and inducing apoptosis. Thus, M. tuberculosis-mediated modulation of eicosanoid production determines the death modality of the infected macrophage, which in turn has a substantial impact on the outcome of infection. PMID:20676146

  7. Modeling immune intervention strategies for HIV1 infection of humans in the macaque model

    Microsoft Academic Search

    Genoveffa Franchini

    2003-01-01

    The introduction of potent antiretroviral therapy (ART) has generated hope and prospects in the management of human immunodeficiency virus-1 (HIV-1) infection. Long-term side effects of ART, however, have also indicated the limitations of this approach alone. A decade ago, immune therapy trials in HIV-1-infected individuals were performed in the absence of ART with a gp160-based vaccine [1]. At that time,

  8. Modular RADAR: An Immune System Inspired Search and Response Strategy for Distributed Systems

    Microsoft Academic Search

    Soumya Banerjee; Melanie E. Moses

    2010-01-01

    The Natural Immune System (NIS) is a distributed system that solves\\u000achallenging search and response problems while operating under constraints\\u000aimposed by physical space and resource availability. Remarkably, NIS search and\\u000aresponse times do not scale appreciably with the physical size of the animal in\\u000awhich its search is conducted. Many distributed systems are engineered to solve\\u000aanalogous problems, and

  9. 76 FR 46757 - Renewal of Department of Defense Federal Advisory Committees

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-03

    ...ability to execute U.S. defense strategy; (c) U.S. regional defense policies; and (d) any other research and analysis of topics raised by the Secretary of Defense, the Deputy Secretary or the Under Secretary of Defense (Policy)....

  10. 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

  11. New therapeutic strategy for hepatocellular carcinoma by molecular targeting agents via inhibition of cellular stress defense mechanisms.

    PubMed

    Honma, Yuichi; Harada, Masaru

    2014-12-01

    The prognosis of advanced hepatocellular carcinoma (HCC) has remained very poor.It has recently been reported that the molecular targeting agent sorafenib can improve the prognosis of patients with advanced HCC. However, the detailed mechanisms of sorafenib, especially its direct effects on hepatoma and hepatocyte cells, are poorly understood, making a more detailed investigation about the molecular mechanism of sorafenib necessary. Endoplasmic reticulum (ER) stress is related to the pathophysiology of various liver diseases, including chronic viral hepatitis, alcoholic and nonalcoholic steatohepatitis and HCC. In this regard, our recent data examining the molecular effects of sorafenib focused on the cellular defense mechanisms from ER stress, the unfolded protein response (UPR) and keratin phosphorylation, demonstrated that sorafenib inhibited both important cytoprotective mechanisms, UPR and keratin phosphorylation, and enhances the anti-tumor effect in combination with proteasome inhibitors. This review summarizes the cytoprotective mechanisms from ER stress and our results about the direct effect of sorafenib on the cytoprotective mechanisms. PMID:25501753

  12. Intranasal Immunization of Mice with a Bovine Respiratory Syncytial Virus Vaccine Induces Superior Immunity and Protection Compared to Those by Subcutaneous Delivery or Combinations of Intranasal and Subcutaneous Prime-Boost Strategies? †

    PubMed Central

    Mapletoft, John W.; Latimer, Laura; Babiuk, Lorne A.; van Drunen Littel-van den Hurk, Sylvia

    2010-01-01

    Bovine respiratory syncytial virus (BRSV) infects cells of the respiratory mucosa, so it is desirable to develop a vaccination strategy that induces mucosal immunity. To achieve this, various delivery routes were compared for formalin-inactivated (FI) BRSV formulated with CpG oligodeoxynucleotide (ODN) and polyphosphazene (PP). Intranasal delivery of the FI-BRSV formulation was superior to subcutaneous delivery in terms of antibody, cell-mediated, and mucosal immune responses, as well as reduction in virus replication after BRSV challenge. Although intranasal delivery of FI-BRSV also induced higher serum and lung antibody titers and gamma interferon (IFN-?) production in the lungs than intranasal-subcutaneous and/or subcutaneous-intranasal prime-boost strategies, no significant differences were observed in cell-mediated immune responses or virus replication in the lungs of challenged mice. Interleukin 5 (IL-5), eotaxin, and eosinophilia were enhanced after BRSV challenge in the lungs of subcutaneously immunized mice compared to unvaccinated mice, but not in the lungs of mice immunized intranasally or through combinations of the intranasal and subcutaneous routes. These results suggest that two intranasal immunizations with FI-BRSV formulated with CpG ODN and PP are effective and safe as an approach to induce systemic and mucosal responses, as well to reduce virus replication after BRSV challenge. Furthermore, intranasal-subcutaneous and subcutaneous-intranasal prime-boost strategies were also safe and almost as efficacious. In addition to the implications for the development of a protective BRSV vaccine for cattle, formulation with CpG ODN and PP could also prove important in the development of a mucosal vaccine that induces protective immunity against human RSV. PMID:19864487

  13. 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

  14. Fighting a Losing Battle: Vigorous Immune Response Countered by Pathogen Suppression of Host Defenses in the Chytridiomycosis-Susceptible Frog Atelopus zeteki

    PubMed Central

    Ellison, Amy R.; Savage, Anna E.; DiRenzo, Grace V.; Langhammer, Penny; Lips, Karen R.; Zamudio, Kelly R.

    2014-01-01

    The emergence of the disease chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd) has been implicated in dramatic global amphibian declines. Although many species have undergone catastrophic declines and/or extinctions, others appear to be unaffected or persist at reduced frequencies after Bd outbreaks. The reasons behind this variance in disease outcomes are poorly understood: differences in host immune responses have been proposed, yet previous studies suggest a lack of robust immune responses to Bd in susceptible species. Here, we sequenced transcriptomes from clutch-mates of a highly susceptible amphibian, Atelopus zeteki, with different infection histories. We found significant changes in expression of numerous genes involved in innate and inflammatory responses in infected frogs despite high susceptibility to chytridiomycosis. We show evidence of acquired immune responses generated against Bd, including increased expression of immunoglobulins and major histocompatibility 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

  15. Plant immunity to insect herbivores.

    PubMed

    Howe, Gregg A; Jander, Georg

    2008-01-01

    Herbivorous insects use diverse feeding strategies to obtain nutrients from their host plants. Rather than acting as passive victims in these interactions, plants respond to herbivory with the production of toxins and defensive proteins that target physiological processes in the insect. Herbivore-challenged plants also emit volatiles that attract insect predators and bolster resistance to future threats. This highly dynamic form of immunity is initiated by the recognition of insect oral secretions and signals from injured plant cells. These initial cues are transmitted within the plant by signal transduction pathways that include calcium ion fluxes, phosphorylation cascades, and, in particular, the jasmonate pathway, which plays a central and conserved role in promoting resistance to a broad spectrum of insects. A detailed understanding of plant immunity to arthropod herbivores will provide new insights into basic mechanisms of chemical communication and plant-animal coevolution and may also facilitate new approaches to crop protection and improvement. PMID:18031220

  16. 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

  17. Enhancing artificial bee colony algorithm with self-adaptive searching strategy and artificial immune network operators for global optimization.

    PubMed

    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

  18. 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

  19. Immunotherapy for Alzheimer's disease: from anti-?-amyloid to tau-based immunization strategies.

    PubMed

    Panza, Francesco; Frisardi, Vincenza; Solfrizzi, Vincenzo; Imbimbo, Bruno P; Logroscino, Giancarlo; Santamato, Andrea; Greco, Antonio; Seripa, Davide; Pilotto, Alberto

    2012-02-01

    The exact mechanisms leading to Alzheimer's disease (AD) are largely unknown, limiting the identification of effective disease-modifying therapies. The two principal neuropathological hallmarks of AD are extracellular ?-amyloid (A?), peptide deposition (senile plaques) and intracellular neurofibrillary tangles containing hyperphosphorylated tau protein. During the last decade, most of the efforts of the pharmaceutical industry were directed against the production and accumulation of A?. The most innovative of the pharmacological approaches was the stimulation of A? clearance from the brain of AD patients via the administration of A? antigens (active vaccination) or anti-A? antibodies (passive vaccination). Several active and passive anti-A? vaccines are under clinical investigation. Unfortunately, the first active vaccine (AN1792, consisting of preaggregate A? and an immune adjuvant, QS-21) was abandoned because it caused meningoencephalitis in approximately 6% of treated patients. Anti-A? monoclonal antibodies (bapineuzumab and solanezumab) are now being developed. The clinical results of the initial studies with bapineuzumab were equivocal in terms of cognitive benefit. The occurrence of vasogenic edema after bapineuzumab, and more rarely brain microhemorrhages (especially in Apo E ?4 carriers), has raised concerns on the safety of these antibodies directed against the N-terminus of the A? peptide. Solanezumab, a humanized anti-A? monoclonal antibody directed against the midregion of the A? peptide, was shown to neutralize soluble A? species. Phase II studies showed a good safety profile of solanezumab, while studies on cerebrospinal and plasma biomarkers documented good signals of pharmacodynamic activity. Although some studies suggested that active immunization may be effective against tau in animal models of AD, very few studies regarding passive immunization against tau protein are currently available. The results of the large, ongoing Phase III trials with bapineuzumab and solanezumab will tell us if monoclonal anti-A? antibodies may slow down the rate of deterioration of AD. Based on the new diagnostic criteria of AD and on recent major failures of anti-A? drugs in mild-to-moderate AD patients, one could argue that clinical trials on potential disease-modifying drugs, including immunological approaches, should be performed in the early stages of AD. PMID:22339463

  20. Structure comparison of human glioma pathogenesis-related protein GliPR and the plant pathogenesis-related protein P14a indicates a functional link between the human immune system and a plant defense system.

    PubMed

    Szyperski, T; Fernández, C; Mumenthaler, C; Wüthrich, K

    1998-03-01

    The human glioma pathogenesis-related protein (GliPR) is highly expressed in the brain tumor glioblastoma multiforme and exhibits 35% amino acid sequence identity with the tomato pathogenesis-related (PR) protein P14a, which has an important role for the plant defense system. A molecular model of GliPR was computed with the distance geometry program DIANA on the basis of a P14a-GliPR sequence alignment and a set of 1,200 experimental NMR conformational constraints collected with P14a. The GliPR structure is represented by a group of 20 conformers with small residual DIANA target function values, low AMBER-energies after restrained energy-minimization with the program OPAL, and an average rms deviation relative to the mean of 1.6 A for the backbone heavy atoms. Comparison of the GliPR model with the P14a structure lead to the identification of a common partially solvent-exposed spatial cluster of four amino acid residues, His-69, Glu-88, Glu-110, and His-127 in the GliPR numeration. This cluster is conserved in all known plant PR proteins of class 1, indicating a common putative active site for GliPR and PR-1 proteins and thus a functional link between the human immune system and a plant defense system. PMID:9482873

  1. 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…

  2. A concept for strategic cyber defense

    Microsoft Academic Search

    Walt Tirenin; Don Faatz

    1999-01-01

    This paper discusses the meaning and challenges of strategic cyber defense (SCD), and some possible strategies for dealing with these challenges. The purpose is to describe and codify the DARPA Information Assurance (IA) program's conceptual framework for defensive techniques in the cyber realm. The focus in the IA program is on cyber defense techniques for threats which are postulated to

  3. The Price of Defense Marios Mavronicolas

    E-print Network

    Mavronicolas, Marios

    The Price of Defense Marios Mavronicolas Loizos Michael Vicky Papadopoulou Anna Philippou Paul deviate from its randomized strategy. The Price of Defense is the worst-case ratio, over all Nash equilibrium. In this work, we provide a comprehensive collection of trade-offs between the Price of Defense

  4. The costs, effects and cost-effectiveness of strategies to increase coverage of routine immunizations in low- and middle- income countries: systematic review of the grey literature

    Microsoft Academic Search

    Katherine Batt; J. A. Fox-Rushby; Marianela Castillo-Riquelme

    2004-01-01

    Evidence-based reviews of published literature can be subject to several biases. Grey literature, however, can be of poor quality and expensive to access. Effective search strategies also vary by topic and are rarely known in advance. This paper complements a systematic review of the published literature on the costs and effects of expanding immunization services in developing countries. The quality

  5. A Heterologous DNA Priming-Mycobacterium bovis BCG Boosting Immunization Strategy Using Mycobacterial Hsp70, Hsp65, and Apa Antigens Improves Protection against Tuberculosis in Mice

    Microsoft Academic Search

    Jose C. Ferraz; Evangelos Stavropoulos; Min Yang; Steve Coade; Clara Espitia; Douglas B. Lowrie; M. Joseph Colston; Ricardo E. Tascon

    2004-01-01

    Tuberculosis is responsible for >2 million deaths a year, and the number of new cases is rising worldwide. DNA vaccination combined with Mycobacterium bovis bacillus Calmette Guerin (BCG) represents a potential strategy for prevention of this disease. Here, we used a heterologous prime-boost immunization approach using a combination of DNA plasmids and BCG in order to improve the efficacy of

  6. 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

  7. New Strategies for Overcoming Limitations of Mesenchymal Stem Cell-Based Immune Modulation

    PubMed Central

    Kim, Nayoun; Cho, Seok-Goo

    2015-01-01

    Mesenchymal stem cells (MSCs) have rapidly been applied in a broad field of immune-mediated disorders since the first successful clinical use of MSCs for treatment of graft-versus-host disease. Despite the lack of supporting data, expectations that MSCs could potentially treat most inflammatory conditions led to rushed application and development of commercialized products. Today, both pre-clinical and clinical studies present mixed results for MSC therapy and the discrepancy between expected and actual efficacy of MSCs in various diseases has evoked a sense of discouragement. Therefore, we believe that MSC therapy may now be at a critical milestone for re-evaluation and re-consideration. In this review, we summarize the current status of MSC-based clinical trials and focus on the discrepancy between expected and actual outcome of MSC therapy from bench to bedside. Importantly, we discuss the underlying limitations of MSCs and suggest a new guideline for MSC therapy in hopes of improving their therapeutic efficacy. PMID:26019755

  8. Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression

    SciTech Connect

    Kimberlin, Christopher R.; Bornholdt, Zachary A.; Li, Sheng; Woods, Jr., Virgil L.; MacRae, Ian J.; Saphire, Erica Ollmann (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.

  9. 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

  10. The Role of Autophagy in Chloroplast Degradation and Chlorophagy in Immune Defenses during Pst DC3000 (AvrRps4) Infection

    PubMed Central

    Dong, Junjian; Chen, Wenli

    2013-01-01

    Background Chlorosis of leaf tissue normally observed during pathogen infection may result from the degradation of chloroplasts. There is a growing evidence to suggest that the chloroplast plays a significant role during pathogen infection. Although most degradation of the organelles and cellular structures in plants is mediated by autophagy, its role in chloroplast catabolism during pathogen infection is largely unknown. Results In this study, we investigated the function of autophagy in chloroplast degradation during avirulent Pst DC3000 (AvrRps4) infection. We examined the expression of defensive marker genes and suppression of bacterial growth using the electrolyte leakage assay in normal light (N) and low light (L) growing environments of wild-type and atg5-1 plants during pathogen treatment. Stroma-targeted GFP proteins (CT-GFP) were observed with LysoTracker Red (LTR) staining of autophagosome-like structures in the vacuole. The results showed that Arabidopsis expressed a significant number of small GFP-labeled bodies when infected with avirulent Pst DC3000 (AvrRps4). While barely detectable, there were small GFP-labeled bodies in plants with the CT-GFP expressing atg5-1 mutation. The results showed that chloroplast degradation depends on autophagy and this may play an important role in inhibiting pathogen growth. Conclusion Autophagy plays a role in chloroplast degradation in Arabidopsis during avirulent Pst DC3000 (AvrRps4) infection. Autophagy dependent chloroplast degradation may be the primary source of reactive oxygen species (ROS) as well as the pathogen-response signaling molecules that induce the defense response. PMID:24023671

  11. Transcriptional networks in plant immunity.

    PubMed

    Tsuda, Kenichi; Somssich, Imre E

    2015-05-01

    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

  12. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system

    PubMed Central

    Pelaseyed, Thaher; Bergström, Joakim H.; Gustafsson, Jenny K.; Ermund, Anna; Birchenough, George M. H.; Schütte, André; van der Post, Sjoerd; Svensson, Frida; Rodríguez-Piñeiro, Ana M.; Nyström, Elisabeth E.L.; Wising, Catharina; Johansson, Malin E.V.; Hansson, Gunnar C.

    2014-01-01

    Summary The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine and colon. The large highly glycosylated gel-forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine mucus limits the number of bacteria that can reach the epithelium and the Peyer’s patches. In the large intestine the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells not only secrete the MUC2 mucin, but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate-keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103+-type. In addition to the gel forming mucins, the transmembrane mucins MUC3, MUC12 and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization suggesting that enterocytes might control and report epithelial microbial challenge. There is not only communication from the epithelial cells to the immune system, but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy. PMID:24942678

  13. 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

  14. Innate Immune Responses in Hepatitis C Virus Infection1

    PubMed Central

    Li, Kui; Lemon, Stanley M.

    2013-01-01

    Hepatitis C virus (HCV) is a major causative agent of chronic hepatitis and hepatocellular carcinoma worldwide and thus poses a significant public health threat. A hallmark of HCV infection is the extraordinary ability of the virus to persist in a majority of infected people. Innate immune responses represent the front line of defense of the human body against HCV immediately after infection. They also play a crucial role in orchestrating subsequent HCV-specific adaptive immunity that is pivotal for viral clearance. Accumulating evidence suggests that the host has evolved multifaceted innate immune mechanisms to sense HCV infection and elicit defense responses, while HCV has developed elaborate strategies to circumvent many of these. Defining the interplay of HCV with host innate immunity reveals mechanistic insights into hepatitis C pathogenesis and informs approaches to therapy. In this review, we summarize recent advances in understanding innate immune responses to HCV infection, focusing on induction and effector mechanisms of the interferon antiviral response as well as the evasion strategies of HCV. PMID:22868377

  15. 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

  16. The Design of an Artificial Immune System

    Microsoft Academic Search

    Purui Su; Dengguo Feng

    2006-01-01

    Nature immune system is an excellent defense system. Inspired by the two immune response mechanisms of nature immune system, a new design of an artificial immune system-COMUS-has been brought forward. COMUS mainly comprises of two parts: PIRM and SIRM. It could detect both known and unknown intrusions. And it could automatically extract signatures for the abnormalities which have not been

  17. 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

  18. Adenosine signaling and the energetic costs of induced immunity.

    PubMed

    Lazzaro, Brian P

    2015-04-01

    Life history theory predicts that trait evolution should be constrained by competing physiological demands on an organism. Immune defense provides a classic example in which immune responses are presumed to be costly and therefore come at the expense of other traits related to fitness. One strategy for mitigating the costs of expensive traits is to render them inducible, such that the cost is paid only when the trait is utilized. In the current issue of PLOS Biology, Bajgar and colleagues elegantly demonstrate the energetic and life history cost of the immune response that Drosophila melanogaster larvae induce after infection by the parasitoid wasp Leptopilina boulardi. These authors show that infection-induced proliferation of defensive blood cells commands a diversion of dietary carbon away from somatic growth and development, with simple sugars instead being shunted to the hematopoetic organ for rapid conversion into the raw energy required for cell proliferation. This metabolic shift results in a 15% delay in the development of the infected larva and is mediated by adenosine signaling between the hematopoietic organ and the central metabolic control organ of the host fly. The adenosine signal thus allows D. melanogaster to rapidly marshal the energy needed for effective defense and to pay the cost of immunity only when infected. PMID:25915419

  19. 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

  20. Implementing the Defense Message System

    Microsoft Academic Search

    G. B. Meyrick; S. M. McDermott

    1995-01-01

    Upon final award of the Defense Message System (DMS) contract, a vast implementation effort will be initiated to deploy DMS-compliant messaging to more than 1.5 million Department of Defense (DoD) users. The implementation strategy for this large deployment calls for fielding the capability in several increments. Initial deployment will be limited to sensitive-but-unclassified message traffic, with support for classified messaging

  1. Network modeling to understand plant immunity.

    PubMed

    Windram, Oliver; Penfold, Christopher A; Denby, Katherine J

    2014-01-01

    Deciphering the networks that underpin complex biological processes using experimental data remains a significant, but promising, challenge, a task made all the harder by the added complexity of host-pathogen interactions. The aim of this article is to review the progress in understanding plant immunity made so far by applying network modeling algorithms and to show how this computational/mathematical strategy is facilitating a systems view of plant defense. We review the different types of network modeling that have been used, the data required, and the type of insight that such modeling can provide. We discuss the current challenges in modeling the regulatory networks that underlie plant defense and the future developments that may help address these challenges. PMID:24821185

  2. Mimicking microbial 'education' of the immune system: a strategy to revert the epidemic trend of atopy and allergic asthma?

    Microsoft Academic Search

    Paolo Maria Matricardi; Sergio Bonini

    2000-01-01

    Deficient microbial stimulation of the immune system, caused by hygiene, may underly the atopy and allergic asthma epidemic\\u000a we are currently experiencing. Consistent with this 'hygiene hypothesis', research on immunotherapy of allergic diseases also\\u000a centres on bacteria-derived molecules (eg DNA immunostimulatory sequences) as adjuvants for allergen-specific type 1 immune\\u000a responses. If we understood how certain microbes physiologically 'educate' our immune

  3. The Quadrennial Defense Review: May 1997

    NSDL National Science Digital Library

    Cohen, William S.

    1998-01-01

    On May 19, 1997, as mandated by the National Defense Authorization Act of 1996, US Secretary of Defense William S. Cohen presented the Quadrennial Defense Review to Congress. This site contains the May 19 Defense Department news release and briefing (along with slides), the text of the report, and the legislation mandating it. The report is composed of ten sections ranging from "The Global Security Environment" to "Force Readiness" to "Achieving a 21st Century Defense Infrastructure." However, its thrust can be ascertained from a single statement by the Secretary: "The strategy devised through the QDR can be summed up in three words: shape, respond, and prepare."

  4. The CAP superfamily: cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins--roles in reproduction, cancer, and immune defense.

    PubMed

    Gibbs, Gerard M; Roelants, Kim; O'Bryan, Moira K

    2008-12-01

    The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily members are found in a remarkable range of organisms spanning each of the animal kingdoms. Within humans and mice, there are 31 and 33 individual family members, respectively, and although many are poorly characterized, the majority show a notable expression bias to the reproductive tract and immune tissues or are deregulated in cancers. CAP superfamily proteins are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumor suppressor or prooncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilization. This review describes mammalian CAP superfamily gene expression profiles, phylogenetic relationships, protein structural properties, and biological functions, and it draws into focus their potential role in health and disease. The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. We conclude that overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters target specificity and, therefore, the biological consequences. PMID:18824526

  5. Heteropentameric Cholera Toxin B Subunit Chimeric Molecules Genetically Fused to a Vaccine Antigen Induce Systemic and Mucosal Immune Responses: a Potential New Strategy To Target Recombinant Vaccine Antigens to Mucosal Immune Systems

    PubMed Central

    Harakuni, Tetsuya; Sugawa, Hideki; Komesu, Ai; Tadano, Masayuki; Arakawa, Takeshi

    2005-01-01

    Noninvasive mucosal vaccines are attractive alternatives to parenteral vaccines. Although the conjugation of vaccine antigens with the B subunit of cholera toxin (CTB) is one of the most promising strategies for vaccine delivery to mucosal immune systems, the molecule cannot tolerate large-protein fusion, as it severely impairs pentamerization and loses affinity for GM1-ganglioside. Here we report a new strategy, in which steric hindrance between CTB-antigen fusion subunits is significantly reduced through the integration of unfused CTB “molecular buffers” into the pentamer unit, making them more efficiently self-assemble into biologically active pentamers. In addition, the chimeric protein took a compact configuration, becoming small enough to be secreted, and one-step affinity-purified proteins, when administered through a mucosal route, induced specific immune responses in mice. Since our results are not dependent on the use of a particular expression system or vaccine antigen, this strategy could be broadly applicable to bacterial enterotoxin-based vaccine design. PMID:16113283

  6. 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

  7. Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Wang, Rong; Zhang, Yan-Jin

    2014-01-01

    Interferons (IFNs) are important components in innate immunity involved in the first line of defense to protect host against viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) leads to severe economic losses for swine industry since being first identified in early 1990s. PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. PRRSV encodes several proteins that act as antagonists for the IFN signaling. In this review, we summarized the various strategies used by PRRSV to antagonize IFN production and thwart IFN-activated antiviral signaling, as well as the variable interference with IFN-mediated immune response by different PRRSV strains. Thorough understanding of the interaction between PRRSV and host innate immune response will facilitate elucidation of PRRSV pathogenesis and development of a better strategy to control PRRS. PMID:25101271

  8. Bacteria Fighting Back – How Pathogens Target and Subvert the Host Innate Immune System

    PubMed Central

    Reddick, L. Evan; Alto, Neal M.

    2014-01-01

    The innate immune system has evolved under selective pressure since the radiation of multicellular life approximately six hundred million years ago. Because of this long history, innate immune mechanisms found in modern eukaryotic organisms today are highly complex, yet are built from common molecular strategies. It is now clear that evolution has selected a conserved set of anti-microbial peptides as well as Pattern Recognition Receptors (PRRs) that initiate cellular-based signals as a first line of defense against invading pathogens. Conversely, microbial pathogens employ their own strategies to evade, inhibit, or otherwise manipulate the innate immune response. Here, we discuss recent discoveries that have changed our view of immune modulatory mechanisms employed by bacterial pathogens, focusing specifically on the initial sites of microbial recognition and extending to host cellular signal transduction, pro-inflammatory cytokine production, and alteration of protein trafficking and secretion. PMID:24766896

  9. 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

  10. Signature Patterns of MHC Diversity in Three Gombe Communities of Wild Chimpanzees Reflect Fitness in Reproduction and Immune Defense against SIVcpz

    PubMed Central

    Wroblewski, Emily E.; Norman, Paul J.; Guethlein, Lisbeth A.; Rudicell, Rebecca S.; Ramirez, Miguel A.; Li, Yingying; Hahn, Beatrice H.; Pusey, Anne E.; Parham, Peter

    2015-01-01

    Major histocompatibility complex (MHC) class I molecules determine immune responses to viral infections. These polymorphic cell-surface glycoproteins bind peptide antigens, forming ligands for cytotoxic T and natural killer cell receptors. Under pressure from rapidly evolving viruses, hominoid MHC class I molecules also evolve rapidly, becoming diverse and species-specific. Little is known of the impact of infectious disease epidemics on MHC class I variant distributions in human populations, a context in which the chimpanzee is the superior animal model. Population dynamics of the chimpanzees inhabiting Gombe National Park, Tanzania have been studied for over 50 years. This population is infected with SIVcpz, the precursor of human HIV-1. Because HLA-B is the most polymorphic human MHC class I molecule and correlates strongly with HIV-1 progression, we determined sequences for its ortholog, Patr-B, in 125 Gombe chimpanzees. Eleven Patr-B variants were defined, as were their frequencies in Gombe’s three communities, changes in frequency with time, and effect of SIVcpz infection. The growing populations of the northern and central communities, where SIVcpz is less prevalent, have stable distributions comprising a majority of low-frequency Patr-B variants and a few high-frequency variants. Driving the latter to high frequency has been the fecundity of immigrants to the northern community, whereas in the central community, it has been the fecundity of socially dominant individuals. In the declining population of the southern community, where greater SIVcpz prevalence is associated with mortality and emigration, Patr-B variant distributions have been changing. Enriched in this community are Patr-B variants that engage with natural killer cell receptors. Elevated among SIVcpz-infected chimpanzees, the Patr-B*06:03 variant has striking structural and functional similarities to HLA-B*57, the human allotype most strongly associated with delayed HIV-1 progression. Like HLA-B*57, Patr-B*06:03 correlates with reduced viral load, as assessed by detection of SIVcpz RNA in feces. PMID:26020813

  11. 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

  12. Innate immune sensing and response to influenza.

    PubMed

    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 immunocompromised 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

  13. 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

  14. 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.

  15. 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

  16. THESIS DEFENSE REPORT FORM Defense Date

    E-print Network

    Yates, Andrew

    THESIS DEFENSE REPORT FORM Defense Date: Student: Department: Dissertation Title: Please hand: (718) 430-8655 Committee Member Decision Signature P CP F (Chair) The decision of the Thesis Defense' on the scientific merit of the Thesis Defense and the Dissertation, but with substantial revisions. If someone other

  17. DEPUTY SECRETARY OF DEFENSE 1010 DEFENSE PENTAGON

    E-print Network

    US Army Corps of Engineers

    DEPUTY SECRETARY OF DEFENSE 1010 DEFENSE PENTAGON WASHINGTON, DC 20301-1010 JAN 10 2013 MEMORANDUM FOR SECRETARIES OF THE MILITARY DEPARTMENTS CHAIRMAN OF THE JOINT CHIEFS OF STAFF UNDER SECRETARIES OF DEFENSE TEST AND EVALUATION GENERAL COUNSEL OF THE DEPARTMENT OF DEFENSE INSPECTOR GENERAL OF THE DEPARTMENT

  18. ASSISTANT SECRETARY OF DEFENSE 4000 DEFENSE PENTAGON

    E-print Network

    US Army Corps of Engineers

    ASSISTANT SECRETARY OF DEFENSE 4000 DEFENSE PENTAGON WASHINGTON, D.C. 20301-4000 READINESS Force Management Reference: (a) Secretary ofDefense Memorandum, "Furloughs", dated 14 May 2013 The Secretary of Defense, per reference (a), directed civilian furloughs beginning July 8, 2013. Reference (a

  19. THESIS DEFENSE REPORT FORM Defense Date

    E-print Network

    Jenny, Andreas

    THESIS DEFENSE REPORT FORM Defense Date: Student: Department: Dissertation Title: Please hand: (718) 430-8655 Committee Member Decision Signature P CP F (Chair) The decision of the Thesis Defense' on the scientific merit of the thesis defense and the dissertation, but with substantial reservation. The candidate

  20. Pathogenicity of and plant immunity to soft rot pectobacteria

    PubMed Central

    Davidsson, Pär R.; Kariola, Tarja; Niemi, Outi; Palva, E. T.

    2013-01-01

    Soft rot pectobacteria are broad host range enterobacterial pathogens that cause disease on a variety of plant species including the major crop potato. Pectobacteria are aggressive necrotrophs that harbor a large arsenal of plant cell wall-degrading enzymes as their primary virulence determinants. These enzymes together with additional virulence factors are employed to macerate the host tissue and promote host cell death to provide nutrients for the pathogens. In contrast to (hemi)biotrophs such as Pseudomonas, type III secretion systems (T3SS) and T3 effectors do not appear central to pathogenesis of pectobacteria. Indeed, recent genomic analysis of several Pectobacterium species including the emerging pathogen Pectobacterium wasabiae has shown that many strains lack the entire T3SS as well as the T3 effectors. Instead, this analysis has indicated the presence of novel virulence determinants. Resistance to broad host range pectobacteria is complex and does not appear to involve single resistance genes. Instead, activation of plant innate immunity systems including both SA (salicylic acid) and JA (jasmonic acid)/ET (ethylene)-mediated defenses appears to play a central role in attenuation of Pectobacterium virulence. These defenses are triggered by detection of pathogen-associated molecular patterns (PAMPs) or recognition of modified-self such as damage-associated molecular patterns (DAMPs) and result in enhancement of basal immunity (PAMP/DAMP-triggered immunity or pattern-triggered immunity, PTI). In particular plant cell wall fragments released by the action of the degradative enzymes secreted by pectobacteria are major players in enhanced immunity toward these pathogens. Most notably bacterial pectin-degrading enzymes release oligogalacturonide (OG) fragments recognized as DAMPs activating innate immune responses. Recent progress in understanding OG recognition and signaling allows novel genetic screens for OG-insensitive mutants and will provide new insights into plant defense strategies against necrotrophs such as pectobacteria. PMID:23781227

  1. Screening the fruitfly immune system

    Microsoft Academic Search

    Marc S Dionne; David S Schneider

    2002-01-01

    The anti-microbial defense system of Drosophila shows functional similarities with the vertebrate innate immune system. Two recent gene-expression profiling studies of fruitflies challenged with infectious agents have identified key molecular players in the fruitfly's response to bacterial and fungal infection, as well as a large number of immune-regulated genes with unknown immunological function.

  2. 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.

  3. Vpu-Deficient HIV Strains Stimulate Innate Immune Signaling Responses in Target Cells

    PubMed Central

    Doehle, Brian P.; Chang, Kristina; Fleming, Lamar; McNevin, John; Hladik, Florian; McElrath, M. Juliana

    2012-01-01

    Acute virus infection induces a cell-intrinsic innate immune response comprising our first line of immunity to limit virus replication and spread, but viruses have developed strategies to overcome these defenses. HIV-1 is a major public health problem; however, the virus-host interactions that regulate innate immune defenses against HIV-1 are not fully defined. We have recently identified the viral protein Vpu to be a key determinant responsible for HIV-1 targeting and degradation of interferon regulatory factor 3 (IRF3), a central transcription factor driving host cell innate immunity. IRF3 plays a major role in pathogen recognition receptor (PRR) signaling of innate immunity to drive the expression of type I interferon (IFN) and interferon-stimulated genes (ISGs), including a variety of HIV restriction factors, that serve to limit viral replication directly and/or program adaptive immunity. Here we interrogate the cellular responses to target cell infection with Vpu-deficient HIV-1 strains. Remarkably, in the absence of Vpu, HIV-1 triggers a potent intracellular innate immune response that suppresses infection. Thus, HIV-1 can be recognized by PRRs within the host cell to trigger an innate immune response, and this response is unmasked only in the absence of Vpu. Vpu modulation of IRF3 therefore prevents virus induction of specific innate defense programs that could otherwise limit infection. These observations show that HIV-1 can indeed be recognized as a pathogen in infected cells and provide a novel and effective platform for defining the native innate immune programs of target cells of HIV-1 infection. PMID:22647704

  4. THE UNDER SECRETARY OF DEFENSE 301 0 DEFENSE PENTAGON

    E-print Network

    US Army Corps of Engineers

    0 TECHNOLOGY AND LOGISTICS MEMORANDUM FOR: SEE DISTRIBUTION SUBJECT: FY 2012 Depaitment of Defense INTELLIGENCE AGENCY DIRECTOR, DEFENSE INSPECTOR GENERAL DIRECTOR, DEFENSE LOGISTICS AGENCY DIRECTOR, DEFENSE SECURITY COOPERATION AGENCY DIRECTOR, DEFENSE THREAT REDUCTION AGENCY DIRECTOR, MISSILE DEFENSE AGENCY

  5. CRISPR/Cas, the immune system of bacteria and archaea.

    PubMed

    Horvath, Philippe; Barrangou, Rodolphe

    2010-01-01

    Microbes rely on diverse defense mechanisms that allow them to withstand viral predation and exposure to invading nucleic acid. In many Bacteria and most Archaea, clustered regularly interspaced short palindromic repeats (CRISPR) form peculiar genetic loci, which provide acquired immunity against viruses and plasmids by targeting nucleic acid in a sequence-specific manner. These hypervariable loci take up genetic material from invasive elements and build up inheritable DNA-encoded immunity over time. Conversely, viruses have devised mutational escape strategies that allow them to circumvent the CRISPR/Cas system, albeit at a cost. CRISPR features may be exploited for typing purposes, epidemiological studies, host-virus ecological surveys, building specific immunity against undesirable genetic elements, and enhancing viral resistance in domesticated microbes. PMID:20056882

  6. Towards a Balanced and Sustainable Defense

    Microsoft Academic Search

    F. G. Hoffman

    2009-01-01

    Secretary of Defense Robert Gates defines “balance” as the critical principle of his defense strategy. This emphasizes achieving a balance between current conflicts and dangerous and more conventional wars in the future. But finding the right balance between types of war is only one form of balance. We also need to balance the nation's checkbook, and define the balance between

  7. Brassinosteroids Antagonize Gibberellin- and Salicylate-Mediated Root Immunity in Rice1[C][W][OA

    PubMed Central

    De Vleesschauwer, David; Van Buyten, Evelien; Satoh, Kouji; Balidion, Johny; Mauleon, Ramil; Choi, Il-Ryong; Vera-Cruz, Casiana; Kikuchi, Shoshi; Höfte, Monica

    2012-01-01

    Brassinosteroids (BRs) are a unique class of plant steroid hormones that orchestrate myriad growth and developmental processes. Although BRs have long been known to protect plants from a suite of biotic and abiotic stresses, our understanding of the underlying molecular mechanisms is still rudimentary. Aiming to further decipher the molecular logic of BR-modulated immunity, we have examined the dynamics and impact of BRs during infection of rice (Oryza sativa) with the root oomycete Pythium graminicola. Challenging the prevailing view that BRs positively regulate plant innate immunity, we show that P. graminicola exploits BRs as virulence factors and hijacks the rice BR machinery to inflict disease. Moreover, we demonstrate that this immune-suppressive effect of BRs is due, at least in part, to negative cross talk with salicylic acid (SA) and gibberellic acid (GA) pathways. BR-mediated suppression of SA defenses occurred downstream of SA biosynthesis, but upstream of the master defense regulators NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 and OsWRKY45. In contrast, BR alleviated GA-directed immune responses by interfering at multiple levels with GA metabolism, resulting in indirect stabilization of the DELLA protein and central GA repressor SLENDER RICE1 (SLR1). Collectively, these data favor a model whereby P. graminicola coopts the plant BR pathway as a decoy to antagonize effectual SA- and GA-mediated defenses. Our results highlight the importance of BRs in modulating plant immunity and uncover pathogen-mediated manipulation of plant steroid homeostasis as a core virulence strategy. PMID:22353574

  8. B cells and antibodies in the defense against Mycobacterium tuberculosis infection.

    PubMed

    Achkar, Jacqueline M; Chan, John; Casadevall, Arturo

    2015-03-01

    Better understanding of the immunological components and their interactions necessary to prevent or control Mycobacterium tuberculosis (Mtb) infection in humans is critical for tuberculosis (TB) vaccine development strategies. Although the contributory role of humoral immunity in the protection against Mtb infection and disease is less defined than the role of T cells, it has been well-established for many other intracellular pathogens. Here we update and discuss the increasing evidence and the mechanisms of B cells and antibodies in the defense against Mtb infection. We posit that B cells and antibodies have a variety of potential protective roles at each stage of Mtb infection and postulate that such roles should be considered in the development strategies for TB vaccines and other immune-based interventions. PMID:25703559

  9. Doctoral Defense "Sustainable Wastewater Management

    E-print Network

    Kamat, Vineet R.

    Doctoral Defense "Sustainable Wastewater Management: Modeling and Decision Strategies for Unused Medications and Wastewater Solids" Sherri Cook Date: May 22, 2014 Time: 11:00 AM Location: 2355 GGB Chair to help decision-makers evaluate new practices for sustainable wastewater management. To this end

  10. Agent Applications in Defense Logistics

    Microsoft Academic Search

    Todd Carrico; Mark Greaves

    During World War II, US Military logistics was the envy of the world. By Desert Storm \\/ Desert Shield, overwhelming mass had\\u000a become the supply strategy of the day. In the years following Desert Storm, the military set out to reinvent its logistics\\u000a strategy through Focused Logistics and the Defense Advanced Research Projects Agency (DARPA) was charged with developing the

  11. 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

  12. Effects of kefir fractions on innate immunity

    Microsoft Academic Search

    Gabriel Vinderola; Gabriela Perdigon; Jairo Duarte; Deepa Thangavel; Edward Farnworth; Chantal Matar

    2006-01-01

    Innate immunity that protects against pathogens in the tissues and circulation is the first line of defense in the immune reaction, where macrophages have a critical role in directing the fate of the infection. We recently demonstrated that kefir modulates the immune response in mice, increasing the number of IgA+ cells in the intestinal and bronchial mucosa and the phagocytic

  13. Artificial Immune System Approaches for Aerospace Applications

    Microsoft Academic Search

    K. KrishnaKumar

    2003-01-01

    Artificial Immune Systems (AIS) combine a priori knowledge with the adapting capabilities of biological immune systems to provide a powerful alternative to currently available techniques for pattern recognition, modeling, design, and control. Immunology is the science of built-in defense mechanisms that are present in all living beings to protect against external attacks. A biological immune system can be thought of

  14. Natural immune regulation of activated cells

    Microsoft Academic Search

    Donna A. Chow; Ricky Kraut; Xiaowei Wang

    2001-01-01

    The natural immune system provides a prompt first-line of defense against invading pathogens. It is comprised of both cellular and humoral mediators including macrophages, NK and T cells, natural antibodies, complement and interferon. Unlike the exquisitely specific, adaptive immune system, natural immunity is polyspecific, recognizing highly conserved homologous or crossreactive epitopes (homotopes), and does not require previous exposure to antigen

  15. The innate immune system in transplantation

    Microsoft Academic Search

    Martin H. Oberbarnscheidt; Daniel Zecher; Fadi G. Lakkis

    2011-01-01

    The vertebrate innate immune system consists of inflammatory cells and soluble mediators that comprise the first line of defense against microbial infection and, importantly, trigger antigen-specific T and B cell responses that lead to lasting immunity. The molecular mechanisms responsible for microbial non-self recognition by the innate immune system have been elucidated for a large number of pathogens. How the

  16. Innate Immune Recognition of HIV-1

    PubMed Central

    Iwasaki, Akiko

    2012-01-01

    In contrast to the extraordinary body of knowledge gained over the past three decades on the virology, pathogenesis, and immunology of HIV-1 infection, innate sensors that detect HIV-1 had remained elusive until recently. By virtue of integration, retroviridae makes up a substantial portion of our genome. Thus, immune strategies that deal with endogenous retroviruses are, by necessity, those of self-preservation and not of virus elimination. Some of the principles of such strategies may also apply for defense against exogenous retroviruses including HIV-1. Here, I highlight several sensors that have recently been revealed to be capable of recognizing distinct features of HIV-1 infection, while taking into account the host-retrovirus relationship that converges on avoiding pathogenic inflammatory consequences. PMID:22999945

  17. Peptidomic and proteomic analyses of the systemic immune response of Drosophila.

    PubMed

    Levy, Francine; Rabel, David; Charlet, Maurice; Bulet, Philippe; Hoffmann, Jules A; Ehret-Sabatier, Laurence

    2004-01-01

    Insects have developed an efficient host defense against microorganisms, which involves humoral and cellular mechanisms. Numerous data highlight similarities between defense responses of insects and innate immunity of mammals. The fruit fly, Drosophila melanogaster, is a favorable model system for the analysis of the first line defense against microorganisms. Taking advantages of improvements in mass spectrometry (MS), two-dimensional (2D) gel electrophoresis and bioinformatics, differential analyses of blood content (hemolymph) from immune-challenged versus control Drosophila were performed. Two strategies were developed: (i) peptidomic analyses through matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS and high performance liquid chromatography for molecules below 15 kDa, and (ii) proteomic studies based on 2D gel electrophoresis, MALDI-TOF fingerprinting and database searches, for compounds of greater molecular masses. The peptidomic strategy led to the detection of a large number of peptides induced in the hemolymph of challenged flies as compared to controls. Of these, 28 were characterized, amongst which were antimicrobial peptides. The 2D gel electrophoresis strategy led to the detection of 70 spots differentially regulated by at least fivefold after microbial infection. This approach yielded the identity of a series of proteins that were related to the Drosophila immune response, such as proteases, protease inhibitors, prophenoloxydase-activating enzymes, serpins and a Gram-negative binding protein-like protein. This strategy also brought to light new candidates with a potential function in the immune response (odorant-binding protein, peptidylglycine alpha-hydroxylating monooxygenase and transferrin). Interestingly, several molecules resulting from the cleavage of proteins were detected after a fungal infection. Together, peptidomic and proteomic analyses represent new tools to characterize molecules involved in the innate immune reactions of Drosophila. PMID:15556270

  18. 76 FR 38642 - Meeting of the Defense Business Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-01

    ...Alternative Plans,'' ``Global Logistics Management'' and ``Corporate Downsizing...Secretary of Defense on effective strategies for implementation of best...Recommendations --Global Logistics Management --Corporate Downsizing...

  19. Innate immunity and aging

    PubMed Central

    Gomez, Christian R.; Nomellini, Vanessa; Faunce, Douglas E.; Kovacs, Elizabeth J.

    2008-01-01

    Advanced age is associated with defects in all of the cells of the innate immune system, including numbers, function, their, and early stages of activation. In this review, the current state of the field on the impact of age on the innate immune system is presented. The analysis of the literature suggests that a dysfunctional innate immune system is a contributing factor to aberrant outcomes after injury or infection and to the development of many of the diseases observed in the elderly. Gaining an understanding of the nature of the defects in innate immune cells may allow the development of therapeutic strategies aimed at restoring innate immune function in aged individuals. PMID:18586079

  20. 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 ...

  1. Modeling Immune Building Systems for Bioterrorism Defense

    Microsoft Academic Search

    Wladyslaw Kowalski; William Bahnfleth; Amy Musser

    2003-01-01

    This paper presents the results of research on the performance of air-cleaning and air-disinfection systems used for protecting buildings against intentional releases of biological agents. The air-cleaning technologies addressed include dilution ventilation, filtration, and ultraviolet germicidal irradiation. A 40-story commercial office building is modeled using typical occupancy levels and leakage rates for doors, walls, and floors. A steady-state single-zone model

  2. 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

  3. Toward understanding of rice innate immunity against Magnaporthe oryzae.

    PubMed

    Azizi, P; Rafii, M Y; Abdullah, S N A; Nejat, N; Maziah, M; Hanafi, M M; Latif, M A; Sahebi, M

    2014-09-01

    Abstract The blast fungus, Magnaporthe oryzae, causes serious disease on a wide variety of grasses including rice, wheat and barley. The recognition of pathogens is an amazing ability of plants including strategies for displacing virulence effectors through the adaption of both conserved and variable pathogen elicitors. The pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) were reported as two main innate immune responses in plants, where PTI gives basal resistance and ETI confers durable resistance. The PTI consists of extracellular surface receptors that are able to recognize PAMPs. PAMPs detect microbial features such as fungal chitin that complete a vital function during the organism's life. In contrast, ETI is mediated by intracellular receptor molecules containing nucleotide-binding (NB) and leucine rich repeat (LRR) domains that specifically recognize effector proteins produced by the pathogen. To enhance crop resistance, understanding the host resistance mechanisms against pathogen infection strategies and having a deeper knowledge of innate immunity system are essential. This review summarizes the recent advances on the molecular mechanism of innate immunity systems of rice against M. oryzae. The discussion will be centered on the latest success reported in plant-pathogen interactions and integrated defense responses in rice. PMID:25198435

  4. Cytokines as a link between innate and adaptive antitumor immunity

    Microsoft Academic Search

    Filippo Belardelli; Maria Ferrantini

    2002-01-01

    Recent studies indicate that cytokines produced by cells of the innate defense system play an essential role in influencing the immune response towards protective antitumor immunity. These cytokines might act as first ‘danger signals’ in alerting the immune system. By promoting the differentiation and activation of dendritic cells, antigen presentation and T-cell-mediated immune responses, these cytokines could be powerful natural

  5. Neonatal Host Defense against Staphylococcal Infections

    PubMed Central

    Power Coombs, Melanie R.; Kronforst, Kenny; Levy, Ofer

    2013-01-01

    Preterm infants are especially susceptible to late-onset sepsis that is often due to Gram-positive bacterial infections resulting in substantial morbidity and mortality. Herein, we will describe neonatal innate immunity to Staphylococcus spp. comparing differences between preterm and full-term newborns with adults. Newborn innate immunity is distinct demonstrating diminished skin integrity, impaired Th1-polarizing responses, low complement levels, and diminished expression of plasma antimicrobial proteins and peptides, especially in preterm newborns. Characterization of distinct aspects of the neonatal immune response is defining novel approaches to enhance host defense to prevent and/or treat staphylococcal infection in this vulnerable population. PMID:23935651

  6. 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

  7. Regulated Nuclear Trafficking of rpL10A Mediated by NIK1 Represents a Defense Strategy of Plant Cells against Virus

    PubMed Central

    Carvalho, Claudine M.; Santos, Anésia A.; Pires, Silvana R.; Rocha, Carolina S.; Saraiva, Daniela I.; Machado, João Paulo B.; Mattos, Eliciane C.; Fietto, Luciano G.; Fontes, Elizabeth P. B.

    2008-01-01

    The NSP-interacting kinase (NIK) receptor-mediated defense pathway has been identified recently as a virulence target of the geminivirus nuclear shuttle protein (NSP). However, the NIK1–NSP interaction does not fit into the elicitor–receptor model of resistance, and hence the molecular mechanism that links this antiviral response to receptor activation remains obscure. Here, we identified a ribosomal protein, rpL10A, as a specific partner and substrate of NIK1 that functions as an immediate downstream effector of NIK1-mediated response. Phosphorylation of cytosolic rpL10A by NIK1 redirects the protein to the nucleus where it may act to modulate viral infection. While ectopic expression of normal NIK1 or a hyperactive NIK1 mutant promotes the accumulation of phosphorylated rpL10A within the nuclei, an inactive NIK1 mutant fails to redirect the protein to the nuclei of co-transfected cells. Likewise, a mutant rpL10A defective for NIK1 phosphorylation is not redirected to the nucleus. Furthermore, loss of rpL10A function enhances susceptibility to geminivirus infection, resembling the phenotype of nik1 null alleles. We also provide evidence that geminivirus infection directly interferes with NIK1-mediated nuclear relocalization of rpL10A as a counterdefensive measure. However, the NIK1-mediated defense signaling neither activates RNA silencing nor promotes a hypersensitive response but inhibits plant growth and development. Although the virulence function of the particular geminivirus NSP studied here overcomes this layer of defense in Arabidopsis, the NIK1-mediated signaling response may be involved in restricting the host range of other viruses. PMID:19112492

  8. Department of Defense INSTRUCTION

    E-print Network

    Department of Defense INSTRUCTION NUMBER 2040.02 July 10, 2008 USD(P) SUBJECT: International Secretary of Defense for Policy (USD(P)) in Deputy Secretary of Defense Memorandum (Reference (b)). b-use and defense-related technology, articles, and services, by implementing relevant portions of section 1701 et

  9. Department of Defense INSTRUCTION

    E-print Network

    Department of Defense INSTRUCTION NUMBER 1400.25-V810 April 12, 2005 Administratively reissued regarding civilian personnel management within the Department of Defense. b. Volume. This Volume, the Office of the Inspector General of the Department of Defense, the Defense Agencies, the DoD Field

  10. 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)

  11. Immune System

    MedlinePLUS

    ... could put us out of commission. What the Immune System Does The immune (pronounced: ih- myoon ) system, which ... Continue Things That Can Go Wrong With the Immune System Disorders of the immune system can be broken ...

  12. 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

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

    PubMed

    Arnaud, Dominique; Hwang, Ildoo

    2015-04-01

    Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. Stomata have been shown to play an important role in plant defense as a part of the innate immune response. Plants actively close their stomata upon contact with microbes, thereby preventing pathogen entry into the leaves and the subsequent colonization of host tissues. In this review, we present current knowledge of molecular mechanisms and signaling pathways implicated in stomatal defenses, with particular emphasis 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, nitric oxide, 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 among the components regulating hormonal signaling pathways. We also discuss the strategies deployed by pathogenic bacteria to counteract stomatal immunity through the example of the phytotoxin coronatine. PMID:25661059

  14. Common loon nest defense against an American mink

    USGS Publications Warehouse

    McCarthy, K.P.; DeStefano, S.

    2011-01-01

    We describe a successful nest defense strategy of an adult Gavia immer (Common Loon) during an attempted predation event by a Nevison vison (American Mink) at Umbagog National Wildlife Refuge, NH. It is suspected that mink occasionally depredate loon nests, but defense strategies have not been described previously.

  15. Harnessing the immune system to treat cancer

    PubMed Central

    Bhardwaj, Nina

    2007-01-01

    A major challenge for the immune system is to recognize and eliminate cells undergoing carcinogenesis. Immune defense against tumors is complex. It can be mediated early by the innate immune system (i.e., phagocytes, NK cells, NKT cells, cytokines, and complement proteins) and later by the adaptive immune system (i.e., B cells and T cells). The eight articles in this Review series on tumor immunology discuss the mechanisms underlying immune surveillance of tumors, the regulation of carcinogenesis by immune inflammatory mediators, current approaches to controlling tumor growth through immunotherapy, and novel targets of immunotherapy. PMID:17476342

  16. 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

  17. 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

  18. A Novel Innate Immune-Enhancement Strategy Combined with IVIG Rescues Mice from Fatal Staphylococcus aureus Septicemia

    PubMed Central

    Rajam, Gowrisankar; Hammons, Gabrielle M.; Carlone, George M.; Sampson, Jacquelyn S.; Ades, Edwin W.

    2011-01-01

    Staphylococcus aureus (SA) is a major community-acquired pathogen. The emergence of drug-resistant strains like, methicillin-resistant SA (MRSA), poses stiff challenges to therapeutic intervention. Passive immune-therapy with specific antibodies is being actively examined to treat fulminant infections with limited success. In this study, we demonstrate that P4, a 28-amino acid peptide, derived from pneumococcal surface adhesin A along with pathogen-specific antibody (IVIG; P4 therapy) is successful in enhancing the opsonophagocytic killing (OPK) of S. aureus in vitro. We questioned if it is possible to expand P4 therapy to treat staphylococcal infections in vivo. P4 therapy in combination with IVIG rescued 7/10 morbidly ill S. aureus-infected mice while only 2/10 survived in the control group. PMID:22164166

  19. A Novel Innate Immune-Enhancement Strategy Combined with IVIG Rescues Mice from Fatal Staphylococcus aureus Septicemia.

    PubMed

    Rajam, Gowrisankar; Hammons, Gabrielle M; Carlone, George M; Sampson, Jacquelyn S; Ades, Edwin W

    2011-01-01

    Staphylococcus aureus (SA) is a major community-acquired pathogen. The emergence of drug-resistant strains like, methicillin-resistant SA (MRSA), poses stiff challenges to therapeutic intervention. Passive immune-therapy with specific antibodies is being actively examined to treat fulminant infections with limited success. In this study, we demonstrate that P4, a 28-amino acid peptide, derived from pneumococcal surface adhesin A along with pathogen-specific antibody (IVIG; P4 therapy) is successful in enhancing the opsonophagocytic killing (OPK) of S. aureus in vitro. We questioned if it is possible to expand P4 therapy to treat staphylococcal infections in vivo. P4 therapy in combination with IVIG rescued 7/10 morbidly ill S. aureus-infected mice while only 2/10 survived in the control group. PMID:22164166

  20. Pseudomonas aeruginosa exploits lipid A and muropeptides modification as a strategy to lower innate immunity during cystic fibrosis lung infection.

    PubMed

    Cigana, Cristina; Curcurù, Laura; Leone, Maria Rosaria; Ieranò, Teresa; Lorè, Nicola Ivan; Bianconi, Irene; Silipo, Alba; Cozzolino, Flora; Lanzetta, Rosa; Molinaro, Antonio; Bernardini, Maria Lina; Bragonzi, Alessandra

    2009-01-01

    Pseudomonas aeruginosa can establish life-long airways chronic infection in patients with cystic fibrosis (CF) with pathogenic variants distinguished from initially acquired strain. Here, we analysed chemical and biological activity of P. aeruginosa Pathogen-Associated Molecular Patterns (PAMPs) in clonal strains, including mucoid and non-mucoid phenotypes, isolated during a period of up to 7.5 years from a CF patient. Chemical structure by MS spectrometry defined lipopolysaccharide (LPS) lipid A and peptidoglycan (PGN) muropeptides with specific structural modifications temporally associated with CF lung infection. Gene sequence analysis revealed novel mutation in pagL, which supported lipid A changes. Both LPS and PGN had different potencies when activating host innate immunity via binding TLR4 and Nod1. Significantly higher NF-kB activation, IL-8 expression and production were detected in HEK293hTLR4/MD2-CD14 and HEK293hNod1 after stimulation with LPS and PGN respectively, purified from early P. aeruginosa strain as compared to late strains. Similar results were obtained in macrophages-like cells THP-1, epithelial cells of CF origin IB3-1 and their isogenic cells C38, corrected by insertion of cystic fibrosis transmembrane conductance regulator (CFTR). In murine model, altered LPS structure of P. aeruginosa late strains induces lower leukocyte recruitment in bronchoalveolar lavage and MIP-2, KC and IL-1beta cytokine levels in lung homogenates when compared with early strain. Histopathological analysis of lung tissue sections confirmed differences between LPS from early and late P. aeruginosa. Finally, in this study for the first time we unveil how P. aeruginosa has evolved the capacity to evade immune system detection, thus promoting survival and establishing favourable conditions for chronic persistence. Our findings provide relevant information with respect to chronic infections in CF. PMID:20037649

  1. 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

  2. Control of adaptive immunity by the innate immune system.

    PubMed

    Iwasaki, Akiko; Medzhitov, Ruslan

    2015-04-01

    Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity. PMID:25789684

  3. 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

  4. Strategic defense initiative: Folly or future

    SciTech Connect

    Haley, P.E.; Merritt, J.

    1986-01-01

    This collection of analyses is a guide through the maze of claims and criticisms about ''Star Wars,'' the controversial effort of the Reagan administration to reorient United States nuclear strategy to strategic defense. The text starts with an introduction by the editors followed by individual chapters outlining the strategic defense initiative as originally conceived and subsequently modified by the Reagan administration; the arguments for and against the plan's strategic and technical feasibility; and assessments of the harmful and constructive effects of strategic defense on U.S.-Soviet and U.S.-allied relations.

  5. Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression.

    PubMed

    Sunkara, Lakshmi T; Achanta, Mallika; Schreiber, Nicole B; Bommineni, Yugendar R; Dai, Gan; Jiang, Weiyu; Lamont, Susan; Lillehoj, Hyun S; Beker, Ali; Teeter, Robert G; Zhang, Guolong

    2011-01-01

    Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. In this study, we tested the hypothesis that exogenous administration of butyrate, a major type of short-chain fatty acids derived from bacterial fermentation of undigested dietary fiber, is capable of inducing HDPs and enhancing disease resistance in chickens. We have found that butyrate is a potent inducer of several, but not all, chicken HDPs in HD11 macrophages as well as in primary monocytes, bone marrow cells, and jejuna and cecal explants. In addition, butyrate treatment enhanced the antibacterial activity of chicken monocytes against Salmonella enteritidis, with a minimum impact on inflammatory cytokine production, phagocytosis, and oxidative burst capacities of the cells. Furthermore, feed supplementation with 0.1% butyrate led to a significant increase in HDP gene expression in the intestinal tract of chickens. More importantly, such a feeding strategy resulted in a nearly 10-fold reduction in the bacterial titer in the cecum following experimental infections with S. enteritidis. Collectively, the results indicated that butyrate-induced synthesis of endogenous HDPs is a phylogenetically conserved mechanism of innate host defense shared by mammals and aves, and that dietary supplementation of butyrate has potential for further development as a convenient antibiotic-alternative strategy to enhance host innate immunity and disease resistance. PMID:22073293

  6. Defense traits of larval Drosophila melanogaster exhibit genetically based tradeoffs against different species of parasitoids

    PubMed Central

    Hodges, Theresa K.; Laskowsk, Kate L.; Squadrito, Giuseppe L.; Luca, Maria De; Leips, Jeff

    2012-01-01

    Populations of Drosophila melanogaster face significant mortality risks from parasitoid wasps that use species-specific strategies to locate and survive in hosts. We tested the hypothesis that parasitoids with different strategies select for alternative host defense characteristics and in doing so contribute to the maintenance of fitness variation and produce trade-offs among traits. We characterized defense traits of Drosophila when exposed to parasitoids with different host searching behaviors (Aphaereta sp. and Leptopilina boulardi). We used host larvae with different natural alleles of the gene Dopa decarboxylase (Ddc), a gene controlling the production of dopamine and known to influence the immune response against parasitoids. Previous population genetic analyses indicate that our focal alleles are maintained by balancing selection. Genotypes exhibited a trade-off between the immune response against Aphaereta sp. and the ability to avoid parasitism by L. boulardi. We also identified a trade off between the ability to avoid parasitism by L. boulardi and larval competitive ability as indicated by differences in foraging and feeding behavior. Genotypes differed in dopamine levels potentially explaining variation in these traits. Our results highlight the potential role of parasitoid biodiversity on host fitness variation and implicate Ddc as an antagonistic pleiotropic locus influencing larval fitness traits. PMID:23461325

  7. Dissertation Defense/Graduation

    E-print Network

    Kovalev, Leonid

    Dissertation Semesters (Years 3+) Defense/Graduation Fellows entering with an M.A. Take 3 or 4 courses. Take 3) Dissertation-writing 4) Defense Before defending, you must 1) submit a program of study and 2) request

  8. Dissertation Defense/Graduation

    E-print Network

    Kovalev, Leonid

    Dissertation Semesters (Years 3+) Defense/Graduation Take 3 courses. T.A. for PHI 171, 172, 191, 197, or 251-writing 4) Defense Before defending, you must 1) submit a program of study and 2) request for examination

  9. The Genome of the Obligately Intracellular Bacterium Ehrlichia canis Reveals Themes of Complex Membrane Structure and Immune Evasion Strategies

    SciTech Connect

    Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Doyle, C Kuyler [Center for Biodenfense and Emerging Infectious Diseases; Lykidis, A [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Francino, M P [U.S. Department of Energy, Joint Genome Institute; Chain, Patrick S [ORNL; Shin, M [U.S. Department of Energy, Joint Genome Institute; Malfatti, Stephanie [Lawrence Livermore National Laboratory (LLNL); Larimer, Frank W [ORNL; Copeland, A [U.S. Department of Energy, Joint Genome Institute; Detter, J C [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Richardson, P M [U.S. Department of Energy, Joint Genome Institute; Yu, X J [Center for Biodenfense and Emerging Infectious Diseases; Walker, D H [Center for Biodenfense and Emerging Infectious Diseases; McBride, J W [Center for Biodenfense and Emerging Infectious Diseases; Kyripides, N C [U.S. Department of Energy, Joint Genome Institute

    2006-01-01

    Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, {alpha}-proteobacterium, is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, 17 putative pseudogenes, and a substantial proportion of noncoding sequence (27%). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences and a unique serine-threonine bias associated with the potential for O glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly(G-C) tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Genes associated with pathogen-host interactions were identified, including a small group encoding proteins (n = 12) with tandem repeats and another group encoding proteins with eukaryote-like ankyrin domains (n = 7).

  10. 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

  11. Defense against ballistic missiles

    Microsoft Academic Search

    1992-01-01

    A development history and development status evaluation is presented for weapons technologies capable of serving as defenses against nuclear-tipped ballistic missiles. The decisive turning-point in this history was the March 23, 1983 announcement by President Reagan of the Strategic Defense Initiative (SDI). Due to President Reagan's emphasis on population protection, 'global' defense systems have tended to dominate SDI design efforts.

  12. Department of Defense INSTRUCTION

    E-print Network

    Weston, Ken

    Department of Defense INSTRUCTION NUMBER 3210.7 May 14, 2004 USD(AT&L) SUBJECT: Research Integrity Regulations, Chapter 2, "Defense Federal Acquisition Regulation Supplement (DFARS)," current edition (e and standards for the Department of Defense for the prevention of research misconduct. This Instruction

  13. 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…

  14. A reasonable defense

    SciTech Connect

    Kaufmann, W.W.

    1986-01-01

    The author traces the growth of defense spending from 1929 to the present and discusses changes in spending and emphasis on programs brought about by President Reagan. He constructs three possible defense postures and budgets and compares their costs and effectiveness, discussing the conditions necessary to adopt a reasonable defense capability and budget.

  15. 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.

  16. Innate immunity in infl ammatory bowel disease

    Microsoft Academic Search

    Jesus K Yamamoto-Furusho; Daniel K Podolsky

    2007-01-01

    The human intestinal tract is home to an enormous bacterial fl ora. The host defense against microorganisms can be divided into innate and adaptive immunity. The former is the most immediate line of response to immunologic challenges presented by bacteria, viruses, and fungi. The mucosal immune system has evolved to balance the need to respond to pathogens while co-existing with

  17. Cascade Defense via Control of the Fluxes in Complex Networks

    Microsoft Academic Search

    Ke Hu; Tao Hu; Yi Tang

    2010-01-01

    Exploring the possible strategies to defense to prevent the cascade from propagating through the entire network is of both\\u000a theoretical interest and practical significance, and several strategies of defense have been developed recently. Following\\u000a the work about the strategy based on the international removal of network elements (Motter in Phys. Rev. Lett. 93:098701,\\u000a 2004), we propose and investigate three novel

  18. A receptor pair with an integrated decoy converts pathogen disabling of transcription factors to immunity.

    PubMed

    Le Roux, Clémentine; Huet, Gaëlle; Jauneau, Alain; Camborde, Laurent; Trémousaygue, Dominique; Kraut, Alexandra; Zhou, Binbin; Levaillant, Marie; Adachi, Hiroaki; Yoshioka, Hirofumi; Raffaele, Sylvain; Berthomé, Richard; Couté, Yohann; Parker, Jane E; Deslandes, Laurent

    2015-05-21

    Microbial pathogens infect host cells by delivering virulence factors (effectors) that interfere with defenses. In plants, intracellular nucleotide-binding/leucine-rich repeat receptors (NLRs) detect specific effector interference and trigger immunity by an unknown mechanism. The Arabidopsis-interacting NLR pair, RRS1-R with RPS4, confers resistance to different pathogens, including Ralstonia solanacearum bacteria expressing the acetyltransferase effector PopP2. We show that PopP2 directly acetylates a key lysine within an additional C-terminal WRKY transcription factor domain of RRS1-R that binds DNA. This disrupts RRS1-R DNA association and activates RPS4-dependent immunity. PopP2 uses the same lysine acetylation strategy to target multiple defense-promoting WRKY transcription factors, causing loss of WRKY-DNA binding and transactivating functions needed for defense gene expression and disease resistance. Thus, RRS1-R integrates an effector target with an NLR complex at the DNA to switch a potent bacterial virulence activity into defense gene activation. PMID:26000483

  19. Immune System

    MedlinePLUS

    ... JavaScript on. Read more information on enabling JavaScript. Immune System Top Banner Content Area Skip Content Marketing Share ... and growth to maintain optimal health. Understanding the Immune System Overview of the Immune System Features of an ...

  20. 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 ...

  1. Integration of Immune Models Using Petri Nets

    Microsoft Academic Search

    Dokyun Na; Inho Park; Kwang Hyung Lee; Doheon Lee

    2004-01-01

    \\u000a Immune system has unique defense mechanisms such as innate, humoral and cellular immunity. These immunities are closely related\\u000a to prevent pathogens from spreading in host and to clear them effectively. To achieve those mechanisms, particular processes,\\u000a such as clonal expansion, positive and negative selection, and somatic hypermutation and so on, have been evolved. These properties\\u000a inspired people to open a

  2. 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.

  3. Molecules participating in insect immunity of Sarcophaga peregrina.

    PubMed

    Natori, Shunji

    2010-01-01

    Pricking the body wall of Sarcophaga peregrina (flesh fly) larvae with a needle activated the immune system of this insect and induced various immune molecules, including antibacterial proteins, in the hemolymph. In this review, I summarize and discuss the functions of these immune molecules, with particular emphasis on the dual roles of some of these molecules in defense and development. PMID:21157125

  4. Innate Immunity: Toll-Like Receptors and Some More

    Microsoft Academic Search

    André Fleer; Tannette G. Krediet

    2007-01-01

    The discovery of Toll-like receptors (TLRs) as essential components of the innate immune system has greatly advanced our knowledge and understanding of immune responses to infection and how these are regulated. Innate immunity in general and TLRs in particular play a crucial role in the front line of host defenses against microbes, but also are a key element in the

  5. TOLL-like receptors linking innate and adaptive immune response

    Microsoft Academic Search

    Dirk Werling; Thomas W. Jungi

    2003-01-01

    Invading pathogens are controlled by the innate and adaptive arms of the immune system. Adaptive immunity, which is mediated by B and T lymphocytes, recognises pathogens by rearranged high affinity receptors. However, the establishment of adaptive immunity is often not rapid enough to eradicate microorganisms as it involves cell proliferation, gene activation and protein synthesis. More rapid defense mechanisms are

  6. 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

  7. Intracellular survival of Candida glabrata in macrophages: immune evasion and persistence.

    PubMed

    Kasper, Lydia; Seider, Katja; Hube, Bernhard

    2015-08-01

    Candida glabrata is a successful human opportunistic pathogen which causes superficial but also life-threatening systemic infections. During infection, C. glabrata has to cope with cells of the innate immune system such as macrophages, which belong to the first line of defense against invading pathogens. Candida glabrata is able to survive and even replicate inside macrophages while causing surprisingly low damage and cytokine release. Here, we present an overview of recent studies dealing with the interaction of C. glabrata with macrophages, from phagocytosis to intracellular growth and escape. We review the strategies of C. glabrata that permit intracellular survival and replication, including poor host cell activation, modification of phagosome maturation and phagosome pH, adaptation to antimicrobial activities, and mechanisms to overcome the nutrient limitations within the phagosome. In summary, these studies suggest that survival within macrophages may be an immune evasion and persistence strategy of C. glabrata during infection. PMID:26066553

  8. 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

  9. 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

  10. 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

  11. Interleukin12 (IL12) and IL18 Are Important in Innate Defense against Genital Herpes Simplex Virus Type 2 Infection in Mice but Are Not Required for the Development of Acquired Gamma Interferon-Mediated Protective Immunity

    Microsoft Academic Search

    ALI M. HARANDI; BO SVENNERHOLM; JAN HOLMGREN; KRISTINA ERIKSSON

    2001-01-01

    Using a combination of gene-targeted mice and neutralizing antibodies, we showed that interleukin-12 (IL-12) and IL-18 are important in the innate control of genital herpes simplex virus type 2 infection but were not found to be critical, either singly or in combination, for the development of a protective gamma interferon- mediated immune response.

  12. Differential gene expression in innate immunity between commercial broilers and layers

    E-print Network

    Shen, Shixue

    2009-06-02

    Tremendous improvements have been achieved in growth rates and feed efficiency in commercial broiler birds. However, fast growth broilers generally show weak immune competence and disease resistance. Innate immunity is the first line of defense...

  13. SOBER1 phospholipase activity suppresses phosphatidic acid accumulation and plant immunity

    E-print Network

    Mudgettt, Mary Beth

    defense cascades, often referred to as effector-triggered immunity (ETI) (6). To suppress plant immunity are consistent with the model that SOBER1 PLA2 activity suppresses PLD-dependent production of PA in response

  14. The fifth dimension of innate immunity.

    PubMed

    Schmidt, C; Schneble, N; Wetzker, R

    2014-12-01

    Innate immunity has evolved as a first line defense against invading pathogens. Cellular and humoral elements of the innate immune system detect infectious parasites, initiate inflammatory resistance reactions and finally contribute to the elimination of the invaders. Repeated attacks by pathogenic agents induce adaptive responses of the innate immune system. Typically, reapplication of pathogens provokes tolerance of the affected organism. However, also stimulatory effects of primary infections on subsequent innate immune responses have been observed. The present overview touches an undervalued aspect in the innate immune response: Its pronounced dependency on pathogen load. In addition to localization and timing of innate immune responses the pathogen dose dependency might be considered as a "fifth dimension of innate immunity". Experimental results and literature data are presented proposing a hormetic reaction pattern of innate immune cells depending on the dose of pathogens. PMID:25278167

  15. Abstract--The safe operation of electrical power systems is an ongoing problem. Despite the existing defense lines in the

    E-print Network

    Paris-Sud XI, Université de

    the existing defense lines in the different electrical systems, they are not immune to widespread incidents leading to tripping of most consumers. In the defense plans against these major incidents, selective load]. In this context, we can imagine a defense system based on an intelligent SLS. The objective of this study

  16. Dynamics of Defense Responses and Cell Fate Change during Arabidopsis-Pseudomonas syringae Interactions

    PubMed Central

    Hamdoun, Safae; Liu, Zhe; Gill, Manroop; Yao, Nan; Lu, Hua

    2013-01-01

    Plant-pathogen interactions involve sophisticated action and counteraction strategies from both parties. Plants can recognize pathogen derived molecules, such as conserved pathogen associated molecular patterns (PAMPs) and effector proteins, and subsequently activate PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI), respectively. However, pathogens can evade such recognitions and suppress host immunity with effectors, causing effector-triggered susceptibility (ETS). The differences among PTI, ETS, and ETI have not been completely understood. Toward a better understanding of PTI, ETS, and ETI, we systematically examined various defense-related phenotypes of Arabidopsis infected with different Pseudomonas syringae pv. maculicola ES4326 strains, using the virulence strain DG3 to induce ETS, the avirulence strain DG34 that expresses avrRpm1 (recognized by the resistance protein RPM1) to induce ETI, and HrcC- that lacks the type three secretion system to activate PTI. We found that plants infected with different strains displayed dynamic differences in the accumulation of the defense signaling molecule salicylic acid, expression of the defense marker gene PR1, cell death formation, and accumulation/localization of the reactive oxygen species, H2O2. The differences between PTI, ETS, and ETI are dependent on the doses of the strains used. These data support the quantitative nature of PTI, ETS, and ETI and they also reveal qualitative differences between PTI, ETS, and ETI. Interestingly, we observed the induction of large cells in the infected leaves, most obviously with HrcC- at later infection stages. The enlarged cells have increased DNA content, suggesting a possible activation of endoreplication. Consistent with strong induction of abnormal cell growth by HrcC-, we found that the PTI elicitor flg22 also activates abnormal cell growth, depending on a functional flg22-receptor FLS2. Thus, our study has revealed a comprehensive picture of dynamic changes of defense phenotypes and cell fate determination during Arabidopsis-P. syringae interactions, contributing to a better understanding of plant defense mechanisms. PMID:24349466

  17. 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,

  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. Chemoimmunotherapy: reengineering tumor immunity

    PubMed Central

    Chen, Gang

    2013-01-01

    Cancer chemotherapy drugs have long been considered immune suppressive. However, more recent data indicate that some cytotoxic drugs effectively treat cancer in part by facilitating an immune response to the tumor when given at the standard dose and schedule. These drugs induce a form of tumor cell death that is immunologically active, thereby inducing an adaptive immune response specific for the tumor. In addition, cancer chemotherapy drugs can promote tumor immunity through ancillary and largely unappreciated immunologic effects on both the malignant and normal host cells present within the tumor microenvironment. These more subtle immunomodulatory effects are dependent on the drug itself, its dose, and its schedule in relation to an immune-based intervention. The recent approvals of two new immune-based therapies for prostate cancer and melanoma herald a new era in cancer treatment and have led to heightened interest in immunotherapy as a valid approach to cancer treatment. A detailed understanding of the cellular and molecular basis of interactions between chemotherapy drugs and the immune system is essential for devising the optimal strategy for integrating new immune-based therapies into the standard of care for various cancers, resulting in the greatest long-term clinical benefit for cancer patients. PMID:23389507

  20. 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

  1. Toxin-mediated effects on the innate mucosal defenses: implications for enteric vaccines.

    PubMed

    Glenn, Gregory M; Francis, David H; Danielsen, E Michael

    2009-12-01

    Recent studies have confirmed older observations that the enterotoxins enhance enteric bacterial colonization and pathogenicity. How and why this happens remains unknown at this time. It appears that toxins such as the heat-labile enterotoxin (LT) from Escherichia coli can help overcome the innate mucosal barrier as a key step in enteric pathogen survival. We review key observations relevant to the roles of LT and cholera toxin in protective immunity and the effects of these toxins on innate mucosal defenses. We suggest either that toxin-mediated fluid secretion mechanically disrupts the mucus layer or that toxins interfere with innate mucosal defenses by other means. Such a breach gives pathogens access to the enterocyte, leading to binding and pathogenicity by enterotoxigenic E. coli (ETEC) and other organisms. Given the common exposure to LT(+) ETEC by humans visiting or residing in regions of endemicity, barrier disruption should frequently render the gut vulnerable to ETEC and other enteric infections. Conversely, toxin immunity would be expected to block this process by protecting the innate mucosal barrier. Years ago, Peltola et al. (Lancet 338:1285-1289, 1991) observed unexpectedly broad protective effects against LT(+) ETEC and mixed infections when using a toxin-based enteric vaccine. If toxins truly exert barrier-disruptive effects as a key step in pathogenesis, then a return to classic toxin-based vaccine strategies for enteric disease is warranted and can be expected to have unexpectedly broad protective effects. PMID:19737904

  2. 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

  3. 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

  4. Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome

    PubMed Central

    Ouchi, Takeshi; Kubo, Akiharu; Yokouchi, Mariko; Adachi, Takeya; Kobayashi, Tetsuro; Kitashima, Daniela Y.; Fujii, Hideki; Clausen, Björn E.; Koyasu, Shigeo; Amagai, Masayuki

    2011-01-01

    Epidermal Langerhans cells (LCs) extend dendrites through tight junctions (TJs) to survey the skin surface, but their immunological contribution in vivo remains elusive. We show that LCs were essential for inducing IgG1 responses to patch-immunized ovalbumin in mice that lacked skin dendritic cell subsets. The significance of LC-induced humoral responses was demonstrated in a mouse model of staphylococcal scalded skin syndrome (SSSS), a severe blistering disease in which the desmosomal protein Dsg1 (desmoglein1) is cleaved by Staphylococcus aureus–derived exfoliative toxin (ET). Importantly, ET did not penetrate TJs, and patch immunization did not alter epidermal integrity. Nevertheless, neutralizing anti-ET IgG1 was induced after patch immunization and abolished upon LC depletion, indicating that antigen capture through TJs by LCs induced humoral immunity. Strikingly, the ET-patched mice were protected from developing SSSS after intraperitoneal ET challenge, whereas LC-depleted mice were susceptible to SSSS, demonstrating a vital role for LC-induced IgG1 in systemic defense against circulating toxin in vivo. Therefore, LCs elicit humoral immunity to antigens that have not yet violated the epidermal barrier, providing preemptive immunity against potentially pathogenic skin microbes. Targeting this immunological process confers protection with minimal invasiveness and should have a marked impact on future strategies for development of percutaneous vaccines. PMID:22143886

  5. Cellular and humoral immune responses during tuberculosis infection: useful knowledge in the era of biological agents.

    PubMed

    Matucci, Andrea; Maggi, Enrico; Vultaggio, Alessandra

    2014-05-01

    In this review, recent insights into innate and adaptive cellular and humoral immune response to Mycobacterium tuberculosis (Mtb) are discussed and the role of specific cytokines such as tumor necrosis factor-? (TNF-?) is highlighted. According to recent findings, the immune system plays a key role in avoiding mycobacteria dissemination. The importance of different cell types (macrophages, dendritic cells, interferon-?-producing T cells) as well as the production of proinflammatory cytokines such as interleukin 6 (IL-6), IL-12, and IL-23/IL-17 have been demonstrated. Alveolar macrophages are considered the first cells infected by Mtb during respiratory infection. Mtb proliferates within alveolar macrophages and dendritic cells and induces the release of cytokines such as TNF-?, IL-1, IL-6, and IL-12. Toll-like receptors-stimulated dendritic cells link innate and adaptive immunity by promoting polarization of effector T cells. The efficient induction of Th1 immunity is decisive in defense against Mtb. In fact, host effector immune response against Mtb is related to the presence of a Th1 response. The definition of the cellular and molecular mechanisms involved in the immune response to Mtb can be helpful in developing new preventive strategies to avoid infection relapse, particularly in patients treated with biological agents. PMID:24788996

  6. Seaweed resistance to microbial attack: A targeted chemical defense against marine fungi

    PubMed Central

    Kubanek, Julia; Jensen, Paul R.; Keifer, Paul A.; Sullards, M. Cameron; Collins, Dwight O.; Fenical, William

    2003-01-01

    Pathogenic microbes can devastate populations of marine plants and animals. Yet, many sessile organisms such as seaweeds and sponges suffer remarkably low levels of microbial infection, despite lacking cell-based immune systems. Antimicrobial defenses of marine organisms are largely uncharacterized, although from a small number of studies it appears that chemical defenses may improve host resistance. In this study, we asked whether the common seaweed Lobophora variegata is chemically defended against potentially deleterious microorganisms. Using bioassay-guided fractionation, we isolated and characterized a 22-membered cyclic lactone, lobophorolide (1), of presumed polyketide origin, with sub-?M activity against pathogenic and saprophytic marine fungi. Deterrent concentrations of 1 were found in 46 of 51 samples collected from 10 locations in the Bahamas over a 4-year period. Lobophorolide (1) is structurally unprecedented, yet parts of the molecule are related to tolytoxin, the scytophycins, and the swinholides, macrolides previously isolated from terrestrial cyanobacteria and from marine sponges and gastropods. Until now, compounds of this structural class have not been associated with marine macrophytes. Our findings suggest that seaweeds use targeted antimicrobial chemical defense strategies and that secondary metabolites important in the ecological interactions between marine macroorganisms and microorganisms could be a promising source of novel bioactive compounds. PMID:12756301

  7. 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

  8. Breast Milk: Components with Immune Modulating Potential and Their Possible Role in Immune Mediated Disease Resistance

    Microsoft Academic Search

    Belinda Land; Günther Boehm; Johan Garssen

    \\u000a Breast milk contains several interesting immune modulating components with specific modulating potentials, which are known\\u000a to have a clear role in immune mediated disease resistance later in life. The development and deterioration of our immune\\u000a defenses show differences as well as similarities in immunological challenges throughout life. Each phase in life puts specific\\u000a requirements on nutrition, although no clear statement

  9. Defensive Demeanor Profiles

    Microsoft Academic Search

    Martha Davis; Stan B. Walters; Neal Vorus; Brenda Connors

    2000-01-01

    One of the reports from an intensive study of videotapes of confessions given by criminal suspects to prosecutors, this focuses primarily on the body movement microanalysis of two subjects to illustrate what are called Defensive Demeanor Profiles. After a summary of the general study and its aims, a 14-step procedure for observing and interpreting defensive demeanor is described. Three levels

  10. 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.

  11. The Economics of Defense

    Microsoft Academic Search

    Todd Sandler; Keith Hartley

    1995-01-01

    This compelling book provides an up-to-date survey of the field of defense economics, the study of defense and peace issues, with the application of economic analysis and methods. The subject embraces both microeconomics and macroeconomics, taking into account such features as growth theory, comparative statistics, game theory and econometrics. A wide range of topics are addressed, including all aspects of

  12. Defense traits of larval Drosophila melanogaster exhibit genetically based trade-offs against different species of parasitoids.

    PubMed

    Hodges, Theresa K; Laskowski, Kate L; Squadrito, Giuseppe L; De Luca, Maria; Leips, Jeff

    2013-03-01

    Populations of Drosophila melanogaster face significant mortality risks from parasitoid wasps that use species-specific strategies to locate and survive in hosts. We tested the hypothesis that parasitoids with different strategies select for alternative host defense characteristics and in doing so contribute to the maintenance of fitness variation and produce trade-offs among traits. We characterized defense traits of Drosophila when exposed to parasitoids with different host searching behaviors (Aphaereta sp. and Leptopilina boulardi). We used host larvae with different natural alleles of the gene Dopa decarboxylase (Ddc), a gene controlling the production of dopamine and known to influence the immune response against parasitoids. Previous population genetic analyses indicate that our focal alleles are maintained by balancing selection. Genotypes exhibited a trade-off between the immune response against Aphaereta sp. and the ability to avoid parasitism by L. boulardi. We also identified a trade-off between the ability to avoid parasitism by L. boulardi and larval competitive ability as indicated by differences in foraging and feeding behavior. Genotypes differed in dopamine levels potentially explaining variation in these traits. Our results highlight the potential role of parasitoid biodiversity on host fitness variation and implicate Ddc as an antagonistic pleiotropic locus influencing larval fitness traits. PMID:23461325

  13. Immune tolerance induction by integrating innate and adaptive immune regulators

    PubMed Central

    Suzuki, Jun; Ricordi, Camillo; Chen, Zhibin

    2009-01-01

    A diversity of immune tolerance mechanisms have evolved to protect normal tissues from immune damage. Immune regulatory cells are critical contributors to peripheral tolerance. These regulatory cells, exemplified by the CD4+Foxp3+ regulatory T (Treg) cells and a recently identified population named myeloid-derived suppressor cells (MDSCs), regulate immune responses and limiting immune-mediated pathology. In a chronic inflammatory setting, such as allograft-directed immunity, there may be a dynamic “crosstalk” between the innate and adaptive immunomodulatory mechanisms for an integrated control of immune damage. CTLA4-B7-based interaction between the two branches may function as a molecular “bridge” to facilitate such “crosstalk”. Understanding the interplays among Treg cells, innate suppressors and pathogenic effector T (Teff) cells will be critical in the future to assist in the development of therapeutic strategies to enhance and synergize physiological immunosuppressive elements in the innate and adaptive immune system. Successful development of localized strategies of regulatory cell therapies could circumvent the requirement for very high number of cells and decrease the risks associated with systemic immunosuppression. To realize the potential of innate and adaptive immune regulators for the still-elusive goal of immune tolerance induction, adoptive cell therapies may also need to be coupled with agents enhancing endogenous tolerance mechanisms. PMID:19919733

  14. 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

  15. Evolutionary insights into the origin of innate and adaptive immune systems: different shades of grey.

    PubMed

    Sirisinha, Stitaya

    2014-03-01

    To struggle for survival, all living organisms, from protists to humans, must defend themselves from attack by predators. From the time when life began around 3,500 million years ago, all living cells have evolved mechanisms and strategies to optimally defend themselves, while the invaders also need to survive by evading these immune defenses. The end results would be healthy co-evolution of both parties. Classically, immune host defense is divided into two main categories, namely, innate and adaptive systems. It is well documented that while vertebrates possess both systems, invertebrates and prokaryotes like bacteria and archaea depend almost exclusively on the innate immune functions. Although the adaptive immune system like antibodies and cellular immunity or their equivalents are believed to have evolved at the time when the vertebrates first appeared about 550 million years ago, more recent information from molecular and genomic studies suggest that different forms of adaptive immune system may also be present in the invertebrates as well. These forms of "adaptive" immune system exhibit, for instance, limited degrees of memory, diversity and similarities of their immune receptors with the immunoglobulin domains of the conventional adaptive immune system of vertebrates. Organized lymphoid tissues have been identified in all vertebrates. Very recent molecular and genetic data further suggest that a special type of adaptive system functioning like RNAi of vertebrates is also present in the very ancient form of life like the bacteria and archaea. In this review, I provide some insights, based on recent information gathering from evolutionary data of innate and adaptive immune receptors of invertebrate and vertebrate animals that should convince the readers that our current view on the innate and adaptive immunity may need to be modified. The distinction between the two systems should not be thought of in terms of a "black and white" phenomenon anymore, as recent molecular and genomic information points to the fact that a line of distinction is not as sharp as it was once thought to be, but it is blurred by different shades of grey. PMID:24641285

  16. GRADUATE COLLEGE ORAL DEFENSE RESULTS

    E-print Network

    Cho, Hokwon

    GRADUATE COLLEGE ORAL DEFENSE RESULTS THESIS, DISSERTATION/MUSIC DOCUMENT, PROFESSIONAL: Phone: MEANS OF PUBLICIZING ORAL DEFENSE Department email Posted flyer UNLV Today Department website GPSA/GPSA Lounge Other (specify): Date: ORAL DEFENSE

  17. Immunization Coverage

    MedlinePLUS

    ... decision-making 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 ...

  18. A recombinant adenovirus-based vector elicits a specific humoral immune response against the V3 loop of HIV-1 gp120 in mice through the “Antigen Capsid-Incorporation” strategy

    PubMed Central

    2014-01-01

    Background Due to potential advantages, human adenoviral vectors have been evaluated pre-clinically as recombinant vaccine vectors against several cancers and infectious diseases, including human immunodeficiency virus (HIV) infection. The V3 loop of HIV-1 glycoprotein 120 (gp120) contains important neutralizing epitopes and plays key roles in HIV entry and infectivity. Methods In order to investigate the humoral immune response development against portions of the V3 loop, we sought to generate four versions of adenovirus (Ad)-based V3 vectors by incorporating four different antigen inserts into the hypervariable region 1 (HVR1) of human adenovirus type 5 (hAd5) hexon. The strategy whereby antigens are incorporated within the adenovirus capsid is known as the “Antigen Capsid-Incorporation” strategy. Results Of the four recombinant vectors, Ad-HVR1-lgs-His6-V3 and Ad-HVR1-long-V3 had the capability to present heterologous antigens on capsid surface, while maintaining low viral particle to infectious particle (VP/IP) ratios. The VP/IP ratios indicated both high viability and stability of these two vectors, as well as the possibility that V3 epitopes on these two vectors could be presented to immune system. Furthermore, both Ad-HVR1-lgs-His6-V3 and Ad-HVR1-long-V3 could, to some extent escape the neutralization by anti-adenovirus polyclonal antibody (PAb), but rather not the immunity by anti-gp120 (902) monoclonal antibody (MAb). The neutralization assay together with the whole virus enzyme-linked immunosorbent assay (ELISA) suggested that these two vectors could present V3 epitopes similar to the natural V3 presence in native HIV virions. However, subsequent mice immunizations clearly showed that only Ad-HVR1-lgs-His6-V3 elicited strong humoral immune response against V3. Isotype ELISAs identified IgG2a and IgG2b as the dominant IgG isotypes, while IgG1 comprised the minority. Conclusions Our findings demonstrated that human adenovirus (hAd) vectors which present HIV antigen via the “Antigen Capsid-Incorporation” strategy could successfully elicit antigen-specific humoral immune responses, which could potentially open an avenue for the development of Ad-based HIV V3 vaccines. PMID:24935650

  19. 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.

  20. Study of Diseases and the Immune System of Bivalves Using Molecular Biology and Genomics

    Microsoft Academic Search

    Camino Gestal; Philippe Roch; Tristan Renault; Alberto Pallavicini; Christine Paillard; Beatriz Novoa; Radouane Oubella; Paola Venier; Antonio Figueras

    2008-01-01

    Environmental chemico-physical factors, pathogens, and biological interactions constantly affect organism physiology and behavior. Invertebrates, including bivalve mollusks do not possess acquired immunity. Their defense mechanisms rely on an innate, non-adaptive immune system employing circulating cells and a large variety of molecular effectors. The mechanisms underlying host defense depend on the presence of functional proteins in appropriate quantities, within a crucial

  1. Multiantibody Strategies for HIV

    PubMed Central

    Whaley, Kevin J.

    2013-01-01

    Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented. PMID:23840243

  2. Two systems and defenses.

    PubMed

    Novick, Jack; Novick, Kerry Kelly

    2013-02-01

    The authors suggest that Freud's concept of defense differentiated psychoanalysis from other medical and psychological theories of personality development and functioning then and now. Reclaiming the concept's centrality and linking it with interdisciplinary research findings, they illustrate their extension of defense into a two-system model of self-protection and self-regulation with a clinical example. The authors suggest that the two-system model allows for the reintegration of defense into a multidimensional psychoanalytic theory and multimodal therapeutic technique. PMID:23421665

  3. 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

  4. The Drosophila immune system detects bacteria through specific peptidoglycan recognition

    Microsoft Academic Search

    François Leulier; Claudine Parquet; Sebastien Pili-Floury; Ji-Hwan Ryu; Martine Caroff; Won-Jae Lee; Dominique Mengin-Lecreulx; Bruno Lemaitre

    2003-01-01

    The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions through selective activation of the Toll and the immune deficiency (Imd) signaling pathways. The Toll pathway mediates most defenses against Gram-positive bacteria and fungi, whereas the Imd pathway is required to resist infection by Gram-negative bacteria. The bacterial components recognized by these pathways

  5. 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

  6. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

    PubMed Central

    Hall, Jessica M. F.; Cruser, desAnges; Podawiltz, Alan; Mummert, Diana I.; Jones, Harlan; Mummert, Mark E.

    2012-01-01

    Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity) and alters antigen presentation by epidermal Langerhans cells (adaptive immunity). Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis. PMID:22969795

  7. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis.

    PubMed

    Hall, Jessica M F; Cruser, Desanges; Podawiltz, Alan; Mummert, Diana I; Jones, Harlan; Mummert, Mark E

    2012-01-01

    Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity) and alters antigen presentation by epidermal Langerhans cells (adaptive immunity). Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis. PMID:22969795

  8. 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

  9. Peptidomic and proteomic analyses of the systemic immune response of Drosophila

    Microsoft Academic Search

    Francine Levy; David Rabel; Maurice Charlet; Philippe Bulet; Jules A. Hoffmann; Laurence Ehret-Sabatier

    2004-01-01

    Insects have developed an efficient host defense against microorganisms, which involves humoral and cellular mechanisms. Numerous data highlight similarities between defense responses of insects and innate immunity of mammals. The fruit fly, Drosophila melanogaster, is a favorable model system for the analysis of the first line defense against microorganisms. Taking advantages of improvements in mass spectrometry (MS), two-dimensional (2D) gel

  10. Defense Health Program Department of Defense Ovarian Cancer Research Program

    E-print Network

    von der Heydt, Rüdiger

    Defense Health Program Department of Defense Ovarian Cancer Research Program Funding Opportunities for Fiscal Year 2013 The Fiscal Year 2013 (FY13) Defense Appropriations Act provides $20 million (M) to the Department of Defense Ovarian Cancer Research Program (OCRP) to support innovative, high- impact ovarian

  11. Defense Health Program Department of Defense Autism Research Program

    E-print Network

    von der Heydt, Rüdiger

    Defense Health Program Department of Defense Autism Research Program Funding Opportunities for Fiscal Year 2013 The Fiscal Year 2013 (FY13) Defense Appropriations Act provides $6 million to the Department of Defense Autism Research Program (ARP). The vision of the ARP is to improve the lives

  12. Defense Health Program Department of Defense Breast Cancer Research Program

    E-print Network

    von der Heydt, Rüdiger

    Defense Health Program Department of Defense Breast Cancer Research Program Funding Opportunities for Fiscal Year 2013 The Fiscal Year 2013 (FY13) Defense Appropriations Act provides $120 million (M) to the Department of Defense Breast Cancer Research Program (BCRP) to support innovative, high-impact breast cancer

  13. 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

  14. Platelets at the Interface between Hemostasis and Innate Immunity

    Microsoft Academic Search

    B. E. Kehrel; K. Jurk

    2004-01-01

    Summary Pathogenic microorganisms often cause severe systemic infectious diseases if they reach the bloodstream. Innate immune defense mechanisms are very fast and one of the most effective weapons against infections. Platelets, known as primary actors in hemostasis and thrombin generation, maintain, like leukocytes, multiple functions of innate defense mechanisms: pathogen sequestration by clotting, pathogen clearance by phagocytosis, pathogen killing by

  15. The molecular basis of innate immunity in the horseshoe crab

    Microsoft Academic Search

    Sadaaki Iwanaga

    2002-01-01

    During the past two decades, the molecular structures and functions have been established for various defense molecules, using horseshoe crab (limulus) as a model animal. These defense molecules include clotting factors, proteinase inhibitors, lectins, antimicrobial peptides and other humoral factors found mainly in the hemolymph. These components of the cellular and humoral systems, which together comprise innate immunity, defend horseshoe

  16. Host defense peptides as new weapons in cancer treatment

    Microsoft Academic Search

    N. Papo; Y. Shai

    2005-01-01

    In the last decade intensive research has been conducted to determine the role of innate immunity host defense peptides (also termed antimicrobial peptides) in the killing of prokaryotic and eukaryotic cells. Many antimicrobial peptides damage the cellular membrane as part of their killing mechanism. However, it is not clear what makes cancer cells more susceptible to some of these peptides,

  17. 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...

  18. Phish Phactors: Offensive and Defensive Strategies

    Microsoft Academic Search

    Ju-Yeon Jo

    2007-01-01

    Phishing attacks attempt to fraudulently solicit sensitive information from a user by masquerading as a known trustworthy agent. They commonly use spoofed emails in association with fake websites in order to coerce a user into revealing personal financial data. Phishing is now a serious problem with criminals adopting the well-developed and well-known techniques to exploit Internet users with sophisticated attacks.

  19. Environmental exposure to lead induces oxidative stress and modulates the function of the antioxidant defense system and the immune system in the semen of males with normal semen profile.

    PubMed

    Kasperczyk, Aleksandra; Dobrakowski, Micha?; Czuba, Zenon P; Horak, Stanis?aw; Kasperczyk, S?awomir

    2015-05-01

    We investigated the associations between environmental exposure to lead and a repertoire of cytokines in seminal plasma of males with normal semen profile according to the WHO criteria. Based on the median lead concentration in seminal plasma, 65 samples were divided into two groups: low (LE) and high exposure to lead (HE). Differences in semen volume and the pH, count, motility and morphology of sperm cells were not observed between the examined groups. The total oxidant status value and the level of protein sulfhydryl groups as well as the activities of manganese superoxide dismutase and catalase were significantly higher in the HE group, whereas the total antioxidant capacity value and the activities of glutathione reductase and glutathione-S-transferase were depressed. IL-7, IL-10, IL-12, and TNF-? levels were significantly higher in the HE group compared with the LE group. Environmental exposure to lead is sufficient to induce oxidative stress in seminal plasma and to modulate antioxidant defense system. PMID:25771126

  20. 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.

  1. Resin-based defenses in conifers.

    PubMed

    Phillips; Croteau

    1999-05-01

    Bark beetle infestation and associated fungal infection are a serious disease problem in conifer species. Conifers have evolved elaborate, constitutive and inducible, terpene-based defense mechanisms to deter insect pests and their symbiotic fungal pathogens. This process involves the secretion of oleoresin, a complex mixture of monoterpenes, sesquiterpenes and diterpenoid acids. Induced oleoresinosis in grand fir (Abies grandis) provides a model system for studying the regulation of defensive terpene biosynthesis and for identifying relevant genes. The ecological relationships between conifers, beetle pests, beetle predators and fungal pathogens present several possible avenues for manipulating oleoresin composition to improve tree resistance. Possible examples include chemically disguising the host, adding toxins and altering the levels of pheromone precursors, attractants for predators or hormone mimics to disrupt insect development. Strategies and prospects for generating transgenic conifers with increased defense capability are discussed. PMID:10322558

  2. Male pregnancy and biparental immune priming.

    PubMed

    Roth, Olivia; Klein, Verena; Beemelmanns, Anne; Scharsack, Jörn P; Reusch, Thorsten B H

    2012-12-01

    In vertebrates, maternal transfer of immunity via the eggs or placenta provides offspring with crucial information on prevailing pathogens and parasites. Males contribute little to such transgenerational immune priming, either because they do not share the environment and parasite pressure of the offspring or because sperm are too small for transfer of immunity. In the teleost group of Syngnathids (pipefish, seahorses, and sea dragons), males brood female eggs in a placenta-like structure. Such sex-role-reversed species provide a unique opportunity to test for adaptive plasticity in immune transfer. Here, males and females should both influence offspring immunity. We experimentally tested paternal effects on offspring immunity by examining immune cell proliferation and immune gene expression. Maternal and paternal bacterial exposure induced offspring immune defense 5 weeks after hatching, and this effect persisted in 4-month-old offspring. For several offspring immune traits, double parental exposure (maternal and paternal) enhanced the response, whereas for another group of immune traits, the transgenerational induction already took place if only one parent was exposed. Our study shows that sex role reversal in connection with male pregnancy opens the door for biparental influences on offspring immunity and may represent an additional advantage for the evolution of male pregnancy. PMID:23149404

  3. Strategic Defense Initiative

    SciTech Connect

    Not Available

    1991-03-01

    This book is an unclassified version of the classified report that reviews the Strategic Defense Initiative Organization's program for developing Brilliant Pebbles, the space-based weapon system for the Phase I Strategic Defense System. The report suggests that the Congress consider whether the concurrency in the program is justified by the President's need to make a decision by the summer of 1993 on whether to begin full-scale development and deployment.

  4. 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

  5. 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

  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. 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

  8. Coagulation and innate immune responses: can we view them separately?

    PubMed

    Delvaeye, Mieke; Conway, Edward M

    2009-09-17

    The horseshoe crab is often referred to as a "living fossil," representative of the oldest classes of arthropods, almost identical to species in existence more than 500 million years ago. Comparative analyses of the defense mechanisms used by the horseshoe crab that allowed it to survive mostly unchanged throughout the millennia reveal a common ancestry of the coagulation and innate immune systems that are totally integrated-indeed, almost inseparable. In human biology, we traditionally view the hemostatic pathways and those regulating innate immune responses to infections and tissue damage as entirely separate entities. But are they? The last couple of decades have revealed a remarkable degree of interplay between these systems, and the linking cellular and molecular mechanisms are rapidly being delineated. In this review, we present some of the major points of intersection between coagulation and innate immunity. We attempt to highlight the potential impact of these findings by identifying recently established paradigms that will hopefully result in the emergence of new strategies to treat a range of inflammatory and hemostatic disorders. PMID:19584396

  9. Transcriptional regulation of the anti-inflammatory cytokine IL-10 in acquired immune cells

    PubMed Central

    Kubo, Masato; Motomura, Yasutaka

    2012-01-01

    Although the major role of the immune response is host defense from a wide range of potentially pathogenic microorganisms, excess immune responses can result in severe host damage. The host thus requires anti-inflammatory mechanisms to prevent reactivity to self. Interleukin-10 (IL-10) is a cytokine with broad anti-inflammatory properties involved in the pathogenesis of various diseases. IL-10 was originally described as a T helper (TH2) derived cytokine, but further studies indicated that IL-10 is expressed not only by many cells of the adaptive immune system, including T and B cells, but also by the innate immune cells, including dendritic cells (DCs), macrophages, mast cells, and natural killer (NK) cells. In addition, IL-10 can be induced in TH1 and TH17 cells by chronic inflammation as a system of feedback regulation. In this review, we focus on the molecular mechanisms underlying IL10 gene expression in adaptive immune cells and summarize the recent progresses in epigenetic and transcriptional regulation of the IL10 gene. Understanding the transcriptional regulatory events may help in the development of new strategies to control inflammatory diseases. PMID:22969768

  10. 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

  11. 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.

  12. Beetle Immunity

    Microsoft Academic Search

    Ji-Won Park; Chan-Hee Kim; Jiang Rui; Keun-HwaPark; Kyung-Hwa Ryu; Jun-Ho Chai; Hyun-Ok Hwang; Kenji Kurokawa; Nam-Chul Ha; Irene Söderhäll; Kenneth Söderhäll; Bok Luel Lee

    \\u000a Genetic studies have elegantly characterized the innate immune response in Drosophila melanogaster. However, these studies have a limited ability to reveal the biochemical mechanisms underlying the innate immune response.\\u000a To investigate the biochemical basis of how insects recognize invading microbes and how these recognition signals activate\\u000a the innate immune response, it is necessary to use insects, from which larger amounts

  13. 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

  14. Disruption of TNF?/TNFR1 function in resident skin cells impairs host immune response against cutaneous vaccinia virus infection

    PubMed Central

    Tian, Tian; Dubin, Krista; Jin, Qiushuang; Qureshi, Ali; King, Sandra L.; Liu, Luzheng; Jiang, Xiaodong; Murphy, George F.; Kupper, Thomas S.; Fuhlbrigge, Robert C.

    2012-01-01

    One strategy adopted by vaccinia virus (VV) to evade the host immune system is to encode homologs of TNF receptors (TNFR) that block TNF? function. The response to VV skin infection under conditions of TNF? deficiency, however, has not been reported. We found that TNFR1?/? mice developed larger primary lesions, numerous satellite lesions and higher skin virus levels after VV scarification. Following their recovery, these TNFR1?/? mice were fully protected against challenge with a lethal intranasal dose of VV, suggesting these mice developed an effective memory immune response. A functional systemic immune response of TNFR1?/? mice was further demonstrated by enhanced production of VV-specific IFN? and VV-specific CD8+ T cells in spleens and draining lymph nodes. Interestingly, bone marrow (BM) reconstitution studies using WT BM in TNFR1?/? host mice, but not TNFR1?/? BM in WT host mice, reproduced the original results seen in TNFR1?/? mice, indicating that TNFR1 deficiency in resident skin cells, rather than hematopoietic cells, accounts for the impaired cutaneous immune response. Our data suggest that lack of TNFR1 leads to a skin-specific immune deficiency and that resident skin cells play a crucial role in mediating an optimal immune defense to VV cutaneous infection via TNF?/TNFR1 signaling. PMID:22318381

  15. Disruption of TNF-?/TNFR1 function in resident skin cells impairs host immune response against cutaneous vaccinia virus infection.

    PubMed

    Tian, Tian; Dubin, Krista; Jin, Qiushuang; Qureshi, Ali; King, Sandra L; Liu, Luzheng; Jiang, Xiaodong; Murphy, George F; Kupper, Thomas S; Fuhlbrigge, Robert C

    2012-05-01

    One strategy adopted by vaccinia virus (VV) to evade the host immune system is to encode homologs of TNF receptors (TNFRs) that block TNF-? function. The response to VV skin infection under conditions of TNF-? deficiency, however, has not been reported. We found that TNFR1-/- mice developed larger primary lesions, numerous satellite lesions, and higher skin virus levels after VV scarification. Following their recovery, VV-scarified TNFR1-/- mice were fully protected against challenge with a lethal intranasal dose of VV, suggesting these mice had developed an effective memory immune response. A functional systemic immune response was further demonstrated by enhanced production of VV-specific IFN-? and VV-specific CD8(+) T cells in spleens and draining lymph nodes. Interestingly, bone marrow (BM)-reconstitution studies using wild-type (WT) BM in TNFR1-/- host mice, but not TNFR1-/- BM in WT host mice, reproduced the original results seen in TNFR1-/- mice, indicating that TNFR1 deficiency in resident skin cells, rather than hematopoietic cells, accounts for the impaired cutaneous immune response. Our data suggest that lack of TNFR1 leads to a skin-specific immune deficiency, and that resident skin cells have a crucial role in mediating an optimal immune defense to VV cutaneous infection via TNF-?/TNFR1 signaling. PMID:22318381

  16. Toll Receptors: a Central Element in Innate Immune Responses

    Microsoft Academic Search

    Thierry Vasselon; Patricia A. Detmers

    2002-01-01

    Innate immunity is an evolutionarily ancient system that provides multicellular organisms with immediately available defense mechanisms against a wide variety of pathogens with- out requiring prior exposure. Hallmarks of innate immune responses include the ability to (i) recognize structures that are present in large groups of microorganisms and are distinct from self, (ii) activate effector mechanisms that will destroy within

  17. Molecular Population Genetics of Drosophila Immune System Genes

    Microsoft Academic Search

    Andrew G. Clark; Lei Wang

    1997-01-01

    A striking aspect of many vertebrate immune system genes is the exceptionally high level of polymor- phism they harbor. A convincing case can be made that this polymorphism is driven by the diversity of pathogens that face selective pressures to evade attack by the host immune system. Different organisms accomplish a defense against diverse pathogens through mechanisms that differ widely

  18. Genetic regulation of immune responses to vaccines in early life

    Microsoft Academic Search

    M J Newport; T Goetghebuer; H A Weiss; H Whittle; C-A Siegrist; A Marchant

    2004-01-01

    Infant immunization is the most cost-effective strategy to prevent infectious diseases in childhood, but is limited by immaturity of the immune system. To define strategies to improve vaccine immunogenicity in early life, the role of genetic and environmental factors in the control of vaccine responses in infant twins was studied. Immune responses to BCG, polio, hepatitis B, diphtheria, pertussis and

  19. Defense against ballistic missiles

    SciTech Connect

    Mark, H. (Texas, University, Austin (United States))

    1992-01-01

    A development history and development status evaluation is presented for weapons technologies capable of serving as defenses against nuclear-tipped ballistic missiles. The decisive turning-point in this history was the March 23, 1983 announcement by President Reagan of the Strategic Defense Initiative (SDI). Due to President Reagan's emphasis on population protection, 'global' defense systems have tended to dominate SDI design efforts. The most important SDI technical achievements to date encompass (1) miniature homig devices, (2) the upgrade of the Patriot SAM for missile-interception capabilities, (3) light exoatmospheric projectiles, such as 'Brilliant Pebbles', (4) successful laser-communications experiments, and (5) the warhead/decoy-discriminating Firepond lidar system. 7 refs.

  20. 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.

  1. 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...

  2. 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.

  3. Leading Edge Innate Immunity Gone Awry

    E-print Network

    Nizet, Victor

    . When coupled with a failure of normal control mechanisms that limit leukocyte activation, a cascade framework and briefly review how alteration of innate immune response genes in murine models can provide, the most effec- tive defense response needs to be sufficiently lethal to rapidly kill invading pathogens

  4. 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

  5. Mucosal immunity and the microbiome.

    PubMed

    Neish, Andrew S

    2014-01-01

    By definition, the mucosal immune system is responsible for interfacing with the outside world, specifically responding to external threats, of which pathogenic microbes represent a primary challenge. However, it has become apparent that the human host possesses a numerically vast and taxonomically diverse resident microbiota, predominantly in the gut, and also in the airway, genitourinary tract, and skin. The microbiota is generally considered symbiotic, and has been implicated in the regulation of cellular growth, restitution after injury, maintenance of barrier function, and importantly, in the induction, development, and modulation of immune responses. The mucosal immune system uses diverse mechanisms that protect the host from overt pathogens, but necessarily has coevolved to monitor, nurture, and exploit the normal microbiota. As a whole, mucosal immunity encompasses adaptive immune regulation that can involve systemic processes, local tissue-based innate and inflammatory events, intrinsic defenses, and highly conserved cell autonomous cytoprotective responses. Interestingly, specific taxa within the normal microbiota have been implicated in roles shaping specific adaptive, innate, and cell autonomous responses. Taken together, the normal microbiota exerts profound effects on the mucosal immune system, and likely plays key roles in human physiology and disease. PMID:24437401

  6. The role of G-proteins in plant immunity

    PubMed Central

    Zhang, Huajian; Gao, Zhimou; Zheng, Xiaobo; Zhang, Zhengguang

    2012-01-01

    Heterotrimeric G-proteins play an important regulatory role in multiple physiological processes, including the plant immune response, and substantial progress has been made in elucidating the G-protein-mediated defense-signaling network. This mini-review discusses the importance of G-proteins in plant immunity. We also provide an overview of how G-proteins affect plant cell death and stomatal movement. Our recent studies demonstrated that G-proteins are involved in signal transduction and induction of stomatal closure and defense responses. We also discuss future directions for G-protein signaling studies involving plant immunity. PMID:22895102

  7. Defense style changes with the addition of psychodynamic group therapy to clonazepam in social anxiety disorder.

    PubMed

    Knijnik, Daniela Z; Salum, Giovanni Abrahão; Blanco, Carlos; Moraes, Carolina; Hauck, Simone; Mombach, Clarissa K; Strapasson, Atahualpa C P; Manfro, Gisele G; Eizirik, Cláudio L

    2009-07-01

    Psychodynamic Group Therapy (PGT) and clonazepam are strategies to reduce symptoms of generalized social anxiety disorder (GSAD). The addition of PGT might lead to changes in defense styles. The objective of this study is to examine changes in defense styles when comparing clonazepam to psychodynamic group therapy plus clonazepam in GSAD during 12 weeks. Fifty-seven patients that met DSM-IV criteria for GSAD participated. social anxiety disorder symptoms were evaluated with the Liebowitz Social Anxiety Scale, and defense styles with the Defense Style Questionnaire. All defense styles changed overtime for both groups, especially mature defense style, which increased independently of the treatment allocation group. Regression analyses found that overtime there was a reduction in neurotic defenses in the combined group, whereas there was an increase in the clonazepam group. Neurotic defense style can change toward greater adaptiveness with the addition of PGT to clonazepam in GSAD, even in 12 weeks. PMID:19597364

  8. THE UNDER SECRETARY OF DEFENSE 3010 DEFENSE PENTAGON

    E-print Network

    Yang, Eui-Hyeok

    SECRETARY OF THE AIR FORCE (CONTRACTING) DIRECTOR, DEFENSE ADVANCED RESEARCH PROJECTS AGENCY ASSISTANT or Defense Agency that may obligate or transfer for obligation Basic Research appropriations, to comply AGENCY DIRECTOR, WASHINGTON HEADQUARTERS SERVICES SUBJECT: Indirect Cost Limitation for Basic Research

  9. 9. BASRELIEF DECORATION, 'DEFENSE', MURAL COMMEMORATING THE DEFENSE OF FORT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. BAS-RELIEF DECORATION, 'DEFENSE', MURAL COMMEMORATING THE DEFENSE OF FORT DEARBORN - Chicago River Bascule Bridge, Michigan Avenue, Spanning Chicago River at North Michigan Avenue, Chicago, Cook County, IL

  10. 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…

  11. Role of early cytokines, including alpha and beta interferons (IFN-?\\\\?), in innate and adaptive immune responses to viral infections

    Microsoft Academic Search

    Christine A Biron

    1998-01-01

    Innate cytokine responses are important mediators of early defense against infections. Certain of their effects can be delivered directly to activate protective mechanisms in infected cells. Others activate innate immune cells, including natural killer (NK) cells and macrophages, to mediate defense. Still others shape adaptive immune responses. The compositions and magnitudes of innate cytokine responses are modulated, by the nature

  12. Effect of dietary selenium on T cell immunity and cancer xenograft in nude mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Selenium is known to regulate carcinogenesis and immunity at nutritional and supranutritional levels. Because the immune system provides one of the main body defenses against cancer, we asked whether T cell immunity can modulate selenium chemoprevention. Twenty-four homozygous NU/J nude mice were fe...

  13. ORIGINAL PAPER Temporal dynamics and plasticity in the cellular immune response

    E-print Network

    Harvell, Catherine Drew

    defense mechanisms. Introduction The invertebrate immune system is distinct from that of vertebrates ancient component of immunity, studies are revealing that vertebrates and invertebrates alike rely heavily; Ausubel 2005). Studying the innate immune system also improves our understanding of disease dynamics

  14. El sistema inmune de los invertebrados - The immune system of the invertebrates)

    Microsoft Academic Search

    Antón Marín

    The immune recognition and physiological mechanisms related with immune system were evolutionary selected to maintain the viable organisms. On the other hand, survive of the organisms, both vertebrate and invertebrates, and their evolution depends of defense mechanisms that helped adapting to different habitats. An efficient immune system was developing in the invertebrates, it has

  15. Summer Dissertation Defense/Graduation

    E-print Network

    Kovalev, Leonid

    Semester 5 (Year 3) Semester 6 (Year 3) Summer Dissertation semesters (Years 4+) Defense/Graduation Fellows) Appointment of supervisory committee 3) Dissertation-writing 4) Defense Before defending, you must submit 1

  16. Salicylic Acid, a Plant Defense Hormone, Is Specifically Secreted by a Molluscan Herbivore

    PubMed Central

    Kästner, Julia; von Knorre, Dietrich; Himanshu, Himanshu; Erb, Matthias; Baldwin, Ian T.; Meldau, Stefan

    2014-01-01

    Slugs and snails are important herbivores in many ecosystems. They differ from other herbivores by their characteristic mucus trail. As the mucus is secreted at the interface between the plants and the herbivores, its chemical composition may play an essential role in plant responses to slug and snail attack. Based on our current knowledge about host-manipulation strategies employed by pathogens and insects, we hypothesized that mollusks may excrete phytohormone-like substances into their mucus. We therefore screened locomotion mucus from thirteen molluscan herbivores for the presence of the plant defense hormones jasmonic acid (JA), salicylic acid (SA) and abscisic acid (ABA). We found that the locomotion mucus of one slug, Deroceras reticulatum, contained significant amounts of SA, a plant hormone that is known to induce resistance to pathogens and to suppress plant immunity against herbivores. None of the other slugs and snails contained SA or any other hormone in their locomotion mucus. When the mucus of D. reticulatum was applied to wounded leaves of A. thaliana, the promotor of the SA-responsive gene pathogenesis related 1 (PR1) was activated, demonstrating the potential of the mucus to regulate plant defenses. We discuss the potential ecological, agricultural and medical implications of this finding. PMID:24466122

  17. Essential Functional Modules for Pathogenic and Defensive Mechanisms in Candida albicans Infections

    PubMed Central

    Tsai, I-Chun; Lin, Che; Chuang, Yung-Jen

    2014-01-01

    The clinical and biological significance of the study of fungal pathogen Candida albicans (C. albicans) has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved in C. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI) networks for both C. albicans and zebrafish were constructed. By comparing PPI networks at the early and late stages of the infection process, several critical functional modules were identified in both pathogenic and defensive mechanisms. Functional modules in C. albicans, like those involved in hyphal morphogenesis, ion and small molecule transport, protein secretion, and shifts in carbon utilization, were seen to play important roles in pathogen invasion and damage caused to host cells. Moreover, the functional modules in zebrafish, such as those involved in immune response, apoptosis mechanisms, ion transport, protein secretion, and hemostasis-related processes, were found to be significant as defensive mechanisms during C. albicans infection. The essential functional modules thus determined could provide insights into the molecular mechanisms of host-pathogen interactions during the infection process and thereby devise potential therapeutic strategies to treat C. albicans infection. PMID:24757665

  18. Immune System 1 Running Head: IMMUNE SYSTEM

    E-print Network

    Meagher, Mary

    Immune System 1 Running Head: IMMUNE SYSTEM Immune System Structure and Function Mary W. Meagher: 979-845-4727 CITATION: Meagher, M. W. (2004). Immune system structure and function. In A. Christensen System 2 Immune System Structure and Function The immune system is engaged in a constant surveillance

  19. Divergence in Structure and Activity of Phenolic Defenses in Young Leaves of Two Co-Occurring Inga Species

    Microsoft Academic Search

    John Lokvam; Thomas A. Kursar

    2005-01-01

    The leaves of tropical forest trees are most likely to suffer herbivore damage during the period of expansion. Herbivore 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 in the Neotropical genus Inga. We have characterized defense metabolites in

  20. The Innate Immune System in Transplantation

    PubMed Central

    Oberbarnscheidt, Martin H.; Zecher, Daniel; Lakkis, Fadi G.

    2012-01-01

    The vertebrate innate immune system consists of inflammatory cells and soluble mediators that comprise the first line of defense against microbial infection and, importantly, trigger antigen-specific T and B cell responses that lead to lasting immunity. The molecular mechanisms responsible for microbial non-self recognition by the innate immune system have been elucidated for a large number of pathogens. How the innate immune system recognizes non-microbial non-self, such as organ transplants, is less clear. In this review, we approach this question by describing the principal mechanisms of non-self, or ‘damaged’ self, recognition by the innate immune system (pattern recognition receptors, the missing self theory, and the danger hypothesis) and discussing whether and how these mechanisms apply to allograft rejection. PMID:21723740

  1. 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...

  2. 75 FR 76423 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    ...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...

  3. Defense waste transportation: cost and logistics studies

    SciTech Connect

    Andrews, W.B.; Cole, B.M.; Engel, R.L.; Oylear, J.M.

    1982-08-01

    Transportation of nuclear wastes from defense programs is expected to significantly increase in the 1980s and 1990s as permanent waste disposal facilities come into operation. This report uses models of the defense waste transportation system to quantify potential transportation requirements for treated and untreated contact-handled transuranic (CH-TRU) wastes and high-level defense wastes (HLDW). Alternative waste management strategies in repository siting, waste retrieval and treatment, treatment facility siting, waste packaging and transportation system configurations were examined to determine their effect on transportation cost and hardware requirements. All cost estimates used 1980 costs. No adjustments were made for future changes in these costs relative to inflation. All costs are reported in 1980 dollars. If a single repository is used for defense wastes, transportation costs for CH-TRU waste currently in surface storage and similar wastes expected to be generated by the year 2000 were estimated to be 109 million dollars. Recovery and transport of the larger buried volumes of CH-TRU waste will increase CH-TRU waste transportation costs by a factor of 70. Emphasis of truck transportation and siting of multiple repositories would reduce CH-TRU transportation costs. Transportation of HLDW to repositories for 25 years beginning in 1997 is estimated to cost $229 M in 1980 costs and dollars. HLDW transportation costs could either increase or decrease with the selection of a final canister configuration. HLDW transportation costs are reduced when multiple repositories exist and emphasis is placed on truck transport.

  4. Contemporary treatment of immune thrombocytopenia.

    PubMed

    Izak, Marina; Bussel, James Bruce

    2013-12-01

    Immune thrombocytopenia is an autoimmune-mediated disorder and the treatment strategies were directed mainly to suppression of the immune system or to removal of the spleen as a place of thrombocyte destruction. In last years, it was shown that other mechanisms are responsible for development of immune thrombocytopenia: reduced thrombocyte lifespan and ineffective marrow platelet production. New treatment strategies, such as thrombopoietin receptor agonists, were developed to overcome this mechanism. Still there are a difficult minority of patients unresponsive to multiple treatments, whose have severe bleeding and another group of patients with extensive morbidity from therapy, not restricted to steroids. In this review, focused on adult patients, we discuss newer results of therapies and consider newer treatment strategies. PMID:24083655

  5. Our Immune System

    MedlinePLUS

    ... story for children with primary immunodeficiency diseases Our Immune System Our Immune IMMUNE DEFICIENCY FOUNDATION A note from ... who are immune deficient to better understand their immune system. What is a “B-cell,” a “T-cell,” ...

  6. Civil defense: Carter's idiot arithmetic

    Microsoft Academic Search

    Lens

    1979-01-01

    President Carter's plan to triple spending on civil defense during the next 5 years bears little relationship to civil defense, but is a ruse to gain votes for the impending SALT II agreement, the author says. The apparent big advantage Russia holds in civil defense over the US is discussed, assuming first one nation, then the other, instigates a nuclear

  7. Situation awareness for cyber defense

    Microsoft Academic Search

    Leslie D. Cumiford; Leslie Dawn

    2006-01-01

    Situation awareness (SA), or the ability to assess situations and prepare timely responses, has long been acknowledged as an important aspect of theater operations for defensive purposes. Likewise, SA is critical in the cyber world. The focus of this paper is SA in the cyber domain with respect to defensive capabilities. The cyber defense domain has an important characteristic in

  8. Assertion and Defense Mechanism Preference.

    ERIC Educational Resources Information Center

    Massong, Stefan R.; And Others

    1982-01-01

    Investigated whether assertive and nonassertive individuals differ in defense mechanisms they most typically rely on when confronted with interpersonal stress and conflict. Results indicated assertive males and females both endorsed the most adaptive defense mechanism cluster, whereas nonassertive males and females endorsed more primitive defense

  9. Clearance Procedures Before Your Defense

    E-print Network

    Clearance Procedures Before Your Defense Familiarize yourself with the Manuscript Clearance section requirements manual, forms and templates. Submit your defense announcement to the Graduate School at this website: http://netprod.oti.fsu.edu/CS_Defense_Announcement Submit your manuscript to the Graduate School

  10. Thesis Proposal Defense Brett Bethke

    E-print Network

    de Weck, Olivier L.

    Thesis Proposal Defense Brett Bethke Aerospace Controls Lab, MIT December 5, 2008 Brett Bethke Aerospace Controls Lab, MIT () Thesis Proposal Defense December 5, 2008 1 / 31 #12;Outline Introduction Lab, MIT () Thesis Proposal Defense December 5, 2008 2 / 31 #12;Introduction Overall thesis objective

  11. Documents about the Missile Defense

    NSDL National Science Digital Library

    Christopher Griffith

    This collection of documents chronicles milestones in the development of a ballistic-missile defense. These include: President Reagan's ?SDI? Speech (excerpts), ?Foreword Written for a Report on the Strategic Defense Initiative,? and President Bush's ?Address to the American People about Ballistic Missile Defense.?

  12. Leishmania donovani: impairment of the cellular immune response against recombinant ornithine decarboxylase protein as a possible evasion strategy of Leishmania in visceral leishmaniasis.

    PubMed

    Yadav, Anupam; Amit, Ajay; Chaudhary, Rajesh; Chandel, Arvind Singh; Mahantesh, Vijay; Suman, Shashi Shekhar; Singh, Subhankar Kumar; Dikhit, Manas Ranjan; Ali, Vahab; Rabidas, Vidyanand; Pandey, Krishna; Kumar, Anil; Das, Pradeep; Bimal, Sanjiva

    2015-01-01

    Ornithine decarboxylase, the rate limiting enzyme of the polyamine biosynthesis pathway, is significant in the synthesis of trypanothione, T(SH)2, the major reduced thiol which is responsible for the modulation of the immune response and pathogenesis in visceral leishmaniasis. Data on the relationship between ornithine decarboxylase and the cellular immune response in VL patients are limited. Therefore, we purified a recombinant ornithine decarboxylase from Leishmania donovani (r-LdODC) of approximately 77kDa and examined its effects on the immunological responses in peripheral blood mononuclear cells of human visceral leishmaniasis cases. For these studies, ?-difluoromethylornithine was tested as an inhibitor and was used in parallel in all experiments. The r-LdODC was identified as having a direct correlation with parasite growth and significantly increased the number of promastigotes as well as axenic amastigotes after 96h of culture. The stimulation of peripheral blood mononuclear cells with r-LdODC up-regulated IL-10 production but not IFN-? production from CD4(+) T cells in active as well as cured visceral leishmaniasis cases, indicating a pivotal role for r-LdODC in causing strong immune suppression in a susceptible host. In addition, severe hindrance of the immune response and anti-leishmanial macrophage function due to r-LdODC, as revealed by decreased IL-12 and nitric oxide production, and down-regulation in mean fluorescence intensities of reactive oxygen species, occurred in visceral leishmaniasis patients. There was little impact of r-LdODC in the killing of L. donovani amastigotes in macrophages of visceral leishmaniasis patients. In contrast, when cultures of promastigotes and amastigotes, and patients' blood samples, were directed against ?-difluoromethylornithine, parasite numbers significantly reduced in culture, whereas the levels of IFN-? and IL-12, and the production of reactive oxygen species and nitric oxide, were significantly elevated. Therefore, we demonstrated cross-talk with the use of ?-difluoromethylornithine which can reduce the activity of ornithine decarboxylase of L. donovani, eliminating the parasite-induced immune suppression and inducing collateral host protective responses in visceral leishmaniasis. PMID:25449949

  13. Immune response

    MedlinePLUS

    ... called innate humoral immunity. Examples include the body's complement system and substances called interferon and interleukin-1 ( ... and proteins in the blood, such as antibodies, complement proteins, and interferon. Some of these directly attack ...

  14. Reciprocal Interactions of the Intestinal Microbiota and Immune System

    PubMed Central

    Maynard, Craig L.; Elson, Charles O.; Hatton, Robin D.; Weaver, Casey T.

    2013-01-01

    Preface Emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether to promote mutualism or host defense. These same attributes carry risk for immune-mediated diseases that are increasingly linked to the intestinal microbiota. Understanding how the adaptive immune system copes with the remarkable number and diversity of microbes that colonize the digestive tract, and how it integrates with more primitive innate immune mechanisms to maintain immune homeostasis, holds considerable promise for new approaches to modulate immune networks in order to treat and prevent disease. PMID:22972296

  15. Defense on the Move: Ant-Based Cyber Defense

    SciTech Connect

    Fink, Glenn A.; Haack, Jereme N.; McKinnon, Archibald D.; Fulp, Errin W.

    2014-04-15

    Many common cyber defenses (like firewalls and IDS) are as static as trench warfare allowing the attacker freedom to probe them at will. The concept of Moving Target Defense (MTD) adds dynamism to the defender side, but puts the systems to be defended themselves in motion, potentially at great cost to the defender. An alternative approach is a mobile resilient defense that removes attackers’ ability to rely on prior experience without requiring motion in the protected infrastructure itself. The defensive technology absorbs most of the cost of motion, is resilient to attack, and is unpredictable to attackers. The Ant-Based Cyber Defense (ABCD) is a mobile resilient defense providing a set of roaming, bio-inspired, digital-ant agents working with stationary agents in a hierarchy headed by a human supervisor. The ABCD approach provides a resilient, extensible, and flexible defense that can scale to large, multi-enterprise infrastructures like the smart electric grid.

  16. Inducible factors with antimicrobial activity after immune challenge in the haemolymph of Red Palm Weevil (Insecta).

    PubMed

    Mastore, Maristella; Binda Rossetti, Simona; Giovannardi, Stefano; Scarì, Giorgio; Brivio, Maurizio F

    2015-05-01

    Insects are capable of innate immune responses elicited after microbial infection. In this process, the receptor-mediated recognition of foreign bodies and the subsequent activation of immunocompetent cells lead to the synthesis ex novo of a peptide pool with antimicrobial activity. We investigated the inducible immune response of a coleopteran, Rhynchophorus ferrugineus, challenged with both Gram-negative and Gram-positive bacteria. After immunization, we evaluated the presence of antimicrobial peptides using either biochemical analyses or microbiological techniques. The antimicrobial properties of the newly synthesized protein pool, detectable in haemolymph fractions of low molecular mass, showed strong antibacterial activity against various bacterial strains (Escherichia coli, Pseudomonas sp. OX1, Bacillus subtilis and Micrococcus luteus). In addition to the preliminary study of the mechanism of action of the pool of antimicrobial peptides, we also investigated its effects on bacterial cell walls by means of fluorescence microscopy and scanning electron microscopy. The data suggest that the main effects seem to be directed at destabilizing and damaging the bacterial wall. This study provides data that help us to understand some aspects of the inducible innate immunity in a system model that lacks anticipatory responses. However, the weevil has finely tuned its defensive strategies to counteract effectively microbial infection. PMID:25114180

  17. Transcriptome Immune Analysis of the Invasive Beetle Octodonta nipae (Maulik) (Coleoptera: Chrysomelidae) Parasitized by Tetrastichus brontispae Ferrière (Hymenoptera: Eulophidae)

    PubMed Central

    Tang, Baozhen; Chen, Jun; Hou, Youming; Meng, E.

    2014-01-01

    The beetle Octodonta nipae (Maulik) (Coleoptera: Chrysomelidae) is a serious invasive insect pest of palm plants in southern China, and the endoparasitoid Tetrastichus brontispae Ferrière (Hymenoptera: Eulophidae) is a natural enemy of this pest that exhibits great ability in the biocontrol of O. nipae. For successful parasitism, endoparasitoids often introduce or secrete various virulence factors to suppress host immunity. To investigate the effects of parasitization by T. brontispae on the O. nipae immune system, the transcriptome of O. nipae pupae was analyzed with a focus on immune-related genes through Illumina sequencing. De novo assembly generated 49,919 unigenes with a mean length of 598 bp. Of these genes, 27,490 unigenes (55.1% of all unigenes) exhibited clear homology to known genes in the NCBI nr database. Parasitization had significant effects on the transcriptome profile of O. nipae pupae, and most of these differentially expressed genes were down-regulated. Importantly, the expression profiles of immune-related genes were significantly regulated after parasitization. Taken together, these transcriptome sequencing efforts shed valuable light on the host (O. nipae) manipulation mechanisms induced by T. brontispae, which will pave the way for the development of novel immune defense-based management strategies of O. nipae, and provide a springboard for further molecular analyses, particularly of O. nipae invasion. PMID:24614330

  18. Natural Resources Defense Council

    NSDL National Science Digital Library

    From the Natural Resources Defense Council, this website has the latest news from the Hill, plus information everyone needs on the state of our air, water, land and health. Initial contents include "State of Nature," a regular bulletin on environmental legislation; action guidelines; and findings on subjects ranging from children and environmental carcinogens to the pollution of U.S. coastal waters. Features in development include action alerts; consumer-oriented facts and FAQs; environmental multimedia clips; research tips; and more. The Natural Resources Defense Council is a national organization working in courtrooms, legislative chambers, regulatory agencies and the public arena to protect the world's natural resources and ensure a healthy environment for all.

  19. Boomeranging in structural defense

    PubMed Central

    Marler, Thomas E.

    2012-01-01

    Plant defensive behaviors that resist arthropod herbivory include trichome-mediated defenses, and variation in plant trichome morphology and abundance provides examples of the mechanistic complexities of insect-plant interactions. Trichomes were removed from Cycas revoluta cataphylls on the island of Guam to reveal Aulacaspis yasumatsui scale infestation, and predation of the newly exposed insects by pre-existing Rhyzobius lophanthae beetles commenced within one day. The quotient of predated/total scale insects was 0.5 by day 4 and stabilized at that found on adjacent glabrous leaves in about one week. The trichome phenotype covering the C. revoluta cataphyll complex offers the invasive A. yasumatsui armored scale effectual enemy-free space in this system. This pest and predator share no known evolutionary history with C. revoluta, therefore, the adaptive significance of this plant behavior in natural habitat is not yet known. PMID:22990448

  20. [Thoughts on "defensive" medicine].

    PubMed

    Csiba, László

    2007-03-25

    "Defensive" medicine is called medical behaviour characterized by deformation of diagnostic and therapeutic activities due to fears endangering existence and work, thus some interventions are omitted or, on the contrary, superfluous examinations are proposed on account of internal uncertainty, the patient's distrust or hostile social environment. Trust relation between patient and physician is the most gravely damaged because of aggravation and distortion of some conscienceless physicians' abuses by the media; patient-physician relations may not be degraded to contractual legal relations. Young physicians must get acquainted with the joy of success in diagnostics that enriches the personality. They shall have healthy self-esteem and be ready to take diagnostic and therapeutic challenges on themselves. All of us have to fight against social atmosphere hostile to physicians, against causes inducing and augmenting practice of defensive medicine. PMID:17444017

  1. Defense Waste Processing Facility

    SciTech Connect

    Haselow, J.S.; Wilhite, E.L.; Stieve, A.L.

    1990-05-01

    The information contained in this report is intended to supplement the original Environmental Impact Statement (EIS) for the Defense Waste Processing Facility (DWPF). Since the original EIS in 1982, alterations have been made to he conceptual process that reduce the impact to the groundwater. This reduced impact is documented in this report along with an update of the understanding of seismology and geology of the Savannah River Site. 6 refs., 2 figs., 2 tabs.

  2. Innate immunity to Paracoccidioides brasiliensis infection.

    PubMed

    Calich, Vera Lúcia Garcia; da Costa, Tânia Alves; Felonato, Maíra; Arruda, Celina; Bernardino, Simone; Loures, Flávio Vieira; Ribeiro, Laura Raquel Rios; de Cássia Valente-Ferreira, Rita; Pina, Adriana

    2008-01-01

    Innate immunity is based in pre-existing elements of the immune system that directly interact with all types of microbes leading to their destruction or growth inhibition. Several elements of this early defense mechanism act in concert to control initial pathogen growth and have profound effect on the adaptative immune response that further develops. Although most studies in paracoccidioidomycosis have been dedicated to understand cellular and humoral immune responses, innate immunity remains poorly defined. Hence, the main purpose of this review is to present and discuss some mechanisms of innate immunity developed by resistant and susceptible mice to Paracoccidioides brasiliensis infection, trying to understand how this initial host-pathogen interface interferes with the protective or deleterious adaptative immune response that will dictate disease outcome. An analysis of some mechanisms and mediators of innate immunity such as the activation of complement proteins, the microbicidal activity of natural killer cells and phagocytes, the production of inflammatory eicosanoids, cytokines, and chemokines among others, is presented trying to show the important role played by innate immunity in the host response to P. brasiliensis infection. PMID:18777631

  3. Soviet strategic defense technology

    SciTech Connect

    Stubbs, E.

    1987-04-01

    The present status of the Soviet program suggests several observations that have a bearing on predicting the future of the Soviet strategic defense program and its implications for the US: 1. The Soviet Union appears to have a continuing interest in ABM defenses, although ASATs seem to be a much lower priority. 2. The Soviet technology fielded to date was well within the American grasp 10 years ago. Where advanced and as yet undeployed technologies are concerned, the difference seems to be smaller; perhaps as little as five or seven years, with approximate parity in particle-beam research. 3. The Soviet Union, possibly more sensitive to prestige considerations, appears to be much more inclined than the US to demonstrate and deploy a technology before it is actually fully operational, and to undertake field modifications later. They also are much more reluctant to retire aging and obsolete technologies. As a result, they presently possess the world's only deployed ASAT and ABM systems, however, doubtful their actual operational effectiveness might be. 4. Soviet strategic defenses tend to be more fragmentary in design, reflecting their difficulties with the supporting and integrative technologies such as sensing, signal processing, heavy-lift boosters, and computing hardware and software. 5. The Soviets should also be expected to explore alternative avenues of near-term response to SDI, for example by expanding their strategic nuclear arsenal. 28 references, 1 figure, 2 tables.

  4. The Project on Defense Alternatives

    NSDL National Science Digital Library

    The Commonwealth Institute's Project on Defense Alternatives (PDA) "offers critical analysis of US [military] policy," promoting the "consideration of the broadest range of defense options" to devise and adapt national and international security policies in the post-Cold War era. The PDA's research and development activities include policy analysis and alternative policy development, as well as technical, historical, and methodological research. This Website provides access to the full text and abstracts of PDA briefing memos, reports, and monographs. The online publications are organized into four sections: US Defense Posture, Global & Regional Issues, Confidence Building Defense, and Opinion & Commentary. In addition, this searchable site provides organizational information, links to related military and defense Websites, and background and commentaries on the first US Quadrennial Defense Review issued by the US Department of Defense.

  5. Innate lymphoid cells in the defense against infections.

    PubMed

    Diefenbach, Andreas

    2013-09-01

    Barrier surfaces are under constant attack by potentially dangerous microbes. Interestingly, mucosal tissues contain a large number of innate lymphocytes now collectively referred to as innate lymphoid cells (ILCs). Different groups of ILCs are being distinguished, each of which produce an array of cytokines strikingly resembling the profile of the various T helper cell effector subsets. Over the last couple of years, evidence has been emerging that the various ILC subsets play important roles in immune defense against mucosal infections. In this review, I will introduce the various groups of ILCs and then focus on their roles for immunity to mucosal infections. PMID:24265932

  6. Ecdysone triggered PGRP-LC expression controls Drosophila innate immunity

    PubMed Central

    Rus, Florentina; Flatt, Thomas; Tong, Mei; Aggarwal, Kamna; Okuda, Kendi; Kleino, Anni; Yates, Elisabeth; Tatar, Marc; Silverman, Neal

    2013-01-01

    Throughout the animal kingdom, steroid hormones have been implicated in the defense against microbial infection, but how these systemic signals control immunity is unclear. Here, we show that the steroid hormone ecdysone controls the expression of the pattern recognition receptor PGRP-LC in Drosophila, thereby tightly regulating innate immune recognition and defense against bacterial infection. We identify a group of steroid-regulated transcription factors as well as two GATA transcription factors that act as repressors and activators of the immune response and are required for the proper hormonal control of PGRP-LC expression. Together, our results demonstrate that Drosophila use complex mechanisms to modulate innate immune responses, and identify a transcriptional hierarchy that integrates steroid signalling and immunity in animals. PMID:23652443

  7. The Innate Immune Playbook for Restricting West Nile Virus Infection

    PubMed Central

    Quicke, Kendra M.; Suthar, Mehul S.

    2013-01-01

    West Nile virus (WNV) is an emerging mosquito-borne flavivirus that causes annual epidemics of encephalitic disease throughout the world. Despite the ongoing risk to public health, no approved vaccines or therapies exist for use in humans to prevent or combat WNV infection. The innate immune response is critical for controlling WNV replication, limiting virus-induced pathology, and programming protective humoral and cell-mediated immunity to WNV infection. The RIG-I like receptors, Toll-like receptors, and Nod-like receptors detect and respond to WNV by inducing a potent antiviral defense program, characterized by production of type I IFN, IL-1? and expression of antiviral effector genes. Recent research efforts have focused on uncovering the mechanisms of innate immune sensing, antiviral effector genes that inhibit WNV, and countermeasures employed by WNV to antagonize innate immune cellular defenses. In this review, we highlight the major research findings pertaining to innate immune regulation of WNV infection. PMID:24178712

  8. Membrane-active host defense peptides – Challenges and perspectives for the development of novel anticancer drugs

    PubMed Central

    Riedl, Sabrina; Zweytick, Dagmar; Lohner, Karl

    2011-01-01

    Although much progress has been achieved in the development of cancer therapies in recent decades, problems continue to arise particularly with respect to chemotherapy due to resistance to and low specificity of currently available drugs. Host defense peptides as effector molecules of innate immunity represent a novel strategy for the development of alternative anticancer drug molecules. These cationic amphipathic peptides are able to discriminate between neoplastic and non-neoplastic cells interacting specifically with negatively charged membrane components such as phosphatidylserine (PS), sialic acid or heparan sulfate, which differ between cancer and non-cancer cells. Furthermore, an increased number of microvilli has been found on cancer cells leading to an increase in cell surface area, which may in turn enhance their susceptibility to anticancer peptides. Thus, part of this review will be devoted to the differences in membrane composition of non-cancer and cancer cells with a focus on the exposure of PS on the outer membrane. Normally, surface exposed PS triggers apoptosis, which can however be circumvented by cancer cells by various means. Host defense peptides, which selectively target differences between cancer and non-cancer cell membranes, have excellent tumor tissue penetration and can thus reach the site of both primary tumor and distant metastasis. Since these molecules kill their target cells rapidly and mainly by perturbing the integrity of the plasma membrane, resistance is less likely to occur. Hence, a chapter will also describe studies related to the molecular mechanisms of membrane damage as well as alternative non-membrane related mechanisms. In vivo studies have demonstrated that host defense peptides display anticancer activity against a number of cancers such as e.g. leukemia, prostate, ascite and ovarian tumors, yet so far none of these peptides has made it on the market. Nevertheless, optimization of host defense peptides using various strategies to enhance further selectivity and serum stability is expected to yield novel anticancer drugs with improved properties in respect of cancer cell toxicity as well as reduced development of drug resistance. PMID:21945565

  9. Insect Innate Immunity Database (IIID): An Annotation Tool for Identifying Immune Genes in Insect Genomes

    PubMed Central

    Brucker, Robert M.; Funkhouser, Lisa J.; Setia, Shefali; Pauly, Rini; Bordenstein, Seth R.

    2012-01-01

    The innate immune system is an ancient component of host defense. Since innate immunity pathways are well conserved throughout many eukaryotes, immune genes in model animals can be used to putatively identify homologous genes in newly sequenced genomes of non-model organisms. With the initiation of the “i5k” project, which aims to sequence 5,000 insect genomes by 2016, many novel insect genomes will soon become publicly available, yet few annotation resources are currently available for insects. Thus, we developed an online tool called the Insect Innate Immunity Database (IIID) to provide an open access resource for insect immunity and comparative biology research (http://www.vanderbilt.edu/IIID). The database provides users with simple exploratory tools to search the immune repertoires of five insect models (including Nasonia), spanning three orders, for specific immunity genes or genes within a particular immunity pathway. As a proof of principle, we used an initial database with only four insect models to annotate potential immune genes in the parasitoid wasp genus Nasonia. Results specify 306 putative immune genes in the genomes of N. vitripennis and its two sister species N. giraulti and N. longicornis. Of these genes, 146 were not found in previous annotations of Nasonia immunity genes. Combining these newly identified immune genes with those in previous annotations, Nasonia possess 489 putative immunity genes, the largest immune repertoire found in insects to date. While these computational predictions need to be complemented with functional studies, the IIID database can help initiate and augment annotations of the immune system in the plethora of insect genomes that will soon become available. PMID:22984621

  10. Prediction of an Epitope-based Computational Vaccine Strategy for Gaining Concurrent Immunization Against the Venom Proteins of Australian Box Jellyfish

    PubMed Central

    Alam, Md. Jibran; Ashraf, Kutub Uddin Muhammad

    2013-01-01

    Background: Australian Box Jellyfish (C. fleckeri) has the most rapid acting venom known to in the arena of toxicological research and is capable enough of killing a person in less than 5 minutes inflicting painful, debilitating and potentially life-threatening stings in humans. It has been understood that C. fleckeri venom proteins CfTX-1, 2 and HSP70-1 contain cardiotoxic, neurotoxic and highly dermatonecrotic components that can cause itchy bumpy rash and cardiac arrest. Subjects and Methods: As there is no effective drug available, novel approaches regarding epitope prediction for vaccine development were performed in this study. Peptide fragments as nonamers of these antigenic venom proteins were analyzed by using computational tools that would elicit humoral and cell mediated immunity, were focused for attempting vaccine design. By ranking the peptides according to their proteasomal cleavage sites, TAP scores and IC50<250 nM, the predictions were scrutinized. Furthermore, the epitope sequences were examined by in silico docking simulation with different specific HLA receptors. Results: Interestingly, to our knowledge, this is the maiden hypothetical immunization that predicts the promiscuous epitopes with potential contributions to the tailored design of improved safe and effective vaccines against antigenic venom proteins of C. fleckeri which would be effective especially for the Australian population. Conclusion: Although the computational approaches executed here are based on concrete confidence which demands more validation and in vivo experiments to validate such in silico approach. PMID:24403734

  11. Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers

    PubMed Central

    Prodeus, Aaron; Abdul-Wahid, Aws; Fischer, Nicholas W.; Huang, Eric H-B; Cydzik, Marzena; Gariépy, Jean

    2015-01-01

    Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a number of other tumor types as both a monotherapy and as part of combination regimens. Here, we report the development of DNA aptamers as synthetic, nonimmunogenic antibody mimics, which bind specifically to the murine extracellular domain of PD-1 and block the PD-1:PD-L1 interaction. One such aptamer, MP7, functionally inhibits the PD-L1-mediated suppression of IL-2 secretion in primary T-cells. A PEGylated form of MP7 retains the ability to block the PD-1:PD-L1 interaction, and significantly suppresses the growth of PD-L1+ colon carcinoma cells in vivo with a potency equivalent to an antagonistic anti-PD-1 antibody. Importantly, the anti-PD-1 DNA aptamer treatment was not associated with off-target TLR-9-related immune responses. Due to the inherent advantages of aptamers including their lack of immunogenicity, low cost, long shelf life, and ease of synthesis, PD-1 antagonistic aptamers may represent an attractive alternative over antibody-based anti PD-1 therapeutics. PMID:25919090

  12. Auxin promotes susceptibility to Pseudomonas syringae via a mechanism independent of suppression of salicylic acid-mediated defenses.

    PubMed

    Mutka, Andrew M; Fawley, Stephen; Tsao, Tiffany; Kunkel, Barbara N

    2013-06-01

    Auxin is a key plant growth regulator that also impacts plant-pathogen interactions. Several lines of evidence suggest that the bacterial plant pathogen Pseudomonas syringae manipulates auxin physiology in Arabidopsis thaliana to promote pathogenesis. Pseudomonas syringae strategies to alter host auxin biology include synthesis of the auxin indole-3-acetic acid (IAA) and production of virulence factors that alter auxin responses in host cells. The application of exogenous auxin enhances disease caused by P. syringae strain DC3000. This is hypothesized to result from antagonism between auxin and salicylic acid (SA), a major regulator of plant defenses, but this hypothesis has not been tested in the context of infected plants. We further investigated the role of auxin during pathogenesis by examining the interaction of auxin and SA in the context of infection in plants with elevated endogenous levels of auxin. We demonstrated that elevated IAA biosynthesis in transgenic plants overexpressing the YUCCA 1 (YUC1) auxin biosynthesis gene led to enhanced susceptibility to DC3000. Elevated IAA levels did not interfere significantly with host defenses, as effector-triggered immunity was active in YUC1-overexpressing plants, and we observed only minor effects on SA levels and SA-mediated responses. Furthermore, a plant line carrying both the YUC1-overexpression transgene and the salicylic acid induction deficient 2 (sid2) mutation, which impairs SA synthesis, exhibited additive effects of enhanced susceptibility from both elevated auxin levels and impaired SA-mediated defenses. Thus, in IAA overproducing plants, the promotion of pathogen growth occurs independently of suppression of SA-mediated defenses. PMID:23521356

  13. Cutaneous defenses against dermatophytes and yeasts.

    PubMed Central

    Wagner, D K; Sohnle, P G

    1995-01-01

    Predispositions to the superficial mycoses include warmth and moisture, natural or iatrogenic immunosuppression, and perhaps some degree of inherited susceptibility. Some of these infections elicit a greater inflammatory response than others, and the noninflammatory ones are generally more chronic. The immune system is involved in the defense against these infections, and cell-mediated immunity appears to be particularly important. The mechanisms involved in generating immunologic reactions in the skin are complex, with epidermal Langerhans cells, other dendritic cells, lymphocytes, microvascular endothelial cells, and the keratinocytes themselves all participating in one way or another. A variety of defects in the immunologic response to the superficial mycoses have been described. In some cases the defect may be preexistent, whereas in others the infection itself may interfere with protective cell-mediated immune responses against the organisms. A number of different mechanisms may underlie these immunologic defects and lead to the development of chronic superficial fungal infection in individual patients. Although the immunologic defects appear to be involved in the chronicity of certain types of cutaneous fungal infections, treatment of these defects remains experimental at the present time. PMID:7553568

  14. Denial Defense Mechanism in Dialyzed Patients.

    PubMed

    Nowak, Zbigniew; Wa?kowicz, Zofia; Laudanski, Krzysztof

    2015-01-01

    BACKGROUND It is a struggle to identify the most adaptive coping strategies with disease-mediated stress. Here, we hypothesize that intensity of coping strategies, including denial, in patients with end-stage renal disease (ESRD), varies with type of renal replacement therapy (RRT). MATERIAL AND METHODS We enrolled 60 in-center hemodialyzed patients (HD) and 55 patients treated with continuous ambulatory peritoneal dialysis (CAPD). We administered the Coping Inventory with Stressful Situation, Profile of Mood States, and Stroop Anxiety Inventory to measure patient coping strategies in the context of their ESRD. Denial defense mechanism was measured via the IBS-R/ED. The Nottingham Health Profile was used to evaluate self-perceived quality of life. Serum potassium, urea, creatinine, phosphorus, calcium, albumin, and hematocrit were utilized as the measurements of adequacy of dialysis. RESULTS HD patients had higher self-reported intensity of denial mechanism and avoidance-oriented strategies versus CAPD patients. Because a single strategy is almost never employed, we conducted cluster analysis. We identify 3 patterns of coping strategies using cluster analysis. "Repressors" employed denial and avoidance strategies and were predominant in HD. The second cluster consists of subjects employing predominantly task-oriented strategies with equal distribution among dialyzed patients. The third cluster encompassed a small group of patients who shared higher intensity of both denial and task-oriented strategies. Health-related outcome, anxiety, and mood profile were similar across all patients. CONCLUSIONS HD patients predominantly used "repressive" strategies. Patients on RRT utilized denial and avoidance-based strategies to achieve satisfactory outcome in terms of perceived quality of life. We conclude that these coping mechanisms that were previously thought to be inferior are beneficial to patient compliance with RRT. PMID:26094792

  15. Denial Defense Mechanism in Dialyzed Patients

    PubMed Central

    Nowak, Zbigniew; Wa?kowicz, Zofia; Laudanski, Krzysztof

    2015-01-01

    Background It is a struggle to identify the most adaptive coping strategies with disease-mediated stress. Here, we hypothesize that intensity of coping strategies, including denial, in patients with end-stage renal disease (ESRD), varies with type of renal replacement therapy (RRT). Material/Methods We enrolled 60 in-center hemodialyzed patients (HD) and 55 patients treated with continuous ambulatory peritoneal dialysis (CAPD). We administered the Coping Inventory with Stressful Situation, Profile of Mood States, and Stroop Anxiety Inventory to measure patient coping strategies in the context of their ESRD. Denial defense mechanism was measured via the IBS-R/ED. The Nottingham Health Profile was used to evaluate self-perceived quality of life. Serum potassium, urea, creatinine, phosphorus, calcium, albumin, and hematocrit were utilized as the measurements of adequacy of dialysis. Results HD patients had higher self-reported intensity of denial mechanism and avoidance-oriented strategies versus CAPD patients. Because a single strategy is almost never employed, we conducted cluster analysis. We identify 3 patterns of coping strategies using cluster analysis. “Repressors” employed denial and avoidance strategies and were predominant in HD. The second cluster consists of subjects employing predominantly task-oriented strategies with equal distribution among dialyzed patients. The third cluster encompassed a small group of patients who shared higher intensity of both denial and task-oriented strategies. Health-related outcome, anxiety, and mood profile were similar across all patients. Conclusions HD patients predominantly used “repressive” strategies. Patients on RRT utilized denial and avoidance-based strategies to achieve satisfactory outcome in terms of perceived quality of life. We conclude that these coping mechanisms that were previously thought to be inferior are beneficial to patient compliance with RRT. PMID:26094792

  16. Soybean and casein hydrolysates induce grapevine immune responses and resistance against Plasmopara viticola

    PubMed Central

    Lachhab, Nihed; Sanzani, Simona M.; Adrian, Marielle; Chiltz, Annick; Balacey, Suzanne; Boselli, Maurizio; Ippolito, Antonio; Poinssot, Benoit

    2014-01-01

    Plasmopara viticola, the causal agent of grapevine downy mildew, is one of the most devastating grape pathogen in Europe and North America. Although phytochemicals are used to control pathogen infections, the appearance of resistant strains and the concern for possible adverse effects on environment and human health are increasing the search for alternative strategies. In the present investigation, we successfully tested two protein hydrolysates from soybean (soy) and casein (cas) to trigger grapevine resistance against P. viticola. On Vitis vinifera cv. Marselan plants, the application of soy and cas reduced the infected leaf surface by 76 and 63%, as compared to the control, respectively. Since both hydrolysates might trigger the plant immunity, we investigated their ability to elicit grapevine defense responses. On grapevine cell suspensions, a different free cytosolic calcium signature was recorded for each hydrolysate, whereas a similar transient phosphorylation of two MAP kinases of 45 and 49 kDa was observed. These signaling events were followed by transcriptome reprogramming, including the up-regulation of defense genes encoding pathogenesis-related (PR) proteins and the stilbene synthase enzyme responsible for the biosynthesis of resveratrol, the main grapevine phytoalexin. Liquid chromatography analyses confirmed the production of resveratrol and its dimer metabolites, ?- and ?-viniferins. Overall, soy effects were more pronounced as compared to the cas ones. Both hydrolysates proved to act as elicitors to enhance grapevine immunity against pathogen attack. PMID:25566290

  17. Hitting the sweet spot-glycans as targets of fungal defense effector proteins.

    PubMed

    Künzler, Markus

    2015-01-01

    Organisms which rely solely on innate defense systems must combat a large number of antagonists with a comparably low number of defense effector molecules. As one solution of this problem, these organisms have evolved effector molecules targeting epitopes that are conserved between different antagonists of a specific taxon or, if possible, even of different taxa. In order to restrict the activity of the defense effector molecules to physiologically relevant taxa, these target epitopes should, on the other hand, be taxon-specific and easily accessible. Glycans fulfill all these requirements and are therefore a preferred target of defense effector molecules, in particular defense proteins. Here, we review this defense strategy using the example of the defense system of multicellular (filamentous) fungi against microbial competitors and animal predators. PMID:25955890

  18. Inter- and intraspecific comparisons of antiherbivore defenses in three species of rainforest understory shrubs.

    PubMed

    Fincher, R M; Dyer, L A; Dodson, C D; Richards, J L; Tobler, M A; Searcy, J; Mather, J E; Reid, A J; Rolig, J S; Pidcock, W

    2008-04-01

    Plants defend themselves against herbivores and pathogens with a suite of morphological, phenological, biochemical, and biotic defenses, each of which is presumably costly. The best studied are allocation costs that involve trade-offs in investment of resources to defense versus other plant functions. Decreases in growth or reproductive effort are the costs most often associated with antiherbivore defenses, but trade-offs among different defenses may also occur within a single plant species. We examined trade-offs among defenses in closely related tropical rain forest shrubs (Piper cenocladum, P. imperiale, and P. melanocladum) that possess different combinations of three types of defense: ant mutualists, secondary compounds, and leaf toughness. We also examined the effectiveness of different defenses and suites of defenses against the most abundant generalist and specialist Piper herbivores. For all species examined, leaf toughness was the most effective defense, with the toughest species, P. melanocladum, receiving the lowest incidence of total herbivory, and the least tough species, P. imperiale, receiving the highest incidence. Although variation in toughness within each species was substantial, there were no intraspecific relationships between toughness and herbivory. In other Piper studies, chemical and biotic defenses had strong intraspecific negative correlations with herbivory. A wide variety of defensive mechanisms was quantified in the three Piper species studied, ranging from low concentrations of chemical defenses in P. imperiale to a complex suite of defenses in P. cenocladum that includes ant mutualists, secondary metabolites, and moderate toughness. Ecological costs were evident for the array of defensive mechanisms within these Piper species, and the differences in defensive strategies among species may represent evolutionary trade-offs between costly defenses. PMID:18317843

  19. IL1beta processing in host defense: beyond the inflammasomes

    Microsoft Academic Search

    Mihai G. Netea; Anna Simon; Frank van de Veerdonk; Bart-Jan Kullberg; Leo A. B. Joosten

    2010-01-01

    Stimulation and release of proinflammatory cytokines is an essential step for the activation of an effective innate host defense, and subsequently for the modulation of adaptive immune responses. Interleukin-1beta (IL-1beta) and IL-18 are important proinflammatory cytokines that on the one hand activate monocytes, macropages, and neutrophils, and on the other hand induce Th1 and Th17 adaptive cellular responses. They are

  20. Identification, expression analysis and characterization of defense and signaling genes in Vitis vinifera

    Microsoft Academic Search

    Julie Chong; Gaëlle Le Henanff; Christophe Bertsch; Bernard Walter

    2008-01-01

    The reduction of phytochemicals applied to grapevine relies on the development of alternative strategies involving activation of the plant's own defense system. The aim of this work was to study the signaling of defense responses to pathogens in Vitis vinifera. We identified in V. vinifera cv. Chardonnay two putative regulatory elements, VvNHL1 and VvEDS1, with similarity to Arabidopsis defense regulators

  1. Artificial Immune Systems 209 Artificial Immune Systems

    E-print Network

    Timmis, Jon

    Artificial Immune Systems 209 Chapter XI Artificial Immune Systems: Using the Immune System, Idea Group Publishing. The immune system is highly distributed, highly adaptive, self encounters. From a computational view- point, the immune system has much to offer by way of inspiration

  2. Defensive work in nursing homes: accountability gone amok.

    PubMed

    Wiener, C L; Kayser-Jones, J

    1989-01-01

    This paper contrasts conditions in intensive care nurseries and skilled nursing facilities in order to bring out certain features of organizational functioning in nursing homes. Data stem from a study of three American nursing homes which focused on the circumstances influencing decision-making in the evaluation and treatment of acute illness. DEFENSIVE WORK--work that is institution-protective and/or self-protective-emerged as a dominant process. It is demonstrated that the avoidance strategies which constitute defensive work lead to a progression of counterstrategies and foster skewed priorities. Consequences are: an acceptance of substandard care and a diversion of attention from therapeutic work. The relationship of defensive work to the larger question of how the nation handles its sick elderly is examined in the conclusion of the paper. Recommendations are offered for organizational steps that would re-channel the wasted energy that is spent on defensive work toward more productive therapeutic work. PMID:2928813

  3. Does self-defense training prevent sexual violence against women?

    PubMed

    Hollander, Jocelyn A

    2014-03-01

    Self-defense classes are offered across the nation as a strategy for reducing women's vulnerability to sexual assault. Yet there has been little systematic research assessing the effectiveness of these classes. In this article, I use data from a mixed methods study of a 10-week, university-based, feminist self-defense class to examine the effectiveness of self-defense training over a 1-year follow-up period. My analyses indicate that women who participate in self-defense training are less likely to experience sexual assault and are more confident in their ability to effectively resist assault than similar women who have not taken such a class. PMID:24626766

  4. OFFICE OF THE ASSISTANT SECRETARY OF DEFENSE 4000 DEFENSE PENTAGON

    E-print Network

    US Army Corps of Engineers

    DIRECTOR, HUMAN RESOURCES (DEFENSE LOGISTICS AGENCY) DIRECTOR, HUMAN RESOURCES (NATIONAL GEOSPATIAL-INTELLIGENCE AGENCY) DIRECTOR, HUMAN RESOURCES SERVICES (NATIONAL SECURITY AGENCY) DIRECTOR, HUMAN RESOURCES

  5. Green Tea: Nature's Defense against Malignancies

    Microsoft Academic Search

    Masood Sadiq Butt; Muhammad Tauseef Sultan

    2009-01-01

    The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green

  6. Assessment of Augmented Immune Surveillance and Tumor Cell Death by Cytoplasmic Stabilization of p53 as a Chemopreventive Strategy of 3 Promising Medicinal Herbs in Murine 2-Stage Skin Carcinogenesis.

    PubMed

    Ali, Farrah; Khan, Rehan; Khan, Abdul Quaiyoom; Lateef, Md Abdul; Maqbool, Tahir; Sultana, Sarwat

    2013-12-19

    Cancer is the final outcome of a plethora of events. Targeting the proliferation or inducing programmed cell death in a proliferating population is a major standpoint in the cancer therapy. However, proliferation is regulated by several cellular and immunologic processes. This study reports the inhibition of proliferation by augmenting immune surveillance, silencing acute inflammation, and inducing p53-mediated apoptosis of skin cancer by 3 promising medicinal extracts. We used the well-characterized model for experimental skin carcinogenesis in mice for 32 weeks to study the chemopreventive effect of the methanolic extracts of Trigonella foenumgraecum, Eclipta alba, and Calendula officinalis. All 3 extracts reduced the number, incidence, and multiplicity of tumors, which was confirmed by the pathologic studies that showed regressed tumors. There was a significant reduction in the PCNA+ nuclei in all treatment groups 32 weeks after the initiation. Mechanistic studies revealed that proliferative population in tumors is diminished by the restoration of the endogenous antioxidant defense, inhibition of the stress-related signal-transducing element NF?B, reduction of inflammation, enhancement of immunosurveillance of the genetically mutated cells, along with silencing of the cell cycle progression signals. Finally, all 3 medicinal extracts induced stable expression of p53 within the tumors, confirmed by the CFDA-Cy3 apoptosis assay. Results of our study confirm that these extracts not only limit the rate of proliferation by inhibition of the processes integral to cancer development but also induce stable cytoplasmic expression of p53-mediated apoptosis, leading to fewer and regressed tumors in mice. PMID:24363284

  7. DERCUM'S DISEASE: Fatty tissue rheumatism caused by immune defense reaction?

    Microsoft Academic Search

    Håkan Brorson; Birger Fagher

    SUMMARY: Dercum's disease, adiposis dolorosa or, more commonly, fatty tissue rheumatism, is a relatively unknown illness in spite of it being described as early as 1888 by the American neurologist Francis Xavier Dercum. It especially affects women of 20-40 years, but can even make an appearance in children. Pain in fatty tissue is the characteristic symptom. The patients, like sufferers

  8. Effects of Marijuana on the Lung and Immune Defenses

    Microsoft Academic Search

    Donald P. Tashkin; Michael D. Roth

    \\u000a Cannabis has been used as a drug for thousands of years, but marijuana smoking has become prevalent in Western society only during\\u000a the last 40 years (1,2). An annual survey conducted in the United States from 1975 to 2002 documented that marijuana is now the second most commonly\\u000a smoked substance after tobacco (1,2). Marijuana smoke, like tobacco smoke, is generated

  9. Microsoft Begins Defense

    NSDL National Science Digital Library

    de Nie, Michael Willem.

    The second half of the US vs. Microsoft antitrust trial began this week with clear indications that it will be as long and contentious as the first half. Microsoft's first witness, MIT's Richard Schmalensee, encountered some difficult cross-examination from Department of Justice (DOJ) lead attorney David Boies, particularly over his testimony based on a Microsoft-designed survey that almost no one believes was unbiased and fair. While this marked a setback for the software giant's defense, the battle is, of course, far from over, and analysts still disagree over the probable final outcome of the trial. The resources discussed in this week's In the News will provide background.

  10. Cross talk in defense signaling

    Microsoft Academic Search

    A. Koornneef; C. M. J. Pieterse

    2008-01-01

    Plants are equipped with an array of defense mechanisms to protect themselves against attack by herbivorous insects and microbial pathogens. Some of these defense mechanisms are preexisting, whereas others are only activated upon insect or pathogen invasion.\\u000aInduced defense responses entail fitness costs. Therefore, plants possess elaborate regulatory mechanisms that efficiently coordinate the activation of attackerspecific\\u000adefenses so that fitness

  11. Identification of a gap junction communication pathway critical in innate immunity

    E-print Network

    Patel, Suraj Jagdish

    2010-01-01

    The innate immune system is the first line of host defense, and its ability to propagate antimicrobial and inflammatory signals from the cellular microenvironment to the tissue at-large is critical for survival. In a ...

  12. Artificial Immune System Approaches for Aerospace Applications

    NASA Technical Reports Server (NTRS)

    KrishnaKumar, Kalmanje; Koga, Dennis (Technical Monitor)

    2002-01-01

    Artificial Immune Systems (AIS) combine a priori knowledge with the adapting capabilities of biological immune system to provide a powerful alternative to currently available techniques for pattern recognition, modeling, design, and control. Immunology is the science of built-in defense mechanisms that are present in all living beings to protect against external attacks. A biological immune system can be thought of as a robust, adaptive system that is capable of dealing with an enormous variety of disturbances and uncertainties. Biological immune systems use a finite number of discrete "building blocks" to achieve this adaptiveness. These building blocks can be thought of as pieces of a puzzle which must be put together in a specific way-to neutralize, remove, or destroy each unique disturbance the system encounters. In this paper, we outline AIS models that are immediately applicable to aerospace problems and identify application areas that need further investigation.

  13. Cholangiopathy with Respect to Biliary Innate Immunity

    PubMed Central

    Harada, Kenichi; Nakanuma, Yasuni

    2012-01-01

    Biliary innate immunity is involved in the pathogenesis of cholangiopathies in cases of biliary disease. Cholangiocytes possess Toll-like receptors (TLRs) which recognize pathogen-associated molecular patterns (PAMPs) and play a pivotal role in the innate immune response. Tolerance to bacterial PAMPs such as lipopolysaccharides is also important to maintain homeostasis in the biliary tree, but tolerance to double-stranded RNA (dsRNA) is not found. Moreover, in primary biliary cirrhosis (PBC) and biliary atresia, biliary innate immunity is closely associated with the dysregulation of the periductal cytokine milieu and the induction of biliary apoptosis and epithelial-mesenchymal transition (EMT), forming in disease-specific cholangiopathy. Biliary innate immunity is associated with the pathogenesis of various cholangiopathies in biliary diseases as well as biliary defense systems. PMID:21994888

  14. Control Processes and Defense Mechanisms

    PubMed Central

    HOROWITZ, MARDI; COOPER, STEVEN; FRIDHANDLER, BRAM; PERRY, J. CHRISTOPHER; BOND, MICHAEL; VAILLANT, GEORGE

    1992-01-01

    Defense-mechanism theory and control-process theory are related psychodynamic approaches to explaining and classifying how people ward off emotional upsets. Although both theories explain defensive maneuvers in the same motivational terms, each defines categories different1y. Classic categories define defense mechanisms at a relatively macroscopic level, whereas control-process theory aims at relatively microgenetic analysis of how cognitive maneuvers—involving what is thought, how it is thought, and how it is organized—may generate defensive states. The theories are not contradictory, but they are focused on different levels of observation; it is useful to compare how these classifications are applied to specific case material. PMID:22700114

  15. Empowering self-defense training.

    PubMed

    Thompson, Martha E

    2014-03-01

    The purpose of self-defense training is to expand people's options, yet it is often framed as a solely physical, and limiting, response to violence. I draw on my own experience as a self-defense instructor and that of others in the self-defense movement to argue that an empowerment approach to self-defense training contributes to the anti-violence movement in multiple ways: providing a pathway to increase women's and girls' safety and their potential for becoming powerful and effective social change agents right now, providing an informed and embodied understanding of violence, and offering comprehensive options to recognize, prevent, and interrupt violence. PMID:24686126

  16. Immune System Involvement

    MedlinePLUS

    ... With Health Plans For Your Patients Donate The Immune System and Psoriasis In 1979, researchers coincidentally found that ... immune system is called immunology. How does the immune system affect psoriasis? A normal immune system protects the ...

  17. Inflammasomes and host defenses against bacterial infections

    PubMed Central

    Vladimer, Gregory I.; Marty-Roix, Robyn; Ghosh, Shubhendu; Weng, Dan; Lien, Egil

    2013-01-01

    The inflammasome has emerged as an important molecular protein complex which initiates proteolytic processing of pro-IL-1? and IL-18 into mature inflammatory cytokines. In addition, inflammasomes initiate pyroptotic cell death that may be independent of those cytokines. Inflammasomes are central to elicit innate immune responses against many pathogens, and are key components in the induction of host defenses following bacterial infection. Here, we review recent discoveries related to NLRP1, NLRP3, NLRC4, NLRP6, NLRP7, NLRP12 and AIM2-mediated recognition of bacteria. Mechanisms for inflammasome activation and regulation are now suggested to involve kinases such as PKR and PKC?, ligand binding proteins such as the NAIPs, and caspase-11 and caspase-8 in addition to caspase-1. Future research will determine how specific inflammasome components pair up in optimal responses to specific bacteria. PMID:23318142

  18. Arabidopsis defense response against Fusarium oxysporum.

    PubMed

    Berrocal-Lobo, Marta; Molina, Antonio

    2008-03-01

    The plant fungal pathogen Fusarium oxysporum (Fox) is the causal agent of root rot or wilt diseases in several plant species, including crops such as tomato (Solanum lycopersicum), banana (Musa sapientum) and asparagus (Asparagus officinalis). Colonization of plants by Fox leads to the necrosis of the infected tissues, a subsequent collapse of vascular vessels and decay of the plant. Plant resistance to Fox appears to be monogenic or oligogenic depending on the host. Perception of Fox by plants follows the concept of elicitor-induced immune response, which in turn activates several plant defense signaling pathways. Here, we review the Fox-derived elicitors identified so far and the interaction among the different signaling pathways mediating plant resistance to Fox. PMID:18289920

  19. The Why, What, and How of the Strategic Defense Initiative.

    ERIC Educational Resources Information Center

    Rankine, Jr., Robert R.

    1985-01-01

    Addresses the strategy and policy implications of effective ballistic missile defense and the scope/priorities of a research program underway to determine its technical feasibility. Several types of "smart bullets" are described, along with sensing devices for space, air, and ground. Procedures established to centrally plan/control the program are…

  20. [Immune evasion of Pseudomonas aeruginosa].

    PubMed

    Shimada, Takahiro; Matsumura, Itaru

    2014-01-01

    Pseudomonas aeruginosa is an indigenous bacteria which inhabits on the surfaces of aqueous environments and is representative pathogen that causes opportunistic infection. P.aeruginosa is classified as low-virulence organism because it rarely causes infection in immunocompetent hosts, but in immunocompromised hosts it can cause a variety of severe infections leading to mortality. P.aeruginosa is also a representative pathogen of nosocomial infection. Emerging multidrug-resistant P.aeruginosa is now causing serious problems on clinical site. Regarding virulence factors, increasing number of studies using gene disrupted mutant bacterial strains revealed that P.aeruginosa possesses a variety of machinaries such as type 3 secretion system, exoenzyme, biofilm formation that impairs or evades host immune system. Also it is getting clarified that the virulence of P.aeruginosa is controlled by an inter-bacterial signal transduction system called quorum sensing. Meanwhile, studies on the host defense system using various gene targeting mice revealed the mechanisms by which host immune system detects and defends against invasion of P.aeruginosa. In this review, we describe these virulence factors, the mechanisms impairing host immune system, host's pathogen recognition system and immune evasion by P.aeruginosa. PMID:24598066

  1. An African perspective on mucosal immunity and HIV1

    Microsoft Academic Search

    P Pala; V R Gomez-Roman; J Gilmour; P Kaleebu

    2009-01-01

    HIV prevention mandates an understanding of the mechanisms of mucosal immunity with attention to some unique features of the epidemic and mucosal environment in the developing world. An effective vaccine will have to induce mucosal protection against a highly diverse virus, which is equipped with a number of immune evasion strategies. Its development will require assessment of mucosal immune responses,

  2. Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments.

    PubMed

    Lai, Rocky; Afkhami, Sam; Haddadi, Siamak; Jeyanathan, Mangalakumari; Xing, Zhou

    2015-06-01

    Despite the use of bacille Calmette-Guérin (BCG) for almost a century, pulmonary tuberculosis (TB) continues to be a serious global health concern. Therefore, there has been a pressing need for the development of new booster vaccines to enhance existing BCG-induced immunity. Protection following mucosal intranasal immunisation with AdHu5Ag85A is associated with the localisation of antigen-specific T-cells to the lung airway. However, parenteral intramuscular immunisation is unable to provide protection despite the apparent presence of antigen-specific T-cells in the lung interstitium. Recent advances in intravascular staining have allowed us to reassess the previously established T-cell distribution profile and its relationship with the observed differential protection. Respiratory mucosal immunisation empowers T-cells to home to both the lung interstitium and the airway lumen, whereas intramuscular immunisation-activated T-cells are largely trapped within the pulmonary vasculature, unable to populate the lung interstitium and airway. Given the mounting evidence supporting the safety and enhanced efficacy of respiratory mucosal immunisation over the traditional parenteral immunisation route, a greater effort should be made to clinically develop respiratory mucosal-deliverable TB vaccines. PMID:26028646

  3. Ten Myths About the Defense Budget

    Microsoft Academic Search

    Baker Spring

    The perception that the nation's defense expenditures are larger than they really are is the result of a widespread acceptance of 10 myths about the defense budget. These myths range from the assertion that defense expenditures impose a large burden on the U.S. economy to the assumption that the defense budget is skewed in favor of the defense contractors that

  4. Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens.

    PubMed

    Knodler, Leigh A; Crowley, Shauna M; Sham, Ho Pan; Yang, Hyungjun; Wrande, Marie; Ma, Caixia; Ernst, Robert K; Steele-Mortimer, Olivia; Celli, Jean; Vallance, Bruce A

    2014-08-13

    Inflammasome-mediated host defenses have been extensively studied in innate immune cells. Whether inflammasomes function for innate defense in intestinal epithelial cells, which represent the first line of defense against enteric pathogens, remains unknown. We observed enhanced Salmonella enterica serovar Typhimurium colonization in the intestinal epithelium of caspase-11-deficient mice, but not at systemic sites. In polarized epithelial monolayers, siRNA-mediated depletion of caspase-4, a human ortholog of caspase-11, also led to increased bacterial colonization. Decreased rates of pyroptotic cell death, a host defense mechanism that extrudes S. Typhimurium-infected cells from the polarized epithelium, accounted for increased pathogen burdens. The caspase-4 inflammasome also governs activation of the proinflammatory cytokine, interleukin (IL)-18, in response to intracellular (S. Typhimurium) and extracellular (enteropathogenic Escherichia coli) enteric pathogens, via intracellular LPS sensing. Therefore, an epithelial cell-intrinsic noncanonical inflammasome plays a critical role in antimicrobial defense at the intestinal mucosal surface. PMID:25121752

  5. Autophagy in innate and adaptive immunity.

    PubMed

    Xu, Yi; Eissa, N Tony

    2010-02-01

    Autophagy (self-eating) is an evolutionary conserved simple process by which cells target their own cellular organelles and long-lived proteins for degradation. Recently, this simple ancient process has proved to be involved in many biological aspects, including host defense, cell survival and death, innate and adaptive immunity, and cancer. The implications of aberrant regulation of autophagy in human diseases are just beginning to unravel. This is a brief review of recent progress in the association of autophagy with innate and adaptive immunity relevant to lung biology and disease. PMID:20160145

  6. Cytokines and immune surveillance in humans

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1993-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to further explore the effects of space flight on cytokines and cytokine-directed immunological function.

  7. 76 FR 72391 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ...Secretary [Docket ID DOD-2011-OS-0055] Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Revised...

  8. 76 FR 53119 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-25

    ...Secretary [Docket ID: DOD-2011-OS-0055] Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Comment...

  9. 76 FR 28757 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ...Secretary [DOCKET ID DOD-2011-OS-0055] Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Notice...

  10. 78 FR 78163 - Eligibility of the Gulf Cooperation Council To Receive Defense Articles and Defense Services...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ...Eligibility of the Gulf Cooperation Council To Receive Defense Articles and Defense Services Under the Foreign Assistance Act of 1961...Control Act, I hereby find that the furnishing of defense articles and defense services to the Gulf Cooperation Council will...

  11. 22 CFR 120.2 - Designation of defense articles and defense services.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false Designation of defense articles and defense services. 120.2 Section 120.2 Foreign...PURPOSE AND DEFINITIONS § 120.2 Designation of defense articles and defense services. The Arms...

  12. 22 CFR 120.2 - Designation of defense articles and defense services.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 2011-04-01 false Designation of defense articles and defense services. 120.2 Section 120.2 Foreign...PURPOSE AND DEFINITIONS § 120.2 Designation of defense articles and defense services. The Arms...

  13. Light-dependent expression of flg22-induced defense genes in Arabidopsis

    PubMed Central

    Sano, Satoshi; Aoyama, Mayu; Nakai, Kana; Shimotani, Koji; Yamasaki, Kanako; Sato, Masa H.; Tojo, Daisuke; Suwastika, I. Nengah; Nomura, Hironari; Shiina, Takashi

    2014-01-01

    Chloroplasts have been reported to generate retrograde immune signals that activate defense gene expression in the nucleus. However, the roles of light and photosynthesis in plant immunity remain largely elusive. In this study, we evaluated the effects of light on the expression of defense genes induced by flg22, a peptide derived from bacterial flagellins which acts as a potent elicitor in plants. Whole-transcriptome analysis of flg22-treated Arabidopsis thaliana seedlings under light and dark conditions for 30 min revealed that a number of (30%) genes strongly induced by flg22 (>4.0) require light for their rapid expression, whereas flg22-repressed genes include a significant number of genes that are down-regulated by light. Furthermore, light is responsible for the flg22-induced accumulation of salicylic acid (SA), indicating that light is indispensable for basal defense responses in plants. To elucidate the role of photosynthesis in defense, we further examined flg22-induced defense gene expression in the presence of specific inhibitors of photosynthetic electron transport: 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-benzoquinone (DBMIB). Light-dependent expression of defense genes was largely suppressed by DBMIB, but only partially suppressed by DCMU. These findings suggest that photosynthetic electron flow plays a role in controlling the light-dependent expression of flg22-inducible defense genes. PMID:25346742

  14. Genetic Requirements for Signaling from an Autoactive Plant NB-LRR Intracellular Innate Immune Receptor

    E-print Network

    Dangl, Jeff

    resemble those that regulate an SA­gradient-dependent signal amplification of defense and cell deathGenetic Requirements for Signaling from an Autoactive Plant NB-LRR Intracellular Innate Immune-LRR) sensor proteins in plants and mammals. Here, we study the genetic requirements for defense responses

  15. Cyber defense Network Maneuver Commander

    Microsoft Academic Search

    P. Beraud; A. Cruz; S. Hassell; J. Sandoval; J. J. Wiley

    2010-01-01

    Network Maneuver Commander (NMC) is a research project to develop a prototype cyber command and control (C2) system that maneuvers network-based elements preemptively, and to develop performance metrics to be used for the evaluation of cyber dynamic defense solutions. The Network Maneuver Commander addresses the gap area between active information operations & reactive information assurance defenses, by focusing on the

  16. A Framework of Coordinated Defense

    Microsoft Academic Search

    Shuyuan Mary Ho

    Coordinated defense in cyber warfare has emerged to protect information as assets through the use of technologies, policy, and best management practices for defending against coordinated attacks. However, combining massive security technologies, policies, procedures and security staff does not guarantee the effectiveness of defense. Without a well-defined and structured element of coordination, an organization can not stand firm during coordinated

  17. Quadrennial Defense Review February 2010

    E-print Network

    of Military Power 9 U.S. Defense Objectives 11 REBALANCING THE FORCE 17 Defend the United States in Cyberspace 37 Guiding the Evolution of the Force 39 Sizing and Shaping the Force 41 Main Elements of U.S STRENGTHENING RELATIONSHIPS 57 Strengthening Key Relationships Abroad 57 The Role of U.S. Defense Posture 62

  18. Self-Defense for Teens

    ERIC Educational Resources Information Center

    Givler, Jill I.

    2005-01-01

    Resources for self-defense training programs have become more popular and available over the last few years. Introducing a self-defense unit as part of a school physical education program is a wonderful way to address a number of psychosocial issues that prevail among teenagers today. The physical skills learned in this type of program allow…

  19. Defense acquisition programs

    SciTech Connect

    Not Available

    1990-06-01

    The continuing instability in the overall defense budget and the recent changes in Eastern Europe are forcing DOD and the military services to reexamine the need, priority, and annual funding levels for many weapon system acquisition programs. GAO reviewed six weapon system acquisition programs that DOD was scheduled to make an acquisition milestone decision on during fiscal year 1991. Under milestone authorization, up to five years funding can be approved to cover the entire acquisition phase for either full-scale development or full-rate production. This report examines the Non-Line-of-Sight Missile, the Light Helicopter, the MK-50 Torpedo, the Sensor Fuzed Weapon, the Advanced Tactical Fighter, and the Joint Tactical Information Distribution System Class 2 Terminals.

  20. Increasing immunization coverage.

    PubMed

    Hammer, Lawrence D; Curry, Edward S; Harlor, Allen D; Laughlin, James J; Leeds, Andrea J; Lessin, Herschel R; Rodgers, Chadwick T; Granado-Villar, Deise C; Brown, Jeffrey M; Cotton, William H; Gaines, Beverly Marie Madry; Gambon, Thresia B; Gitterman, Benjamin A; Gorski, Peter A; Kraft, Colleen A; Marino, Ronald Vincent; Paz-Soldan, Gonzalo J; Zind, Barbara

    2010-06-01

    In 1977, the American Academy of Pediatrics issued a statement calling for universal immunization of all children for whom vaccines are not contraindicated. In 1995, the policy statement "Implementation of the Immunization Policy" was published by the American Academy of Pediatrics, followed in 2003 with publication of the first version of this statement, "Increasing Immunization Coverage." Since 2003, there have continued to be improvements in immunization coverage, with progress toward meeting the goals set forth in Healthy People 2010. Data from the 2007 National Immunization Survey showed that 90% of children 19 to 35 months of age have received recommended doses of each of the following vaccines: inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella-zoster virus (VZB), hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib). For diphtheria and tetanus and acellular pertussis (DTaP) vaccine, 84.5% have received the recommended 4 doses by 35 months of age. Nevertheless, the Healthy People 2010 goal of at least 80% coverage for the full series (at least 4 doses of DTaP, 3 doses of IPV, 1 dose of MMR, 3 doses of Hib, 3 doses of HBV, and 1 dose of varicella-zoster virus vaccine) has not yet been met, and immunization coverage of adolescents continues to lag behind the goals set forth in Healthy People 2010. Despite these encouraging data, a vast number of new challenges that threaten continued success toward the goal of universal immunization coverage have emerged. These challenges include an increase in new vaccines and new vaccine combinations as well as a significant number of vaccines currently under development; a dramatic increase in the acquisition cost of vaccines, coupled with a lack of adequate payment to practitioners to buy and administer vaccines; unanticipated manufacturing and delivery problems that have caused significant shortages of various vaccine products; and the rise of a public antivaccination movement that uses the Internet as well as standard media outlets to advance a position, wholly unsupported by any scientific evidence, linking vaccines with various childhood conditions, particularly autism. Much remains to be accomplished by physician organizations; vaccine manufacturers; third-party payers; the media; and local, state, and federal governments to ensure dependable vaccine supply and payments that are sufficient to continue to provide immunizations in public and private settings and to promote effective strategies to combat unjustified misstatements by the antivaccination movement. Pediatricians should work individually and collectively at the local, state, and national levels to ensure that all children without a valid contraindication receive all childhood immunizations on time. Pediatricians and pediatric organizations, in conjunction with government agencies such as the Centers for Disease Control and Prevention, must communicate effectively with parents to maximize their understanding of the overall safety and efficacy of vaccines. Most parents and children have not experienced many of the vaccine-preventable diseases, and the general public is not well informed about the risks and sequelae of these conditions. A number of recommendations are included for pediatricians, individually and collectively, to support further progress toward the goal of universal immunization coverage of all children for whom vaccines are not contraindicated. PMID:20513736