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1

Ecological restoration strategy for Yuanmou dry-hot valley based on immune defensive structure  

NASA Astrophysics Data System (ADS)

It is necessary to take a more effective ecological restoration strategy in ecosystem-degraded regions typically represented by Yuanmou Dry-hot Valley, in order to reverse the trend of ecosystem services degradation. The four defensive hierarchical structures of natural immune system can resist the invasion of pathogenic microorganism and keep the organism healthy. The defensive hierarchical structure of immune system can be used for reference to build a strategy framework for sustainable ecological restoration, which is a trinity - the best way is to control or eliminate degradation factors, the lesser one is to cut off their contact with ecosystem, and the unwise but needed way is to take pertinence measures to control the degradation that has occurred. Accordingly, a strategy for restoring the Yuanmou Dry-hot Valley ecosystem is presented. The ecological restoration strategy based on defensive hierarchical structure has important guiding significance to restoration and control of other ecology degraded regions.

Zhang, Bin; Qin, Fachao; Liu, Gangcai; Ai, Nanshan; Di, Baofeng

2009-07-01

2

Molluscan immune defenses.  

PubMed

The interest of marine invertebrates as food resources provides a major interest to study molluscan immunity for better understanding of the host response to pathogens. Molluscs possess a natural immunity formed by anatomical and chemical protective barriers that prevent damage of the underlying tissues, body fluid losses and the infections of pathogenic microorganisms and parasites. The main physical barrier is shell and mucus which cover the soft body of molluscs. The integrity of body coverings is supported by blood clotting and wound healing. The internal defense mechanisms of molluscs involve such cellular reactions as: phagocytosis, nodule formation, encapsulation, pearl formation, atrophy, necrosis and tissue liquefaction. Granular hemocytes are the most numerous cell type of molluscan blood active in cellular defenses. Invaders small in size are eliminated by phagocytosis in which participate lectins and products of prophenyloxidase system activation. Numerous and large intruders are eliminated by nodule formation or encapsulation, either cellular or humoral. Humoral components of molluscan immunity are formed by lysozyme activity, lectins and the phenyloxidase system. Up to now the role of mercenenes, paolins, acute phase reactants, alpha 2-macroglobulins and multifunctional binding proteins with anti-protease activity is not well clarified yet. Research prospects on the field of molluscan immunology should essentially be devoted to study cellular defense functions and humoral effectors to select pathogen-resistant molluscs. This aim could also be achieved by the identification and characterization of immune genes which are candidates for molluscs genetic transformation. PMID:9597080

Gli?ski, Z; Jarosz, J

1997-01-01

3

Immune defense against pneumonic plague  

PubMed Central

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

Smiley, Stephen T.

2009-01-01

4

Immune defense and reproductive pace of life in Peromyscus mice.  

PubMed

Immune activity is variable within and among vertebrates despite the potentially large fitness costs of pathogens to their hosts. From the perspective of life history theory, immunological variability may be the consequence of counterbalancing investments in immune defense against other expensive physiological processes, namely, reproduction. In the present study, we tested the hypothesis that immune defense among captive-bred, disease-free Peromyscus mice would be influenced by their reproductive life history strategies. Specifically, we expected that small species that reproduce prolifically and mature rapidly (i.e., fast pace of life) would favor inexpensive, nonspecific immune defenses to promote reproductive proclivity. Alternatively, we expected that large species that mature slowly and invest modestly in reproduction over multiple events (i.e., slow pace of life) would favor developmentally expensive, specific immune defenses and avoid cheap, nonspecific ones because such defenses are predisposed to self-damage. We found that species exhibited either strong ability to kill (gram-negative) bacteria, a developmentally inexpensive defense, or strong ability to produce antibodies against a novel protein, a developmentally expensive defense, but not both. Cell-mediated inflammation also varied significantly among species, but in a unique fashion relative to bacteria killing or antibody production; wound healing was comparatively similar among species. These results indicate that Peromyscus species use immune strategies that are constrained to a dominant axis, but this axis is not determined solely by reproductive pace of life. Further comparisons, ideally with broader phylogenetic coverage, could identify what ecological and evolutionary forces produce the pattern we detected. Importantly, our study indicates that species may not be differentially immunocompetent; rather, they use unique defense strategies to prevent infection. PMID:18027755

Martin, Lynn B; Weil, Zachary M; Nelson, Randy J

2007-10-01

5

Defensive strategies in rugby union.  

PubMed

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

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

2013-08-01

6

Testicular defense systems: immune privilege and innate immunity  

PubMed Central

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

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

2014-01-01

7

Defensive Marketing Strategies  

Microsoft Academic Search

This paper analyzes how a firm should adjust its marketing expenditures and its price to defend its position in an existing market from attack by a competitive new product. Our focus is to provide usable managerial recommendations on the strategy of response. In particular we show that if products can be represented by their position in a multiattribute space, consumers

John R. Hauser; Steven M. Shugan

2008-01-01

8

Defensive Marketing Strategies  

Microsoft Academic Search

This paper analyzes how a firm should adjust its marketing expenditures and its price to defend its position in an existing market from attack by a competitive new product. Our focus is to provide usable managerial recommendations on the strategy of response. In particular we show that if products can be represented by their position in a multiattribute space, consumers

John R. Hauser; Steven M. Shugan

1983-01-01

9

Defense display strategy and roadmaps  

NASA Astrophysics Data System (ADS)

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.

Hopper, Darrel G.

2002-08-01

10

Network Intrusion Active Defense Model Based on Artificial Immune System  

Microsoft Academic Search

Based on artificial immune theory, a new model of active defense for analyzing the network intrusion is presented. Dynamically evaluative equations for self, antigen, immune tolerance, mature-lymphocyte lifecycle and immune memory are presented. The concepts and formal definitions of immune cells are given, the hierarchical and distributed management framework of the proposed model are built. Furthermore, the idea of biology

Cheng Zhang; Jing Zhang; Sunjun Liu; Yintian Liu

2008-01-01

11

The role of Innate Immunity in the Host Defense Against intestinal Bacterial Pathogens  

PubMed Central

Eradication of infectious disease is our global health challenge. After encountering intestinal infection with a bacterial pathogen, the host defense program is initiated by local antigen-presenting cells (APCs) that eliminate invading pathogens by phagocytosis and establish localized inflammation by secreting cytokines and chemokines. These pathogen-experienced APCs migrate to the mesenteric lymph nodes, where host immune responses are precisely orchestrated. Initiation and regulation of this defense program appear to be largely dependent on innate immunity which is antigen non-specific and provides a rapid defense against broader targets. On the other hand, many bacterial enteropathogens have evoked abilities to modify the host defense program to their advantage. Therefore, better understanding of the host-pathogen interactions is essential to establish effective eradication strategies for enteric infectious diseases. In this review, we will discuss the current understanding of innate immune regulation of the host defense mechanisms against intestinal infection by bacterial pathogens. PMID:22139594

Sotolongo, John; Ruiz, Jose; Fukata, Masayuki

2012-01-01

12

Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses  

PubMed Central

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

Mogensen, Trine H.

2009-01-01

13

Topical immunization strategies  

Microsoft Academic Search

Research has yielded an abundance of vaccine candidates against mucosal infections, but only few mucosal vaccines have been registered for human use. Extensive research is being carried out to identify new and safe adjuvants for mucosal immunization, novel delivery systems, including live vectors and reporter molecules for tissue- and cell-specific targeting of vaccine antigens. If these candidates are to reach

C Czerkinsky; J Holmgren

2010-01-01

14

Restoring immune defenses via lymphotoxin signaling  

Microsoft Academic Search

Although primary infection with human cytomegalovirus (HCMV), a ?-herpesvirus, is widespread and acquired early in life, it\\u000a rarely causes disease in immune-competent individuals. However, in immune-compromised patients HCMV infection or reactivation\\u000a invariably leads to serious disease, the effective treatment of which remains a difficult clinical problem. Current antiviral\\u000a therapy is limited not only by toxicity but also by the continual

Theresa A. Banks; Sandra Rickert; Carl F. Ware

2006-01-01

15

Clotting and immune defense in Limulidae.  

PubMed

The blue blood of the horseshoe crab contains a sophisticated defense system very sensitive to pathogens or foreign materials. The hemocytes circulating in the hemolymph detect trace amounts of LPS molecules on the invading microorganisms and respond quickly to release the granular components into the external milieu. The coagulation system composed of three serine protease zymogens, factor C, factor B, and proclotting enzyme, and a clottable protein, coagulogen, is activated by LPS to form insoluble coagulin gel. The coagulation system also responds to beta-(1,3) glucan through the activation of unique heterodimeric serine protease zymogen, factor G. The pathogens are, thus, engulfed in the gel and subsequently killed by antimicrobial substances with various specificities, which are also released from cells. The horseshoe crab has developed two kinds of serine protease zymogens as biological sensors, factor C and factor G, which are responsive to LPS and beta-(1,3) glucan on the surface of Gram-negative bacteria and fungi, respectively. These are possible invaders for horseshoe crabs and also for most animals including humans. This novel heterodimeric serine protease zymogen, factor G, may open a new way to develop an innovative assay system to quantitate beta-(1,3) glucans. Furthermore, these LPS and beta-(1,3) glucan sensitive factors could be utilized as a unique tool to analyze other biological reactions caused by LPS or the glucan. Although the coagulation reaction in horseshoe crabs is famous, it is not the only defense mechanism of this animal. Many agglutinins are present either in hemolymph plasma or in the cell. The hemolymph plasma also has cytolytic activity against foreign cells. These cellular and humoral defense systems, in concert, defend themselves from invading foreign organisms. Such a sophisticated defense system has allowed the horseshoe crab to survive for more than 200 million years on the earth. Horseshoe crabs are often called ¿living fossils." However, they are not fossils. They are living. PMID:8963461

Muta, T; Iwanaga, S

1996-01-01

16

Immune Building Technology and Bioterrorism Defense  

NSDL National Science Digital Library

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

Bahnfleth, William P. (William Parry), 1957-; Kowalski, Wladyslaw J.

2008-01-04

17

Modulation of host innate and adaptive immune defenses by cytomegalovirus: timing is everything  

PubMed Central

Loewendorf A, Benedict CA (La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA). Modulation of host innate and adaptive immune defenses by cytomegalovirus: timing is everything (Symposium). Human cytomegalovirus (HCMV) (HHV-5, a ?-herpesvirus) causes the vast majority of infection-related congenital birth defects, and can trigger severe disease in immune suppressed individuals. The high prevalence of societal infection, the establishment of lifelong persistence and the growing number of immune-related diseases where HCMV is touted as a potential promoter is slowly heightening public awareness to this virus. The millions of years of co-evolution between CMV and the immune system of its host provides for a unique opportunity to study immune defense strategies, and pathogen counterstrategies. Dissecting the timing of the cellular and molecular processes that regulate innate and adaptive immunity to this persistent virus has revealed a complex defense network that is shaped by CMV immune modulation, resulting in a finely tuned host–pathogen relationship. PMID:20433576

Loewendorf, A.; Benedict, C. A.

2010-01-01

18

T Cell-Mediated Host Immune Defenses in the Lung  

PubMed Central

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

Chen, Kong; Kolls, Jay K.

2014-01-01

19

Immunity and other defenses in pea aphids, Acyrthosiphon pisum  

PubMed Central

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

2010-01-01

20

Passive and active components of neonatal innate immune defenses.  

PubMed

Innate immune defenses are crucial for survival in the first days and weeks of life. At birth, newborns are confronted with a vast array of potentially pathogenic microorganisms that were not encountered in utero. At this age, cellular components of the adaptive immune system are in a naive state and are slow to respond. Antibodies received from the dam are essential for defense, but represent a finite and dwindling resource. Innate components of the immune system detect pathogen-associated molecular patterns (PAMPs) on microorganisms (and their products) by means of pattern-recognition receptors (PRRs). Soluble mediators of the innate system such as complement proteins, pentraxins, collectins, ficolins, defensins, lactoferrin, lysozyme etc. can bind to structures on pathogens, leading to agglutination, interference with receptor binding, opsonization, neutralization, direct membrane damage and recruitment of additional soluble and cellular elements through inflammation. Cell-associated receptors such as the Toll-like receptors (TLRs) can activate cells and coordinate responses (both innate and adaptive). In this paper, accumulated knowledge of the receptors, soluble and cellular elements that contribute to innate defenses of young animals is reviewed. Research interest in this area has been intermittent, and the literature varies in quantity and quality. It is hoped that documentation of the limitations of our knowledge base will lead to more extensive and enlightening studies. PMID:16583779

Firth, Matthew A; Shewen, Patricia E; Hodgins, Douglas C

2005-12-01

21

Contrasting adaptive immune defenses and blood parasite prevalence in closely related Passer sparrows  

Microsoft Academic Search

Immune system components differ in their functions and costs, and immune defense profiles are likely to vary among species with differing ecologies. We compared adaptive immune defenses in two closely related species that have contrasting inflammatory immune responses, the widespread and abundant house sparrow (Passer domesticus) and the less abundant tree sparrow (Passer montanus). We found that the house sparrow,

Kelly A. Lee; Lynn B. Martin II; Dennis Hasselquist; Robert E. Ricklefs; Martin Wikelski

2006-01-01

22

Efficient immunization strategies to prevent financial contagion.  

PubMed

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

Kobayashi, Teruyoshi; Hasui, Kohei

2014-01-01

23

Efficient immunization strategies to prevent financial contagion  

PubMed Central

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

Kobayashi, Teruyoshi; Hasui, Kohei

2014-01-01

24

PERSPECTIVE D Passive Antibody Administration (Immediate Immunity) as a Specific Defense against Biological Weapons  

E-print Network

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

Arturo Casadevall

25

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

PubMed

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

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

2014-08-01

26

Phylogenetic escalation and decline of plant defense strategies  

E-print Network

- tionary dynamics between plants and herbivores and suggests a revision of classic plant defense theoryPhylogenetic escalation and decline of plant defense strategies Anurag A. Agrawal* and Mark resource in most food webs, plants have evolved myriad strategies to battle consumption by herbivores. Over

Agrawal, Anurag

27

Dynamical Immunization Strategy for Seasonal Epidemics  

E-print Network

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

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

2014-01-01

28

Dynamical immunization strategy for seasonal epidemics  

NASA Astrophysics Data System (ADS)

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

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

2014-08-01

29

Intracellular Innate Immune Cascades and Interferon Defenses That Control Hepatitis C Virus  

PubMed Central

Hepatitis C virus (HCV) is a global public health problem that mediates a persistent infection in nearly 200 million people. HCV is efficient in establishing chronicity due in part to the inefficiency of the host immune system in controlling and counteracting HCV-mediated evasion strategies. HCV persistence is linked to the ability of the virus to suppress the RIG-I pathway and interferon production from infected hepatocytes, thus evading innate immune defenses within the infected cell. This review describes the virus and host processes that regulate the RIG-I pathway during HCV infection. An understanding of these HCV–host interactions could lead to more effective therapies for HCV designed to reactivate the host immune response following HCV infection. PMID:19708811

Horner, Stacy M.

2009-01-01

30

Filicide: Gender Bias in California Defense Attorneys' Perception of Motive And Defense Strategies  

Microsoft Academic Search

This study is the first of its kind to evaluate attorneys' perception of motive and defense strategies when presented with a fictional filicide case. A vignette-based survey was designed to elicit data regarding perception of motive and willingness to use various defenses. Participants were more likely to agree that jealousy and retaliation were motivating factors when the perpetrator was male,

Jennifer Orthwein; Wendy Packman; Rebecca Jackson; Bruce Bongar

2010-01-01

31

Thermoregulatory strategy may shape immune investment in Drosophila melanogaster.  

PubMed

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

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

2014-10-15

32

Immune defense to dietary cow milk in healthy infants.  

PubMed

The healthy young infant is immunologically adapted to receiving vast amounts of antigens in diet. At the age of 6 months, nine infants were put on a CM elimination diet for 3 weeks and then challenged with CM. Gut immune response was evaluated indirectly with ELISPOT assay at 6 months, after CM elimination (Day 1) and challenge (Day 8), and at 11 months. CM elimination decreased the numbers of immunoglobulin secreting cells (ISC): in the IgM class from mean [95% CI] 4969 [2555, 9653] at 6 months to 1716 [1024, 2873]/10(6) cells on Day 1 (t = 3.14, p = 0.01); and in the IgG class from 5547 [3562, 8630] to 2684 [1383, 5208]/10(6) cells (t = 3.29, p = 0.01). CM challenge further reduced inter-individual variation, and at 11 months the scatter of ISC was comparable to that at 6 months. Specific antibody-secreting cells of the IgA and IgG class were seen at 6 months and again at 11 months, while specific IgM-secreting cells persisted throughout the dietary manipulation. The results indicate that diet profoundly affects the immune defense system, and further suggest that a focused immune response is vital in acquisition of tolerance to dietary antigens. PMID:8348255

Kaila, M

1993-02-01

33

Degree-based attacks and defense strategies in complex networks  

NASA Astrophysics Data System (ADS)

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.

Yehezkel, Aviv; Cohen, Reuven

2012-12-01

34

Degree-based attacks and defense strategies in complex networks.  

PubMed

We study the stability of random scale-free networks to degree-dependent attacks. We present analytical and numerical results to compute the critical fraction p_{c} 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. PMID:23368011

Yehezkel, Aviv; Cohen, Reuven

2012-12-01

35

Racquetball Beginner Strategies: Reading the Defense  

ERIC Educational Resources Information Center

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

Strand, Brad; Albrecht, Jay; Traschel, Jamie

2007-01-01

36

Connecting growth and defense: the emerging roles of brassinosteroids and gibberellins in plant innate immunity.  

PubMed

Brassinosteroids (BRs) and gibberellins (GAs) are two groups of phytohormones that regulate many common developmental processes throughout the plant life cycle. Fueled by large-scale 'omics' technologies and the burgeoning field of plant computational biology, the past few years have witnessed paradigm-shifting advances in our understanding of how BRs and GA are perceived and their signals transduced. Accumulating evidence also implicates BR and GA in the coordination and integration of plant immune responses. Similarly to other growth regulators, BR and GA play ambiguous roles in molding pathological outcomes, the effects of which may depend not only on the pathogen's lifestyle and infection strategy, but also on specialized features of each interaction. Analysis of the underpinning molecular mechanisms points to a crucial role of GA-inhibiting DELLA proteins and the BR-regulated transcription factor BZR1. Acting at the interface of developmental and defense signaling, these proteins likely serve as central hubs for pathway crosstalk and signal integration, allowing appropriate modulation of plant growth and defense in response to various stimuli. In this review, we outline the latest discoveries dealing with BR and GA modulation of plant innate immunity and highlight interactions between BR and GA signaling, plant defense, and microbial virulence. PMID:24777987

De Bruyne, Lieselotte; Höfte, Monica; De Vleesschauwer, David

2014-06-01

37

Learning Attack Strategies from Intrusion Alerts Cyber Defense Laboratory  

E-print Network

Learning Attack Strategies from Intrusion Alerts Peng Ning Cyber Defense Laboratory Department of Computer Science North Carolina State University Raleigh, NC 27695-8207 ning@csc.ncsu.edu Dingbang Xu Cyber-8207 dxu@unity.ncsu.edu ABSTRACT Understanding strategies of attacks is crucial for security applica- tions

Ning, Peng

38

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

PubMed

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

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

2009-04-01

39

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

E-print Network

immune system that uses somatic gene rearrangement to diversify receptors built from LRR (leucine rich6/29/11 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

Utrecht, Universiteit

40

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

PubMed Central

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

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

2013-01-01

41

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

PubMed

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

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

2013-04-01

42

Immune evasion strategies used by Helicobacter pylori  

PubMed Central

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.

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

2014-01-01

43

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

PubMed Central

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

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

2012-01-01

44

Agent-based modeling approach of immune defense against spores of opportunistic human pathogenic fungi.  

PubMed

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

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

2012-01-01

45

An alternative to present United States defense strategy  

E-print Network

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...

Anthony, William Wallace

2012-06-07

46

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

Microsoft Academic Search

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

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

2009-01-01

47

Normal Gut Mucosal Immunity: A Dynamic Balance of Tolerance and Defense  

Microsoft Academic Search

The gut mucosal immune system is a complex, integrated network of tissues and cells that performs the work of defense against pathogens and the management of high antigenic exposure from intestinal microbes and food. This network includes the epithelial barrier, the innate and adaptive immune systems, regulatory cells, and probably the commensal gut flora itself. Emerging data from animal and

Peter Mannon

2005-01-01

48

An engineered innate immune defense protects grapevines from Pierce disease  

PubMed Central

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

Dandekar, Abhaya M.; Gouran, Hossein; Ibanez, Ana Maria; Uratsu, Sandra L.; Aguero, 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

49

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

PubMed Central

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

Naseem, Muhammad; Kunz, Meik; Dandekar, Thomas

2014-01-01

50

Strategy alternatives for homeland air and cruise missile defense.  

PubMed

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

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

2010-10-01

51

Mucosal Immunity: Its Role in Defense and Allergy  

Microsoft Academic Search

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

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

2002-01-01

52

Plant mating system transitions drive the macroevolution of defense strategies.  

PubMed

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

Campbell, Stuart A; Kessler, André

2013-03-01

53

Investment in immune defense is linked to pace of life in house sparrows  

Microsoft Academic Search

The evidence for a relationship between life history and immune defense is equivocal, although the basic premise is intuitively\\u000a appealing: animals that live short lives and reproduce early and rapidly should not waste resources on defenses they might\\u000a never use. One possible reason for a lack of strong support for this hypothesis could be the inherent complexity of the vertebrate

Lynn B. Martin II; Dennis Hasselquist; Martin Wikelski

2006-01-01

54

Immune system activation affects song and territorial defense  

Microsoft Academic Search

Previous studies have demonstrated that bird song is influenced by infection. We investigated how mounting an immune response by mountain white-crowned sparrows (Zonotrichia leucophrys oriantha) affects specific aspects of territorial song and behavior. We used song playback to simulate a territorial intrusion and elicit baseline song and behavioral responses. Individuals were then either injected with a saline control or with

Nicole E. Munoz; Daniel T. Blumstein; Johannes Foufopoulos

2010-01-01

55

Control Systems Cyber Security: Defense-in-Depth Strategies  

SciTech Connect

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.

Mark Fabro

2007-10-01

56

Control Systems Cyber Security:Defense in Depth Strategies  

SciTech Connect

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.

David Kuipers; Mark Fabro

2006-05-01

57

Evolution and phylogeny of defense molecules associated with innate immunity in horseshoe crab.  

PubMed

This short review describes the molecular evolution and phylogeny of various defense molecules participating in the host defense of horseshoe crab. It is well known that invertebrate animals, which lack adaptive immune systems, have developed various defense systems, so called innate immunity, that respond to common antigens on the surface of potential pathogens. The systems include hemolymph coagulation, melanization, cell agglutination, antimicrobial action, active oxygen formation, and phagocytic action. Among them, hemolymph coagulation and phenoloxidase-mediated melanization, in addition to cell agglutination, are directly induced by foreign substances, that result in the engulfment of invading microbes. The immobilized invaders are finally killed by antimicrobial substances released mainly from many kinds of hemocytes. In the past two decades, we have investigated biochemically various defense molecules, using horseshoe crab as a model animal, and established extensively their molecular structures. These results now make it possible to discuss evolution and phylogeny of the defense molecules at a molecular level, in comparison with those derived from vertebrate animals. Here, the authors will describe the present state of our knowledge concerning molecules mainly associated with innate immunity. PMID:9727083

Iwanaga, S; Kawabata, S

1998-09-01

58

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

Microsoft Academic Search

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

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

59

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

PubMed

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

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

2014-04-01

60

A Pulmonary Perspective on GASPIDs: Granule-Associated Serine Peptidases of Immune Defense  

PubMed Central

Airways are protected from pathogens by forces allied with innate and adaptive immunity. Recent investigations establish critical defensive roles for leukocyte and mast cell serine-class peptidases garrisoned in membrane-bound organelles-here termed Granule-Associated Serine Peptidases of Immune Defense, or GASPIDs. Some better characterized GASPIDs include neutrophil elastase and cathepsin G (which defend against bacteria), proteinase-3 (targeted by antineutrophil antibodies in Wegener’s vasculitis), mast cell ?-tryptase and chymase (which promote allergic inflammation), granzymes A and B (which launch apoptosis pathways in infected host cells), and factor D (which activates complement’s alternative pathway). GASPIDs can defend against pathogens but can harm host cells in the process, and therefore become targets for pharmaceutical inhibition. They vary widely in specificity, yet are phylogenetically similar. Mammalian speciation supported a remarkable flowering of these enzymes as they co-evolved with specialized immune cells, including mast cells, basophils, eosinophils, cytolytic T-cells, natural killer cells, neutrophils, macrophages and dendritic cells. Many GASPIDs continue to evolve rapidly, providing some of the most conspicuous examples of divergent protein evolution. Consequently, students of GASPIDs are rewarded not only with insights into their roles in lung immune defense but also with clues to the origins of cellular specialization in vertebrate immunity. PMID:18516248

Caughey, George H.

2008-01-01

61

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

PubMed

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

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

2014-01-01

62

Hyaluronan Breakdown Contributes to Immune Defense against Group A Streptococcus.  

PubMed

Group A Streptococcus (GAS) commonly infects human skin and occasionally causes severe and life-threatening invasive diseases. The hyaluronan (HA) capsule of GAS has been proposed to protect GAS from host defense by mimicking endogenous HA, a large and abundant glycosaminoglycan in the skin. However, HA is degraded during tissue injury, and the functions of short-chain HA that is generated during infection have not been studied. To examine the impact of the molecular mass of HA on GAS infection, we established infection models in vitro and in vivo in which the size of HA was defined by enzymatic digestion or custom synthesis. We discovered that conversion of high molecular mass HA to low molecular mass HA facilitated GAS phagocytosis by macrophages and limited the severity of infection in mice. In contrast, native high molecular mass HA significantly impaired internalization by macrophages and increased GAS survival in murine blood. Thus, our data demonstrate that GAS virulence can be influenced by the size of HA derived from both the bacterium and host and suggest that high molecular mass HA facilitates GAS deep tissue infections, whereas the generation of short-chain HA can be protective. PMID:25122767

Schommer, Nina N; Muto, Jun; Nizet, Victor; Gallo, Richard L

2014-09-26

63

Self/nonself perception in plants in innate immunity and defense  

PubMed Central

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

Sanabria, Natasha M; Huang, Ju-Chi

2010-01-01

64

Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies  

Microsoft Academic Search

Short cationic amphiphilic peptides with antimicrobial and\\/or immunomodulatory activities are present in virtually every life form, as an important component of (innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new

Hans-Georg Sahl; Robert E W Hancock

2006-01-01

65

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

PubMed

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

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

2014-09-10

66

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

PubMed

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

Leicht, Katja; Jokela, Jukka; Seppälä, Otto

2013-12-01

67

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

PubMed Central

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

Leicht, Katja; Jokela, Jukka; Seppala, Otto

2013-01-01

68

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

Microsoft Academic Search

L-amino acid oxidases (LAOs), because they produce hydrogen peroxide as a by-product, function in innate immune defenses of\\u000a both vertebrates and mollusks. Phylogenetic analysis revealed two major subfamilies of LAOs: (1) a subfamily including LAOs\\u000a from vertebrates and mainly from Terrabacteria and (2) a subfamily including LAOs from mollusks and Hydrobacteria. These subfamilies\\u000a thus originated early in the history of

Austin L. Hughes

2010-01-01

69

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

PubMed

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

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

2014-11-01

70

Alteration of antioxidant defense status precedes humoral immune response abnormalities in macrosomia  

PubMed Central

Summary Background This study aimed to investigate whether the anomalies affecting the antioxidant and humoral immune defenses could start at birth and to check whether the decrease in antioxidant defenses may precede the immune abnormalities in macrosomic newborns. Material/Methods Thirty macrosomic and 30 sex-matched control newborns were recruited for a retrospective case-control study at the Maghnia Maternity Hospital of Tlemcen Department (Algeria). Results The serum IgG levels were similar in both groups. However, plasma ORAC, albumin, vitamin E, SOD, CAT and GSH-Px levels were significantly decreased in macrosomic as compared to control newborns, yet no difference was observed after adjustment for weight. Additionally, serum concentrations of complement C3, MDA and XO were significantly higher in macrosomic as compared to controls before adjustment for weight. Moreover, macrosomia was significantly associated with high levels of complement C3 (OR=8, p=0.002); whereas no association with those of IgG was observed (OR<1, p>0.05). Furthermore, macrosomia was significantly associated with low levels of ORAC (OR=4.96, p=0.027), vitamin E (OR=4.5, p=0.018), SOD (OR=6.88, p=0.020) and CAT (OR=5.67, p=0.017), and with high levels of MDA (OR=10.29, p=0.005). Conclusions Abnormalities of the humoral defense system in excessive weight could be preceded by alterations of the anti-oxidative defense and by inflammatory response and activation of innate immunity at birth. Additionally, excessive weight could be a potential factor contributing to decreased anti-oxidative capacity and increased oxidative stress. PMID:22037745

Haddouche, Mustapha; Aribi, Mourad; Moulessehoul, Soraya; Smahi, Mohammed Chems-Eddine Ismet; Lammani, Mohammed; Benyoucef, Mohammed

2011-01-01

71

Increased activity correlates with reduced ability to mount immune defenses to endotoxin in zebra finches.  

PubMed

When suffering from infection, animals experience behavioral and physiological alterations that potentiate the immune system's ability to fight pathogens. The behavioral component of this response, termed "sickness behavior," is characterized by an overall reduction in physical activity. A growing number of reports demonstrate substantial flexibility in these sickness behaviors, which can be partially overcome in response to mates, intruders and parental duties. Since it is hypothesized that adopting sickness behaviors frees energetic resources for mounting an immune response, we tested whether diminished immune responses coincided with reduced sickness behaviors by housing male zebra finches (Taeniopygia guttata) in social conditions that alter their behavioral response to an endotoxin. To facilitate our data collection, we developed and built a miniaturized sensor capable of detecting changes in dorsoventral acceleration and categorizing them as different behaviors when attached to the finches. We found that the immune defenses (quantified as haptoglobin-like activity, ability to change body temperature and bacterial killing capacity) increased as a function of increased time spent resting. The findings indicate that when animals are sick attenuation of sickness behaviors may exact costs, such as reduced immune function. The extent of these costs depends on how relevant the affected components of immunity are for fighting a specific infection. J. Exp. Zool. 321A: 422-431, 2014. © 2014 Wiley Periodicals, Inc. PMID:24888267

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

2014-10-01

72

Adaptive Immune Regulation of Glial Homeostasis as an Immunization Strategy for Neurodegenerative Diseases  

PubMed Central

Neurodegenerative diseases, notably Alzheimer's and Parkinson's diseases, are amongst the most devastating disorders afflicting the elderly. Currently, no curative treatments or treatments that interdict disease progression exist. Over the past decade, immunization strategies have been proposed to combat disease progression. Such strategies induce humoral immune responses against misfolded protein aggregates to facilitate their clearance. Robust adaptive immunity against misfolded proteins, however, accelerates disease progression, precipitated by induced effector T cell responses that lead to encephalitis and neuronal death. Since then, mechanisms that attenuate such adaptive neurotoxic immune responses have been sought. We propose that shifting the balance between effector and regulatory T cell activity can attenuate neurotoxic inflammatory events. This review summarizes advances in immune regulation to achieve a homeostatic glial response for therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are also discussed. PMID:20524958

Kosloski, Lisa M.; Ha, Duy M.; Stone, David K.; Hutter, Jessica A. L.; Pichler, Michael R.; Reynolds, Ashley D.; Gendelman, Howard E.; Mosley, R. Lee

2010-01-01

73

WHY INDUCED DEFENSES MAY BE FAVORED OVER CONSTITUTIVE STRATEGIES IN PLANTS  

E-print Network

of an herbivore that feeds on a damaged plant. We reserve the term "induced defense" for responses that conferChapter 3 WHY INDUCED DEFENSES MAY BE FAVORED OVER CONSTITUTIVE STRATEGIES IN PLANTS Anurag A of induction. Given that most plants interact with multiple specialist and generalist herbivores, various

Agrawal, Anurag

74

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

ERIC Educational Resources Information Center

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…

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

2008-01-01

75

Judged Effectiveness of Common Rape Prevention and Self-Defense Strategies  

Microsoft Academic Search

All women face the threat of rape, forcing them to (a) decide what to do to reduce their chances of being assaulted (rape prevention) and (b) how to defend themselves if assaulted (self-defense). A principal basis for such decisions should be women's estimates of the effectiveness of possible prevention and self-defense strategies for reducing the risk of rape. This study

LITA FURBY; BARUCH FISCHHOFF; MARCIA MORGAN

1989-01-01

76

C.S. Lewis, Jesus, and Plato: rhetorical strategies for the defense of Christianity  

E-print Network

The defense of Christianity through apologetic discourse is an important function of modern day Christianity. To better understand the necessary strategies behind successful use of apologetic discourse, apologetic essays of C. S. Lewis in God...

Chivvis, John Carlton

2012-06-07

77

An Efficient Immunization Strategy for Community Networks  

PubMed Central

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

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

2013-01-01

78

The structure of the human vaginal stratum corneum and its role in immune defense.  

PubMed

The superficial layers of the human vaginal epithelium, which form an interface between host and environment, are comprised of dead flattened cells that have undergone a terminal cell differentiation program called cornification. This entails extrusion of nuclei and intercellular organelles, and the depletion of functional DNA and RNA precluding the synthesis of new proteins. As a consequence, the terminally differentiated cells do not maintain robust intercellular junctions and have a diminished capacity to actively respond to microbial exposure, yet the vaginal stratum corneum (SC) mounts an effective defense against invasive microbial infections. The vaginal SC in reproductive-aged women is comprised of loosely connected glycogen-filled cells, which are permeable to bacterial and viral microbes as well as molecular and cellular mediators of immune defense. We propose here that the vaginal SC provides a unique microenvironment that maintains vaginal health by fostering endogenous lactobacilli and retaining critical mediators of acquired and innate immunity. A better understanding of the molecular and physicochemical properties of the vaginal SC could promote the design of more effective topical drugs and microbicides. PMID:24661416

Anderson, Deborah J; Marathe, Jai; Pudney, Jeffrey

2014-06-01

79

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

PubMed

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

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

2013-01-01

80

Microbial Symbiosis with the Innate Immune Defense System of the Skin  

PubMed Central

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

Gallo, Richard L.; Nakatsuji, Teruaki

2011-01-01

81

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

PubMed

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

Gallo, Richard L; Nakatsuji, Teruaki

2011-10-01

82

Immune evasion strategies of Porphyromonas gingivalis  

PubMed Central

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

Hajishengallis, George

2011-01-01

83

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

PubMed Central

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

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

2013-01-01

84

Optimal Treatment Strategy for a Tumor Model under Immune Suppression  

PubMed Central

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

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

2014-01-01

85

From immune surveillance to tumor-immune escape: the story of an enemy with multiple strategies of resistance and counterattack  

Microsoft Academic Search

Tumors must circumvent the immune response of the host to become clinically detectable. For this purpose, malignant cells have devised multiple strategies to thwart immune attack. These mechanisms are suggested to conspire in advanced stages of can- cer to limit the ability of the immune system to restrain the tumor and the effectiveness of immunotherapy strategies to successfully eradicate malignant

O. G. Scharovsky; P. Matar; M. Z. Fluck; M. J. Rico; G. A. Rabinovich

86

Defensive strategy of two Hypselodoris nudibranchs from Italian and Spanish coasts  

Microsoft Academic Search

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

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

1991-01-01

87

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

PubMed

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

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

2008-05-01

88

Aggregation and cnidae development as early defensive strategies in Favia fragum and Porites astreoides  

NASA Astrophysics Data System (ADS)

To survive, corals possess a variety of active and passive defenses. This study examined the effectiveness of aggregation and cnidae development as defensive strategies in enhancing post-settlement survival and growth of two brooding corals, Favia fragum and Porites astreoides, in Bermuda. Growth and survival of solitary and aggregated spat were monitored over seven weeks; cnidae were extracted from surviving spat. F. fragum aggregated spat had higher mortality, slower growth, and more cnidae than solitary spat. On the other hand, aggregation proved beneficial for P. astreoides spat, which had significantly lower mortality, faster growth, and fewer cnidae. Aggregated and solitary F. fragum spat displayed negative correlations between cnidae density and growth, suggesting a trade-off between defense and growth; however, P. astreoides spat did not demonstrate such a trade-off. These differing responses suggest that early patterns of survivorship and defensive strategies are highly species specific and complex.

Rivera, H. E.; Goodbody-Gringley, G.

2014-12-01

89

Identification of two secreted ferritin subunits involved in immune defense of Yesso scallop Patinopecten yessoensis.  

PubMed

As an important iron storage protein, ferritin plays a crucial role in the iron-withholding defense system. In this study, two secreted ferritin subunits (PyFerS1 and PyFerS2) were identified from the Yesso scallop, Patinopecten yessoensis. The complete DNA sequences of the two ferritins are 7101 and 5359 bp, consisting of seven and five exons, respectively. The full-length cDNAs of PyFerS1 and PyFerS2 are 960 and 956 bp in length, encoding 228 and 220 amino acids, respectively. They have typical ferritin structures, with four long ?-helices, one short ?-helix and an L-loop. Signal peptides were found at the N-terminus of both ferritins, and phylogenetic analysis showed that they both clustered with secreted mollusc ferritins. PyFerS1 possesses all seven conserved residues of the ferroxidase center, whereas PyFerS2 only has two. Real-time PCR analysis indicated high expression level of PyFerS2 in the D-shaped larvae, and PyFerS1 in both D-shaped larvae and fertilized eggs. In adult scallops, PyFerS1 was only detected in the hepatopancreas, whereas PyFerS2 was detected in both hepatopancreas and mantle. After the scallops were challenged by iron ion or bacteria Vibrio anguillarum, the expression of both PyFerS1 and PyFerS2 was significantly elevated, suggesting they may play a role in scallop innate immune defense. For the first time, secreted ferritins were cloned and comprehensively characterized in bivalve molluscs. It will assist in better understanding of the role of secreted ferritins in bivalve innate immunity. PMID:24434645

Sun, Yan; Zhang, Yueyue; Fu, Xiaoteng; Zhang, Ru; Zou, Jiajun; Wang, Shi; Hu, Xiaoli; Zhang, Lingling; Bao, Zhenmin

2014-03-01

90

Induced immunity against belowground insect herbivores- activation of defenses in the absence of a jasmonate burst.  

PubMed

Roots respond dynamically to belowground herbivore attack. Yet, little is known about the mechanisms and ecological consequences of these responses. Do roots behave the same way as leaves, or do the paradigms derived from aboveground research need to be rewritten? This is the central question that we tackle in this article. To this end, we review the current literature on induced root defenses and present a number of experiments on the interaction between the root herbivore Diabrotica virgifera and its natural host, maize. Currently, the literature provides no clear evidence that plants can recognize root herbivores specifically. In maize, mild mechanical damage is sufficient to trigger a root volatile response comparable to D. virgifera induction. Interestingly, the jasmonate (JA) burst, a highly conserved signaling event following leaf attack, is consistently attenuated in the roots across plant species, from wild tobacco to Arabidopsis. In accordance, we found only a weak JA response in D. virgifera attacked maize roots. Despite this reduction in JA-signaling, roots of many plants start producing a distinct suite of secondary metabolites upon attack and reconfigure their primary metabolism. We, therefore, postulate the existence of additional, unknown signals that govern induced root responses in the absence of a jasmonate burst. Surprisingly, despite the high phenotypic plasticity of plant roots, evidence for herbivore-induced resistance below ground is virtually absent from the literature. We propose that other defensive mechanisms, including resource reallocation and compensatory growth, may be more important to improve plant immunity below ground. PMID:22527052

Erb, Matthias; Glauser, Gaetan; Robert, Christelle A M

2012-06-01

91

A Defensive Grand Strategy for the United States  

Microsoft Academic Search

By adopting a bold and ambitious strategy and pursuing it aggressively, the Bush administration has divided the Western alliance; altered the nature of international politics in the Gulf, South Asia, and the Middle East; and crystallized popular opposition to the U.S. in many countries. The new Bush strategy impinges on a number of critical social and military issues for the

P. Edward Haley

2004-01-01

92

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

PubMed Central

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

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

2013-01-01

93

Defensive strategies of Bacillus anthracis that promote a fatal disease  

PubMed Central

Bacillus anthracis is a Gram-positive bacterium that causes anthrax. Bacterial spores that enter the host germinate into metabolically active bacilli that disseminate throughout the body and replicate to high numbers. Two virulence factors are essential for this unrestrained growth. The first is a weakly immunogenic poly ?-D-glutamic acid capsule that surrounds the bacilli and confers resistance to phagocytosis. The second virulence factor, anthrax toxin, disrupts multiple host functions to diminish the immune response. PMID:19081825

Mogridge, Jeremy

2008-01-01

94

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

PubMed Central

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

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

2012-01-01

95

Symbiotic bacteria contribute to innate immune defenses of the threatened mountain yellow-legged frog, Rana muscosa  

Microsoft Academic Search

Symbiotic microorganisms influence health and disease and may contribute to the innate immune defenses of amphibians. The mountain yellow-legged frog, Rana muscosa, is currently undergoing unprecedented population declines. One cause of recent declines is the pathogenic chytrid fungus, Batrachochytrium dendrobatidis (Bd). Skin swabs for detection of Bd, skin peptide secretions, and symbiotic skin bacteria were collected from 70 adult R.

Douglas C. Woodhams; Vance T. Vredenburg; Mary-Alice Simon; Dean Billheimer; Bashar Shakhtour; Yu Shyr; Cheryl J. Briggs; Louise A. Rollins-Smith; Reid N. Harris

2007-01-01

96

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

PubMed Central

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

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

2013-01-01

97

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

PubMed

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

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

2014-03-01

98

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

PubMed

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

Rada, Balázs; Leto, Thomas L

2008-01-01

99

Recurrent infections and immune evasion strategies of Staphylococcus aureus  

PubMed Central

Staphylococcus aureus causes purulent skin and soft tissue infections (SSTIs) that frequently reoccur. Staphylococal SSTIs can lead to invasive disease and sepsis, which are among the most significant causes of infectious disease mortality in both developed and developing countries. Human or animal infections with S. aureus do not elicit protective immunity against staphylococcal diseases. Here we review what is known about the immune evasive strategies of S. aureus that enable the pathogen’s escape from protective immune responses. Three secreted products are discussed in detail, staphylococcal protein A (SpA), staphylococcal binder of immunoglobulin (Sbi) and adenosine synthase A (AdsA). By forming a complex with VH3-type IgM on the surface of B cells, SpA functions as a superantigen to modulate antibody responses to staphylococcal infection. SpA also captures pathogen-specific antibodies by binding their Fc? portion. The latter activity of SpA is shared by Sbi, which also associates with complement factors 3d and factor H to promote the depletion of complement. AdsA synthesizes the immune signaling molecule adenosine, thereby dampening innate and adaptive immune responses during infection. We discuss strategies how the three secreted products of staphylococci may be exploited for the development of vaccines and therapeutics. PMID:22088393

Kim, Hwan Keun; Thammavongsa, Vilasack; Schneewind, Olaf; Missiakas, Dominique

2012-01-01

100

Natural History of Innate Host Defense Peptides  

Microsoft Academic Search

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,

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

2009-01-01

101

[Japanese college students' pessimism, coping strategies and anxiety: validation of the Japanese Defensive Pessimism Inventory (JDPI)].  

PubMed

The purpose of this study was to develop the Japanese Defensive Pessimism Inventory (JDPI), which measures defensive pessimism in an academic achievement situation for Japanese undergraduate students and differentiates between those who are realistically pessimistic and those who are defensively pessimistic. In Study 1,695 undergraduates completed the JDPI. A factor analysis revealed that the 24 items of the JDPI comprised four factors: Pessimism, Past experience, Positive reflectivity, and Effort. In Study 2, 618 undergraduates completed the JDPI, the Test Coping Strategy Scale, and the State-Trait Anxiety Inventory. The JDPI had high internal consistency and test-retest reliability. Defensive pessimists and strategic optimists had higher scores on the active coping strategy and lower scores on the avoidant-thinking coping strategy than did realistic pessimists. Furthermore, defensive pessimists and realistic pessimists had higher scores on the state anxiety and lower scores on the optimistic-thinking coping strategy than did strategic optimists. The results indicate that the JDPI had high concurrent validity. PMID:18516953

Araki, Yukiko

2008-04-01

102

Social marketing as a strategy to increase immunization rates.  

PubMed

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

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

2009-05-01

103

Immune defence mechanisms and immunoenhancement strategies in oropharyngeal candidiasis  

PubMed Central

The prevalence of oropharyngeal candidiasis continues to be high, mainly because of an increasing population of immunocompromised patients. Traditional treatment of oropharyngeal candidiasis has relied on the use of antimicrobial drugs. However, unsatisfactory results with drug monotherapy and the emergence of resistant strains have prompted investigations into the potential use of adjunctive immunoenhancing therapies for the treatment of these infections. Here we review the host-recognition systems of Candida albicans, the immune and inflammatory response to infection, and antifungal effector mechanisms. The potential of immune modulation as a therapeutic strategy in oropharyngeal candidiasis is also discussed. PMID:18847522

Villar, Cristina Cunha; Dongari-Bagtzoglou, Anna

2009-01-01

104

Antimicrobial defense of the earthworm  

Microsoft Academic Search

Discrimination of self and nonself is one of the features of all animal species but the ways of elimination of nonself are\\u000a different. Defense strategies of invertebrates, which lack antibodies and lymphocytes, are based on innate defense mechanisms.\\u000a The study of such, undoubtedly less complex, defense mechanisms in invertebrates may shed a new light on the more sophisticated\\u000a immunity of

M. Bilej; P. De Baetselier; A. Beschin

2000-01-01

105

Space Strategy: Defensive Shields or Death from Above.  

National Technical Information Service (NTIS)

For the last year I have heard time and time again that 'the cold war is over'. Articles were published by the NDU Press which spoke of 'US Strategy After The Cold War', and the Washington Post headlines screamed (before 2 August) of the 'Peace Dividend' ...

D. E. Kersey

1991-01-01

106

Defensive Marketing Strategies: An Equilibrium Analysis Based on Decoupled Response Function Models  

Microsoft Academic Search

The entry of a new product (attacker) into a competitive market is likely to provoke responses from some or all of the existing products (defenders). This paper investigates the development of optimal defensive strategies based on an understanding of the possible reactions of all the defenders to an optimal attack. Following Lane (Lane, W. J. 1980. Product differentiation in a

K. Ravi Kumar; D. Sudharshan

1988-01-01

107

When anxiety is not always a handicap in physical education and sport: Some implications of the defensive pessimism strategy  

Microsoft Academic Search

In this article we present a defensive strategy that individuals may use to cope with sporting events in that they present the possibility of failure and potential threat to self-esteem. Previous research has indicated that failures in sport and educational contexts are related to high anxiety and low self-estimates of ability. The defensive pessimism strategy lead anxious people to perform

Céline Pérès; François Cury; Jean-pierre Famose; Philippe Sarrazin

2002-01-01

108

Difference in defense strategy in flower heads and leaves of Asteraceae: multiple-species approach.  

PubMed

Although a vast number of studies have investigated defenses against herbivores in leaves, relatively little is known about defenses in flowers. Using wild individuals of 34 species of Asteraceae, we investigated differences in five traits that are thought to affect the intensity of herbivory (C, N, P, water, and total phenolic contents). Combinations of these traits between flower heads and leaves were studied as well. We also evaluated phylogenetic patterns of flower head and leaf traits. Flower heads had higher P and lower total phenolics than leaves. Water and C contents were negatively correlated both in the flower heads and leaves. N, P, and water contents were positively correlated in the flower heads, whereas this pattern was not found in the leaves. Thus, the traits we measured were more tightly inter-correlated in flower heads than in leaves. Because the flower heads had a lower total phenolic content, the relative allocation of defensive compounds could not be explained solely by fitness values of the organs. Perhaps plants employ an escape strategy rather than a defense strategy to cope with floral herbivores and higher allocation in P may enhance their escape from herbivores by improving the growth rate of flower heads, though our result might be affected in part by the plasticity of plants growing at different sites. Moreover, we found weak phylogenetic signals in the defensive traits. Because we found significant differences in the flower head traits, these weak signals may imply that the traits we measured evolved frequently. PMID:24036932

Oguro, Michio; Sakai, Satoki

2014-01-01

109

Parasite biodiversity and host defenses: chewing lice and immune response of their avian hosts  

Microsoft Academic Search

Antagonistic host-parasite interactions lead to coevolution of host defenses and parasite virulence. Such adaptation by parasites to host defenses may occur to the detriment of the ability of parasites to exploit alternative hosts, causing parasite specialization and speciation. We investigated the relationship between le- vel of anti-parasite defense in hosts and taxonomic richness of two chewing louse suborders (Phthiraptera: Amblycera,

Anders Pape Møller; Lajos Rozsa

2005-01-01

110

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

Microsoft Academic Search

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

Sarah J. Erickson; Sarah W. Feldstein

2007-01-01

111

Hiding the evidence: two strategies for innate immune evasion by hemorrhagic fever viruses.  

PubMed

The innate immune system is one of the first lines of defense against invading pathogens. Pathogens have, in turn, evolved different strategies to counteract these responses. Recent studies have illuminated how the hemorrhagic fever viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a unique bimodal configuration to mask key cellular recognition sites on dsRNA. Conversely, the Lassa fever virus nucleoprotein actually digests the dsRNA signature. Collectively, these structural and functional studies shed new light on the mechanisms of pathogenesis of these viruses and provide new targets for therapeutic intervention. PMID:22482712

Hastie, Kathryn M; Bale, Shridhar; Kimberlin, Christopher R; Saphire, Erica Ollmann

2012-04-01

112

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

PubMed

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

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

2012-07-01

113

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

Microsoft Academic Search

Viruses may be viewed as genetic information whose success depends on avoiding elimination from individual hosts, or, if this is not possible, in persisting in the population of their hosts. The immune system represents the crucial defense mechanism responsible for the elimination of viruses from individual hosts and for the establishment of immunity that prevents a recurring infection by the

Ernst Peterhans; Reto Zanoni; Giuseppe Bertoni

1999-01-01

114

Chapter 13 Adaptive Defense Responses to Pathogens and Insects  

Microsoft Academic Search

The relative resistance of a plant to pathogens is determined by preformed, constitutive defenses, and the quality and diversity of the induced defenses deployed upon attack. Pathogens have evolved strategies to breach structural barriers and avoid or counter preformed and induced chemical defenses of their host plants. Plants have evolved sensitive mechanisms to perceive bioagressors and innate immune responses are

Linda L. Walling

2009-01-01

115

Immune Defenses against Batrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog, Xenopus laevis?  

PubMed Central

Batrachochytrium dendrobatidis is a chytrid fungus that causes the lethal skin disease chytridiomycosis in amphibians. It is regarded as an emerging infectious disease affecting diverse amphibian populations in many parts of the world. Because there are few model amphibian species for immunological studies, little is known about immune defenses against B. dendrobatidis. We show here that the South African clawed frog, Xenopus laevis, is a suitable model for investigating immunity to this pathogen. After an experimental exposure, a mild infection developed over 20 to 30 days and declined by 45 days postexposure. Either purified antimicrobial peptides or mixtures of peptides in the skin mucus inhibited B. dendrobatidis growth in vitro. Skin peptide secretion was maximally induced by injection of norepinephrine, and this treatment resulted in sustained skin peptide depletion and increased susceptibility to infection. Sublethal X-irradiation of frogs decreased leukocyte numbers in the spleen and resulted in greater susceptibility to infection. Immunization against B. dendrobatidis induced elevated pathogen-specific IgM and IgY serum antibodies. Mucus secretions from X. laevis previously exposed to B. dendrobatidis contained significant amounts of IgM, IgY, and IgX antibodies that bind to B. dendrobatidis. These data strongly suggest that both innate and adaptive immune defenses are involved in the resistance of X. laevis to lethal B. dendrobatidis infections. PMID:20584973

Ramsey, Jeremy P.; Reinert, Laura K.; Harper, Laura K.; Woodhams, Douglas C.; Rollins-Smith, Louise A.

2010-01-01

116

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

PubMed Central

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

2013-01-01

117

Behavioral defense strategies of the stingless bee, Austroplebeia australis , against the small hive beetle, Aethina tumida  

Microsoft Academic Search

Small hive beetle, Aethina tumida Murray, is a parasite of social bee colonies and has become an invasive species, raising concern of the potential threat\\u000a to native pollinators in its new ranges. Here, we report the defensive behavior strategies used by workers of the Australian\\u000a stingless bee, Austroplebeia australis Friese, against the small hive beetle. A non-destructive method was used

M. Halcroft; R. Spooner-Hart; P. Neumann

2011-01-01

118

Paramyxovirus evasion of innate immunity: Diverse strategies for common targets  

PubMed Central

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

Audsley, Michelle D; Moseley, Gregory W

2013-01-01

119

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

PubMed Central

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

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

2014-01-01

120

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

PubMed

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

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

2014-04-01

121

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

PubMed Central

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

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

2013-01-01

122

Androgen Receptor Influences on Body Defense System via Modulation of Innate and Adaptive Immune Systems  

PubMed Central

Upon insult, such as infection or tissue injury, the innate and adaptive immune systems initiate a series of responses to defend the body. Recent studies from immune cell-specific androgen receptor (AR) knockout mice demonstrated that androgen and its receptor (androgen/AR) play significant roles in both immune regulations. In the innate immunity, androgen/AR is required for generation and proper function of neutrophils; androgen/AR also regulates wound healing processes through macrophage recruitment and proinflammatory cytokine production. In adaptive immunity, androgen/AR exerts suppressive effects on development and activation of T and B cells. Removal of such suppression causes thymic enlargement and excessive export of immature B cells. Altogether, androgen/AR plays distinct roles in individual immune cells, and targeting androgen/AR may help in treatment and management of immune-related diseases. PMID:22959669

Lai, Jiann-Jyh; Lai, Kuo-Pao; Zeng, Weiping; Chuang, Kuang-Hsiang; Altuwaijri, Saleh; Chang, Chawnshang

2013-01-01

123

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

PubMed Central

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

2012-01-01

124

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

PubMed

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

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

2013-06-01

125

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

SciTech Connect

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.

Fink, Glenn A.; Oehmen, Christopher S.

2012-09-01

126

Strategies to Modulate Immune Responses: A New Frontier for Gene Therapy  

Microsoft Academic Search

The success of gene therapy strategies to cure disease relies on the control of unwanted immune responses to transgene products, genetically modified cells and\\/or to the vector. Effective treatment of an established immune response is much harder to achieve than prevention of a response before it has had a chance to develop. However, preventive strategies are not always effective in

Valder R Arruda; Patricia Favaro; Jonathan D Finn

2009-01-01

127

Chemokines and chemokine receptors: positioning cells for host defense and immunity.  

PubMed

Chemokines are chemotactic cytokines that control the migratory patterns and positioning of all immune cells. Although chemokines were initially appreciated as important mediators of acute inflammation, we now know that this complex system of approximately 50 endogenous chemokine ligands and 20 G protein-coupled seven-transmembrane signaling receptors is also critical for the generation of primary and secondary adaptive cellular and humoral immune responses. Recent studies demonstrate important roles for the chemokine system in the priming of naive T cells, in cell fate decisions such as effector and memory cell differentiation, and in regulatory T cell function. In this review, we focus on recent advances in understanding how the chemokine system orchestrates immune cell migration and positioning at the organismic level in homeostasis, in acute inflammation, and during the generation and regulation of adoptive primary and secondary immune responses in the lymphoid system and peripheral nonlymphoid tissue. PMID:24655300

Griffith, Jason W; Sokol, Caroline L; Luster, Andrew D

2014-01-01

128

The relationship of coping strategies, affect, and immune function among individuals at risk for acquired immune deficiency syndrome  

Microsoft Academic Search

The present study was an investigation of the relationships between coping strategies, affect and immune function among individuals at risk for the development of Acquired Immune Deficiency Syndrome (AIDS). Ninety-nine homosexual male volunteers whose Human Immunodeficiency Virus: Type 1 (HIV-1) antibody status tested: HIV-1 seronegative (n = 30); HIV-1 seropositive, asymptomatic (CDC-2) (n = 31); or HIV-1 seropositive, with persistent

David Alan Goldstein

1991-01-01

129

A Multipopulation Coevolutionary Strategy for Multiobjective Immune Algorithm  

PubMed Central

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

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

2014-01-01

130

Testing Strategies To Raise Immunization Rates. Report of the Joyce Foundation's Special Project on Immunization.  

ERIC Educational Resources Information Center

In many low-income communities, children are not properly immunized and are left vulnerable to completely preventable illnesses. This report provides information gained as a result of a 1-year funding project in the Chicago area to determine why so many children were not being immunized and how to increase immunization rates. The project tested 5…

Fischer, Sunny; Baron, Dan

131

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

PubMed Central

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

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

2012-01-01

132

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

PubMed

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

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

2014-01-01

133

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

PubMed Central

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

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

2012-01-01

134

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

PubMed Central

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

Escalante-Perez, Maria; Jaborsky, Mario; Lautner, Silke; Fromm, Jorg; Muller, Tobias; Dittrich, Marcus; Kunert, Maritta; Boland, Wilhelm; Hedrich, Rainer; Ache, Peter

2012-01-01

135

Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation.  

PubMed

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

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

2014-03-13

136

Immune control strategies for vaccinia virus-related laboratory-acquired infections.  

PubMed

While presenting biological characteristics of vaccinia virus and laboratory-acquired infections during related research processes, this paper focuses on benefits and risks of vaccinia virus immunization in relation to laboratory-acquired infections, describes characteristics and the adaptation of vaccinia virus vaccine, analyses the role vaccinia virus immunization plays in the prevention and control of laboratory-acquired infections, and finally proposes solutions and countermeasures to further promote and implement immune control strategies. The problem related to immune strategy and laboratory- acquired infections which is being raised, analyzed and explored plays an active and instructive role in vaccinia virus related researches and laboratory- acquired infections, and also helps to recommend and develop relevant immune strategy for future vaccine control of such infections. PMID:24625408

Wei, Qiang; Jiang, Meng Nan; Han, Jun; Wang, Zi Jun

2014-02-01

137

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

PubMed

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

McAleer, Jeremy P; Kolls, Jay K

2014-07-01

138

RNAi and antiviral defense in Drosophila: setting up a systemic immune response.  

PubMed

RNA interference (RNAi) controls gene expression in eukaryotic cells and thus, cellular homeostasis. In addition, in plants, nematodes and arthropods it is a central antiviral effector mechanism. Antiviral RNAi has been well described as a cell autonomous response, which is triggered by double-stranded RNA (dsRNA) molecules. This dsRNA is the precursor for the silencing of viral RNA in a sequence-specific manner. In plants, systemic antiviral immunity has been demonstrated, however much less is known in animals. Recently, some evidence for a systemic antiviral response in arthropods has come to light. Cell autonomous RNAi may not be sufficient to reach an efficient antiviral response, and the organism might rely on the spread and uptake of an RNAi signal of unknown origin. In this review, we offer a perspective on how RNAi-mediated antiviral immunity could confer systemic protection in insects and we propose directions for future research to understand the mechanism of RNAi-immune signal sorting, spreading and amplification. PMID:23684730

Karlikow, Margot; Goic, Bertsy; Saleh, Maria-Carla

2014-01-01

139

Effects of dietary L-glutamine supplementation on specific and general defense responses in mice immunized with inactivated Pasteurella multocida vaccine.  

PubMed

Little is known about effects of dietary glutamine supplementation on specific and general defense responses in a vaccine-immunized animal model. Thus, this study determined roles for dietary glutamine supplementation in specific and general defense responses in mice immunized with inactivated Pasteurella multocida vaccine. The measured variables included: (1) the production of pathogen-specific antibodies; (2) mRNA levels for pro-inflammatory cytokines, toll-like receptors and anti-oxidative factors; and (3) the distribution of P. multocida in tissues and the expression of its major virulence factors in vivo. Dietary supplementation with 0.5 % glutamine had a better protective role than 1 or 2 % glutamine against P. multocida infection in vaccine-immunized mice, at least partly resulting from its effects in modulation of general defense responses. Dietary glutamine supplementation had little effects on the production of P. multocida-specific antibodies. Compared to the non-supplemented group, dietary supplementation with 0.5 % glutamine had no effect on bacterial burden in vivo but decreased the expression of major virulence factors in the spleen. Collectively, supplementing 0.5 % glutamine to a conventional diet provides benefits in vaccine-immunized mice by enhancing general defense responses and decreasing expression of specific virulence factors. PMID:24993936

Chen, Shuai; Liu, Shuping; Zhang, Fengmei; Ren, Wenkai; Li, Nengzhang; Yin, Jie; Duan, Jielin; Peng, Yuanyi; Liu, Gang; Yin, Yulong; Wu, Guoyao

2014-10-01

140

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

PubMed Central

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

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

2014-01-01

141

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

PubMed

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

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

2014-01-01

142

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

PubMed Central

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

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

2013-01-01

143

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

PubMed Central

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

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

2010-01-01

144

Comparative Analysis of the Effectiveness of Three Immunization Strategies in Controlling Disease Outbreaks in Realistic Social Networks  

PubMed Central

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

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

2014-01-01

145

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

PubMed

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

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

2011-09-01

146

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

PubMed Central

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

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

2013-01-01

147

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

PubMed

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

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

2014-09-01

148

Evaluating the Case, Evaluating the Cost: Criteria for Constructing the Defense Strategy of Persons Suffering from Mental Illness  

Microsoft Academic Search

This article examines the challenges and problems faced by attorneys defending, in criminal courts, clients suffering from mental health problems, and who are generally socially and economically fragile. The analysis is based on 14 in-depth interviews with defense attorneys who practice criminal law at the Montreal Municipal Court. Through their descriptions, this article will explore how attorneys determine their strategies

Danielle Laberge; Daphné Morin

1998-01-01

149

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

150

The evolution of immune mechanisms.  

PubMed

From early on in evolution, organisms have had to protect themselves from pathogens. Mechanisms for discriminating "self" from "non-self" evolved to accomplish this task, launching a long history of host-pathogen co-evolution. Evolution of mechanisms of immune defense has resulted in a variety of strategies. Even unicellular organisms have rich arsenals of mechanisms for protection, such as restriction endonucleases, antimicrobial peptides, and RNA interference. In multicellular organisms, specialized immune cells have evolved, capable of recognition, phagocytosis, and killing of foreign cells as well as removing their own cells changed by damage, senescence, infection, or cancer. Additional humoral factors, such as the complement cascade, have developed that co-operate with cellular immunity in fighting infection and maintaining homeostasis. Defensive mechanisms based on germline-encoded receptors constitute a system known as innate immunity. In jaw vertebrates, this system is supplemented with a second system, adaptive immunity, which in contrast to innate immunity is based on diversification of immune receptors and on immunological memory in each individual.Usually, each newly evolved defense mechanism did not replace the previous one, but supplemented it, resulting in a layered structure of the immune system. The immune system is not one system but rather a sophisticated network of various defensive mechanisms operating on different levels, ranging from mechanisms common for every cell in the body to specialized immune cells and responses at the level of the whole organism. Adaptive changes in pathogens have shaped the evolution of the immune system at all levels. PMID:16619242

Danilova, Nadia

2006-11-15

151

Strategies to Modulate Immune Responses: A New Frontier for Gene Therapy  

PubMed Central

The success of gene therapy strategies to cure disease relies on the control of unwanted immune responses to transgene products, genetically modified cells and/or to the vector. Effective treatment of an established immune response is much harder to achieve than prevention of a response before it has had a chance to develop. However, preventive strategies are not always effective in avoiding immune responses, thus the use of drugs to induce immunosuppression (IS) is required. The growing discovery of novel drugs provides a conceptual shift from using generalized, moderately intensive immunosuppressive regimens towards a refined approach to attain the optimal balance of naive cells, effector cells, memory cells, and regulatory cells, harnessing the natural tolerance mechanisms of the body. We review several strategies based on transient IS coupled with gene therapy for sustained immune tolerance induction to the therapeutic transgene. PMID:19584819

Arruda, Valder R; Favaro, Patricia; Finn, Jonathan D

2009-01-01

152

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

PubMed

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

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

2013-06-21

153

Possible New Antiaging Strategies Related to Neuroendocrine-Immune Interactions  

Microsoft Academic Search

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

Eugenio Mocchegiani; Marco Malavolta

2008-01-01

154

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

PubMed

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

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

2014-08-01

155

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

PubMed Central

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

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

2013-01-01

156

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

PubMed

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

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

2013-01-01

157

T-cell apoptosis in autoimmune diseases: termination of inf lammation in the nervous system and other sites with specialized immune-defense mechanisms  

Microsoft Academic Search

We have studied T-cell apoptosis in animal models of human autoimmune disorders of the nervous system and in other tissues devoid of specialized immune-defense mechanisms. Our data suggest that the CNS has high potential for elimination of T-cell-dependent inflammation, whereas this mechanism is less effective in the PNS, and is almost absent in other tissues such as muscle and skin.

Ralf Gold; Hans-Peter Hartung; Hans Lassmann

1997-01-01

158

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

PubMed

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

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

2010-04-01

159

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

PubMed Central

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

Vanpouille-Box, Claire; Hindré, François

2012-01-01

160

Immune responses against virus and tumor in cervical carcinogenesis: treatment strategies for avoiding the HPV-induced immune escape.  

PubMed

Despite the availability of prophylactic vaccines against human papillomavirus (HPV), cervical cancer (CC) is still a major problem globally. It is the cancer with the second highest incidence and the third highest mortality in women worldwide, but, in less developed countries, it is an even greater problem being the second most common cause of cancer death. Although HPV infection is one of the most common sexually transmitted diseases, and high-risk HPV16 is the most frequent genotype involved, only a small number of HPV-infected women develop high-grade squamous intraepithelial lesions whereas, in the remainder of the women, the virus disappears spontaneously. There is a lot of evidence to support the view that host-dependent immunologic status and HPV-induced immune evasion are responsible for persistent HPV infection and subsequent development of cervical neoplasia. Therefore, the role of the immune system, not only in viral clearance but also in tumor antigen recognition, is particularly relevant in the case of cervical carcinogenesis. A better understanding of these processes would help in the development of therapeutic vaccines. This review aims to explain which immune cells and molecules are involved in the process of viral and tumor recognition, how their failure can lead to cervical carcinoma and what are the main therapeutic strategies so far tested in preclinical models and clinical trials to stimulate the immune system in cervical carcinoma. PMID:23994536

Conesa-Zamora, Pablo

2013-11-01

161

Strategies and challenges in eliciting immunity to melanoma  

PubMed Central

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

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

2010-01-01

162

Sympathetic Modulation of Immunity: Relevance to Disease  

PubMed Central

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

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

2008-01-01

163

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

PubMed

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

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

164

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

SciTech Connect

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.

Parlier, G.H.

1996-05-20

165

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

PubMed

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

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

166

Body Defenses Immune System  

E-print Network

organs (red bone marrow and thymus) Secondary organs (lymph nodes and spleen) Lymphatic Organs Red Bone Marrow Thymus Lymphatic Organs Secondary Lymphatic Organs The spleen contains white pulp the blood. Removes damaged, dying red blood cells In the case of infection or a blow, the spleen can burst

Cochran-Stafira, D. Liane

167

IMMUNE DEFICIENCY AND DYSREGULATION (DP HUSTON, SECTION EDITOR) Strategies for Molecular Classification of Asthma  

E-print Network

IMMUNE DEFICIENCY AND DYSREGULATION (DP HUSTON, SECTION EDITOR) Strategies for Molecular patients who are at increased risk of morbidity. This syndrome presents with common clinical signs to variable airflow obstruction and airway hyper-responsiveness affecting close to 300 million people globally

Bhavnani, Suresh K.

168

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

Microsoft Academic Search

The human neutrophil is a professional phagocyte of fundamental importance for defense against microorganisms, as witnessed by the life- threatening infections occurring in patients with neutropenia or with defects that result in decreased microbicidal activity of the neutrophil (1, 2). Like- wise, the skin and mucosal surfaces provide impor- tant barriers against infections. Traditionally, these major defense systems, the epithelial

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

2004-01-01

169

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

PubMed Central

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

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

2010-01-01

170

Immunization  

MedlinePLUS

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

171

PLANT DEFENSE SYNDROMES  

Microsoft Academic Search

Given that a plant's defensive strategy against herbivory is never likely to be a single trait, we develop the concept of plant defense syndromes, where association with specific ecological interactions can result in convergence on suites of covarying defensive traits. Defense syndromes can be studied within communities of diverse plant species as well as within clades of closely related species.

Anurag A. Agrawal; Mark Fishbein

2006-01-01

172

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

PubMed Central

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

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

2012-01-01

173

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

PubMed Central

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

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

2007-01-01

174

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

PubMed

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

Siddle, Hannah V; Kaufman, Jim

2013-09-01

175

Reproduction and love: strategies of the organism’s cellular defense system?  

Microsoft Academic Search

A novel view is presented which states that primordial germ cells and their descendants can be regarded as ‘cancerous cells’ which emit signals that activate a whole array of cellular defensive mechanisms by the somatoplasm. These cells have become unrestrained in response to the lack of typical cell adhesion properties of epithelial cells. From this point of view: (1) the

A De Loof; R Huybrechts; S Kotanen

1998-01-01

176

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

SciTech Connect

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

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

1984-05-16

177

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

Microsoft Academic Search

Roots play a critical, but largely unappreciated, role in aboveground anti-herbivore plant defense (e.g. resistance and tolerance) and root-leaf connections may therefore result in unexpected coupling between above- and belowground consumers. Using the tobacco (Nicotiana tabacum) system we highlight two examples of this phenomenon. First, the secondary metabolite nicotine is produced in roots, yet translocated aboveground for use as a

Ian Kaplan; Rayko Halitschke; Andre Kessler; Brian J. Rehill; Sandra Sardanelli; Robert F. Denno

2008-01-01

178

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

NASA Astrophysics Data System (ADS)

The basic genetic characteristics, important functional genes, and entire transcriptome of Solen grandis Dunker were investigated by constructing a full-length cDNA library with the `switching mechanism at the 5'-end of the RNA transcript' (SMART) technique. Total RNA was isolated from the immune-relevant tissues, gills and hemocytes, using the Trizol reagent, and cDNA fragments were digested with Sfi I before being ligated to the pBluescript II SK* vector. The cDNA library had a titer of 1048 cfu ?L-1 and a storage capacity of 1.05×106 cfu. Approximately 98% of the clones in the library were recombinants, and the fragment lengths of insert cDNA ranged from 0.8 kb to 3.0 kb. A total of 2038 expressed sequence tags were successfully sequenced and clustered into 965 unigenes. BLASTN analysis showed that 240 sequences were highly similar to the known genes (E-value < 1e -5; percent identity >80%), accounting for 25% of the total unigenes. According to the Gene Ontology, these unigenes were related to several biological processes, including cell structure, signal transport, protein synthesis, transcription, energy metabolism, and immunity. Fifteen of the identified sequences were related to defense and immunity. The full-length cDNA sequence of HSC70 was obtained. The cDNA library of S. grandis provided a useful resource for future researches of functional genomics related to stress tolerance, immunity, and other physiological activities.

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

2013-11-01

179

Enhancement of survivin-specific anti-tumor immunity by adenovirus prime protein-boost immunity strategy with DDA/MPL adjuvant in a murine melanoma model.  

PubMed

As an ideal tumor antigen, survivin has been widely used for tumor immunotherapy. Nevertheless, no effective protein vaccine targeting survivin has been reported, which may be due to its poor ability to induce cellular immunity. Thus, a suitable immunoadjuvant and optimized immunization strategy can greatly enhance the cellular immune response to this protein vaccine. DDA/MPL (monophosphoryl lipid A formulated with cationic dimethyldioctadecylammonium) has been reported to enhance the antigen uptake and presentation to T cells as an adjuvant. Meanwhile, a heterologous prime-boost strategy can enhance the cellular immunity of a protein vaccine by applying different antigen-presenting systems. Here, DDA/MPL and an adenovirus prime-protein boost strategy were applied to enhance the specific anti-tumor immunity of a truncated survivin protein vaccine. Antigen-specific IFN-?-secreting T cells were increased by 10-fold, and cytotoxic T lympohocytes (CTLs) were induced effectively when the protein vaccine was combined with the DDA/MPL adjuvant. Meanwhile, the Th1 type cellular immune response was strongly enhanced and tumor inhibition was significantly increased by 96% with the adenovirus/protein prime-boost strategy, compared to the protein homologous prime-boost strategy. Moreover, this adjuvanted heterologous prime-boost strategy combined with oxaliplatin could significantly enhance the efficiency of tumor growth inhibition through promoting the proliferation of splenocytes. Thus, our results provide a novel vaccine strategy for cancer therapy using an adenovirus prime-protein boost strategy in a murine melanoma model, and its combination with oxaliplatin may further enhance the anti-tumor efficacy while alleviating side effects of the drug. PMID:23624214

Wang, Yu-Qian; Zhang, Hai-Hong; Liu, Chen-Lu; Wu, Hui; Wang, Peng; Xia, Qiu; Zhang, Li-Xing; Li, Bo; Wu, Jia-Xin; Yu, Bin; Gu, Tie-Jun; Yu, Xiang-Hui; Kong, Wei

2013-09-01

180

Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy  

Microsoft Academic Search

Metazoan organisms may discriminate between self and non-self not only by the presence of foreign antigens but also by the absence of normal self markers1. Mammalian adaptive immune responses use the first strategy, with the additional requirement that foreign antigens are recognized in the context of self-major histocompatibility complex (MHC) products at the cell surface2. Aberrant cells which fail to

Klas Kärre; Hans Gustaf Ljunggren; Gerald Piontek; Rolf Kiessling

1986-01-01

181

Host defenses in murine malaria: analysis of the mechanisms of immunity to Plasmodium berghei generated in response to immunization with formalin-killed blood-stage parasites.  

PubMed Central

Syngeneic B6D2F1 (C57Bl/6 x DBA/2) mice were immunized with a nonliving antigen prepared from mixed blood forms of Plasmodium berghei strain NYU-2. Consistently greater than 80% of the vaccinated mice survived virulent challenge, and protective immunity was demonstrable from 1 week through at least 4 months after immunization. However, vaccination did not prevent the development of patient infection after challenge. Instead, infections in vaccinated mice progressed to about 10% parasitemia and were then subsequently cleared. In contrast, infections initiated in nonvaccinated mice progressed beyond 10% parasitemia and were uniformly fatal within 4 weeks. Sera collected from normal mice, nonvaccinated mice infected with P. berghei, or vaccinated mice before challenge failed to passively protect recipients against virulent infection. On the other hand, sera collected from vaccinated mice after recovery from a challenge infection conferred upon passively immunized recipients protection from homologous virulent challenge, which was manifest as a delay in the onset of overt infection. It was concluded, therefore, that vaccination altered the immunological potential of the host in such a way as to allow the production of a protective humoral factor, probably specific antibody, in response to infection with the virulent parasites. PMID:381198

Murphy, J R

1979-01-01

182

Concurrent evaluation of general, immune, and genetic toxicity endpoints as part of an integrated testing strategy.  

PubMed

Integrated testing strategies involve the assessment of multiple endpoints within a single toxicity study and represent an important approach for reducing animal use and streamlining testing. The present study evaluated the ability to combine general, immune, and genetic toxicity endpoints into a single study. Specifically, this study evaluated the impact of sheep red blood cell (SRBC) immunization, as part of the T-cell dependent antibody response (TDAR) assay, on organ weights, micronuclei (MN) formation (bone marrow and peripheral blood), and the Comet assay response in the liver of female F344/DuCrl rats treated with cyclophosphamide (CP) a known immunosuppressive chemical and genotoxicant. For the TDAR assay, treatment with CP resulted in a dose-dependent decrease in the antibody response with a suppression of greater than 95% at the high dose. Injection with SRBC had no impact on evaluated organ weights, histopathology, hematology, and clinical chemistry parameters. Analysis of MN formation in bone marrow and peripheral blood revealed a dose-dependent increase in response to CP treatment. Injection with SRBC had no impact on the level of MN in control animals and did not alter the dose response of CP. There was a slight increase in liver DNA damage in response to CP as measured by the Comet assay; however, injection with SRBCs did not alter this endpoint. Overall these data provide strong support for the concurrent assessment of general, immune, and genetic toxicology endpoints within a single study as part of an integrated testing strategy approach. PMID:24976023

Schisler, Melissa R; Sura, Radhakrishna; Visconti, Nicolo R; Sosinski, Lindsay K; Murphy, Lynea A; LeBaron, Matthew J; Boverhof, Darrell R

2014-08-01

183

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

SciTech Connect

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

Bier, Asmeret Brooke

2014-01-01

184

Host-pathogen interactions and immune evasion strategies in Francisella tularensis pathogenicity  

PubMed Central

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

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

2014-01-01

185

The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection  

PubMed Central

Acinetobacter baumannii is a major extensively drug-resistant lethal human nosocomial bacterium. However, the host innate immune mechanisms controlling A. baumannii are not well understood. Although viewed as an extracellular pathogen, A. baumannii can also invade and survive intracellularly. However, whether host innate immune pathways sensing intracellular bacteria contribute to immunity against A. baumannii is not known. Here, we provide evidence for the first time that intracellular antibacterial innate immune receptors Nod1 and Nod2, and their adaptor Rip2, play critical roles in the sensing and clearance of A. baumannii by human airway epithelial cells in vitro. A. baumannii infection upregulated Rip2 expression. Silencing of Nod1, Nod2, and Rip2 expression profoundly increased intracellular invasion and prolonged the multiplication and survival of A. baumannii in lung epithelial cells. Notably, the Nod1/2-Rip2 axis did not contribute to the control of A. baumannii infection of human macrophages, indicating that they play cell type-specific roles. The Nod1/2-Rip2 axis was needed for A. baumannii infection-induced activation of NF-?B but not mitogen-activated protein kinases. Moreover, the Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine responses to A. baumannii infection. Mechanistic studies showed that the Nod1/2 pathway contributed to the innate control of A. baumannii infection through the production of ?-defensin 2 by airway epithelial cells. This study revealed new insights into the immune control of A. baumannii and may contribute to the development of effective immune therapeutics and vaccines against A. baumannii. PMID:24366254

Bist, Pradeep; Dikshit, Neha; Koh, Tse Hsien; Mortellaro, Alessandra; Tan, Thuan Tong

2014-01-01

186

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

PubMed Central

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.

Niewiesk, Stefan

2014-01-01

187

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

PubMed

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

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

2014-07-01

188

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

Microsoft Academic Search

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

Jun Zhuang; Vicki M. Bier

2007-01-01

189

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

E-print Network

disposal sites, disposal costs etc. This raises an economic issue that will be addressed in this paperEconomics and Homeland Security Strategies: Issues regarding Carcass Disposal in Design of Animal and rapid mechanism to control the disease spread and minimize the cost in terms of livestock losses

McCarl, Bruce A.

190

Modulation of Human Immune Response by Echinococcus granulosus Antigen B and Its Possible Role in Evading Host Defenses  

Microsoft Academic Search

By directly suppressing the function of certain immune cell subsets and by stimulating other cell populations related to immunopathology, parasite-derived substances play an important role in the chronic establishment of parasitic disease. Our objective was twofold: (i) to investigate further the role of Echinococcus granulosus antigen B (AgB) in the human early inflammatory response by determining its effect on polymorphonuclear

R. Rigano; E. Profumo; F. Bruschi; G. Carulli; A. Azzara; S. Ioppolo; B. Buttari; E. Ortona; P. Margutti; A. Teggi; A. Siracusano

2001-01-01

191

A putative G protein-coupled receptor involved in innate immune defense of Procambarus clarkii against bacterial infection.  

PubMed

The immune functions of G protein-coupled receptor (GPCR) were widely investigated in mammals. However, limited researches on immune function of GPCRs were reported in invertebrates. In the present study, the immune functions of HP1R gene, a putative GPCR identified from red swamp crayfish Procambarus clarkii were reported. Expression of HP1R gene was significant up-regulated in response to heat-killed Aeromonas hydrophila challenge. HP1R gene silencing mediated by RNA interference significantly enhanced the susceptibility of red swamp crayfish to A. hydrophila and Vibrio alginolyticus, indicating that HP1R was required for red swamp crayfish to defend against bacterial challenge. In HP1R-silenced crayfish, increased bacterial burden and decreased THC in response to bacterial challenge were observed when compared with control crayfish. No significant difference of proPO gene expression was observed between HP1R-silenced and control crayfish after challenge with heat-killed A. hydrophila. However, PO activity in response to bacterial challenge was significantly reduced in HP1R-silenced crayfish. The results collectively indicated that HP1R was an important immune molecule which was required for red swamp crayfish to defend against bacterial infection. PMID:21964155

Dong, Chaohua; Zhang, Peng

2012-02-01

192

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

PubMed

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

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

2013-08-25

193

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

NASA Astrophysics Data System (ADS)

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

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

2012-09-01

194

Biochemical defense strategies in sterilized seedlings of Nymphoides peltatum adapted to lead stress.  

PubMed

In order to study potential antioxidant defense mechanisms, the effects of increasing concentrations of lead (Pb) on polyamines (PAs), various thiols, vitamins C and E, and proline contents in sterilized seedlings of Nymphoides peltata (S.G. mel.) Kuntze were investigated after 5 days of exposure. The levels of total putrescine (Put), spermidine (Spd), and spermine (Spm) decreased significantly, while the ratio of (Spd?+?Spm)/Put first increased but then declined as the concentration of Pb increased. The trends for free, perchloric acid soluble-conjugated (PS-conjugated), and perchloric acid insoluble-bound (PIS-bound) PAs were similar to the trend seen for total PAs. Moreover, reduced glutathione (GSH), nonprotein thiols (NP-SH), phytochelatins (PCs), and vitamin C were induced at high Pb concentrations. No significant change was observed in vitamin E. An initial decline in proline content was followed by an increase as the Pb concentration rose. The reduced level of Put and elevated contents of GSH, NP-SH, PCs, vitamin C, and proline were found to be associated with antioxidant efficiency, which supports the hypothesis that they could play a significant role in the adaptation mechanisms of N. peltatum under Pb stress. PMID:24705892

Qiao, Xuqiang; Shi, Guoxin; Yang, Xiaoke; Zheng, Zhenzhen; Xu, Xiaoying; Yang, Haiyan

2014-07-01

195

Immune Evasion, Immunopathology and the Regulation of the Immune System  

PubMed Central

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.

Sorci, Gabriele; Cornet, Stéphane; Faivre, Bruno

2013-01-01

196

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

PubMed

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

Nelson, E W

1991-01-01

197

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

Microsoft Academic Search

Peptidoglycan recognition protein (PGRP) is an essential molecule in innate immunity for both invertebrates and vertebrates, owing to its prominent ability in detecting and eliminating the invading bacteria. Several PGRPs have been identified from mollusk, but their functions and the underlined mechanism are still unclear. In the present study, the mRNA expression profiles, location, and possible functions of PGRP-S1 from

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

2010-01-01

198

Guinea pigs sublethally infected with aerosolized Legionella pneumophila develop humoral and cell-mediated immune responses and are protected against lethal aerosol challenge. A model for studying host defense against lung infections caused by intracellular pathogens  

PubMed Central

We have employed the guinea pig model of L. pneumophila infection, which mimics Legionnaires' disease in humans both clinically and pathologically, to study humoral and cell-mediated immune responses to L. pneumophila and to examine protective immunity after aerosol exposure, the natural route of infection. Guinea pigs exposed to sublethal concentrations of L. pneumophila by aerosol developed strong humoral immune responses. By the indirect fluorescent antibody assay, exposed guinea pigs had a median serum antibody titer (expressed as the reciprocal of the highest positive dilution) of 32, whereas control guinea pigs had a median titer of less than 1. Sublethally infected (immunized) guinea pigs also developed strong cell-mediated immune responses. In response to L. pneumophila antigens, splenic lymphocytes from immunized but not control animals proliferated strongly in vitro, as measured by their capacity to incorporate [3H]thymidine. Moreover, immunized but not control guinea pigs developed strong cutaneous delayed-type hypersensitivity to intradermally injected L. pneumophila antigens. Sublethally infected (immunized) guinea pigs exhibited strong protective immunity to L. pneumophila. In two independent experiments, all 22 immunized guinea pigs survived aerosol challenge with one or three times the lethal dose of L. pneumophila whereas none of 16 sham- immunized control guinea pigs survived (p less than 0.0001 in each experiment). Immunized guinea pigs were not protected significantly from challenge with 10 times the lethal dose. Immunized but not control animals cleared the bacteria from their lungs. This study demonstrates that guinea pigs sublethally infected with L. pneumophila by the aerosol route develop strong humoral immune responses to this pathogen, develop strong cell-mediated immune responses and cutaneous delayed- type hypersensitivity to L. pneumophila antigens, are protected against subsequent lethal aerosol challenge, and are able to clear the bacteria from their lungs. The guinea pig model of L. pneumophila pulmonary infection is as an excellent one for studying general principles of host defense against pulmonary infections caused by intracellular pathogens. PMID:3819647

1987-01-01

199

Managing heat and immune stress in athletes with evidence-based strategies.  

PubMed

Heat and immune stress can affect athletes in a wide range of sports and environmental conditions. The classical thermoregulatory model of heat stress has been well characterized, as has a wide range of practical strategies largely centered on cooling and heat-acclimation training. In the last decade evidence has emerged of an inflammatory pathway that can also contribute to heat stress. Studies are now addressing the complex and dynamic interplay between hyperthermia, the coagulation cascade, and a systemic inflammatory response occurring after transient damage to the gastrointestinal tract. Damage to the intestinal mucosal membrane increases permeability, resulting in leakage of endotoxins into the circulation. Practical strategies that target both thermoregulatory and inflammatory causes of heat stress include precooling; short-term heat-acclimation training; nutritional countermeasures including hydration, energy replacement, and probiotic supplementation; pacing strategies during events; and postevent cooling measures. Cooperation between international, national, and local sporting organizations is required to ensure that heat-management policies and strategies are implemented effectively to promote athletes' well-being and performance. PMID:24911928

Pyne, David B; Guy, Joshua H; Edwards, Andrew M

2014-09-01

200

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

PubMed

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

Kubli, Shawn P; MacDougall-Shackleton, Elizabeth A

2014-05-01

201

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

SciTech Connect

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

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

1984-05-15

202

A neonatal Fc receptor-targeted mucosal vaccine strategy effectively induces HIV1 antigen-specific immunity to genital infection  

Microsoft Academic Search

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

L Lu; S Palaniyandi; R Zeng; Y Bai; X Liu; Y Wang; C D Pauza; D C Roopenian; X Zhu

2011-01-01

203

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

PubMed Central

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

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

2014-01-01

204

Regulation of plant immunity to necrotrophic fungi  

Microsoft Academic Search

We examined Arabidopsis resistance mechanisms to Botrytis cinerea and Alternaria brassicicola, two necrotrophic fungal pathogens with overlapping pathogenesis strategies. B. cinerea is the causal agent of gray mold whereas A. brassicicola causes the black spot disease in cruciferous plants.^ In an effort to isolate regulators of plant defense, we used functional genomics approaches to identify genes involved in immune responses

Kristin A Laluk

2010-01-01

205

Courtship Disruptions and Male Mating Strategies: Examples from Female-Defense Mating Systems.  

PubMed

Males frequently interrupt the copulation attempts of other males, and these courtship disruptions may limit the extent to which a few males are able to monopolize mating access to females. Males actively defend sexually receptive females in many species in which females form dense aggregations during the breeding season. Across and within such species there is considerable variation in the mating tactics adopted by males, with males in some cases defending groups of females and in other cases sequentially consorting with individual females. Colonial blackbirds have been central to studying this mating system, and we develop a conceptual model for how courtship disruption may account for variation in male mating tactics in this group. Our model assumes that the frequency of disruptions increases with greater colony size. As a consequence, successful copulations are less likely to occur at large colonies than at small colonies, and males are expected to switch from defending multiple females at the colony to consorting individual females away from it. Results from two species of blackbird support the basic assumptions of this model. In one species, the Montezuma oropendola, disruptions occur rarely and males defend groups of females, whereas in the other species, the yellow-rumped cacique, disruptions are frequent and males defend single females. Moreover, consistent with a key prediction, within each species, males associated with small colonies remain at the colony and defend groups of females, whereas males spend little time defending groups of females at large colonies and rarely attempt copulations there. This model has the potential to explain variation in male mating strategies and female monopolization for other taxa in which females form breeding aggregations. PMID:10600615

Webster; Robinson

1999-12-01

206

Evidence for two immune inhibitors from Bacillus thuringiensis interfering with the humoral defense system of saturniid pupae.  

PubMed Central

Mutants of Bacillus thuringiensis lacking either beta-exotoxin or gamma-endotoxin were compared for their virulence using pupae of a giant silk moth. Known doses of viable log-phase bacteria were injected, and the response was followed as the number of viable bacteria in the hemolymph. The results obtained imply that, in the system used, neither the beta-exotoxin nor the gamma-endotoxin and the sporeforming ability are of importance for virulence. Results with sterile culture filtrate from B. thuringiensis have given evidence for the production of two inhibitors, A and B, which interfere with the humoral defense system in pupae of Hyalophora cecropia. Inhibitor A, which blocked the lysis of Escherichia coli,was precipitated by trichloroacetic acid and sensitive to heating. Inhibitor B, which blocked the killing of Bacillus cereus, was soluble in trichloroacetic acid and resistant to 90 degrees C for 5 min. Both inhibitors are believed to contribute to the insecticidal nature of B. thuringiensis. PMID:992874

Edlund, T; Siden, I; Boman, H G

1976-01-01

207

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

PubMed

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

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

2014-12-01

208

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

PubMed Central

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

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

2013-01-01

209

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

PubMed

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

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

2014-01-01

210

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

PubMed Central

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

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

2014-01-01

211

Cutaneous Defense Mechanisms by Antimicrobial Peptides  

Microsoft Academic Search

The skin actively contributes to host defense by mounting an innate immune response that includes the production of antimicrobial peptides. These peptides, which include but are not limited to the cathelicidin and defensin gene families, provide rapid, broad-spectrum defense against infection by acting as natural antibiotics and by participating in host cell processes involved in immune defense. This review discusses

Marissa H. Braff; Antoanella Bardan; Victor Nizet; Richard L. Gallo

2005-01-01

212

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

PubMed Central

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

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

2014-01-01

213

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

PubMed Central

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

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

1999-01-01

214

Influenza Virus: Immunity and Vaccination Strategies. Comparison of the Immune Response to Inactivated and Live, Attenuated Influenza Vaccines  

Microsoft Academic Search

Influenza virus is a globally important respiratory pathogen which causes a high degree of morbidity and mortality annually. The virus is continuously under- going antigenic change and thus bypasses the host's acquired immunity to influenza. Despite the improvement in antiviral therapy during the last decade, vaccination is still the most effective method of prophylaxis. Vaccination induces a good degree of

R. J. Cox; K. A. Brokstad; P. Ogra

2004-01-01

215

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

ERIC Educational Resources Information Center

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.…

Naji, Simon; And Others

1986-01-01

216

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

PubMed Central

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

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

2013-01-01

217

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

Federal Register 2010, 2011, 2012, 2013

...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...

2013-12-30

218

Child Immunization Status Among a Sample of Adolescent Mothers: Comparing the Validity of Measurement Strategies  

Microsoft Academic Search

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

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

2011-01-01

219

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

PubMed Central

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

Moussa, Sandrine; Jenabian, Mohammad-Ali; Gody, Jean Chrysostome; Leal, Josiane; Gresenguet, Gerard; Le Faou, Alain; Belec, Laurent

2013-01-01

220

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

PubMed

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

Godeau, Bertrand; Stasi, Roberto

2014-04-01

221

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

PubMed

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

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

2013-07-18

222

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

Microsoft Academic Search

This study assesses Chinese defense and foreign policy perspectives, especially as they influence, and are influenced by, China's strategic approach to international issues. Special emphasis is placed on China's recent perspectives on the Soviet Union, Japan, and the United States, together with other major countries, as well as the Third World. China's views on international and regional security issues are

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

1984-01-01

223

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

PubMed Central

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.

Poggi, Alessandro; Zocchi, Maria Raffaella

2014-01-01

224

Mosquito Immunity against Arboviruses  

PubMed Central

Arthropod-borne viruses (arboviruses) pose a significant threat to global health, causing human disease with increasing geographic range and severity. The recent availability of the genome sequences of medically important mosquito species has kick-started investigations into the molecular basis of how mosquito vectors control arbovirus infection. Here, we discuss recent findings concerning the role of the mosquito immune system in antiviral defense, interactions between arboviruses and fundamental cellular processes such as apoptosis and autophagy, and arboviral suppression of mosquito defense mechanisms. This knowledge provides insights into co-evolutionary processes between vector and virus and also lays the groundwork for the development of novel arbovirus control strategies that target the mosquito vector. PMID:25415198

Sim, Shuzhen; Jupatanakul, Natapong; Dimopoulos, George

2014-01-01

225

Maternal tetanus immunization in Aceh Province, Sumatra: The cost-effectiveness of alternative strategies  

Microsoft Academic Search

This paper compares the cost per completed maternal tetanus immunization and an estimate of the cost per death averted in the routine EPI program with similar results from an experimental mass campaign in Aceh Province, Indonesia. The cost-effectiveness of the mass campaign in achieving complete immunization is similar to the routine program. However, the mass campaign is probably less cost-effective

Peter Berman; John Quinley; Burhannuddin Yusuf; Syaifuddin Anwar; Udin Mustaini; A. Azof; Iskandar

1991-01-01

226

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

Microsoft Academic Search

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

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

2010-01-01

227

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

ERIC Educational Resources Information Center

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

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

2011-01-01

228

The Immune Strategy and Stress Response of the Mediterranean Species of the Bemisia tabaci Complex to an Orally Delivered Bacterial Pathogen  

PubMed Central

Background The whitefly, Bemisia tabaci, a notorious agricultural pest, has complex relationships with diverse microbes. The interactions of the whitefly with entomopathogens as well as its endosymbionts have received great attention, because of their potential importance in developing novel whitefly control technologies. To this end, a comprehensive understanding on the whitefly defense system is needed to further decipher those interactions. Methodology/Principal Findings We conducted a comprehensive investigation of the whitefly's defense responses to infection, via oral ingestion, of the pathogen, Pseudomonas aeruginosa, using RNA-seq technology. Compared to uninfected whiteflies, 6 and 24 hours post-infected whiteflies showed 1,348 and 1,888 differentially expressed genes, respectively. Functional analysis of the differentially expressed genes revealed that the mitogen associated protein kinase (MAPK) pathway was activated after P. aeruginosa infection. Three knottin-like antimicrobial peptide genes and several components of the humoral and cellular immune responses were also activated, indicating that key immune elements recognized in other insect species are also important for the response of B. tabaci to pathogens. Our data also suggest that intestinal stem cell mediated epithelium renewal might be an important component of the whitefly's defense against oral bacterial infection. In addition, we show stress responses to be an essential component of the defense system. Conclusions/Significance We identified for the first time the key immune-response elements utilized by B. tabaci against bacterial infection. This study provides a framework for future research into the complex interactions between whiteflies and microbes. PMID:24722540

Xia, Jun; Li, Fang-Fang; Xia, Wen-Qiang; Liu, Shu-Sheng; Wang, Xiao-Wei

2014-01-01

229

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

PubMed

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

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

2014-01-01

230

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

Microsoft Academic Search

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

Magdalena Krzes?owska

2011-01-01

231

Chaos Optimization Strategy on Fuzzy-immune-PID Control of the Turbine Governing System  

Microsoft Academic Search

Aiming at the non-linear links such as time lag, inertia, dead time and saturation within the steam turbine governing system, we designed a fuzzy-immune-PID control system based on a mutative scale chaos optimization method, the principium of immune feedback system and the theory of fuzzy control. The proposed algorithm was used in tuning-parameter design of the steam turbine governing system

Shuangxin Wang; Yan Jiang; Hui Yang

2006-01-01

232

Hyposoter didymator uses a combination of passive and active strategies to escape from the Spodoptera frugiperda cellular immune response.  

PubMed

An endoparasitic life style is widespread among Hymenoptera, and various different strategies allowing parasitoids to escape from the host encapsulation response have been reported. Species carrying polydnaviruses (PDVs), such as the ichneumonid Hyposoter didymator, generally rely on the viral symbionts to evade host immune responses. In this work, we show that H. didymator eggs can evade encapsulation by the host in the absence of calyx fluid (containing the viral particles), whereas protection of the larvae requires the presence of calyx fluid. This evasion by the eggs depends on proteins associated with the exochorion. This type of local passive strategy has been described for a few species carrying PDVs. Immune evasion by braconid eggs appears to be related to PDVs or proteins synthesized in the oviducts being associated with the egg. We report that in H. didymator, by contrast, proteins already present in the ovarian follicles are responsible for the eggs avoiding encapsulation. Mass spectrometry analysis of the egg surface proteins revealed the presence of host immune-related proteins, including one with similarities with apolipophorin-III, and also the presence of three viral proteins encoded by IVSPERs (Ichnovirus Structural Protein Encoding Regions). PMID:23458339

Dorémus, Tristan; Jouan, Véronique; Urbach, Serge; Cousserans, François; Wincker, Patrick; Ravallec, Marc; Wajnberg, Eric; Volkoff, Anne-Nathalie

2013-04-01

233

Quadrennial Defense Review, 2001  

NSDL National Science Digital Library

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

2001-01-01

234

Strategies to Improve Child Immunization via Antenatal Care Visits in India: A Propensity Score Matching Analysis  

PubMed Central

Numerous studies have examined the empirical evidence concerning the influence of demographic and socio-economic factors influencing child immunization, but no documentation is available which shows the actual impact of antenatal care (ANC) visits on subsequent child immunization. Therefore, this paper aims to examine the net impact of ANC visits on subsequent utilization of child immunization after removing the presence of selection bias. Nationwide data from India’s latest National Family Health Survey conducted during 2005–06 is used for the present study. The analysis has been carried out in the two separate models, in the first model 1–2 ANC visit and in the second model three or more ANC visits has been compared with no visit. We have used propensity score matching method with a counterfactual model that assesses the actual ANC visits effect on treated (ANC visits) and untreated groups (no ANC visit), and have employed Mantel-Haenszel bounds to examine whether result would be free from hidden bias or not. Using matched sample analysis result shows that child immunization among the groups of women who have completed 1–2 ANC visits and those who had more than two visits was about 13 percent and 19 percent respectively, higher than the group of women who have not made any ANC visit. Findings of nearest neighbor matching with replacement method, which completely eliminated the bias, indicate that selection bias present in data set leads to overestimates the positive effects of ANC visits on child immunization. Result based on Mantel-Haenszel bounds method suggest that if around 19 percent bias would be involved in the result then also we could observe the true positive effect of 1–2 ANC visits on child immunization. This also indicates that antenatal clinics are the conventional platforms for educating pregnant women on the benefits of child immunization. PMID:23824555

Dixit, Priyanka; Dwivedi, Laxmi Kant; Ram, Faujdar

2013-01-01

235

76 FR 14413 - Risk Mitigation Strategies To Address Potential Procoagulant Activity in Immune Globulin...  

Federal Register 2010, 2011, 2012, 2013

...FDA-2011-N-0002] Risk Mitigation Strategies To Address Potential...Globulin Intravenous Products; Public Workshop AGENCY...workshop on risk mitigation strategies to address procoagulant...Intravenous (IGIV) products. The purposes of...

2011-03-16

236

Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses.  

PubMed

Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime. PMID:25196393

Khan, Shahneaz Ali; Waugh, Courtney; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

2014-10-01

237

Novel mobilization strategies to enhance autologous immune effector cells in multiple myeloma  

PubMed Central

The immune system plays a critical role determining the outcomes in transplanted multiple myeloma patients, since enhanced lymphocyte recovery results in improved survival. Since mobilization regimens influence the cellular subsets collected and infused for transplant, these regimens may determine immune recovery following transplant. We hypothesized that a mobilized stem cell product harboring an increased number of lymphocytes would enhance immune recovery following autologous stem cell infusion, increase lymphocyte recovery, and improve clinical outcomes. We designed a phase I immune mobilization trial using IL-2 and growth factors to increase the number of lymphocytes within the stem cell product. This regimen efficiently mobilized CD34+ progenitor cells (median: 3.6 × 106 cells/kg; range 1.9–6.6 × 106 cells/kg) and improved the immune properties of the mobilized stem cells, including an increase in CD8+ T cells expressing an NK activating receptor called NKG2D (P< 0.004), cells that are extremely potent at killing myeloma cells using non-MHC-I restricted and TCR-independent mechanisms. Novel mobilization techniques can improve the mobilized graft and may improve clinical outcomes in myeloma patients. PMID:21622154

Talebian, Laleh; Wu, Jia Yan; Fischer, Dawn A.; Hill, John M.; Szczepiorkowski, Zbigniew M.; Ernstoff, Marc S.; Sentman, Charles L.; Meehan, Kenneth R.

2012-01-01

238

Sialic acids siglec interaction: A unique strategy to circumvent innate immune response by pathogens  

PubMed Central

Sialic acids (Sias) are nine-carbon keto sugars primarily present on the terminal residue of cell surface glycans. Sialic acid binding immunoglobulins (Ig)-like lectins (siglecs) are generally expressed on various immune cells. They selectively recognize different linkage-specific sialic acids and undertake a variety of cellular functions. Many pathogens either synthesize or acquire sialic acids from the host. Sialylated pathogens generally use siglecs to manipulate the host immune response. The present review mainly deals with the newly developed information regarding mechanism of acquisition of sialic acids by pathogens and their biological relevance especially in the establishment of successful infection by impairing host innate immunity. The pathogens which are unable to synthesize sialic acids might adsorb these from the host as a way to engage the inhibitory siglecs. They promote association with the immune cells through sialic acids-siglec dependent manner. Such an association plays an important role to subvert host's immunity. Detailed investigation of these pathways has been discussed in this review. Particular attention has been focused on Pseudomonas aeruginosa (PA) and Leishmania donovani. PMID:24434319

Khatua, Biswajit; Roy, Saptarshi; Mandal, Chitra

2013-01-01

239

Iron in Infection and Immunity  

PubMed Central

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

Cassat, James E.; Skaar, Eric P.

2013-01-01

240

Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection  

PubMed Central

Background To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-?-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice. Conclusion/Significance We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections. PMID:17637846

Barquero-Calvo, Elias; Chaves-Olarte, Esteban; Weiss, David S.; Guzman-Verri, Caterina; Chacon-Diaz, Carlos; Rucavado, Alexandra; Moriyon, Ignacio; Moreno, Edgardo

2007-01-01

241

Macroevolution of plant defense Anurag A. Agrawal  

E-print Network

strategies and plant­ herbivore coevolutionary interactions. I focus particularly on multivariate defenseMacroevolution of plant defense strategies Anurag A. Agrawal Department of Ecology and Evolutionary University, Comstock Hall, Ithaca, NY 14853-2601, USA Theories of plant defense expression are typically

Agrawal, Anurag

242

Jasmonate-triggered plant immunity.  

PubMed

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

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

2014-07-01

243

Adaptive Immune System TH1\\/TH2 Differentiation Mechanism Inspired Perimeter Patrol Control Strategy  

Microsoft Academic Search

This brief investigates a perimeter patrol control problem in which multiple agents travel back and forth defending a border. A decentralized control inspired from the adaptive immune system TH1\\/TH2 differentiation mechanism has been proposed. The resulting patrol control exhibits robustness under adversarial conditions. This is primarily because the motion pe- riod can be arbitrary, which makes it difficult for intruders

Ruoting Yang; Sharon Bewick; Mingjun Zhang; William R. Hamel

2011-01-01

244

Modulating T-cell immunity to tumours: new strategies for monitoring T-cell responses  

Microsoft Academic Search

Advances in immunological monitoring provide the means to analyse the cellular immune response with greater sensitivity and precision than ever before. Novel immunological tools can be used not only to quantify the antigen-specific response, but also to analyse the phenotype and function of individual effector cells. Application of these tools to dissect the antitumour responses will lead to a greater

Philip Greenberg; Cassian Yee

2002-01-01

245

Development of Oral Vaccines to Stimulate Mucosal and Systemic Immunity: Barriers and Novel Strategies  

Microsoft Academic Search

Many questions regarding the induction of mucosal and humoral immunity through oral vaccination exist. Efficacy is dependent on the physicochemical properties of the antigen, the gastrointestinal environment, the presence of adjuvants, and the mode of delivery. Understanding how these factors interrelate will be critical to the development of new oral vaccines. A number of approaches are currently being studied to

Waleed S. W. Shalaby

1995-01-01

246

POLYCLONAL IMMUNE RESPONSES TO ANTIGENS ASSOCIATED WITH CANCER SIGNALING PATHWAYS AND NEW STRATEGIES TO ENHANCE CANCER VACCINES  

PubMed Central

Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been amongst the most successful. A challenge for these therapies is therapeutic unresponsiveness and acquired resistance due to mutations in the receptors, upregulation of alternate growth and survival pathways or inadequate function of the monoclonal antibodies. Vaccines are able to induce polyclonal responses which can have a multitude of affects against the target molecule. We began to explore therapeutic vaccine development to antigens associated with these signaling pathways. We provide an illustrative example in developing therapeutic cancer vaccines inducing polyclonal adaptive immune responses targeting the ErbB family member HER2. Further, we will discuss new strategies to augment the clinical efficacy of cancer vaccines by enhancing vaccine immunogenicity and reversing the immunosuppressive tumor microenvironment. PMID:21136201

Clay, Timothy M.; Osada, Takuya; Hartman, Zachary C.; Hobeika, Amy; Devi, Gayathri; Morse, Michael A.; Lyerly, H. Kim

2013-01-01

247

Mechanisms for a novel immune evasion strategy in the scabies mite sarcoptes scabiei: a multigene family of inactivated serine proteases.  

PubMed

Parasitic infestation of the skin by the mite Sarcoptes scabiei is a significant problem worldwide, particularly in socially disadvantaged communities. A multigene family of at least 24 homologs of a serine protease allergen have been identified in S. scabiei. Surprisingly, the products of all but one of these genes are predicted to be catalytically inactive, due to mutations at a critical triad of amino acids at the active site. We discuss the possibility that these genes for inactivated proteases have been conserved because they mediate a novel host defense evasion strategy that the mite has evolved as an adaptation to parasitism of the epidermis. The identification of this family, and elucidation of its value to the parasite, may present an unanticipated approach to protective vaccination. PMID:14675192

Holt, Deborah C; Fischer, Katja; Allen, George E; Wilson, Danny; Wilson, Peter; Slade, Robert; Currie, Bart J; Walton, Shelley F; Kemp, David J

2003-12-01

248

Targeting inflammation as a therapeutic strategy for drug-resistant epilepsies: an update of new immune-modulating approaches.  

PubMed

An increasing body of literature data suggests that inflammation, and in particular neuroinflammation, is involved in the pathophysiology of particular forms of epilepsy and convulsive disorders. Animal models have been used to identify inflammatory triggers in epileptogenesis and inflammation has recently been shown to enhance seizures. For example, pharmacological blockade of the IL-1beta/IL-1 receptor type 1 axis during epileptogenesis has been demonstrated to provide neuroprotection in temporal lobe epilepsy. Furthermore, experimental models have suggested that neural damage and the onset of spontaneous recurrent seizures are modulated via complex interactions between innate and adaptive immunity. However, it has also been suggested that inflammation can occur as a result of epilepsy, since animal models have also shown that seizure activity can induce neuroinflammation, and that recurrent seizures maintain chronic inflammation, thereby perpetuating seizures. On the basis of these observations, it has been suggested that immune-mediated therapeutic strategies may be beneficial for treating some drug resistant epilepsies with an underlying demonstrable inflammatory process. Although the potential mechanisms of immunotherapeutic strategies in drug-resistant seizures have been extensively discussed, evidence on the efficacy of such therapy is limited. However, recent research efforts have been directed toward utilizing the potential therapeutic benefits of anti-inflammatory agents in neurological disease and these are now considered prime candidates in the ongoing search for novel anti-epileptic drugs. The objective of our review is to highlight the immunological features of the pathogenesis of seizures and to analyze possible immunotherapeutic approaches for drug resistant epilepsies that can alter the immune-mediated pathogenesis. PMID:24609096

Vitaliti, Giovanna; Pavone, Piero; Mahmood, Fahad; Nunnari, Giuseppe; Falsaperla, Raffaele

2014-04-01

249

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

Microsoft Academic Search

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

Fabrizio Bruschi; Lorena Chiumiento; Gianfranco Del Prete

250

Pharmacy-based Immunization in Rural Communities Strategy (PhICS)  

PubMed Central

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

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

2014-01-01

251

Fighting a losing battle: vigorous immune response countered by pathogen suppression of host defenses in the chytridiomycosis-susceptible frog Atelopus zeteki.  

PubMed

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

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

2014-07-01

252

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

E-print Network

Insect pests such as termites cause damages to crops and man-made structures estimated at over $30 billion per year, imposing a global challenge for the human economy. Here, we report a strategy for compromising insect ...

Raman, Rahul

253

Stability of Microbiota Facilitated by Host Immune Regulation: Informing Probiotic Strategies to Manage Amphibian Disease  

PubMed Central

Microbial communities can augment host immune responses and probiotic therapies are under development to prevent or treat diseases of humans, crops, livestock, and wildlife including an emerging fungal disease of amphibians, chytridiomycosis. However, little is known about the stability of host-associated microbiota, or how the microbiota is structured by innate immune factors including antimicrobial peptides (AMPs) abundant in the skin secretions of many amphibians. Thus, conservation medicine including therapies targeting the skin will benefit from investigations of amphibian microbial ecology that provide a model for vertebrate host-symbiont interactions on mucosal surfaces. Here, we tested whether the cutaneous microbiota of Panamanian rocket frogs, Colostethus panamansis, was resistant to colonization or altered by treatment. Under semi-natural outdoor mesocosm conditions in Panama, we exposed frogs to one of three treatments including: (1) probiotic - the potentially beneficial bacterium Lysinibacillus fusiformis, (2) transplant – skin washes from the chytridiomycosis-resistant glass frog Espadarana prosoblepon, and (3) control – sterile water. Microbial assemblages were analyzed by a culture-independent T-RFLP analysis. We found that skin microbiota of C. panamansis was resistant to colonization and did not differ among treatments, but shifted through time in the mesocosms. We describe regulation of host AMPs that may function to maintain microbial community stability. Colonization resistance was metabolically costly and microbe-treated frogs lost 7–12% of body mass. The discovery of strong colonization resistance of skin microbiota suggests a well-regulated, rather than dynamic, host-symbiont relationship, and suggests that probiotic therapies aiming to enhance host immunity may require an approach that circumvents host mechanisms maintaining equilibrium in microbial communities. PMID:24489847

Kung, Denise; Bigler, Laurent; Davis, Leyla R.; Gratwicke, Brian; Griffith, Edgardo; Woodhams, Douglas C.

2014-01-01

254

Strategies of Echinococcus species responses to immune attacks: implications for therapeutic tool development.  

PubMed

Echinococcus species have been studied as a model to investigate parasite-host interactions. Echinococcus spp. can actively communicate dynamically with a host to facilitate infection, growth and proliferation partially via secretion of molecules, especially in terms of harmonization of host immune attacks. This review systematically outlines our current knowledge of how the Echinococcus species have evolved to adapt to their host's microenvironment. This understanding of parasite-host interplay has implications in profound appreciation of parasite plasticity and is informative in designing novel and effective tools including vaccines and drugs for the treatment of echinococcosis and other diseases. PMID:23973651

Zheng, Yadong

2013-11-01

255

De-submergence responses of antioxidative defense systems in two wetland plants having escape and quiescence strategies.  

PubMed

Fast recovery after de-submergence requires efficient protection against oxidative injuries. We investigated whether de-submergence responses of antioxidant systems differ in two wetland plants, Alternanthera philoxeroides and Hemarthria altissima, characterized by 'escape' and 'quiescence' strategies of flood tolerance, respectively. The antioxidant capacity was assessed in the two species during 10d of recovery following 20d of complete submergence (low light+low O(2)) or severe shading (low light+ambient O(2)). The activities of superoxide dismutase and catalase were measured in leaf and root tissues, along with the concentrations of reduced ascorbate, malondialdehyde, and acetaldehyde. In addition, formation of superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) was detected in leaves by chemical staining. Following de-submergence, plants of A. philoxeroides showed a transient burst of acetaldehyde, while the concentration of acetaldehyde increased slowly and stayed high in leaves of H. altissima. In leaves of A. philoxeroides, the variations in O(2)(-) and H(2)O(2) correlated with the levels of light and O(2), respectively, whereas neither of the two reactive oxygen species was detected in H. altissima. For A. philoxeroides, the antioxidant capacities changed mainly in leaves during the recovery. For H. altissima, changes in reduced ascorbate were found in leaves and those of antioxidant enzyme activities in roots. De-submergence caused some lipid peroxidation in leaves of both species. We conclude that de-submergence responses of the detoxification systems differ between A. philoxeroides and H. altissima, especially in leaves. Dynamic changes were found in A. philoxeroides (having the escape strategy), as opposed to little or slow changes in H. altissima (having the quiescence strategy). Whereas the antioxidant capacities are often strongly influenced by light environments, the toxic compounds and lipid peroxidation indicate harmful effects of changing O(2) concentration which accompanies submergence and de-submergence. PMID:22884406

Luo, Fang-Li; Thiele, Björn; Janzik, Ingar; Zeng, Bo; Schurr, Ulrich; Matsubara, Shizue

2012-11-15

256

Plant Defense against Insect Herbivores.  

PubMed

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

Fürstenberg-Hägg, Joel; Zagrobelny, Mika; Bak, Søren

2013-01-01

257

Plant Defense against Insect Herbivores  

PubMed Central

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

Furstenberg-Hagg, Joel; Zagrobelny, Mika; Bak, S?ren

2013-01-01

258

Surfactant Collectins and Innate Immunity  

Microsoft Academic Search

Respiratory pathogens encounter various lines of defenses before infection of the host is established. The innate immune response represents an important first-line protection mechanism against potentially pathogenic microorganisms during early stages of infection of the naive host. Important players in this host defense system are ‘collectins’, a class of soluble innate immune proteins. Well-characterized members of the collectin family are

Henk P. Haagsman; Astrid Hogenkamp; Martin van Eijk; Edwin J. A. Veldhuizen

2008-01-01

259

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

PubMed

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

Boliar, Saikat; Chambers, Thomas M

2010-08-15

260

Systematic Method for Determining Intravenous Drug Treatment Strategies Aiding the Humoral Immune Response 1  

E-print Network

into a larger class of uncertain systems, by a finite dimensional approximation and a transformation to a linear and represent a first step in obtaining a systematic method for determining optimal drug delivery strategies. II with a specific humoral response producing antibodies which bind to the bacteria. These bound antibodies

Balakrishnan, Venkataramanan "Ragu"

261

Systematic Method for Determining Intravenous Drug Treatment Strategies Aiding the Humoral Immune Response1  

E-print Network

into a larger class of uncertain systems, by a finite dimensional approximation and a transformation to a linear and represent a first step in obtaining a systematic method for determining optimal drug delivery strategies. II with a specific humoral response producing antibodies which bind to the bacteria. These bound antibodies

Balakrishnan, Venkataramanan "Ragu"

262

Enhancing Artificial Bee Colony Algorithm with Self-Adaptive Searching Strategy and Artificial Immune Network Operators for Global Optimization  

PubMed Central

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

Chen, Tinggui; Xiao, Renbin

2014-01-01

263

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

PubMed

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

Chen, Tinggui; Xiao, Renbin

2014-01-01

264

Prevention of Immune Cell Apoptosis as Potential Therapeutic Strategy for Severe Infections  

PubMed Central

Some labile cell types whose numbers are normally controlled through programmed cell death are subject to markedly increased destruction during some severe infections. Lymphocytes, in particular, undergo massive and apparently unregulated apoptosis in human patients and laboratory animals with sepsis, potentially playing a major role in the severe immunosuppression that characterizes the terminal phase of fatal illness. Extensive lymphocyte apoptosis has also occurred in humans and animals infected with several exotic agents, including Bacillus anthracis, the cause of anthrax; Yersinia pestis, the cause of plague; and Ebola virus. Prevention of lymphocyte apoptosis, through either genetic modification of the host or treatment with specific inhibitors, markedly improves survival in murine sepsis models. These findings suggest that interventions aimed at reducing the extent of immune cell apoptosis could improve outcomes for a variety of severe human infections, including those caused by emerging pathogens and bioterrorism agents. PMID:17479879

Parrino, Janie; Hotchkiss, Richard S.

2007-01-01

265

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

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

Li, Yan; Ma, Qiu-Gang; Zhao, Li-Hong; Wei, Hua; Duan, Guo-Xiang; Zhang, Jian-Yun; Ji, Cheng

2014-01-01

266

Effects of lipoic acid on immune function, the antioxidant defense system, and inflammation-related genes expression of broiler chickens fed aflatoxin contaminated diets.  

PubMed

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

Li, Yan; Ma, Qiu-Gang; Zhao, Li-Hong; Wei, Hua; Duan, Guo-Xiang; Zhang, Jian-Yun; Ji, Cheng

2014-01-01

267

[Therapeutic strategy in inflammatory myopathies (polymyositis, dermatomyositis, overlap myositis, and immune-mediated necrotizing myopathy)].  

PubMed

Inflammatory myopathies (IM) are a heterogeneous group of autoimmune muscle disorders of unknown origin that share clinical symptoms such as muscle weakness and histological features with the presence in muscle of inflammatory infiltrate. Based on clinical, histological and serological characteristics, IM can be divided into polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, immune-mediated necrotizing myopathy, and inclusion-body myositis. Because of their resistance to corticosteroids and immunosuppressive drugs, inclusion-body myositis will be treated separately in this issue. Major obstacles in conducting high quality randomized controlled trials in inflammatory myopathies include the low prevalence and the heterogeneity of these diseases as well as the lack of international consensus on the outcome measures. In the absence of adequate controlled therapeutic trials, treatment of these disorders remains largely empirical. Corticosteroids are the cornerstone therapy. Due to the chronic course of the disease, there is a frequent need to use additional immunosuppressive treatment both to improve the disease response and to reduce the side effects of corticosteroids. Intravenous immunoglobulin infusion is a costly treatment option that is reserved in the presence of refractory dermatomyositis based on a trial showing superior efficacy against control in patients with impaired swallowing or with contraindications to immunosuppressive drugs. In patients who fail second-line therapy, which usually consists of methotrexate plus corticosteroids, the diagnosis should be carefully reassessed before considering other treatment options including methotrexate plus azathioprine or biological agents such as rituximab. PMID:24144868

Tournadre, A

2014-07-01

268

The genome of obligately intracellular Ehrlichia canis revealsthemes of complex membrane structure and immune evasion strategies  

SciTech Connect

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

Mavromatis, K.; Kuyler Doyle, C.; Lykidis, A.; Ivanova, N.; Francino, P.; Chain, P.; Shin, M.; Malfatti, S.; Larimer, F.; Copeland,A.; Detter, J.C.; Land, M.; Richardson, P.M.; Yu, X.J.; Walker, D.H.; McBride, J.W.; Kyrpides, N.C.

2005-09-01

269

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

PubMed Central

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

Dong, Junjian; Chen, Wenli

2013-01-01

270

Immunity at Mucosal Surfaces  

Microsoft Academic Search

The mucosae form a barrier between our bodies and a hostile external environment. Diseases and extrinsic factors which impair mucosal function may lead to serious consequences. The mucosal immune system is the primary mediator of specific immunity at mucosal surfaces. As such, it is responsible for maintaining homeostasis and for defense against both overt and opportunistic pathogens. For this reason,

T. A. Brown

1996-01-01

271

Immunity and Nutrition.  

ERIC Educational Resources Information Center

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…

Dupin, Henri; Guerin, Nicole

1990-01-01

272

Computer defense using artificial intelligence  

Microsoft Academic Search

As library-based techniques of virus and intrusion detection prove insufficient to be means of protection for computer systems and networks, alternate methods must be incorporated into computer defense. This paper surveys a variety of Artificial Intelligence methods aimed at improving the effectiveness of modern computer security in the face of more prevalent, sophisticated, and ever-changing threats. Specifically, Artificial Immune Systems,

Winard Britt; Sundeep Gopalaswamy; John. A. Hamilton; Gerry V. Dozier; Kai H. Chang

2007-01-01

273

The personal touch: strategies toward personalized vaccines and predicting immune responses to them.  

PubMed

The impact of vaccines on public health and wellbeing has been profound. Smallpox has been eradicated, polio is nearing eradication, and multiple diseases have been eliminated from certain areas of the world. Unfortunately, we now face diseases such as hepatitis C, malaria or tuberculosis, as well as new and re-emerging pathogens for which we lack effective vaccines. Empirical approaches to vaccine development have been successful in the past, but may not be up to the current infectious disease challenges facing us. New, directed approaches to vaccine design, development, and testing need to be developed. Ideally these approaches will capitalize on cutting-edge technologies, advanced analytical and modeling strategies, and up-to-date knowledge of both pathogen and host. These approaches will pay particular attention to the causes of inter-individual variation in vaccine response in order to develop new vaccines tailored to the unique needs of individuals and communities within the population. PMID:24702429

Kennedy, Richard B; Ovsyannikova, Inna G; Lambert, Nathaniel D; Haralambieva, Iana H; Poland, Gregory A

2014-05-01

274

Passive immune neutralization strategies for prevention and control of influenza A infections  

PubMed Central

Although vaccination significantly reduces influenza severity, seasonal human influenza epidemics still cause more than 250,000 deaths annually. Vaccine efficacy is limited in high-risk populations such as infants, the elderly and immunosuppressed individuals. In the event of an influenza pandemic (such as the 2009 H1N1 pandemic), a significant delay in vaccine availability represents a significant public health concern, particularly in high-risk groups. The increasing emergence of strains resistant to the two major anti-influenza drugs, adamantanes and neuraminidase inhibitors, and the continuous circulation of avian influenza viruses with pandemic potential in poultry, strongly calls for alternative prophylactic and treatment options. In this review, we focus on passive virus neutralization strategies for the prevention and control of influenza type A viruses. PMID:22339460

Ye, Jianqiang; Shao, Hongxia; Perez, Daniel R

2012-01-01

275

Avian host defense peptides.  

PubMed

Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds. PMID:23644014

Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

2013-11-01

276

Innate immunity activation on biomaterial surfaces: A mechanistic model and coping strategies  

PubMed Central

When an artificial biomaterial (e.g., a stent or implantable pump) is exposed to blood, plasma proteins immediately adhere to the surface, creating a new interface between the biomaterial and the blood. The recognition proteins within the complement and contact activation/coagulation cascade systems of the blood will be bound to, or inserted into, this protein film and generate different mediators that will activate polymorphonuclear leukocytes and monocytes, as well as platelets. Under clinical conditions, the ultimate outcome of these processes may be thrombotic and inflammatory reactions, and consequently the composition and conformation of the proteins in the initial layer formed on the surface will to a large extent determine the outcome of a treatment involving the biomaterial, affecting both the functionality of the material and the patient’s life quality. This review presents models of biomaterial-induced activation processes and describes various strategies to attenuate potential adverse reactions by conjugating bioactive molecules to surfaces or by introducing nanostructures. PMID:21771620

Ekdahl, Kristina N; Lambris, John D.; Elwing, Hans; Ricklin, Daniel; Nilsson, Per H.; Teramura, Yuji; Nicholls, Ian A.; Nilsson, Bo

2011-01-01

277

Immunomodulation Therapy for Invasive Aspergillosis: Discussion on Myeloid Growth Factors, Recombinant Cytokines, and Antifungal Drug Immune Modulation  

Microsoft Academic Search

Understanding fungal pathogenesis and host-pathogen immune interaction at various stages of infection is critical to examine\\u000a strategies for bolstering antifungal immune defenses. Recombinant myeloid growth factors, especially granulocyte-macrophage\\u000a colony-stimulating factor and the protagonist T helper (Th) 1 cytokine, interferon-?, are most frequently used in patients\\u000a with refractory invasive aspergillosis. These cytokines are given alone or in combination and have also

Amar Safdar

2010-01-01

278

Staphylococcus aureus sortase A contributes to the Trojan Horse mechanism of immune defense evasion with its intrinsic resistance to Cys184 oxidation†  

PubMed Central

Staphylococcus aureus is a Gram-positive bacterial pathogen that causes serious infections which have become increasingly difficult to treat due to antimicrobial resistance and natural virulence strategies. Bacterial sortase enzymes are important virulence factors and good targets for future antibiotic development. It has recently been shown that sortase enzymes are integral to bacterial survival of phagocytosis, an underappreciated, but vital, step in S. aureus pathogenesis. Of note, the reaction mechanism of sortases relies on a solvent-accessible cysteine for transpeptidation. Due to the common strategy of oxidative damage employed by professional phagocytes to kill pathogens, it is possible that this cysteine may be oxidized inside the phagosome, thereby inhibiting the enzyme. This study addresses this apparent paradox by assessing the ability of physiological reactive oxygen species, hydrogen peroxide and hypochlorite, to inhibit sortase A (SrtA) from S. aureus. Surprisingly, we found that SrtA is highly resistant to oxidative inhibition, both in vitro and in vivo. The mechanism of resistance to oxidative damage is likely mediated by maintaining a high reduction potential of the catalytic cysteine residue, Cys184. This is due to the unusual active site utilized by S. aureus SrtA, which employs a reverse protonation mechanism for transpeptidation, resulting in a high pKa as well as reduction potential for Cys184. The results of this study suggest that S. aureus SrtA is able to withstand the extreme conditions encountered in the phagosome and maintain function, contributing to survival of phagocytotic killing. PMID:21812416

Melvin, Jeffrey A.; Murphy, Christine F.; Dubois, Laura G.; Thompson, J. Will; Moseley, M. Arthur; McCafferty, Dewey G.

2013-01-01

279

Immunization for atherosclerosis  

Microsoft Academic Search

This review summarizes experimental findings that highlight the complex roles of the immune system in atherogenesis. Immune\\u000a activation can have either proatherogenic or atheroprotective effects. Immune-modulation therapy via an active or passive\\u000a immunization strategy aims to exploit the atheroprotective aspects of the immune system to modulate atherosclerosis. Several\\u000a experimental studies have demonstrated that such an approach is feasible and effective,

Kuang-Yuh Chyu; Jan Nilsson; Prediman K. Shah

2007-01-01

280

Staphylococcus aureus sortase A contributes to the Trojan horse mechanism of immune defense evasion with its intrinsic resistance to Cys184 oxidation.  

PubMed

Staphylococcus aureus is a Gram-positive bacterial pathogen that causes serious infections which have become increasingly difficult to treat due to antimicrobial resistance and natural virulence strategies. Bacterial sortase enzymes are important virulence factors and good targets for future antibiotic development. It has recently been shown that sortase enzymes are integral to bacterial survival of phagocytosis, an underappreciated, but vital, step in S. aureus pathogenesis. Of note, the reaction mechanism of sortases relies on a solvent-accessible cysteine for transpeptidation. Because of the common strategy of oxidative damage employed by professional phagocytes to kill pathogens, it is possible that this cysteine may be oxidized inside the phagosome, thereby inhibiting the enzyme. This study addresses this apparent paradox by assessing the ability of physiological reactive oxygen species, hydrogen peroxide and hypochlorite, to inhibit sortase A (SrtA) from S. aureus. Surprisingly, we found that SrtA is highly resistant to oxidative inhibition, both in vitro and in vivo. The mechanism of resistance to oxidative damage is likely mediated by maintaining a high reduction potential of the catalytic cysteine residue, Cys184. This is due to the unusual active site utilized by S. aureus SrtA, which employs a reverse protonation mechanism for transpeptidation, resulting in a high pK(a) as well as reduction potential for Cys184. The results of this study suggest that S. aureus SrtA is able to withstand the extreme conditions encountered in the phagosome and maintain function, contributing to survival of phagocytotic killing. PMID:21812416

Melvin, Jeffrey A; Murphy, Christine F; Dubois, Laura G; Thompson, J Will; Moseley, M Arthur; McCafferty, Dewey G

2011-09-01

281

Aging and Immune Function: Molecular Mechanisms to Interventions  

PubMed Central

Abstract The immune system of an organism is an essential component of the defense mechanism aimed at combating pathogenic stress. Age-associated immune dysfunction, also dubbed “immune senescence,” manifests as increased susceptibility to infections, increased onset and progression of autoimmune diseases, and onset of neoplasia. Over the years, extensive research has generated consensus in terms of the phenotypic and functional defects within the immune system in various organisms, including humans. Indeed, age-associated alterations such as thymic involution, T cell repertoire skewing, decreased ability to activate naïve T cells and to generate robust memory responses, have been shown to have a causative role in immune decline. Further, understanding the molecular mechanisms underlying the generation of proteotoxic stress, DNA damage response, modulation of ubiquitin proteasome pathway, and regulation of transcription factor NF?B activation, in immune decline, have paved the way to delineating signaling pathways that cross-talk and impact immune senescence. Given the role of the immune system in combating infections, its effectiveness with age may well be a marker of health and a predictor of longevity. It is therefore believed that a better understanding of the mechanisms underlying immune senescence will lead to an effective interventional strategy aimed at improving the health span of individuals. Antioxid. Redox Signal. 14, 1551–1585. PMID:20812785

Ponnappan, Subramaniam

2011-01-01

282

137 Interplay between host defenses and viral anti-defenses as a major factor of viral cytopathogenicity  

PubMed Central

The prevailing paradigm posits that virus-induced cellular injuries (cytopathic effect, CPE) are caused by hijacking of cellular substrates, energy, and infrastructure by the pathogens for the needs of their reproduction. However, this appears to be not the sole, and even not the most important, mechanism of cellular pathology triggered by viral infections. There is ground to believe that the most severe harm may come not from viral reproduction as such but rather from (miscalculated) host defenses as well as from viral anti-defensive activities. The experiments to be presented strongly support this notion. By using as a model system HeLa cells infected with mengovirus (a strain of encephalomyocarditis virus, a lytic picornavirus), we show that the major signs of CPE caused by this virus can be uncoupled from its reproduction. This can be achieved by partial mutual disarmament of the virus (by mutational inactivation of one of its anti-defensive “security” proteins, the leader protein) and the host (by chemical inhibition of one of its defensive innate immunity mechanisms, apoptosis). Under such conditions, the appearance of major cellular injuries is postponed until well after the completion of the viral reproduction. Remarkably, a more profound disarmament of the virus (by additional deletion of its second security protein, 2A) accompanied with a marked suppression of the viral reproduction leads to a faster death of the infected apoptosis-deficient cells due primarily to their defensive suicidal programmed necrosis. Thus, efficient strategies to ameliorate virus-induced injuries may include measures aimed at suppression of not only viral reproduction or viral anti-host functions but also of host defenses.

Agol, Vadim I.

2014-01-01

283

Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus  

PubMed Central

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

Yeaman, Michael R.; Filler, Scott G.; Schmidt, Clint S.; Ibrahim, Ashraf S.; Edwards, John E.; Hennessey, John P.

2014-01-01

284

Tsetse immune responses and trypanosome transmission: Implications for the development of tsetse-based strategies to reduce trypanosomiasis  

PubMed Central

Tsetse flies are the medically and agriculturally important vectors of African trypanosomes. Information on the molecular and biochemical nature of the tsetse/trypanosome interaction is lacking. Here we describe three antimicrobial peptide genes, attacin, defensin, and diptericin, from tsetse fat body tissue obtained by subtractive cloning after immune stimulation with Escherichia coli and trypanosomes. Differential regulation of these genes shows the tsetse immune system can discriminate not only between molecular signals specific for bacteria and trypanosome infections but also between different life stages of trypanosomes. The presence of trypanosomes either in the hemolymph or in the gut early in the infection process does not induce transcription of attacin and defensin significantly. After parasite establishment in the gut, however, both antimicrobial genes are expressed at high levels in the fat body, apparently not affecting the viability of parasites in the midgut. Unlike other insect immune systems, the antimicrobial peptide gene diptericin is constitutively expressed in both fat body and gut tissue of normal and immune stimulated flies, possibly reflecting tsetse immune responses to the multiple Gram-negative symbionts it naturally harbors. When flies were immune stimulated with bacteria before receiving a trypanosome containing bloodmeal, their ability to establish infections was severely blocked, indicating that up-regulation of some immune responsive genes early in infection can act to block parasite transmission. The results are discussed in relation to transgenic approaches proposed for modulating vector competence in tsetse. PMID:11592981

Hao, Zhengrong; Kasumba, Irene; Lehane, Michael J.; Gibson, Wendy C.; Kwon, Johnny; Aksoy, Serap

2001-01-01

285

A rapid immunization strategy with a live-attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates.  

PubMed

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

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

286

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

PubMed Central

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

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

287

Responses of innate immune cells to group A Streptococcus  

PubMed Central

Group A Streptococcus (GAS), also called Streptococcus pyogenes, is a Gram-positive beta-hemolytic human pathogen which causes a wide range of mostly self-limiting but also several life-threatening diseases. Innate immune responses are fundamental for defense against GAS, yet their activation by pattern recognition receptors (PRRs) and GAS-derived pathogen-associated molecular patterns (PAMPs) is incompletely understood. In recent years, the use of animal models together with the powerful tools of human molecular genetics began shedding light onto the molecular mechanisms of innate immune defense against GAS. The signaling adaptor MyD88 was found to play a key role in launching the immune response against GAS in both humans and mice, suggesting that PRRs of the Toll-like receptor (TLR) family are involved in sensing this pathogen. The specific TLRs and their ligands have yet to be identified. Following GAS recognition, induction of cytokines such as TNF and type I interferons (IFNs), leukocyte recruitment, phagocytosis, and the formation of neutrophil extracellular traps (NETs) have been recognized as key events in host defense. A comprehensive knowledge of these mechanisms is needed in order to understand their frequent failure against GAS immune evasion strategies.

Fieber, Christina; Kovarik, Pavel

2014-01-01

288

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

SciTech Connect

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

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

1984-05-16

289

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

Microsoft Academic Search

This report provides a summary, analysis and categorization of the perspectives of defense elites in Western Europe, together with an examination of such perspective in the People's Republic of China, with special emphasis on nuclear capabilities and directly related security issues. In Europe, attention is focused on Great Britain, France, the Federal Republic of Germany, Belgium, The Netherlands, Portugal, and

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

1984-01-01

290

Immune System Defender  

NSDL National Science Digital Library

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.

2012-06-18

291

Doctoral Defense "Sustainable Wastewater Management  

E-print Network

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

Kamat, Vineet R.

292

Bacteria fighting back: how pathogens target and subvert the host innate immune system.  

PubMed

The innate immune system has evolved under selective pressure since the radiation of multicellular life approximately 600 million years ago. Because of this long history, innate immune mechanisms found in modern eukaryotic organisms today are highly complex but yet built from common molecular strategies. It is now clear that evolution has selected a conserved set of antimicrobial 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 in order 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, proinflammatory cytokine production, and alteration of protein trafficking and secretion. PMID:24766896

Reddick, L Evan; Alto, Neal M

2014-04-24

293

Agent Applications in Defense Logistics  

Microsoft Academic Search

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

Todd Carrico; Mark Greaves

294

MAIT cells and pathogen defense.  

PubMed

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

Cowley, Siobhán C

2014-12-01

295

Making sense of hormone-mediated defense networking: from rice to Arabidopsis  

PubMed Central

Phytohormones are not only essential for plant growth and development but also play central roles in triggering the plant immune signaling network. Historically, research aimed at elucidating the defense-associated role of hormones has tended to focus on the use of experimentally tractable dicot plants such as Arabidopsis thaliana. Emerging from these studies is a picture whereby complex crosstalk and induced hormonal changes mold plant health and disease, with outcomes largely dependent on the lifestyle and infection strategy of invading pathogens. However, recent studies in monocot plants are starting to provide additional important insights into the immune-regulatory roles of hormones, often revealing unique complexities. In this review, we address the latest discoveries dealing with hormone-mediated immunity in rice, one of the most important food crops and an excellent model for molecular genetic studies in monocots. Moreover, we highlight interactions between hormone signaling, rice defense and pathogen virulence, and discuss the differences and similarities with findings in Arabidopsis. Finally, we present a model for hormone defense networking in rice and describe how detailed knowledge of hormone crosstalk mechanisms can be used for engineering durable rice disease resistance.

De Vleesschauwer, David; Xu, Jing; Höfte, Monica

2014-01-01

296

Targeted Deletion of Regions Rich in Immune-Evasive Genes from the Cytomegalovirus Genome as a Novel Vaccine Strategy?  

PubMed Central

Human cytomegalovirus (CMV), a ubiquitous human pathogen, is a leading cause of congenital infections and represents a serious health risk for the immunosuppressed patient. A vaccine against CMV is currently not available. CMV is characterized by its large genome and by multiple genes modulating the immunity of the host, which cluster predominantly at genome termini. Here, we tested whether the deletion of gene blocks rich in immunomodulatory genes could be used as a novel concept in the generation of immunogenic but avirulent, herpesvirus vaccines. To generate an experimental CMV vaccine, we selectively deleted 32 genes from the mouse cytomegalovirus (MCMV) genome. The resulting mutant grew to titers similar to that of wild-type MCMV in vitro. In vivo, the mutant was 10,000-fold attenuated and well tolerated, even by highly susceptible mice deficient for B, T, and NK cells or for the interferon type I receptor. Equally relevant for safety concerns, immune suppression did not lead to the mutant's reactivation from latency. Immunization with the replication-competent mutant, but not with inactivated virus, resulted in protective immunity, which increased over time. Vaccination induced MCMV-specific antibodies and a strong T-cell response. We propose that a targeted and rational approach can improve future herpesvirus vaccines and vaccine vectors. PMID:17913824

Cicin-Sain, Luka; Bubic, Ivan; Schnee, Margit; Ruzsics, Zsolt; Mohr, Christian; Jonjic, Stipan; Koszinowski, Ulrich H.

2007-01-01

297

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

PubMed Central

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

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

2008-01-01

298

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

PubMed Central

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

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

2012-01-01

299

Endogenous production of antimicrobial peptides in innate immunity and human disease  

Microsoft Academic Search

Antimicrobial peptides are diverse and evolutionarily ancient molecules produced by all living organisms. Peptides belonging\\u000a to the cathelicidin and defensin gene families exhibit an immune strategy as they defend against infection by inhibiting microbial\\u000a survival, and modify hosts through triggering tissue-specific defense and repair events. A variety of processes have evolved\\u000a in microbes to evade the action of antimicrobial peptides,

Richard L. Gallo; Victor Nizet

2003-01-01

300

Worm defense system research based on intelligent maintenance trees  

Microsoft Academic Search

Worm defense is an important security problem that has long aroused people's attention. With an eye to improve intranet security, an intelligent maintenance tree- based worm defense strategy is put forward by analyzing intranet worm propagation characteristics. Mobile agent- based down automatic maintenance line and detection-based up alarm line constitute an intranet active defense circuit and the mathematical model of

Qin-ying Lina; De-qin Shi; Lei Huang; Xiao-lin Gui; Ya-nan Kou; Xiao-ping Wang

2011-01-01

301

Brassinosteroids antagonize gibberellin- and salicylate-mediated root immunity in rice.  

PubMed

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

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

2012-04-01

302

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

PubMed Central

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

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

2012-01-01

303

Artificial Immune System Approaches for Aerospace Applications  

Microsoft Academic Search

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

K. KrishnaKumar

2003-01-01

304

Genetics of innate immunity and UTI susceptibility  

Microsoft Academic Search

A functional and well-balanced immune response is required to resist most infections. Slight dysfunctions in innate immunity can turn the 'friendly' host defense into an unpleasant foe and give rise to disease. Beneficial and destructive forces of innate immunity have been discovered in the urinary tract and mechanisms by which they influence the severity of urinary tract infections (UTIs) have

Bryndís Ragnarsdóttir; Nataliya Lutay; Jenny Grönberg-Hernandez; Bela Köves; Catharina Svanborg

2011-01-01

305

Effects of kefir fractions on innate immunity  

Microsoft Academic Search

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

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

2006-01-01

306

Antiviral innate immune response of RNA interference.  

PubMed

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

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

2014-07-01

307

Comparative genomics of defense systems in archaea and bacteria  

PubMed Central

Our knowledge of prokaryotic defense systems has vastly expanded as the result of comparative genomic analysis, followed by experimental validation. This expansion is both quantitative, including the discovery of diverse new examples of known types of defense systems, such as restriction-modification or toxin-antitoxin systems, and qualitative, including the discovery of fundamentally new defense mechanisms, such as the CRISPR-Cas immunity system. Large-scale statistical analysis reveals that the distribution of different defense systems in bacterial and archaeal taxa is non-uniform, with four groups of organisms distinguishable with respect to the overall abundance and the balance between specific types of defense systems. The genes encoding defense system components in bacterial and archaea typically cluster in defense islands. In addition to genes encoding known defense systems, these islands contain numerous uncharacterized genes, which are candidates for new types of defense systems. The tight association of the genes encoding immunity systems and dormancy- or cell death-inducing defense systems in prokaryotic genomes suggests that these two major types of defense are functionally coupled, providing for effective protection at the population level. PMID:23470997

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

2013-01-01

308

Innate immunity and aging  

PubMed Central

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

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

2008-01-01

309

The Host Defense of Drosophila melanogaster  

Microsoft Academic Search

To combat infection, the fruit fly Drosophila melanogaster relies on multiple innate defense reactions, many of which are shared with higher organisms. These reactions include the use of physical bar- riers together with local and systemic immune responses. First, ep- ithelia, such as those beneath the cuticle, in the alimentary tract, and in tracheae, act both as a physical barrier

Bruno Lemaitre; Jules Hoffmann

2007-01-01

310

Induced defense in Nicotiana attenuata (Solanaceae) fruit and flowers  

Microsoft Academic Search

Plants protect themselves against herbivory using a continuum of strategies, ranging from constitutive defenses to intermittent\\u000a induced responses. Induced defenses may not provide immediate and maximum protection, but could be advantageous when continuous\\u000a defense is either energetically or ecologically costly. As such, induced defenses in flowers could help defend relatively\\u000a valuable tissue while keeping reproductive structures accessible and attractive to

Andrew C. McCall; Richard Karban

2006-01-01

311

Single-cell technologies for monitoring interactions between immune cells  

E-print Network

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 ...

Yamanaka, Yvonne J. (Yvonne Joy)

2014-01-01

312

In Defense of Self-Defense  

Microsoft Academic Search

Some feminist theorists have argued that emphasizing women's self-defense mistakenly emphasizes women's behavior and choices rather than male aggression as a cause of sexual violence. I argue here that such critiques of self-defense are misguided, and do not sufficiently take into account the ways in which feminist self-defense courses can constitute embodied transformations of the meanings of femininity and rape.

Ann J. Cahill

2009-01-01

313

Rhamnolipid Biosurfactants as New Players in Animal and Plant Defense against Microbes  

PubMed Central

Rhamnolipids are known as very efficient biosurfactant molecules. They are used in a wide range of industrial applications including food, cosmetics, pharmaceutical formulations and bioremediation of pollutants. The present review provides an overview of the effect of rhamnolipids in animal and plant defense responses. We describe the current knowledge on the stimulation of plant and animal immunity by these molecules, as well as on their direct antimicrobial properties. Given their ecological acceptance owing to their low toxicity and biodegradability, rhamnolipids have the potential to be useful molecules in medicine and to be part of alternative strategies in order to reduce or replace pesticides in agriculture. PMID:21614194

Vatsa, Parul; Sanchez, Lisa; Clement, Christophe; Baillieul, Fabienne; Dorey, Stephan

2010-01-01

314

Community Immunity (Herd Immunity)  

MedlinePLUS

... protecting most community members. The principle of community immunity applies to control of a variety of contagious diseases, including influenza, measles, mumps, rotavirus, and pneumococcal disease. Credit: NIAID ...

315

Viral myocarditis: potential defense mechanisms within the cardiomyocyte against virus infection  

PubMed Central

Virus infection can inflict significant damage on cardiomyocytes through direct injury and secondary immune reactions, leading to myocarditis and dilated cardiomyopathy. While viral myocarditis or cardiomyopathy is a complication of systemic infection of cardiotropic viruses, most individuals infected with the viruses do not develop significant cardiac disease. However, some individuals proceed to develop severe virus-mediated heart disease. Recent studies have shown that viral infection of cardiomyocytes is required for the development of myocarditis and subsequent cardiomyopathy. This suggests that viral infection of cardiomyocytes can be an important step that determines the pathogenesis of viral myocarditis during systemic infection. Accordingly, this article focuses on potential defense mechanisms within the cardiomyocyte against virus infection. Understanding of the cardiomyocyte defense against invading viruses may give us novel insights into the pathophysiology of viral myocarditis, and enable us to develop innovative strategies of diagnosis and treatment for this challenging clinical entity. PMID:21585262

Yajima, Toshitaka

2011-01-01

316

Pseudomonas aeruginosa Exploits Lipid A and Muropeptides Modification as a Strategy to Lower Innate Immunity during Cystic Fibrosis Lung Infection  

PubMed Central

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-1? 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

Ierano, Teresa; Lore, Nicola Ivan; Bianconi, Irene; Silipo, Alba; Cozzolino, Flora; Lanzetta, Rosa; Molinaro, Antonio; Bernardini, Maria Lina; Bragonzi, Alessandra

2009-01-01

317

Common loon nest defense against an American mink  

USGS Publications Warehouse

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.

McCarthy, K.P.; DeStefano, S.

2011-01-01

318

Molecular Mechanisms of Aging and Immune System Regulation in Drosophila  

PubMed Central

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

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

319

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

Microsoft Academic Search

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

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

2007-01-01

320

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

Microsoft Academic Search

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

Yannick Moret; Paul Schmid-Hempel

2000-01-01

321

Quadrennial Defense Review 2014.  

National Technical Information Service (NTIS)

The 2014 Quadrennial Defense Review (QDR) seeks to adapt, reshape, and rebalance our military to prepare for the strategic challenges and opportunities we face in the years ahead. Building on the 2012 Defense Strategic Guidance, the QDR prioritizes three ...

2014-01-01

322

See related Commentary on page xiv Cutaneous Defense Mechanisms by Antimicrobial Peptides  

E-print Network

to host defense by mounting an innate immune response that includes the production of antimicrobialSee related Commentary on page xiv Cutaneous Defense Mechanisms by Antimicrobial Peptides Marissa H, provide rapid, broad-spectrum defense against infection by acting as natural antibiotics and by partic

Nizet, Victor

323

Antiviral Immunity in Amphibians  

PubMed Central

Although a variety of virus species can infect amphibians, diseases caused by ranaviruses ([RVs]; Iridoviridae) have become prominent, and are a major concern for biodiversity, agriculture and international trade. The relatively recent and rapid increase in prevalence of RV infections, the wide range of host species infected by RVs, the variability in host resistance among population of the same species and among different developmental stages, all suggest an important involvement of the amphibian immune system. Nevertheless, the roles of the immune system in the etiology of viral diseases in amphibians are still poorly investigated. We review here the current knowledge of antiviral immunity in amphibians, focusing on model species such as the frog Xenopus and the salamander (Ambystoma tigrinum), and on recent progress in generating tools to better understand how host immune defenses control RV infections, pathogenicity, and transmission. PMID:22163335

Chen, Guangchun; Robert, Jacques

2011-01-01

324

PLANT-ANIMAL INTERACTIONS -ORIGINAL RESEARCH Plant defense, herbivory, and the growth of Cordia alliodora trees  

E-print Network

defense, tolerance, and herbivore pressure. In symbiotic ant­plant mutualisms, plants provide nesting in defense are idiosyn- cratic, depending on plant growth form, herbivore guild, and defensive trait strategyPLANT-ANIMAL INTERACTIONS - ORIGINAL RESEARCH Plant defense, herbivory, and the growth of Cordia

Gordon, Deborah

325

Radiological Defense. Textbook.  

ERIC Educational Resources Information Center

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…

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

326

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

PubMed Central

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

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

2006-01-01

327

Budgeting For Defense: Maintaining Today's Forces  

NSDL National Science Digital Library

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

328

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

SciTech Connect

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).

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

329

Immune modulations during chemoimmunotherapy & novel vaccine strategies--in metastatic melanoma and non small-cell lung cancer.  

PubMed

This thesis describes the treatment of metastatic melanoma (MM) and non small-cell lung cancer (NSCLC) from an immunotherapeutic approach. The purpose of the first part of the thesis was to assess how treatment with Temozolomide (TMZ) chemotherapy affects the immune system in patients with metastatic MM. Our results showed that the number of T lymphocytes was significantly reduced after 3 treatment cycles. Furthermore, the induced lymphopenia was positive correlated to achievement of clinical benefit. We demonstrated that the proportion of CD4+ and Treg lymphocytes decreased whereas the CD8+ T cells increased. In particular, we demonstrated that mature CD8+ T cells increased during treatment. Analyses of peripheral blood before and after treatment showed that T cell responses against common viral epitopes were conserved despite chemotherapy. Surprisingly, we found a significant increase in T cell responses against well-known MM tumour specific antigens. Overall, we have verified that TMZ in addition to being an alkylating and cytotoxic chemotherapy, also possess immune modulatory effect in MM patients treated with standard dosage of TMZ. In the second part of the thesis we examined how treatment with Interferon alfa-2b and Interleukin 2 (IFN?/IL2) affects the immune system. We demonstrated a significant induced lymphocytosis during treatment. Furthermore, we showed that the percentage increase in lymphocytes was positively correlated to clinical outcome. Moreover, we have seen that IFN?/IL2 leads to significant increase in NK and Treg cells in both patients with and without clincal effect. In general, T cell responses against common viral epitopes and well-known melanoma tumour specific antigens were low. Furthermore, the study confirmed that elevated LDH is negatively correlated with both treatment response and median overall survival. Overall, we have characterized changes of immune cells and correlated them with clinical efficacy during the couse of IFN?/IL2 used in standard dosage. In the third part we investigated if vaccination with a peptide derived from IDO was feasible in patients with metastatic NSCLC. This "First in Man" trial was safe and showed modest side effects only. Since IDO was expressed in NSCLC tissues it was found to be a relevant target. One patient achieved significant regression of liver metastases (confirmed partial response) and another 6/15 patients achieved prolonged disease stabilization. Furthermore, median overall survival was 25.9 months demonstrating a better survival in vaccinated compared to non-vaccinated comparable NSCLC patients. The presence of IDO specific CD8+ T cells were detected by IFNy Elispot. In patients with clinical effect of the vaccine IDO-specific CD8+ T cells at pre-treatment was significanctly increased. Moreover, low-frequent IDO positive tetramer CD8+ T cells were detected and led to effective killing of an IDO+ HLA-A2 positive cancer cell line (SW480) in 1 patient. Moreover, flow cytometry was performed and in general no significant changes in CD8+ and CD4+ T cells were seen, although patients with clinical response showed a trend towards increased mature CD8+ T cells during treatment. In addition, we found lower levels of Tregs as well as an increased level of NK cells after 6 vaccinations. Elevated Kyn/Trp ratio is suggested to mirror IDO activity. In 8/11 patients the level after the 6th vaccine was stable compared to baseline. No differences between patients with clinical benefit (4/5) and patients with progressive disease (4/6) were demonstrated. Two patients had an increase in Kyn/Trp ration meanwhile demonstrating a high expression of IDO. In 2 patients with clinical response long-term stabilization of Kyn/Trp was observed. Overall, the vaccine was well tolerated with no adverse toxicity. Median overall survival was 25.9 months with long term disease stabilization achieved in 47% of the treated patients. Based on the promising clinical results achieved in the vaccine trial for NSCLC patients, we launched a new clinical trial for MM patients (on

Iversen, Trine Zeeberg

2013-12-01

330

Mucosal immunity.  

PubMed

Mucosal defense is provided by a number of host factors countering the specific virulence factors of the many microorganisms infecting the mucous membranes. Secretory IgA antibodies presumably play an important role. Increase of the sIgA antibodies may most advantageously be attained by parenteral immunization, following mucosal priming. This was demonstrated in a rat model, where it was also noted that antigen injection into PP induced high milk IgA antibody levels. In man, parenteral vaccination against polio increased the sIgA antibody levels in the milk of mothers previously exposed naturally to the poliovirus. The response was relatively short-lived. In the previously unexposed, there was little or no response. By contrast peroral immunization with live poliovirus vaccine did not increase, or even decrease, the milk sIgA poliovirus antibody levels. Although salivary sIgA antibodies against antigens of colonizing E. coli appear during the first days of life, they are slow to increase. This deficiency is richly compensated for by all the sIgA antibodies that are provided the baby through the milk. No transfer of dimeric IgA into the milk could be shown in lactating rats, in contrast to what has been reported in mice. There is no evidence for a contribution to milk sIgA from serum in man. Close to parturition, human milk often contains some 7S IgA and various sizes of free SC, in addition to the dominating 11S sIgA. A few days later there is almost exclusively monomeric SC and 11S sIgA. IgG antibodies also play a role at the mucosal level. IgG2 antibodies against the bacterial polysaccharide capsule are as slow to appear as sIgA in ontogeny, possibly explaining the prevalence of infections with encapsulated bacteria and the poor response to polysaccharide vaccines in early childhood. Other defense factors preventing infections by way of mucous membranes may be important. Thus, oligosaccharides present in human milk seem to specifically prevent pneumococcal attachment to retropharyngeal cells. This anti-attachment capacity, in addition to that provided by milk and salivary IgA antibodies, may explain why breast-fed babies have less otitis media than formula-fed ones. PMID:6191608

Hanson, L A; Ahlstedt, S; Andersson, B; Carlsson, B; Cole, M F; Cruz, J R; Dahlgren, U; Ericsson, T H; Jalil, F; Khan, S R; Mellander, L; Schneerson, R; Edén, C S; Söderström, T; Wadsworth, C

1983-06-30

331

Autophagy, Immunity, and Microbial Adaptations  

PubMed Central

Autophagy adjusts cellular biomass and function in response to diverse stimuli, including infection. Autophagy plays specific roles in shaping immune system development, fueling host innate and adaptive immune responses, and directly controlling intracellular microbes as a cell-autonomous innate defense. As an evolutionary counterpoint, intracellular pathogens have evolved to block autophagic microbicidal defense and subvert host autophagic responses for their survival or growth. The ability of eukaryotic pathogens to deploy their own autophagic machinery may also contribute to microbial pathogenesis. Thus, a complex interplay between autophagy and microbial adaptations against autophagy governs the net outcome of host-microbe encounters. PMID:19527881

Deretic, Vojo; Levine, Beth

2009-01-01

332

Enteric Immunization: Promises and Challenges  

Microsoft Academic Search

Immunization to prevent many intestinal infections is inadequate because most available vaccines are given parenterally, a route that does not effectively stimulate the intestinal immune system. Thus, investigators are pursuing several strategies for achieving enteric protection through oral immunization. The most promising approaches are the incorporation of immunogens into microparticles for protection and enhanced uptake of the immunogen by intestinal

William R. Brown

1996-01-01

333

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

PubMed Central

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

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

2011-01-01

334

Strategis  

NSDL National Science Digital Library

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.

1998-01-01

335

Toll-like receptor control of the adaptive immune responses  

Microsoft Academic Search

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

Akiko Iwasaki; Ruslan Medzhitov

2004-01-01

336

Validity of Self-Report Measures of Defense Mechanisms  

PubMed

The Life Style Index (LSI), the Defense Style Questionnaire (DSQ), the Defense Mechanisms Inventory (DMI), and the FIRO Coping Operations Preferences Enquiry (FIRO) were administered to 187 undergraduates in order to determine convergent and discriminant validity of self-report measures of defense mechanisms. A correlational analysis of the four scales resulted in low correlations among subscales measuring similar defense mechanisms. A factor analysis produced factors based on particular scales rather than identical or similar constructs. Results suggest that self-report measures may not be an effective method for assessing various ego defense strategies. PMID:9465149

Mehlman; Slane

1994-06-01

337

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

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

338

Immune regulation in the retina  

Microsoft Academic Search

Immune reactivity in the retina can be critically important in inflammation and infections, but regulation of this response\\u000a is essential. The retinal pigment epithelial (RPE), a unique retinal cell, displays a number of essential functions to support\\u000a the health of the retina. In this review, we highlight how the RPE cell plays a pivotal role in immune defense. The RPE

Barbara Detrick; John J. Hooks

2010-01-01

339

Vitamin D and Innate Immunity  

Microsoft Academic Search

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

Philip Liu; Martin Hewison; John S. Adams

2009-01-01

340

Alphacoronavirus Protein 7 Modulates Host Innate Immune Response  

PubMed Central

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

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

2013-01-01

341

No evidence for phylogenetic constraint on natural defense evolution among wild tomatoes.  

PubMed

Plant defense traits can be shaped by evolutionary and physiological constraints, as well as local ecological selection. We assessed the relative importance of these factors in shaping defense trait variation across the wild tomato clade (a group of 13 closely related species) using an herbivore bioassay (Manduca sexta). With phylogenetic comparative methods, we evaluated patterns of constitutive and induced defense variation, and the extent of coupling between alternative defense strategies. We detected substantial variation among species and found no evidence for phylogenetic conservatism among defensive traits, unlike for two other ecologically relevant (reproductive) traits. In addition, constitutive and induced defense syndromes were unassociated. These data indicate that, in this group, there is no evidence for either phylogenetic conservatism of shared consumer guilds that shape defense traits, or for constraints on defense trait evolution, including mechanistic trade-offs between defense strategies. Our data suggest that defense trait variation in this clade instead results from rapid responses to local ecological conditions. PMID:25039227

Haak, David C; Ballenger, Blake A; Moyle, Leonie C

2014-06-01

342

Plant Exocytic Secretion of Toxic Compounds for Defense  

PubMed Central

In contrast to animals, plants do not have a circulatory system as well as mobile immune cells that allow them to protect themselves against pathogens. Instead, plants exclusively depend on the innate immune system to defend against pathogens. As typically observed in the animal innate immunity, plant immune responses are composed of pathogen detection, defense signaling which includes transcriptional reprogramming, and secretion of antimicrobial compounds. Although knowledge on recognition and subsequent signaling of pathogen-derived molecules called elicitors is now expanding, the mechanisms of how these immune molecules are excreted are yet poorly understood. Therefore, current understandings of how plants secrete defense products especially via exocytosis will be discussed in this review. PMID:25071916

Kwon, Chian

2014-01-01

343

Immunizations - diabetes  

MedlinePLUS

Immunizations (vaccines or vaccinations) help protect you from some diseases. When you have diabetes, you need to ... for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Adults Aged ...

344

The Immune System - Nobel Prize Educational Game  

NSDL National Science Digital Library

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 ÃÂ for identifying certain body cells that engulfe bacteria and for work on trying to explain how antibodies are formed in the body.

2009-01-01

345

Ontogeny of the Immune System  

Microsoft Academic Search

SummaryThe various means of defense against infections develop progressively during the prenatal period. Innate immunity is not yet mature at birth because phagocytes cannot migrate towards infectious sites although their bactericidal activity is normal. Natural killer cell cytotoxicity is also incomplete. These abnormalities are probably caused by defects in cytokine production of T cells and monocytes. The complement system, immature

A. Durandy

2003-01-01

346

Improved immune genetic algorithm for JSP  

Microsoft Academic Search

According to the information processing mechanism of immune system in life sciences, based on simple genetic algorithm, a new approach of immune genetic algorithm for job shop scheduling is proposed through combining immune algorithm with improved genetic algorithm (strategy of multiple crossover per couple with incest prevention). A immune genetic algorithm aiming at job shop scheduling is set up. The

Quanyong Ju; Jianying Zhu

2008-01-01

347

Priming in Systemic Plant Immunity  

SciTech Connect

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

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

2009-01-01

348

Schools and Civil Defense.  

ERIC Educational Resources Information Center

Civil defense is a planned, coordinated action to protect the population during any emergency whether arising from thermonuclear attack or natural disaster. The Federal Government has assumed four responsibilities--(1) to keep track of the nature of the threat which the civil defense program must meet, (2) to prepare and disseminate information…

Office of Civil Defense (DOD), Washington, DC.

349

Defense Mechanisms: A Bibliography.  

ERIC Educational Resources Information Center

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

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

350

Skunk Defensive Secretion  

NSDL National Science Digital Library

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.

Wood, William F.

1999-01-01

351

Microanatomy of the liver immune system  

Microsoft Academic Search

The critical metabolic functions of the liver often eclipse any perception of its role as an immune organ. However, the liver\\u000a as a mediator of systemic and local innate immunity and an important site of immune regulation is now an accepted concept.\\u000a Complex repertoires of lymphoid and non-lymphoid cells are key to hepatic defense and immunoregulation. Hepatic cells of myeloid

Eszter Nemeth; Alan W. Baird; Cliona O’Farrelly

2009-01-01

352

Immunity: plants as effective mediators.  

PubMed

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

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

2014-01-01

353

OFFICE OF THE ASSISTANT SECRETARY OF DEFENSE 4000 DEFENSE PENTAGON  

E-print Network

(DEFENSE INTELLIGENCE AGENCY) DIRECTOR, HUMAN RESOURCES OFFICER (DEFENSE SECURITY SERVICE) EXECUTIVE DIRECTOR, HUMAN RESOURCES (DEFENSE LOGISTICS AGENCY) DIRECTOR, HUMAN RESOURCES (NATIONAL GEOSPATIAL-INTELLIGENCE any past practice or collective bargaining agreement. All bargaining obligations must be met prior

US Army Corps of Engineers

354

Intracellular immunity: finding the enemy within--how cells recognize and respond to intracellular pathogens  

PubMed Central

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

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

2014-01-01

355

Insect herbivory, plant defense, and early Cenozoic climate change  

E-print Network

Insect herbivory, plant defense, and early Cenozoic climate change Peter Wilf* , Conrad C with evergreen, thick- textured, small leaves characterized by elevated insect resistance. Leaf galling, which of plant hosts (1, 2). In any climate, insect herbivores either adapt to the range of defense strategies

Wilf, Peter

356

SDI (Strategic Defense Initiative): a policy analysis  

SciTech Connect

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

Fought, S.O.

1987-01-01

357

An Empirical Study of Immune System Based On Bipartite Network  

Microsoft Academic Search

Immune system is the most important defense system to resist human pathogens. In this paper we present an immune model with bipartite graphs theory. We collect data through COPE database and construct an immune cell- mediators network. The act degree distribution of this network is proved to be power-law, with index of 1.8. From our analysis, we found that some

Sheng-Rong Zou; Yu-Jing Peng; Zhong-Wei Guo; Ta Zhou; Chang-gui Gu; Da-Ren He

2007-01-01

358

Mucosal immunity of the gastrointestinal tract and oral tolerance  

Microsoft Academic Search

To guard against disease, mucosal surfaces of the intestinal, respiratory and urogenital tracts are protected by a carefully regulated system of defenses known as the mucosal immune system. The hallmark of mucosal immunity is secretory IgA which can prevent infection and remove antigen crossing the mucosal barrier. IgE responses are also associated with mucosal immunity. In addition, a lymphocyte population

Jerry W Simecka

1998-01-01

359

TOLL-like receptors linking innate and adaptive immune response  

Microsoft Academic Search

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

Dirk Werling; Thomas W. Jungi

2003-01-01

360

The role of innate immune responses in autoimmune disease development  

Microsoft Academic Search

Autoimmune diseases are systemic or organ-specific disorders that are the result of an attack of the immune system against the body's own tissue. Development of autoimmune disease is generally avoided by distinct mechanisms that silence adaptive self-reactive T or B cells. The innate immune system is critically involved in the defense against pathogens and the induction of primary adaptive immune

Hanspeter Waldner

2009-01-01

361

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

PubMed Central

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

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

2013-01-01

362

Immunization of Epidemics in Multiplex Networks  

PubMed Central

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

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

2014-01-01

363

Directed energy planetary defense  

NASA Astrophysics Data System (ADS)

Asteroids and comets that cross Earth's orbit pose a credible risk of impact, with potentially severe disturbances to Earth and society. Numerous risk mitigation strategies have been described, most involving dedicated missions to a threatening object. We propose an orbital planetary defense system capable of heating the surface of potentially hazardous objects to the vaporization point as a feasible approach to impact risk mitigation. We call the system DE-STAR for Directed Energy System for Targeting of Asteroids and exploRation. DE-STAR is a modular phased array of kilowatt class lasers powered by photovoltaic's. Modular design allows for incremental development, test, and initial deployment, lowering cost, minimizing risk, and allowing for technological co-development, leading eventually to an orbiting structure that would be developed in stages with both technological and target milestones. The main objective of DE-STAR is to use the focused directed energy to raise the surface spot temperature to ~3,000K, allowing direct vaporization of all known substances. In the process of heating the surface ejecting evaporated material a large reaction force would alter the asteroid's orbit. The baseline system is a DE-STAR 3 or 4 (1-10km array) depending on the degree of protection desired. A DE-STAR 4 allows for asteroid engagement starting beyond 1AU with a spot temperature sufficient to completely evaporate up to 500-m diameter asteroids in one year. Small asteroids and comets can be diverted/evaporated with a DESTAR 2 (100m) while space debris is vaporized with a DE-STAR 1 (10m).

Lubin, Philip; Hughes, Gary B.; Bible, Johanna; Bublitz, Jesse; Arriola, Josh; Motta, Caio; Suen, Jon; Johansson, Isabella; Riley, Jordan; Sarvian, Nilou; Clayton-Warwick, Deborah; Wu, Jane; Milich, Andrew; Oleson, Mitch; Pryor, Mark; Krogen, Peter; Kangas, Miikka

2013-09-01

364

Defense Advanced Research Projects Agency Strategic Plan, February 2007.  

National Technical Information Service (NTIS)

This document describes the Defense Advanced Research Projects Agency's (DARPA) strategy, as required by Section 2352, Title 10 of the United States Code. It provides a top-level view of DARPA's activities for Congress, the research community, and various...

2007-01-01

365

Segmenting consumers for food defense communication strategies  

Microsoft Academic Search

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

Dennis Degeneffe; Jean Kinsey; Thomas Stinson; Koel Ghosh

2009-01-01

366

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

E-print Network

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

Waite, Janelle C.

367

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

PubMed Central

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

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

2003-01-01

368

Bacillus anthracis Interacts with Plasmin(ogen) to Evade C3b-Dependent Innate Immunity  

PubMed Central

The causative agent of anthrax, Bacillus anthracis, is capable of circumventing the humoral and innate immune defense of the host and modulating the blood chemistry in circulation to initiate a productive infection. It has been shown that the pathogen employs a number of strategies against immune cells using secreted pathogenic factors such as toxins. However, interference of B. anthracis with the innate immune system through specific interaction of the spore surface with host proteins such as the complement system has heretofore attracted little attention. In order to assess the mechanisms by which B. anthracis evades the defense system, we employed a proteomic analysis to identify human serum proteins interacting with B. anthracis spores, and found that plasminogen (PLG) is a major surface-bound protein. PLG efficiently bound to spores in a lysine- and exosporium-dependent manner. We identified ?-enolase and elongation factor tu as PLG receptors. PLG-bound spores were capable of exhibiting anti-opsonic properties by cleaving C3b molecules in vitro and in rabbit bronchoalveolar lavage fluid, resulting in a decrease in macrophage phagocytosis. Our findings represent a step forward in understanding the mechanisms involved in the evasion of innate immunity by B. anthracis through recruitment of PLG resulting in the enhancement of anti-complement and anti-opsonization properties of the pathogen. PMID:21464960

Chung, Myung-Chul; Tonry, Jessica H.; Narayanan, Aarthi; Manes, Nathan P.; Mackie, Ryan S.; Gutting, Bradford; Mukherjee, Dhritiman V.; Popova, Taissia G.; Kashanchi, Fatah; Bailey, Charles L.; Popov, Serguei G.

2011-01-01

369

Bacillus anthracis interacts with plasmin(ogen) to evade C3b-dependent innate immunity.  

PubMed

The causative agent of anthrax, Bacillus anthracis, is capable of circumventing the humoral and innate immune defense of the host and modulating the blood chemistry in circulation to initiate a productive infection. It has been shown that the pathogen employs a number of strategies against immune cells using secreted pathogenic factors such as toxins. However, interference of B. anthracis with the innate immune system through specific interaction of the spore surface with host proteins such as the complement system has heretofore attracted little attention. In order to assess the mechanisms by which B. anthracis evades the defense system, we employed a proteomic analysis to identify human serum proteins interacting with B. anthracis spores, and found that plasminogen (PLG) is a major surface-bound protein. PLG efficiently bound to spores in a lysine- and exosporium-dependent manner. We identified ?-enolase and elongation factor tu as PLG receptors. PLG-bound spores were capable of exhibiting anti-opsonic properties by cleaving C3b molecules in vitro and in rabbit bronchoalveolar lavage fluid, resulting in a decrease in macrophage phagocytosis. Our findings represent a step forward in understanding the mechanisms involved in the evasion of innate immunity by B. anthracis through recruitment of PLG resulting in the enhancement of anti-complement and anti-opsonization properties of the pathogen. PMID:21464960

Chung, Myung-Chul; Tonry, Jessica H; Narayanan, Aarthi; Manes, Nathan P; Mackie, Ryan S; Gutting, Bradford; Mukherjee, Dhritiman V; Popova, Taissia G; Kashanchi, Fatah; Bailey, Charles L; Popov, Serguei G

2011-01-01

370

Nonoffensive defense is overrated  

SciTech Connect

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

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

1988-09-01

371

Insect Chemical Defense  

Microsoft Academic Search

Research on the defensive chemistry of insects during the last decade is reviewed, with special emphasis on non-volatile compounds. The isolation and structure determination of defensive chemicals, of glandular and non-glandular origins, are first discussed, followed by an overview of the synthesis and biological\\/pharmacological activities of some of them. Biosynthesis has been largely omitted since this topic has been addressed

Pascal Laurent; Jean-Claude Braekman; Désiré Daloze

372

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

NASA Astrophysics Data System (ADS)

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

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

2005-03-01

373

Simultaneous targeting of toll- and nod-like receptors induces effective tumor-specific immune responses.  

PubMed

Toll-like receptor (TLR) ligands are increasingly being used as adjuvants in cancer vaccine trials to harness innate immunity and prime effective antitumor immune responses. Despite some success, enhancing tumor antigen presentation, promoting a protective antitumor response, and overcoming the immunosuppressive tumor microenvironment pose considerable challenges that necessitate further improvements in vaccine design. Here, we show that expression of the TLR ligand flagellin within tumor cells constitutes an effective antitumor vaccination strategy that relies on simultaneous engagement of TLR5 and the Nod-like receptors (NLRs) NLRC4/NAIP5 (neuronal apoptosis inhibitory protein 5) by flagellin along with associative recognition of tumor antigen for optimal antigen presentation to T cells. Although TLR5 signaling was critical for mediating rapid macrophage-dependent clearance of flagellin-expressing tumor cells in vivo, TLR5 and NLRC4/NAIP5 were equally important for priming antitumor CD4(+) and CD8(+) T cells and suppressing tumor growth. Vaccination with irradiated flagellin-expressing tumor cells prevented tumor development, and disrupting flagellin recognition by TLR5 or NLRC4/NAIP5 impaired protective immunization against an existing or subsequent tumor. Our findings delineate a new strategy to induce anticancer immune responses consisting of introducing microbial structures with dual TLR and NLR stimulatory activity into tumor cells. This ensures recognition of tumor-derived antigen within the inflammatory context of microbial recognition and additionally activates both the phagocytic and the cytosolic pathways of innate immune defense against the tumor. PMID:22323829

Garaude, Johan; Kent, Andrew; van Rooijen, Nico; Blander, J Magarian

2012-02-01

374

New technology favors defense  

SciTech Connect

Many new technological developments thus serve offensive plans. But in most cases the new technology can serve both offensive and defensive purposes. In fact, the technological trends actually favor the defense overall, partly because of some inherent weaknesses in an offensive military posture. Not only is the technology itself versatile, but some components and even some weapons now under development or in operation are suitable for strictly defensive activities. Moreover, some technologies would work much better in a defensive context than they would in the offensive missions for which they were designed. Not all proponents of nonoffensive defense would agree that defensive plans should take advantage of new technologies. The Study Group on Alternative Security Policy, for one, has warned against technical fetishism and recommends extreme caution in accepting the products of modern technology. Some analysts also prefer simple, sturdy systems to complicated, high-tech ones which tend to be fragile. Some of the technologies now under development are considered expensive, vulnerable, and easy to counteract.

Herolf, G. (Univ. of Stockholm (Sweden))

1988-09-01

375

Immune System  

MedlinePLUS

... New Scientists Identify Important Genetic Changes in 21 Autoimmune Diseases —Oct. 29, 2014 New Regulator of Autoimmune Cells ... 26, 2014 All Immune System News Releases All Autoimmune Diseases News Releases All Primary Immune Deficiency Disease News ...

376

Immunization Coverage  

MedlinePLUS

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

377

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

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

2014-01-01

378

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

Microsoft Academic Search

\\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

Belinda Land; Günther Boehm; Johan Garssen

379

INTERACTIVE IMMUNITY  

NSDL National Science Digital Library

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.

European Federation Of Immunological Societies, Efis

2012-07-19

380

Optimization of immune strategy for a construct of Salmonella-delivered ApxIA, ApxIIA, ApxIIIA and OmpA antigens of Actinobacillus pleuropneumoniae for prevention of porcine pleuropneumonia using a murine model.  

PubMed

In this study, the Actinobacillus pleuropneumoniae antigens ApxIA, ApxIIA, ApxIIIA and OmpA were expressed in an attenuated strain of Salmonella (?lon?cpxR?asd) for prevention of porcine pleuropneumonia. In order to evaluate the immunization strategy of the construct, a total 60 BALB/c mice were equally divided into four groups (n?=?15). Group A mice were intranasally immunized only at 6-weeks-of-age, while group B mice were intransally primed and boosted at 6- and 9-weeks-of-age, respectively, and group C mice were intransally primed at 6-weeks-of-age and subsequently boosted twice at 9- and 12-weeks-of-age. Group D mice were used as a control, which were inoculated with sterile PBS. Groups A, B, and C showed significantly higher serum IgG and fecal IgA immune responses than those of the control group. After virulent challenge with a wild type A. pleuropneumoniae, the immunized groups A, B and C showed 33.3 %, 13.3 % and 26.7 % mortality as the control group showed 60 % mortality. These results showed that the protection against porcine pleuropneumonia using the construct can be optimized by a double intranasal vaccination. PMID:24307459

Hur, Jin; Lee, John Hwa

2014-03-01

381

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

PubMed

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 IgG(1) 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 IgG(1) 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 IgG(1) 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

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

2011-12-19

382

Cascade Defense via Control of the Fluxes in Complex Networks  

NASA Astrophysics Data System (ADS)

Exploring the possible strategies to defense to prevent the cascade from propagating through the entire network is of both theoretical interest and practical significance, and several strategies of defense have been developed recently. Following the work about the strategy based on the international removal of network elements (Motter in Phys. Rev. Lett. 93:098701, 2004), we propose and investigate three novel strategies of defense by controlling the fluxes. Extensive simulations on both an artificially created scale-free network and the Internet at autonomous system level reveal that these strategies can suppress the propagation of the cascade, even avoid the cascading failure. In addition, a more intuitive and important measure to quantify the damage caused by a cascade is developed and some new features are, thus, clearly displayed.

Hu, Ke; Hu, Tao; Tang, Yi

2010-11-01

383

Evolutionary Dynamics of Human Toll-Like Receptors and Their Different Contributions to Host Defense  

E-print Network

. Natural selection is therefore expected to act strongly on host defense genes, particularly on innate Defense Luis B. Barreiro1,2 , Meriem Ben-Ali1 , He´le`ne Quach1 , Guillaume Laval1 , Etienne Patin1 be redundant for protective immunity. We investigated how natural selection has acted upon human TLRs

Kidd, Kenneth

384

Cathelicidins and Innate Defense Against Invasive Bacterial Infection  

Microsoft Academic Search

Cathelicidins are small cationic peptides that possess broad-spectrum antimicrobial activity. These gene-encoded 'natural antibiotics' are produced by several mammalian species on epithelial surfaces and within the granules of phagocytic cells. Since their discovery over a decade ago, cathelicidins have been speculated to function within the innate immune system, contributing to a first line of host defense against an array of

Victor Nizet; Richard L. Gallo

2003-01-01

385

Multiantibody Strategies for HIV  

PubMed Central

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

Whaley, Kevin J.

2013-01-01

386

The 2.0-A crystal structure of tachylectin 5A provides evidence for the common origin of the innate immunity and the blood coagulation systems.  

PubMed

Because invertebrates lack an adaptive immune system, they had to evolve effective intrinsic defense strategies against a variety of microbial pathogens. This ancient form of host defense, the innate immunity, is present in all multicellular organisms including humans. The innate immune system of the Japanese horseshoe crab Tachypleus tridentatus, serving as a model organism, includes a hemolymph coagulation system, which participates both in defense against microbes and in hemostasis. Early work on the evolution of vertebrate fibrinogen suggested a common origin of the arthropod hemolymph coagulation and the vertebrate blood coagulation systems. However, this conjecture could not be verified by comparing the structures of coagulogen, the clotting protein of the horseshoe crab, and of mammalian fibrinogen. Here we report the crystal structure of tachylectin 5A (TL5A), a nonself-recognizing lectin from the hemolymph plasma of T. tridentatus. TL5A shares not only a common fold but also related functional sites with the gamma fragment of mammalian fibrinogen. Our observations provide the first structural evidence of a common ancestor for the innate immunity and the blood coagulation systems. PMID:11707569

Kairies, N; Beisel, H G; Fuentes-Prior, P; Tsuda, R; Muta, T; Iwanaga, S; Bode, W; Huber, R; Kawabata, S

2001-11-20

387

The 2.0-? crystal structure of tachylectin 5A provides evidence for the common origin of the innate immunity and the blood coagulation systems  

PubMed Central

Because invertebrates lack an adaptive immune system, they had to evolve effective intrinsic defense strategies against a variety of microbial pathogens. This ancient form of host defense, the innate immunity, is present in all multicellular organisms including humans. The innate immune system of the Japanese horseshoe crab Tachypleus tridentatus, serving as a model organism, includes a hemolymph coagulation system, which participates both in defense against microbes and in hemostasis. Early work on the evolution of vertebrate fibrinogen suggested a common origin of the arthropod hemolymph coagulation and the vertebrate blood coagulation systems. However, this conjecture could not be verified by comparing the structures of coagulogen, the clotting protein of the horseshoe crab, and of mammalian fibrinogen. Here we report the crystal structure of tachylectin 5A (TL5A), a nonself-recognizing lectin from the hemolymph plasma of T. tridentatus. TL5A shares not only a common fold but also related functional sites with the ? fragment of mammalian fibrinogen. Our observations provide the first structural evidence of a common ancestor for the innate immunity and the blood coagulation systems. PMID:11707569

Kairies, Norman; Beisel, Hans-Georg; Fuentes-Prior, Pablo; Tsuda, Ryoko; Muta, Tatsushi; Iwanaga, Sadaaki; Bode, Wolfram; Huber, Robert; Kawabata, Shun-ichiro

2001-01-01

388

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

PubMed

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

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

2014-12-01

389

Dynamic cross-talk between tumor and immune cells in orchestrating the immunosuppressive network at the tumor microenvironment.  

PubMed

Accumulating evidence indicates that a dynamic cross-talk between tumors and the immune system can regulate tumor growth and metastasis. Increased understanding of the biochemical nature of tumor antigens and the molecular mechanisms responsible for innate and adaptive immune cell activation has revolutionized the fields of tumor immunology and immunotherapy. Both the protective effects of the immune system against tumor cells (immunosurveillance) and the evasion of tumor cells from immune attack (tumor-immune escape) have led to the concept of cancer immunoediting, a proposal which infers that a bidirectional interaction between tumor and inflammatory/regulatory cells is ultimately responsible for orchestrating the immunosuppressive network at the tumor site. In this context, a major challenge is the potentiation or redirection of tumor antigen-specific immune responses. The success in reaching this goal is highly dependent on an improved understanding of the interactions and mechanisms operating during the different phases of the cancer immunoediting process. In this review, we discuss the multiple defense and counterattack strategies that tumors have devised in order to evade immune attack and to thwart the effectiveness of several immunotherapeutic approaches. PMID:17571260

Croci, Diego O; Zacarías Fluck, Mariano F; Rico, María J; Matar, Pablo; Rabinovich, Gabriel A; Scharovsky, O Graciela

2007-11-01

390

The spiderweb defense  

SciTech Connect

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.

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

1988-09-01

391

Herpes Simplex Virus as a Tool to Define the Role of Complement in the Immune Response to Peripheral Infection  

PubMed Central

A complex network of interactions exist between the innate and adaptive immune pathways, which act together to elicit a broad and durable host response following pathogen infection. The importance of the complement system in the host’s defense against viruses has become increasingly clear as a result of detailed studies using transgenic mouse models that disrupt specific components of this host immune mechanism. We have utilized herpes simplex virus and replication-defective mutant strains to examine the impact of the complement system on development and maintenance of humoral immune responses. Here we review work from our group and others that highlight the central role that complement proteins C3 and C4 and complement receptors Cr1/Cr2 play during viral infection. We discuss the implications of these results in the context of pathogen infection and current vaccine strategies. PMID:19388172

Brockman, Mark A.; Knipe, David M.

2009-01-01

392

Value of space defenses  

SciTech Connect

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

Canavan, G.H.

1992-10-29

393

The role of hemolymph coagulation in innate immunity.  

PubMed

Invertebrate animals, which lack adaptive immune systems, have developed defense systems that respond to common antigens on the surface of potential pathogens. Hemolymph coagulation is one such defense system in innate immunity. The discovery of lipopolysaccharide-sensitive and (1-->3)-beta-D-glucan-sensitive serine protease zymogens in horseshoe crab (limulus) hemocytes, both of which trigger the coagulation cascade, has exemplified how the animals detect and respond to foreign materials. PMID:8729445

Muta, T; Iwanaga, S

1996-02-01

394

The Drosophila immune system detects bacteria through specific peptidoglycan recognition  

Microsoft Academic Search

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

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

2003-01-01

395

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors  

PubMed Central

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review. Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as ‘immune privileged’, brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another important aspect of implementing gene therapy in the clinical arena is to be able to image the targeting of the therapeutics to the tumors, treatment effectiveness and progression of disease. We have therefore reviewed the most exciting non-invasive, in vivo imaging techniques which can be used in combination with gene therapy to monitor therapeutic efficacy over time. PMID:16248789

Curtin, James F.; King, Gwendalyn D.; Candolfi, Marianela; Greeno, Remy B.; Kroeger, Kurt M.; Lowenstein, Pedro R.; Castro, Maria G.

2006-01-01

396

Strategic Defense Initiative - strategic implications. Study project  

SciTech Connect

In March 1983, during this address to the nation, President Reagan initiated a major shift in U.S. strategic policy, as he indicated his desire to move away from the condition of mutual vulnerability as the primary deterrent to nuclear war. The Strategic Defense Initiative (SDI), as the vehicle for this shift, has become the focus of debate over implications of a new strategic policy. This study seeks to examine the strategic relationship, and the role of arms control during a transition from an offensive-dominant strategy to a defensive-dominant strategy. The methodology for the study is to present arguments for and against SDI, as they relate to the issues of stability and arms control, evaluate their validity, draw conclusions, and provide recommendations that may enhance international security during a transition period of SDI.

Russell, T.L.

1988-03-31

397

Innate Immunity: A Cutaneous Perspective  

Microsoft Academic Search

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

Heidi Goodarzi; Janet Trowbridge; Richard L. Gallo

2007-01-01

398

Male pregnancy and biparental immune priming.  

PubMed

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

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

2012-12-01

399

DNA Immunization  

PubMed Central

DNA immunization was discovered in early 1990s and its use has been expanded from vaccine studies to a broader range of biomedical research, such as the generation of high quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation and gene gun. In addition, several common considerations related to DNA immunization are discussed. PMID:24510291

Wang, Shixia; Lu, Shan

2013-01-01

400

Cascade Control and Defense in Complex Networks  

Microsoft Academic Search

Complex networks with heterogeneous distribution of loads may undergo a\\u000aglobal cascade of overload failures when highly loaded nodes or edges are\\u000aremoved due to attacks or failures. Since a small attack or failure has the\\u000apotential to trigger a global cascade, a fundamental question regards the\\u000apossible strategies of defense to prevent the cascade from propagating through\\u000athe entire

Adilson E. Motter

2004-01-01

401

Self-Defense  

MedlinePLUS

... Attackers are looking for vulnerable targets. Carry a cell phone if possible. Make sure it's programmed with your parents' phone number. Be willing to report crimes in your neighborhood and school to the police. Back Continue Take a Self-Defense Class ...

402

The entrapment defense  

Microsoft Academic Search

Most American jurisdictions follow either asubjective or anobjective approach to the entrapment defense. In order to test some of the differences between the two approaches, student jurors viewed a videotaped cocaine trial and were presented with either subjective test or objective test instructions. The admission of prior conviction evidence was also varied. The jurors deliberated, returned a verdict, and then

Eugene Borgida; Roger Park

1988-01-01

403

FORMERLY USED DEFENSE SITES  

EPA Science Inventory

This data layer represents point locations for Formerly Used Defense Sites (FUDS) located in California, Arizona and Nevada. The original data was extracted from the U.S. Army Corp of Engineer's FUDSIS database. Each site has information about it's inventory status and...

404

The Weekly Defense Monitor  

NSDL National Science Digital Library

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

1997-01-01

405

Moscow's defense intellectuals  

Microsoft Academic Search

This essay was originally written two decades ago as a seminar paper. A substantial portion of it addresses what were then only the first steps toward the establishment of a community of professional civilian defense analysts in the Soviet Union. Throughout most of the intervening period, that community found itself mired in immobilism as jurisdiction over such key Soviet national

Lambeth

1990-01-01

406

Radiological Defense Manual.  

ERIC Educational Resources Information Center

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…

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

407

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

PubMed Central

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

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

2012-01-01

408

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

PubMed

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

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

2012-01-01

409

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

PubMed Central

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

Hernangomez, Miriam; Carrillo-Salinas, Francisco J; Mecha, Miriam; Correa, Fernando; Mestre, Leyre; Loria, Frida; Feliu, Ana; Docagne, Fabian; Guaza, Carmen

2014-01-01

410

Manipulation of EAT-2 expression promotes induction of multiple beneficial regulatory and effector functions of the human innate immune system as a novel immunomodulatory strategy.  

PubMed

The signaling lymphocytic activation molecule (SLAM) receptor-associated adaptor Ewing's sarcoma-associated transcript-2 (EAT-2) is primarily expressed in innate immune cells including dendritic cells (DCs), macrophages and NK cells. A recent human HIV vaccine study confirmed that EAT-2 expression was associated with the enhanced immunogenicity induced by the MRKAd5/HIV vaccine. We previously harnessed the capability of EAT-2 to modulate signaling mediated by SLAM receptors and demonstrated that by incorporating EAT-2 expression into vaccines, one could enhance innate and adaptive immune responses in mice, even in the face of pre-existing immunity to the vaccine vectors. Herein, we investigated the innate immune responses of human cells exposed to EAT-2-over-expressing vaccines. Our results demonstrate that EAT-2 over-expression can significantly alter the kinetics of critical pro-inflammatory cytokine and chemokine responses elaborated by human PBMCs. In addition, enhanced DC maturation and increased monocyte phagocytosis were observed in EAT-2-transduced human cells. We also found that EAT-2 over-expression improved antigen presentation by human cells. Moreover, EAT-2 over-expression increased the anti-tumor activity of human NK cells against K562 tumor cell targets. Many of these responses were extinguished with use of an EAT-2 variant carrying a mutant SH2 domain (R31Q), suggesting a critical role for the interaction between EAT-2 and SLAM receptors in mediating these responses. In conclusion, these results provide evidence that EAT-2 interacts with key components of multiple arms of the human innate immune system, and that this role highlights the potential for targeting EAT-2 functions so as to improve a number of human immunotherapeutic approaches, including vaccine development. PMID:24374770

Aldhamen, Yasser A; Seregin, Sergey S; Aylsworth, Charles F; Godbehere, Sarah; Amalfitano, Andrea

2014-05-01

411