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Sample records for idiotypic immune networks

  1. Idiotypic immune networks in mobile-robot control.

    PubMed

    Whitbrook, Amanda M; Aickelin, Uwe; Garibaldi, Jonathan M

    2007-12-01

    Jerne's idiotypic-network theory postulates that the immune response involves interantibody stimulation and suppression, as well as matching to antigens. The theory has proved the most popular artificial immune system (AIS) model for incorporation into behavior-based robotics, but guidelines for implementing idiotypic selection are scarce. Furthermore, the direct effects of employing the technique have not been demonstrated in the form of a comparison with nonidiotypic systems. This paper aims to address these issues. A method for integrating an idiotypic AIS network with a reinforcement-learning (RL)-based control system is described, and the mechanisms underlying antibody stimulation and suppression are explained in detail. Some hypotheses that account for the network advantage are put forward and tested using three systems with increasing idiotypic complexity. The basic RL, a simplified hybrid AIS-RL that implements idiotypic selection independently of derived concentration levels, and a full hybrid AIS-RL scheme are examined. The test bed takes the form of a simulated Pioneer robot that is required to navigate through maze worlds detecting and tracking door markers.

  2. Stochastic dynamics for idiotypic immune networks

    NASA Astrophysics Data System (ADS)

    Barra, Adriano; Agliari, Elena

    2010-12-01

    In this work we introduce and analyze the stochastic dynamics obeyed by a model of an immune network recently introduced by the authors. We develop Fokker-Planck equations for the single lymphocyte behavior and coarse grained Langevin schemes for the averaged clone behavior. After showing agreement with real systems (as a short path Jerne cascade), we suggest, both with analytical and numerical arguments, explanations for the generation of (metastable) memory cells, improvement of the secondary response (both in the quality and quantity) and bell shaped modulation against infections as a natural behavior. The whole emerges from the model without being postulated a-priori as it often occurs in second generation immune networks: so the aim of the work is to present some out-of-equilibrium features of this model and to highlight mechanisms which can replace a-priori assumptions in view of further detailed analysis in theoretical systemic immunology.

  3. The Murine Humoral Immune Response to Hepatitis B Surface Antigen: Idiotype Network Pathways.

    NASA Astrophysics Data System (ADS)

    Schick, Michael Roy

    Recognition of a wide spectrum in disease outcomes following Hepatitis B Virus (HBV) infection has led to the suggestion that individual differences may be due to characteristics of the immune response. HBV, a hepatotropic virus, is not directly cytopathic to the host hepatocytes but the cellular damage which does not occur may be due to the host's own immune response. It is this variety in immune response capabilities following natural infection or vaccination which led to the present study in which the murine humoral immune response to hepatitis B surface antigen (HBsAg) was examined. Following immunization with purified HBsAg an anti-HBs response could be detected in 19 inbred strains of mice. The response, which varied among the strains, was linked to the major histocompatibility complex (MHC). Among high responders to HBsAg were two strains in which a poor response to a single epitope could be detected. Although quantitatively serum from these strains resembled serum from other high responders, there was a major difference in the qualitative aspects. Included within this study was the role of idotype networks within the murine anti-HBs response. By directly targeting HBsAg-specific B cells within the framework of an idiotype network by an Ab-2, it was possible to circumvent T cell-dependent regulation of an immune response. In each of five inbred strains of mice immunized with a polyclonal rabbit Ab-2 an Ab-3 population with HBsAg-specificity (Ab -1^') was induced. These mice were also immunized with HBsAg resulting in a higher anti-HBs response as compared to HBsAg immunization alone in all of the strains tested except for one. The response in this strain, normally a low responder to HBsAg, indicated that the mechanisms for genetic restriction of the anti -HBs response was still active, although it was not apparent during anti-Id immunization. The effects of an anti-Id on the murine antibody response to HBsAg may lead to insights on the presence of idiotype

  4. Idiotypic networks: toward a renaissance?

    PubMed

    Behn, Ulrich

    2007-04-01

    Idiotypic networks, after being a dominating paradigm for more than a decade, have fallen out of fashion in parallel with the rapid success of molecular immunobiology. Today signs of a possible renaissance in idiotypic network studies are visible. For system biologists and also for physicists, the network idea remains attractive. Herein, a short account of the historical development of the paradigm is given. The necessary technical and conceptual ingredients for a theoretical description of idiotypic networks are briefly reviewed, and previous approaches are discussed. We also describe a minimalistic model developed in our group that allows for understanding the random evolution toward a highly non-trivial complex architecture. In the network, a connected large cluster of idiotype clones and many disconnected ones coexist, thus resembling the notion of central and peripheral parts proposed in the 'second-generation' version of the paradigm. The connected cluster consists of groups of idiotypic clones with clearly distinct statistical properties. The simplicity of the model allows for calculating the size of the groups and the number of inter- and intragroup links, which define the architecture. Aspects of idiotypic interactions in experimental medicine are discussed, along with the challenges to theory and experimentation. PMID:17367340

  5. Idiotypic networks incorporating T-B cell co-operation. The conditions for percolation.

    PubMed

    de Boer, R J; Hogeweg, P

    1989-07-10

    Previous work was concerned with symmetric immune networks of idiotypic interactions amongst B cell clones. The behaviour of these networks was contrary to expectations. This was caused by an extensive percolation of idiotypic signals. Idiotypic activation was thus expected to affect almost all (greater than 10(7] B cell clones. We here analyse whether the incorporation of helper T cells (Th) into these B cell models could cause a reduction in the percolation. Empirical work on idiotypic interactions between Th and B cells however, would suggest that two different idiotypic Th models should be developed: (1) a Th which recognises native B cell idiotypes, i.e. a non-MHC-restricted "ThId" model, and (2) a "classical" MHC-restricted helper T cell model. In the ThId model, the Th-B cell interaction is symmetric. A 2-D model of a Th and a B cell clone that interact idiotypically with each other accounts for various equilibria (i.e. one virgin and two immune states). Introduction of antigen does indeed lead to a state switch from the virgin to the immune state; such a system is thus able to "remember" its exposure to antigen. Idiotypic signals do however, percolate in ThId models via these "B-Th-B-Th" pathways: proliferating Th and B cell clones that interact idiotypically, will always activate each other reciprocally. In the MHC-restricted Th model, Th-B interactions are asymmetric. Because the B cell idiotypes are processed and subsequently presented by MHC molecules, the Th receptor and the native B cell receptor are not expected to be complementary. Thus the Th and the B cells are unable to activate each other reciprocally, and a 2-D Th-B cell model cannot account for idiotypic memory. In contrast to the ThId model, idiotypic activation cannot percolate via "B-Th-B-Th" interactions. Due to the assymmetry idiotypic activation stops at the first Th level. A Th clone cannot activate a subsequent B cell clone: if the B cells recognise the Th cells, they see idiotype but

  6. Quasispecies dynamics on a network of interacting genotypes and idiotypes: applications to autoimmunity and immunodeficiency

    NASA Astrophysics Data System (ADS)

    Barbosa, Valmir C.; Donangelo, Raul; Souza, Sergio R.

    2016-06-01

    In spite of their many facets, the phenomena of autoimmunity and immunodeficiency seem to be related to each other through the subtle links connecting the mutation and action of retroviruses (viruses whose genetic material can find its way into that of the host’s cells and destroy them) to immune response and adaptation. In a previous work, we introduced a network model of how a set of interrelated genotypes (called a quasispecies, in the stationary state, representing for example a population of viruses) and a set of interrelated idiotypes (an idiotypic network, representing the immune system through its population of B and T cells) interact. That model, which does not cover the case of a retroviral quasispecies, is here extended by the addition of a further parameter (ν) to account for the action of retroviruses (i.e. the destruction of idiotypes by genotypes). We give simulation results within a suitable parameter niche, highlighting the issues of quasispecies survival and of the onset of autoimmunity through the appearance of the so-called pathogenic idiotypes (those that mimic some external pathogen). Our main findings refer to how ν and λ, a parameter describing the rate at which idiotypes get stimulated, relate to each other. While for ν >λ the quasispecies survives at the expense of weakening the immune system significantly or even destroying it, for ν <λ the fittest genotypes of the quasispecies become mimicked inside the immune system as pathogenic idiotypes. The latter is in agreement with the current understanding of the HIV quasispecies.

  7. Random Evolution of Idiotypic Networks: Dynamics and Architecture

    NASA Astrophysics Data System (ADS)

    Brede, Markus; Behn, Ulrich

    The paper deals with modelling a subsystem of the immune system, the so-called idiotypic network (INW). INWs, conceived by N.K. Jerne in 1974, are functional networks of interacting antibodies and B cells. In principle, Jernes' framework provides solutions to many issues in immunology, such as immunological memory, mechanisms for antigen recognition and self/non-self discrimination. Explaining the interconnection between the elementary components, local dynamics, network formation and architecture, and possible modes of global system function appears to be an ideal playground of statistical mechanics. We present a simple cellular automaton model, based on a graph representation of the system. From a simplified description of idiotypic interactions, rules for the random evolution of networks of occupied and empty sites on these graphs are derived. In certain biologically relevant parameter ranges the resultant dynamics leads to stationary states. A stationary state is found to correspond to a specific pattern of network organization. It turns out that even these very simple rules give rise to a multitude of different kinds of patterns. We characterize these networks by classifying `static' and `dynamic' network-patterns. A type of `dynamic' network is found to display many features of real INWs.

  8. Idiotype and antigen-specific T cell responses in mice on immunization with antigen, antibody, and anti-idiotypic antibody.

    PubMed

    Mitra-Kaushik, S; Shaila, M S; Karande, A K; Nayak, R

    2001-05-01

    Idiotypic determinants of immunoglobulin molecules can evoke both CD4(+) and CD8(+) T responses and exist not only as the integral components of a bona fide antigen binding receptor but also as distinct molecular entities in the processed forms on the cell surface of B lymphocytes. The present work provides experimental evidence for the concept that regulation of memory B cell populations can be achieved through the presentation of idiotypic and anti-idiotypic determinants to helper and cytotoxic cell. The potential of B cells to present antigens to helper and cytotoxic T cells through class II and class I MHC suggests a mechanism by which both B and T cell homeostasis can be maintained. We provide evidence for the generation of idiotype- and antigen-specific Th and Tc cells upon immunization of syngenic mice with antigen or idiotypic antibody (Ab1) or anti-idiotypic antibody (Ab2). The selective activation and proliferation of the antigen-specific Th and Tc cells mediated by idiotypic stimulation observed in these experiments suggests a B-cell-driven mechanism for the maintenance of antigen-specific T cell memory in the absence of antigenic stimulation, under certain conditions.

  9. Antigen Receptor-Intrinsic Non-Self: The Key to Understanding Regulatory Lymphocyte-Mediated Idiotypic Control of Adaptive Immune Responses.

    PubMed

    Lemke, Hilmar

    2016-01-01

    The clone-specific or idiotypic characters of B as well as T cell antigen receptors (BCRs/TCRs) are associated with (1) the third-complementarity-determining regions (CDR3s) that are created during V(D)J recombination (they scarcely occur in antibody light chains) and (2) BCR idiotopes created by somatic hypermutations (SHMs) during immune responses. Therefore, BCR/TCR idiotypic sites are antigen receptor-intrinsic Non-Self (AgR-iNS) portions that fulfill two tasks: serving as a crucial component of the epitope-binding paratope and serving as target sites for anti-idiotypic BCR/TCR paratopes of other anti-Non-Self clones that are contained in both normal repertoires. The antigen-induced immune response is thus directed not only toward the environmental stimulus but also against the AgR-iNS portions of the directly and further activated clones that form a subsiding idiotypic cascade. These idiotypic chain reactions form a completely integrated idiotypic control circuit among B and T cells which contains all regulatory T and B cells. However, this circuit cannot be viewed as a network of fixed interacting nodes but rather uses the genetic Self as reference. Hence, AgR-iNS offers a mechanistic understanding of regulatory lymphocyte-mediated idiotypic control of adaptive immune responses and reconciles clonal selection and idiotypic network theories hitherto believed to be incompatible. PMID:27480901

  10. Antigen Receptor-Intrinsic Non-Self: The Key to Understanding Regulatory Lymphocyte-Mediated Idiotypic Control of Adaptive Immune Responses.

    PubMed

    Lemke, Hilmar

    2016-01-01

    The clone-specific or idiotypic characters of B as well as T cell antigen receptors (BCRs/TCRs) are associated with (1) the third-complementarity-determining regions (CDR3s) that are created during V(D)J recombination (they scarcely occur in antibody light chains) and (2) BCR idiotopes created by somatic hypermutations (SHMs) during immune responses. Therefore, BCR/TCR idiotypic sites are antigen receptor-intrinsic Non-Self (AgR-iNS) portions that fulfill two tasks: serving as a crucial component of the epitope-binding paratope and serving as target sites for anti-idiotypic BCR/TCR paratopes of other anti-Non-Self clones that are contained in both normal repertoires. The antigen-induced immune response is thus directed not only toward the environmental stimulus but also against the AgR-iNS portions of the directly and further activated clones that form a subsiding idiotypic cascade. These idiotypic chain reactions form a completely integrated idiotypic control circuit among B and T cells which contains all regulatory T and B cells. However, this circuit cannot be viewed as a network of fixed interacting nodes but rather uses the genetic Self as reference. Hence, AgR-iNS offers a mechanistic understanding of regulatory lymphocyte-mediated idiotypic control of adaptive immune responses and reconciles clonal selection and idiotypic network theories hitherto believed to be incompatible.

  11. On the genesis of the idiotypic network theory.

    PubMed

    Civello, Andrea

    2013-01-01

    The idiotypic network theory (INT) was conceived by the Danish immunologist Niels Kaj Jerne in 1973/1974. It proposes an overall view of the immune system as a network of lymphocytes and antibodies. The paper tries to offer a reconstruction of the genesis of the theory, now generally discarded and of mostly historical interest, first of all, by taking into account the context in which Jerne's theoretical proposal was advanced. It is argued the theory challenged, in a sense, the supremacy of the clonal selection theory (CST), this being regarded as the predominant paradigm in the immunological scenario. As CST found shortcomings in explaining certain phenomena, anomalies, one could view INT as a competing paradigm claiming to be able to make sense of such phenomena in its own conceptual framework. After a summary outline of the historical background and some relevant terminological elucidations, a narrative of the various phases of elaboration of the theory is proposed, up to its official public presentation.

  12. Modulation of immune response to Lol p I by pretreatment with anti-idiotypic antibody is not restricted to the idiotypic expression.

    PubMed

    Boutin, Y; Hébert, J

    1994-05-01

    To study the role of anti-idiotypic antibodies in the regulation of the immune response to Lol p I (the major allergenic component of rye grass pollen), we have recently generated a panel of three MoAbs directed against distinct epitopes of Lolp I and an anti-idiotypic MoAb directed against the idiotype borne by one of the anti-Lol p I MoAbs (290A-167). The effects of pretreatment with this anti-idiotypic MoAb in BALB/c mice before immunization with the antigen have been examined. The anti-idiotypic MoAb or unrelated MoAb were given weekly for 8 weeks intraperitoneally. Mice then received the antigen (2 micrograms) adsorbed with alum (2 mg) at weeks 9, 11 and 13. Serum anti-Lol p I antibodies (IgG or IgE) and specific idiotypic responses were measured. Anti-Lol p I IgG antibodies could be detected before immunization with Lol p I only in mice pretreated with anti-idiotypic MoAb. Immunization with Lol p I induced an anti-Lol p I IgG response in both groups, but this response was higher in mice that received anti-idiotypic MoAb. Similar profiles were seen for specific IgE antibodies and idiotypic responses. Surprisingly, idiotypes borne by other anti-Lol p I MoAbs (539A-6 and 348A-6) had also been enhanced after pretreatment with the anti-290A-167 MoAb. These observations suggested that the pretreatment with this anti-idiotypic MoAb modulates not only the expression of the respective idiotype, but also affects other idiotype responses.

  13. Quasispecies dynamics on a network of interacting genotypes and idiotypes: formulation of the model

    NASA Astrophysics Data System (ADS)

    Barbosa, Valmir C.; Donangelo, Raul; Souza, Sergio R.

    2015-01-01

    A quasispecies is the stationary state of a set of interrelated genotypes that evolve according to the usual principles of selection and mutation. Quasispecies studies have for the most part concentrated on the possibility of errors during genotype replication and their role in promoting either the survival or the demise of the quasispecies. In a previous work, we introduced a network model of quasispecies dynamics, based on a single probability parameter (p) and capable of addressing several plausibility issues of previous models. Here we extend that model by pairing its network with another one aimed at modeling the dynamics of the immune system when confronted with the quasispecies. The new network is based on the idiotypic-network model of immunity and, together with the previous one, constitutes a network model of interacting genotypes and idiotypes. The resulting model requires further parameters and as a consequence leads to a vast phase space. We have focused on a particular niche in which it is possible to observe the trade-offs involved in the quasispecies' survival or destruction. Within this niche, we give simulation results that highlight some key preconditions for quasispecies survival. These include a minimum initial abundance of genotypes relative to that of the idiotypes and a minimum value of p. The latter, in particular, is to be contrasted with the stand-alone quasispecies network of our previous work, in which arbitrarily low values of p constitute a guarantee of quasispecies survival.

  14. Anti-idiotypes, receptors, and molecular mimicry

    SciTech Connect

    Linthicum, D.S.; Farid, N.R.

    1987-01-01

    This book provides a review of new methods and results in anti-idiotypes, receptors, and molecular mimicry. It begins with a discussion of the theoretical background of the anti-idiotypic network, it's role in the regulation of immune response, and the physical characteristics of anti-idiotypic antibodies. It then goes on to explore many applications in such areas as insulin action, thyroid cell function, the neurosciences, cardiology, virology, pharmacology, and reproduction.

  15. Immunization of cats against feline infectious peritonitis with anti-idiotypic antibodies.

    PubMed

    Escobar, J C; Kochik, S A; Skaletsky, E; Rosenberg, J S; Beardsley, T R

    1992-01-01

    Anti-idiotypic antibodies (Ab2s) generated against neutralizing antibodies (Ab1s) specific for feline infectious peritonitis virus (FIPV) were shown to be specific for paratope-associated idiotopes of the Ab1s and not against isotypic determinants. In a study to determine the efficacy of an anti-idiotypic vaccine against feline infectious peritonitis (FIP), cats that were immunized with a pool of monoclonal Ab2s developed Ab3s that recognized the variable regions of the Ab2s as well as the natural antigen. In cats challenged with a lethal dose of virus the control group followed a predictable course of infection ultimately succumbing to FIP. Two immunized cats survived virus challenge and a third cat lived twice as long as the controls. The fourth immunized cat showed no evidence of protection. The ability to induce levels of protection against FIP lends support to the concept of using anti-idiotypic antibodies as a prophylactic vaccine.

  16. A response to P.H. Duesberg with reference to an idiotypic network model of AIDS immunopathogenesis.

    PubMed

    Hoffmann, G W

    1990-10-01

    Professors in British Columbia, Canada have devised an autoimmunity model of AIDS (MIAMI model) based on an atypical network theory of regulation of the immune system. It presents different stimuli as cofactors for AIDS: allogenic stimuli in some risk groups and MHC mimicking antigenic stimuli in other risk groups. V regions are on helper T cells that are somewhat anti-self class II MCH. Helper T cell idiotypes interact with both class II MHC and particular suppressor T cell idiotypes, therefore both may be similar. In fact, foreign lymphocytes also can induce an immune response similar to that of MHC image (MI). Hence the MI response is against the anti-self MHC, i.e., foreign idiotypes identify self, particularly self MHC. Further, the HIV envelope protein (gp120) binds to CD4 at a site that overlaps the site where CD4 interacts with class II MHC. Thus recombinant gp120 well as antibodies that recognize the gp120 undying site of CD4 can prevent the interaction of CD4 with class II MHC. Some mutations of CD4 effect the gp120 binding site but not the class II binding site and vice versa and others effect both. This similarity and others HIV can be considered an image of class II MHC, and the anti HIV immune response may be anti MHC image (AMI). MI and AMI responses are against each other and against idiotypic determinants expressed on helper and suppressor T cells respectively. A dual attack on the idiotypes of helper and suppressor T cells accompany these responses thereby causing an imminent collapse of the entire immune system. The model's significant predictive power thereby suggests that we may be able to prevent HIV from causing AIDS by inducing immunological tolerance to HIV components that resemble MHC molecules. This model rejects the 11 paradoxes identified by Duesberg who surmises that HIV is not a cofactor or cause of AIDS.

  17. Suppression of the immune response to ovalbumin in vivo by anti-idiotypic antibodies

    SciTech Connect

    Grinevich, A.S.; Pinegin, B.V.

    1986-12-01

    Conditions of suppression of the immune response to a food allergin (ovalbumin) were studied with the aid of anti-idiotypic (AID) antibodies. Hen ovalbumin was used and the experiments were performed on mice. Antibodies were isolated from the resulting protein fractions and tested for inhibitor activity by the method of direct radioimmunologic analysis. The test system consisted of the reaction of binding the globulin fraction to the total preparation of antibodies to ovalbumin from mice and a /sup 125/I-labeled total preparation of antibodies to ovalbumin of the same animals.

  18. The Significance of a Common Idiotype (1F7) on Antibodies against Human Immune Deficiency Virus Type 1 and Hepatitis C Virus

    PubMed Central

    Muller, Sybille; Parsons, Matthew S.; Kohler, Heinz; Grant, Michael

    2016-01-01

    In this review, we trace the concept and potential functional role of regulatory idiotypes in the immune response to human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus, and hepatitis C virus (HCV). A major idiotype involved in these viral infections is recognized and defined by a murine monoclonal antibody (1F7). Antibodies expressing the idiotype defined by 1F7 are dominant in HIV-1 infection and are also found on many broadly neutralizing antibodies against HIV-1. This regulatory idiotypic axis offers opportunities for exploitation in vaccine development for HIV-1, HCV, and other chronic viral infections. PMID:26904499

  19. Self-tolerance in a minimal model of the idiotypic network.

    PubMed

    Schulz, Robert; Werner, Benjamin; Behn, Ulrich

    2014-01-01

    We consider the problem of self-tolerance in the frame of a minimalistic model of the idiotypic network. A node of this network represents a population of B-lymphocytes of the same idiotype, which is encoded by a bit string. The links of the network connect nodes with (nearly) complementary strings. The population of a node survives if the number of occupied neighbors is not too small and not too large. There is an influx of lymphocytes with random idiotype from the bone marrow. Previous investigations have shown that this system evolves toward highly organized architectures, where the nodes can be classified into groups according to their statistical properties. The building principles of these architectures can be analytically described and the statistical results of simulations agree very well with results of a modular mean-field theory. In this paper, we present simulation results for the case that one or several nodes, playing the role of self, are permanently occupied. These self nodes influence their linked neighbors, the autoreactive clones, but are themselves not affected by idiotypic interactions. We observe that the group structure of the architecture is very similar to the case without self antigen, but organized such that the neighbors of the self are only weakly occupied, thus providing self-tolerance. We also treat this situation in mean-field theory, which give results in good agreement with data from simulation. The model supports the view that autoreactive clones, which naturally occur also in healthy organisms are controlled by anti-idiotypic interactions, and could be helpful to understand network aspects of autoimmune disorders. PMID:24653720

  20. Self-tolerance in a minimal model of the idiotypic network.

    PubMed

    Schulz, Robert; Werner, Benjamin; Behn, Ulrich

    2014-01-01

    We consider the problem of self-tolerance in the frame of a minimalistic model of the idiotypic network. A node of this network represents a population of B-lymphocytes of the same idiotype, which is encoded by a bit string. The links of the network connect nodes with (nearly) complementary strings. The population of a node survives if the number of occupied neighbors is not too small and not too large. There is an influx of lymphocytes with random idiotype from the bone marrow. Previous investigations have shown that this system evolves toward highly organized architectures, where the nodes can be classified into groups according to their statistical properties. The building principles of these architectures can be analytically described and the statistical results of simulations agree very well with results of a modular mean-field theory. In this paper, we present simulation results for the case that one or several nodes, playing the role of self, are permanently occupied. These self nodes influence their linked neighbors, the autoreactive clones, but are themselves not affected by idiotypic interactions. We observe that the group structure of the architecture is very similar to the case without self antigen, but organized such that the neighbors of the self are only weakly occupied, thus providing self-tolerance. We also treat this situation in mean-field theory, which give results in good agreement with data from simulation. The model supports the view that autoreactive clones, which naturally occur also in healthy organisms are controlled by anti-idiotypic interactions, and could be helpful to understand network aspects of autoimmune disorders.

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

    NASA Astrophysics Data System (ADS)

    Bartolucci, Silvia; Mozeika, Alexander; Annibale, Alessia

    2016-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Bartolucci, Silvia; Mozeika, Alexander; Annibale, Alessia

    2016-08-01

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

  3. Idiotype-recognizing T helper cells that are not idiotype specific.

    PubMed

    McNamara, M; Kohler, H

    1983-09-01

    In this study T helper cells that recognize idiotypes as carriers for a hapten-specific B cell response were analyzed under limiting dilution conditions. T helper cells, induced by phosphorylcholine-hemocyanin (PC-Hy) priming, recognize trinitrophenylated TEPC-15 and MOPC-167 (TNP-T15, TNP-167) equally well. Limiting dilution analysis indicates identical frequencies of helper cells for TNP-T15 and TNP-167. Double immunization protocols using TNP-T15 and TNP-167 fail to demonstrate additive effects. Inhibition of carrier recognition in vitro using free hapten, PC, and unconjugated T15 or M167 indicates identical specificities of helper cells for T15 and M167. Collectively, these results provide strong evidence that PC-Hy priming induces only one population of idiotype-recognizing helper cells that are unable to distinguish between the T15 and the M167 idiotopes. The helper cell induction circuit was further analyzed. PC-Hy priming induces T15/167-specific helper T cells in X-linked immune defect-expressing F1 mice. This indicates that a B cell response to PC is not required to induce idiotype-recognizing T cells. Adoptive cotransfer of B cells from PC-Hy-primed mice together with normal T cells fails to induce idiotype-recognizing T cells. These results indicate the existence of a T helper1-T helper2 induction loop. In this scheme, the T helper1 cell carries T15-like receptors and the T helper2 cells, anti-T15-like receptors. Monoclonal antiidiotypic antibodies specific for T15 also induce a T15/167-recognizing T helper cell population. This finding demonstrates that idiotope-specific priming induces non-idiotype-specific T cells. Evidently, the idiotypic T cell network is based on a different selection of idiotope determinants than the selection of the B cell idiotype network.

  4. Evidence of idiotypic modulation in the immune response to gp43, the major antigenic component of Paracoccidioides brasiliensis in both mice and humans

    PubMed Central

    Souza, A R; Gesztesi, J -L; Moraes, J Z; Cruz, C R B; Sato, J; Mariano, M; Lopes, J D

    1998-01-01

    Paracoccidioidomycosis (PCM) is a systemic mycosis endemic in Latin America, with a high prevalence in Brazil, Argentina, Colombia and Venezuela. The aetiologic agent of disease is a thermal dimorphic fungus, Paracoccidioides brasiliensis. A glycoprotein of 43 000 D (gp43) is the major antigen of P. brasiliensis. Antibodies directed to this antigen are detected in the sera of all patients with PCM. Gp43 binds to laminin, thus participating in adhesion, invasion and pathogenesis of the fungus. As the role of antibodies in PCM is not fully understood, we decided to investigate the outcome of mice immunization with three distinct anti-gp43 MoAbs (17c, 8a and 24a) coupled with keyhole limpet haemocyanin (KLH). Results show not only the expected presence of anti-Id (AB2) antibodies in the sera of these animals but also a spontaneous and increasing amount of anti-anti-Id (AB3) antibodies after the third course of immunization. Hybridomas producing both AB2 and AB3 MoAbs were obtained using spleen cells from mice immunized with MoAb 17c. AB3 MoAbs were also obtained with spleen cells of mice immunized with MoAbs 8a and 24a. It was also shown that human PCM patients' sera with high titres of anti-gp43 antibodies generate anti-Id antibodies. These data suggest that the immune response to P. brasiliensis can be spontaneously modulated by the idiotypic network. PMID:9764601

  5. Molecular characterization of the anti-idiotypic immune response of a relapse-free neuroblastoma patient following antibody therapy: a possible vaccine against tumors of neuroectodermal origin?

    PubMed

    Uttenreuther-Fischer, Martina M; Krüger, Jörg A; Fischer, Peter

    2006-06-15

    Neuroblastoma treatment with chimeric antidisialoganglioside GD2 Ab ch14.18 showed objective antitumor responses. Production of anti-idiotypic Abs (Ab2) against ch14.18 (Ab1) in some cases was positively correlated with a more favorable prognosis. According to Jerne's network theory, a subset of anti-idiotypic Abs (Ab2beta) carries an "internal image" of the Ag and induces Abs (Ab3) against the original Ag. The molecular origin of an anti-idiotypic Ab response in tumor patients was not investigated previously. To clone anti-idiotypic Abs, B cells of a ch14.18-treated neuroblastoma patient with Ab2 serum reactivity were used to construct Ab phage display libraries. After repeated biopannings on ch14.18 and its murine relative, anti-GD2 mAb 14G2a, we selected 40 highly specific clones. Sequence analysis revealed at least 10 of 40 clones with different Ig genes. Identities to putative germline genes ranged between 94.90 and 100% for V(H) and between 93.90 and 99.60% for V(L). An overall high rate of replacement mutations suggested a strong Ag-driven maturation of the anti-idiotypic Abs. Two clones that were analyzed further, GK2 and GK8, inhibited binding of ch14.18 to GD2 just as the patient's serum did. GK8 alone inhibited >80% of the patient's anti-idiotypic serum Abs in binding to ch14.18. Rabbits vaccinated with GK8 or GK2 (weaker) produced Ab3 against the original target Ag GD2. GK8 may be useful as a tumor vaccine for GD2-positive [corrected] tumors. PMID:16751426

  6. Single peptide and anti-idiotype based immunizations can broaden the antibody response against the variable V3 domain of HIV-1 in mice.

    PubMed

    Boudet, F; Keller, H; Kieny, M P; Thèze, J

    1995-05-01

    The third variable (V3) domain of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein gp120 is a major target of neutralizing antibodies in infected persons and in experimental immunized animals. Given the high degree of sequence variability of V3, the humoral response toward this region is very type-specific. In the present study, we evaluated the potential of a single peptide and an anti-idiotypic antibody to broaden the anti-V3 antibody specificity in BALB/c mice. We show that a synthetic peptide derived from the V3 determinant of HIV-1 MN isolate (V3MN), when used as an immunogen, was able to induce an antibody response to multiple (up to six) HIV-1 strains. The extent of this cross-reactivity, which tended to enlarge as the injections increased, appeared to be inversely correlated with the binding affinity to V3MN peptide. These data thus present evidence that, despite its great sequence heterogeneity, the V3 loop encompasses conserved amino-acid positions and/or stretches which may be less immunogenic than their variable counterparts. We additionally demonstrate that a rabbit anti-idiotype (Ab2), recognizing a binding site related idiotype on a V3-specific mouse monoclonal antibody (Ab1), could mount a broadened humoral response (Ab3) in mice. Unlike nominal antibody Ab1 which strictly reacted with the European HIV-1 LAI isolate, elicited Ab3 recognized the two divergent HIV-1 strains SF2 and 1286, originating respectively from North America and Central Africa, in addition to LAI. The reasons accounting for this Ab2-induced enlargement of the V3 antibody response are discussed. Our findings suggest that single peptide and anti-idiotype based immunizations may provide viable approaches to overcome, at least in part, HIV epitope variability. PMID:7783749

  7. Binding-site analysis of opioid receptors using monoclonal anti-idiotypic antibodies

    SciTech Connect

    Conroy, W.G.

    1988-01-01

    Structural relatedness between the variable region of anti-ligand antibodies and opioid binding sites allowed the generation of anti-idiotypic antibodies which recognized opioid receptors. The IgG{sub 3}k antibodies which bound to opioid receptors were obtained when an anti-morphine antiserum was the idiotype. Both antibodies bound to opioid receptors, but only one of these blocked the binding of ({sup 3}H)naloxone. The antibody which did not inhibit the binding of ({sup 3}H)naloxone was itself displaced from the receptor by opioid ligands. The unique binding properties displayed by this antibody indicated that anti-idiotypic antibodies are not always a perfect image of the original ligand, and therefore may be more useful than typical ligands as probes for the receptor. An auto-anti-idiotypic technique was successfully used to obtain anti-opioid receptor antibodies. Another IgG{sub 3}k antibody that blocked the binding of ({sup 3}H)naloxone to rat brain opioid receptors was obtained when a mouse was immunized with naloxone conjugated to bovine serum albumin. These data confirmed that an idiotype-anti-idiotype network which can generate an anti-receptor antibody normally functions when an opioid ligand is introduced into an animal in an immunogenic form.

  8. Application of immune network theory for target-oriented multi-spectral remote sensing information mining

    NASA Astrophysics Data System (ADS)

    Liu, Qing-jie; Lin, Qi-zhong

    2008-12-01

    To use target information for space transformation in remote sensing data field, artificial immune network theory is introduced to multi-spectral remote sensing information mining, based on the knowledge of target spectrum. First, the target spectrums are fuzzy clustered into several subclasses, to retain different features of target in different subclasses. Then we develop a novel Regional-memory-pattern Artificial Immune Idiotypic Network (RAIN) model based on artificial idiotypic network theory, and train RAIN with subclasses samples. And then, the affinities of the target spectrum and other objects can be calculated according to the immune microscopic dynamics including stimulation and suppression effect. Finally, principal component analysis (PCA) is performed to affinities to explore more weak and hidden information. With its application in Baoguto Area, Xinjiang Uyghur Autonomous Region China, choosing tuffaceous siltstone as target object, the result supports the efficiency of the RAIN-affinity-PCA scheme.

  9. Protection of mice against the lethal toxicity of a lipopolysaccharide (LPS) by immunization with anti-idiotype antibody to a monoclonal antibody to lipid A from Eikenella corrodens LPS.

    PubMed Central

    Kato, T; Takazoe, I; Okuda, K

    1990-01-01

    We produced anti-idiotype antibodies to antibody to lipid A from Eikenella corrodens. The ALA-1 monoclonal antibody (immunoglobulin M [IgM] isotype), which had already been produced in our laboratory (T. Kato, I. Takazoe, and K. Okuda, Infect. Immun. 57:656-659, 1989), had reacted strongly with lipid A from E. corrodens, Escherichia coli, and Salmonella minnesota. Four anti-idiotype monoclonal antibodies to ALA-1 (Ab1), designated A2LA-1 (IgG1 isotype), A2LA-2 (IgG2a isotype), A2LA-3 (IgG2a isotype), and A2LA-4 (IgG3 isotype), which recognized the idiotype Ab1, were produced. A2LA-1, A2LA-2, and A2LA-3 were capable of over 61% inhibition of ALA-1 reactivity to E. coli J5 lipid A in an enzyme-linked immunosorbent assay system. The sera of mice and rabbits immunized with the anti-idiotype antibodies revealed that the internal image anti-idiotype antibody induced the production of IgG antibodies that cross-reacted with or bound to lipid A. These studies indicate that A2LA-1 and A2LA-2 contained an antigenic epitope that mimicked lipid A. Immunization of mice with A2LA-1 resulted in prevention of lethal toxicity from E. coli J5 lipopolysaccharide. PMID:2404870

  10. Chemically linked phage idiotype vaccination in the murine B cell lymphoma 1 model

    PubMed Central

    2013-01-01

    Background B cell malignancies are characterized by clonal expansion of B cells expressing tumor-specific idiotypes on their surface. These idiotypes are ideal target antigens for an individualized immunotherapy. However, previous idiotype vaccines mostly lacked efficiency due to a low immunogenicity of the idiotype. The objective of the present study was the determination of the feasibility, safety and immunogenicity of a novel chemically linked phage idiotype vaccine. Methods In the murine B cell lymphoma 1 model, tumor idiotypes were chemically linked to phage particles used as immunological carriers. For comparison, the idiotype was genetically expressed on the major phage coat protein g8 or linked to keyhole limpet hemocynanin. After intradermal immunizations with idiotype vaccines, tolerability and humoral immune responses were assessed. Results Feasibility and tolerability of the chemically linked phage idiotype vaccine was demonstrated. Vaccination with B cell lymphoma 1 idiotype expressing phage resulted in a significant survival benefit in the murine B cell lymphoma 1 protection model (60.2 ± 23.8 days vs. 41.8 ± 1.6 days and 39.8 ± 3.8 days after vaccination with wild type phage or phosphate buffered saline, respectively). Superior immunogenicity of the chemically linked phage idiotype vaccine compared to the genetically engineered phage idiotype and keyhole limpet hemocynanin-coupled idiotype vaccine was demonstrated by significantly higher B cell lymphoma 1 idiotype-specific IgG levels after vaccination with chemically linked phage idiotype. Conclusion We present a novel, simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible therapy and may produce a superior immune response compared to previously employed idiotype vaccination strategies. PMID:24152874

  11. Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens.

    PubMed

    Tani, K; Murphy, W J; Chertov, O; Salcedo, R; Koh, C Y; Utsunomiya, I; Funakoshi, S; Asai, O; Herrmann, S H; Wang, J M; Kwak, L W; Oppenheim, J J

    2000-05-01

    Defensins released by neutrophils are able to kill a broad spectrum of microbes. They also induce leukocyte migration in vitro and elicit inflammatory leukocyte responses at s.c. injection sites in mice. In vitro experiments showed that human defensins enhanced concanavalin A-stimulated murine spleen cell proliferation and IFN-gamma production. This led us to examine the effects of human defensins on specific immune responses in vivo. BALB/c mice were immunized with 50 microg of keyhole limpet hemocyanin (KLH) adsorbed to aluminum hydroxide and administered with defensins in aqueous solution. Intraperitoneal administration of defensins significantly increased the production of KLH-specific IgG1, IgG2a and IgG2b antibodies 14 days after immunization. In vitro splenic KLH-specific proliferative responses were higher in mice treated with KLH and defensins than in those treated with KLH alone. Increased IFN-gamma and, to a lesser extent, IL-4 production were also detected in the supernatants of ex vivoKLH-activated spleen cells from mice treated with defensins. Finally, defensins significantly enhanced the antibody response to a syngeneic tumor antigen, lymphoma Ig idiotype and also augmented resistance to tumor challenge. These results indicate that defensins act as potent immune adjuvants by inducing the production of lymphokines, which promote T cell-dependent cellular immunity and antigen-specific Ig production. Thus, defensins appear to function as neutrophil-derived signals that promote adaptive immune responses. PMID:10784615

  12. QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES

    PubMed Central

    Kuettner, Mirta Goffan; Wang, Ai-Lan; Nisonoff, Alfred

    1972-01-01

    Antisera were prepared in rabbits against anti-p-azobenzoate antibodies of an A/J and a BALB/c mouse and anti-p-azophenylarsonate antibodies of an A/J mouse. After appropriate absorption the antisera reacted with the anti-hapten antibody of the donor mouse but, by sensitive quantitative tests, not at all with other components of the hyperimmune serum or with preimmune serum of the donor mouse. The absorbed antiserum therefore appeared to be specific for idiotypic determinants. Nearly all idiotypic specificities identified in the serum of the donor were also present in the serum of other mice of the same strain, immunized against the same hapten group, but not in mice immunized with a different hapten. In each case the antibodies of the donor mouse reacted most effectively on a weight basis with antiidiotypic antiserum. Cross-reactions were observed among different strains of mice but homologous anti-bodies reacted most effectively with antiidiotypic antisera. C57/BL and DBA antisera contained very low concentrations of specificities present in the A/J and BALB/c antibody populations; antibodies of A/J and BALB/c antisera are more closely related to one another. The results indicate that idiotypic specificity may provide a genetic marker for the variable regions of immunoglobulin polypeptide chains. PMID:4110016

  13. Idiotypic expression of antibodies to retinal S-antigen in experimental autoimmune uveoretinitis.

    PubMed Central

    Suleyman, S; Dumonde, D C; Banga, J P

    1987-01-01

    Retinal S-antigen (S-ag), found in the rod photoreceptors of the eye, is a potent autoantigen that is commonly involved in inflammatory eye disease leading to blindness in man. Antibodies, induced in the experimental model by immunizing rats with S-ag purified from porcine retina, were used to prepare heterologous rabbit anti-idiotypic antibodies. The binding of the four rabbit anti-idiotypes to S-ag antibodies was partially inhibitable by porcine S-ag but not by ovalbumin. The idiotypic determinants were localized to the heavy chains by Western blotting with the anti-idiotypes. The presence of the idiotype recognized by the rabbit anti-idiotype was assessed in antisera from various species containing antibodies to S-ag. All rat sera from animals undergoing experimental autoimmune uveoretinitis by immunization with S-ag from porcine or bovine retina contained antibodies that react to varying degrees with the rabbit anti-idiotype. The intraspecies nature of the idiotypic determinants recognized was demonstrated by the fact that none of the anti-idiotypes showed any reactivity with rabbit or murine antisera to S-ag from porcine, bovine or human retina or to human autoantibodies to S-ag from patients with inflammatory eye disease. Thus, all private and recurrent idiotypic determinants induced in rats by immunization with S-ag appear to be restricted to that species. Images Figure 5 PMID:2448224

  14. Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. IV. Occurrence of natural autologous anti-idiotypic antibodies.

    PubMed

    Saint-Remy, J M; Lebecque, S J; Lebrun, P M; Jacquemin, M G

    1988-01-01

    IgG isolated from the plasma of seven individuals hypersensitive to the common house dust mite Dermatophagoides pteronyssinus (DPT) was exhaustively adsorbed onto insolubilized DPT. The unbound fraction was found by radioimmunoassay to contain antibodies recognizing the variable region of both anti-DPT IgG and IgE antibodies. This recognition was idiotype (Id)-specific as it persisted after passage over insolubilized polyclonal IgG of unrelated specificity. Most of these anti-Id IgG carried the internal image of the initial antigen in that they competitively inhibited the binding of anti-DPT antibodies to DPT. Immunoadsorption of anti-Id IgG onto insolubilized anti-DPT IgG antibodies from the same individual completely eliminated their reaction with anti-DPT IgG but not with anti-DPT IgE, suggesting that idiotopes included in the antigen-binding site of specific IgG and IgE antibodies were not identical. Anti-Id IgG recognizing idiotopes located outside the antigen-binding site (bystander idiotopes) were also completely removed by passage over insolubilized anti-DPT IgG; in this case the reaction of the anti-Id IgG with both anti-DPT IgG and anti-DPT IgE was inhibited, indicating that, for a given individual, bystander idiotopes were shared between anti-DPT antibodies pertaining to these two isotypes.

  15. Immune response to phosphorylcholine. IX. Characterization of hybridoma anti-TEPC15 antibodies.

    PubMed

    Wittner, M K; Bach, M A; Köhler, H

    1982-02-01

    Hybridoma antibodies against the PC-binding T15 BALB/c myeloma protein were raised by cell fusion with anti-T15 A/He immune cells. The idiotype specificity of these monoclonal anti-T15 antibodies was determined with a panel of different myeloma and hybridoma immunoglobulins. Two types of anti-T15 antibodies are seen. One reacts with a number of different IgA myeloma proteins and with serum IgA of certain strains of mice; this reactivity most likely is due to allotypy. The other group consists of anti-T15 antibodies that are specific for the T15 idiotype and are therefore termed anti-idiotypic. The bindings of the anti-idiotype antibodies to T15 were specifically inhibited by T15 (F(ab')2 but not by other PC-binding myeloma proteins of different idiotypes. The relationship of the idiotype-specific anti-T15 antibodies to the PC-binding site of the T15 idiotype was analyzed by hapten inhibition of anti-idiotypic binding and by inhibition of BALB/c anti-PC splenic hemolytic plaque formation. Anti-T15 antibodies, for which the T15 binding is inhibited by PC or PC-BSA, also specifically inhibit anti-PC plaque formation. These antibodies are labeled site and near-site anti-idiotypic antibodies. Site and near-site-specific anti-idiotypic antibodies recognize different idiotopes on the T15 molecules. The possible differential biologic activities of these anti-idiotopes in idiotype network regulation is considered.

  16. Suppression of experimental systemic lupus erythematosus (SLE) with specific anti-idiotypic antibody-saporin conjugate.

    PubMed Central

    Blank, M; Manosroi, J; Tomer, Y; Manosroi, A; Kopolovic, J; Charcon-Polak, S; Shoenfeld, Y

    1994-01-01

    The importance of the idiotypic network is represented in experimental SLE induced by active immunization of naive mice with an anti-DNA idiotype (Ab1) emulsified in adjuvant. The mice after 4 months of incubation generate Ab3 having anti-DNA activity. In addition, the mice develop other serological markers for SLE associated with clinical and histopathological manifestations characteristic of the disease. To confirm further the etiological role of the idiotype in this experimental model, the mice were treated with specific anti-idiotypic antibodies (anti-Id) which were also conjugated to a toxin-saporin (Immunotoxin (IT)). Pretreatment of hybridoma cell line producing the anti-anti-Id (anti-DNA = (Ab3)) for 48 h with the anti-Id MoAb (Ab2) reduced the production of anti-DNA by 58%, while pretreatment with the IT resulted in 86% decrease in anti-DNA secretion (saporin alone had only 12% effect). The anti-Id MoAb had no effect on the production of immunoglobulin by an unrelated cell line. In vivo treatment of mice with experimental SLE led to a significant decrease in titres of serum autoantibodies, with diminished clinical manifestations. The results were more remarkable when the IT was employed. These suppressive effects were specific, since an anti-Id treatment of experimental anti-phospholipid syndrome was of no avail. The anti-Id effect was mediated via a reduction in specific anti-DNA antibody-forming cells, and lasted only while anti-Id injections were given. Discontinuation of the anti-Id injection was followed by a rise in titres of anti-DNA antibodies. No immunological escape of new anti-DNA Ids was noted. Our results point to the importance of pathogenic idiotypes in SLE and to the specific potential of implementing anti-idiotypic therapy, enhanced by the conjugation of the anti-Id to an immunotoxin, in particular one with low spontaneous toxicity. Images Fig. 1 Fig. 5 PMID:7994908

  17. QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES

    PubMed Central

    Daugharty, Harry; Hopper, John E.; MacDonald, A. Bruce; Nisonoff, Alfred

    1969-01-01

    Specifically purified anti-p-azobenzoate antibodies of the IgG class from individual rabbits were used to elicit anti-idiotypic antibodies in recipient rabbits. Allotypes of each donor and recipient were matched. When polymerized antibodies were used for immunization, more than 80% of the recipients responded with the formation of antibodies that precipitated the monomeric donor antibody. Percentages of precipitable molecules in the donor antibody population (D) varied from 4 to 56. As little as 4% was readily detectable by the Ouchterlony method or precipitin test. Specificity of the reaction was tested by double diffusion in agar gel against a panel of purified antibenzoate antibodies from 14 heterologous rabbits and, quantitatively, in three systems by measurement of the extent of coprecipitation of heterologous, radiolabeled antibenzoate antibodies. No cross-reactions were observed. Reactions were shown to be attributable to antibenzoate antibodies in the donor serum, and contributions of allotypic reactions were excluded. In three systems investigated quantitatively, and in one studied qualitatively, two recipients of the same donor antibody produced anti-antibody that reacted with essentially the same subfraction of the donor antibody population. The findings that only a portion of the D population is immunogenic, and that the same subfraction is frequently immunogenic in different recipients, suggest that the immunogenic population comprises a limited number of homogeneous groups of antibody molecules. This is supported by the small number of bands usually observed by the Ouchterlony technique. Quantitative methods of analysis should provide an approach to the study of cell populations producing antibodies of a particular idiotype. PMID:5347693

  18. QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES

    PubMed Central

    Spring, Susan B.; Schroeder, Kenneth W.; Nisonoff, Alfred

    1971-01-01

    The effect of challenge by antigen on persistence of clones of antibody-producing cells and on the induction of new clones was investigated through quantitative measurements of idiotypic specificities. In each of nine rabbits idiotypic specificities present in the earliest bleedings were completely replaced after a few months; subsequent changes occurred much more slowly. On a quantitative basis the population of molecules used as immunogen always reacted most effectively with the homologous anti-idiotypic antiserum. Little effect of increased antigen dose on the rate of change of idiotype was observed. Even large amounts of antigen administered every 2 wk caused only gradual changes in idiotypic specificities. This was attributed either to more effective capture of antigen by memory cells, as compared to precursor cells, or to the induction of tolerance in those clones that were not expressed. In two of three rabbits on a monthly injection schedule, the idiotypic specificities identified underwent very slow changes over a period as long as 17 months. Changes occurred more rapidly when antigen was administered every 2 wk. In each of four rabbits investigated, all idiotypic specificities identified before a 5 month rest period were still present afterwards, indicating the survival of essentially all clones of antibody-producing cells during that interval. Quantitative inhibition data indicated that some new clones of cells were initiated. PMID:15776574

  19. Studies of guinea pig immunoglobulin isotype, idiotype and antiidiotype

    SciTech Connect

    Tirrell, S.M.

    1988-01-01

    Immunization of Guinea pigs with diphtheria toxoid generated antibodies of the IgG class that were capable of neutralizing native toxin in vivo. Sera from these animals were used to affinity purify idiotypic antibodies (AB1). AB1 vaccines derived from the IgG1 class and from F(ab{prime}){sub 2} of IgG1 + IgG2 (IgG1/2) classes were effective in inducing a syngeneic anti-idiotype (AB2) response. Animals immunized with AB1 consisting of both IgG1/2 did not elicit a detectable AB2 response. Binding of homologous {sup 125}I-F(ab{prime}){sub 2} (AB1) to the antiidiotype was inhibited 90% in the presence of DT.F(ab{prime}){sub 2} derived from preimmune serum or had no inhibitory effects on the idiotype-antiidiotype interactions. Two groups of outbred guinea pigs were vaccinated with alum absorbed F(ab{prime}){sub 2} of anti-idiotype IgG1/2 (AB2). Of the ten animals inoculated with AB2, three tested positive by RIA against {sup 125}I-DT. Two of the RIA positive sera contained antibodies that neutralized diphtheria toxin in a rabbit intracutaneous assay. Purification of guinea pig IgG by protein A-Sepharose affinity chromatography resulted in the separation of three distinct IgG populations.

  20. QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES

    PubMed Central

    Hopper, John E.; MacDonald, A. Bruce; Nisonoff, Alfred

    1970-01-01

    Idiotypic antibodies were investigated quantitatively by a method of indirect precipitation, which utilizes labeled F(ab')2 fragments of specifically purified antibenzoate antibody from the donor, anti-antibody, and an antiglobulin reagent. The contribution of allotypic and hidden determinants to these reactions was excluded. Greater fractions of an idiotypic antibody population are precipitated by this method, as compared to direct precipitation, and in two instances large proportions of idiotypic antibodies were detected in populations which failed to form precipitates by double diffusion in agar gel. The greater sensitivity of the indirect method was attributed to its capacity to detect molecules bearing a small number of antigenic determinants. Extensive studies of cross-reactions, carried out by an inhibition technique, failed to reveal any strong reactions of anti-idiotypic antibodies with heterologous antibenzoate antibody preparations, heterologous sera, or IgG, although a few weak cross-reactions were noted. One definite cross-reaction was observed by a direct binding measurement with heterologous antiserum. Antisera prepared in more than one recipient against a single donor preparation reacted with identical or overlapping subpopulations of the donor molecules. Instances in which two recipient antisera reacted with different proportions of the molecules of a single donor provided evidence for the existence of more than one idiotypic antibody population in the antibenzoate antibody of an individual rabbit. PMID:5308065

  1. Immunization of epidemics in multiplex networks.

    PubMed

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

    2014-01-01

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

  2. Parallel processing in immune networks

    NASA Astrophysics Data System (ADS)

    Agliari, Elena; Barra, Adriano; Bartolucci, Silvia; Galluzzi, Andrea; Guerra, Francesco; Moauro, Francesco

    2013-04-01

    In this work, we adopt a statistical-mechanics approach to investigate basic, systemic features exhibited by adaptive immune systems. The lymphocyte network made by B cells and T cells is modeled by a bipartite spin glass, where, following biological prescriptions, links connecting B cells and T cells are sparse. Interestingly, the dilution performed on links is shown to make the system able to orchestrate parallel strategies to fight several pathogens at the same time; this multitasking capability constitutes a remarkable, key property of immune systems as multiple antigens are always present within the host. We also define the stochastic process ruling the temporal evolution of lymphocyte activity and show its relaxation toward an equilibrium measure allowing statistical-mechanics investigations. Analytical results are compared with Monte Carlo simulations and signal-to-noise outcomes showing overall excellent agreement. Finally, within our model, a rationale for the experimentally well-evidenced correlation between lymphocytosis and autoimmunity is achieved; this sheds further light on the systemic features exhibited by immune networks.

  3. Transcriptional networks in plant immunity.

    PubMed

    Tsuda, Kenichi; Somssich, Imre E

    2015-05-01

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

  4. Anti-idiotype vaccine against cancer.

    PubMed

    Bhattacharya-Chatterjee, M; Chatterjee, S K; Foon, K A

    2000-09-15

    Immunization with anti-idiotype (Id) antibodies represents a novel new approach to active immunotherapy. Extensive studies in animal tumor models have demonstrated the efficacy of anti-Id vaccines in preventing tumor growth and curing mice with established tumor. We have developed and characterized several murine monoclonal anti-Id antibodies (Ab2) which mimic distinct human tumor-associated antigens (TAA) and can be used as surrogate antigens for triggering active anti-tumor immunity in cancer patients. Encouraging results have been obtained in recent clinical trials. In this article, we will review the existing literature and summarize our own findings showing the potential of this approach for various human cancers. We will also discuss where anti-Id vaccines may perform better than traditional antigen vaccines. PMID:10996628

  5. QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES

    PubMed Central

    Brient, Bruce W.; Nisonoff, Alfred

    1970-01-01

    Rabbit anti-idiotypic antibodies were prepared by injection of specifically purified anti-p-azobenzoate antibodies (D) from individual donor rabbits. Benzoate derivatives were found to be strong inhibitors of the reactions of D with anti-D antisera. There was a close correlation between the combining affinities of the benzoate derivatives used and their effectiveness as inhibitors. Compounds tested that are chemically unrelated to benzoate were ineffective. The results indicate either that the combining site of anti-benzoate antibody is part of an important idiotypic determinant, which is sterically blocked by hapten, or that the hapten induces a conformational change which alters idiotypic determinants not involving the active site. Such conformational changes, if they occur, must be restricted since hapten has little effect on the reactions of F(ab')2 fragments of anti-benzoate antibodies with antisera directed to rabbit fragment Fab and no detectable effect on reactions with antibodies directed to allotypic determinants. PMID:4097134

  6. Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. V. Auto-anti-idiotypic antibody characterization and cross-reactivity.

    PubMed

    Saint-Remy, J M; Lebecque, S J; Lebrun, P M; Jacquemin, M G

    1988-07-01

    From the serum of 10 allergic subjects we have prepared IgG antibodies recognizing idiotopes carried by specific antibodies to Dermatophagoides pteronyssinus (Dpt) allergens, and studied cross-reactivity of anti-Dpt IgG bystander and antigen-binding site-associated idiotopes by latex agglutination assays. Idiotopes of specific anti-Dpt IgE were evaluated by radioimmunoassays. Depending on the assay, a binding or inhibition of more than 50%, as compared to the reactivity of specific antibodies with the corresponding anti-idiotypic (anti-Id) IgG, was considered significant. Cross-reactivity of antigen-binding site-associated idiotopes attained a mean proportion of 6/10 for IgG and 9.6/10 for IgE. By contrast, bystander idiotopes cross-reacted only occasionally with a mean proportion of 2/10 for both IgG and IgE antibodies. Anti-Id antibodies from two subjects have been isolated by adsorption on insolubilized anti-Dpt antibodies of the corresponding patient. Using this purified material we have confirmed that (a) the majority of anti-Id antibodies carry an "internal image" of the initial antigen and compete in a dose-dependent manner with Dpt allergens for the binding to the anti-Dpt antibodies and (b) paratope-associated idiotopes of anti-Dpt antibodies are shared by unrelated individuals.

  7. Autoantibodies against bromelainized mouse erythrocyte: strain distribution of serum idiotype expression and relative peritoneal cell activity.

    PubMed

    Kaushik, A; Poncet, P; Bussard, A

    1986-10-15

    Previously, we demonstrated that the naturally occurring mouse autoantibodies directed against bromelainized mouse red blood cells (BrMRBC) comprised a family of structurally related molecules bearing a common idiotypic determinant (CP) based on structural and idiotypic analysis of a series of anti-BrMRBC monoclonal autoantibodies derived from a fusion of peritoneal cells (PerC) with plasmacytomas. In the present studies, we have evaluated the quantitative expression of circulating CP idiotype related to autoantibodies against BrMRBC in relation to specific PerC anti-BrMRBC plaque-forming activity in an individual mouse of different strains. The data presented here show no direct relationship between serum CP idiotype expression and PerC anti-BrMRBC plaque-forming activity in an individual mouse of all strains tested. However, the circulating CP idiotype content is higher in strains, viz., CBA/J, NZB, C3H, BXSB, and Biozzi high responder (H) mice which exhibit a high perC autoantibody secretory activity against BrMRBC. The strains such as BALB/c, DBA2, SJL/J, CBA/N, and Biozzi low responder (L) express little or no circulating CP idiotype with a corresponding small or no PerC anti-BrMRBC activity. Furthermore, the PerC "auto"-immune phenomenon is markedly expressed in the normal CBA/J strain since these mice show a higher percentage ratio of CP idiotype over serum IgM (2.68%) as well as highest PerC anti-BrMRBC plaque-forming activity (11,319 +/- 18,029 plaques per million viable cells) compared to other normal and autoimmune strains tested. Nevertheless, the highest circulating serum CP idiotype (49.4 micrograms/ml) is observed in the autoimmune NZB mouse. The immunodeficient CBA/N mice fail to express detectable levels of CP idiotype in their serum. The experiments conducted in genetically selected outbred Biozzi (H and L) strain have revealed remarkable differences in serum CP idiotype expression as well as PerC anti-BrMRBC plaque-forming activity in these two

  8. Generation of Anti-Idiotype scFv for Pharmacokinetic Measurement in Lymphoma Patients Treated with Chimera Anti-CD22 Antibody SM03

    PubMed Central

    Zhao, Qi; Wong, Pui-Fan; Lee, Susanna S. T.; Leung, Shui-On; Cheung, Wing-Tai; Wang, Jun-Zhi

    2014-01-01

    Pre-clinical and clinical studies of therapeutic antibodies require highly specific reagents to examine their immune responses, bio-distributions, immunogenicity, and pharmacodynamics in patients. Selective antigen-mimicking anti-idiotype antibody facilitates the assessment of therapeutic antibody in the detection, quantitation and characterization of antibody immune responses. Using mouse specific degenerate primer pairs and splenocytic RNA, we generated an idiotype antibody-immunized phage-displayed scFv library in which an anti-idiotype antibody against the therapeutic chimera anti-CD22 antibody SM03 was isolated. The anti-idiotype scFv recognized the idiotype of anti-CD22 antibody and inhibited binding of SM03 to CD22 on Raji cell surface. The anti-idiotype scFv was subsequently classified as Ab2γ type. Moreover, our results also demonstrated firstly that the anti-idiotype scFv could be used for pharmacokinetic measurement of circulating residual antibody in lymphoma patients treated with chimera anti-CD22 monoclonal antibody SM03. Of important, the present approach could be easily adopted to generate anti-idiotype antibodies for therapeutic antibodies targeting membrane proteins, saving the cost and time for producing a soluble antigen. PMID:24816427

  9. Immunity of multiplex networks via acquaintance vaccination

    NASA Astrophysics Data System (ADS)

    Wang, Zhen; Zhao, Da-Wei; Wang, Lin; Sun, Gui-Quan; Jin, Zhen

    2015-11-01

    How to find the effective approach of immunizing a population is one open question in the research of complex systems. Up to now, there have been a great number of works focusing on the efficiency of various immunization strategies. However, the majority of these existing achievements are limited to isolated networks, how immunization affects disease spreading in multiplex networks seems to need further exploration. In this letter, we explore the impact of the acquaintance immunization in multiplex networks, where two kinds of immunization strategies, multiplex node-based acquaintance immunization and layer node-based acquaintance immunization, are proposed. With the generating function method, our theoretical framework is able to accurately calculate the critical immunization threshold which is one of the most important indexes to predict the epidemic regime. Moreover, we further uncover that, with the increment of degree correlation between network layers, the immunization threshold declines for multiplex node-based acquaintance immunization, but slowly increases for layer node-based acquaintance immunization.

  10. Network representations of immune system complexity.

    PubMed

    Subramanian, Naeha; Torabi-Parizi, Parizad; Gottschalk, Rachel A; Germain, Ronald N; Dutta, Bhaskar

    2015-01-01

    The mammalian immune system is a dynamic multiscale system composed of a hierarchically organized set of molecular, cellular, and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single-cell responses to increasingly complex networks of in vivo cellular interaction, positioning, and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather nonlinear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multiscale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels, while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating 'omics' and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular- and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks.

  11. Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma

    PubMed Central

    2014-01-01

    Background Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies. Methods Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups. Results Phage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests. Conclusion We present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients. PMID:24885819

  12. Expression of public idiotypes in patients with Lyme arthritis.

    PubMed Central

    Axford, J S; Watts, R A; Long, A A; Isenberg, D A; Steere, A C

    1993-01-01

    OBJECTIVE: Joints are often affected in Lyme disease and in some instances this may be due to immune autoreactivity. To characterise further the immune response in this disease investigations were carried out to determine the expression of three public idiotypes on serum immunoglobulins in patients with Lyme disease during the development of varying degrees of arthritis. METHODS: The expression of idiotypes (Ids) 16/6, BEG2, and PR4, first identified on monoclonal antibodies to DNA, was determined by an enzyme linked immunosorbent assay (ELISA) in serial blood samples from 12 patients with Lyme disease over a mean period of six years during the development of a variety of arthritic symptoms, and in serum samples from healthy control subjects and control subjects with systemic lupus erythematosus. RESULTS: Expression of serum IgM or IgG public Ids 16/6 and BEG2 was significantly increased in patients with Lyme disease. IgA Id 16/6 expression, in contrast, was significantly increased only during episodes of arthritis and was also related to its severity. IgM and IgG Id 16/6 expression was related to their respective total immunoglobulin concentration and, in the case of IgM, to the level of IgM antibodies to Borrelia burgdorferi, whereas similar findings were not apparent with IgA antibodies. This may indicate that the IgA response is related to the pathogenesis of arthritis, especially as total IgA and IgA Id 16/6 levels were found to increase over the duration of disease. Sequential analysis of antibodies also showed restriction in the expression of Id 16/6 as it was never found on all immunoglobulin isotypes at the same time, and Id PR4 was never expressed. Ids 16/6 and BEG2 expression, however, may be associated as seven patients expressed these idiotypes simultaneously. CONCLUSIONS: These data indicate the use of public idiotypes in the immune response against B burgdorferi, which may be restricted in terms of idiotype class and isotype expression, and a

  13. Network of immune-neuroendocrine interactions.

    PubMed Central

    Besedovsky, H; Sorkin, E

    1977-01-01

    In order to bring the self-regulated immune system into conformity with other body systems its functioning within the context of an immune-neuroendocrine network is proposed. This hypothesis is based on the existence of afferent--efferent pathways between immune and neuroendocrine structures. Major endocrine responses occur as a consequence of antigenic stimulation and changes in the electrical activity of the hypothalamus also take place; both of these alterations are temporally related to the immune response itself. This endocrine response has meaningful implications for immunoregulation and for immunospecificity. During ontogeny, there is also evidence for the operations of a complex network between the endocrine and immune system, a bidirectional interrelationship that may well affect each developmental stage of both functions. As sequels the functioning of the immune system and the outcome of this interrelation could be decisive in lymphoid cell homeostasis, self-tolerance, and could also have significant implications for pathology. PMID:849642

  14. Neutralisation of factor VIII inhibitors by anti-idiotypes isolated from phage-displayed libraries.

    PubMed

    Schmidt, Anja; Brettschneider, Kerstin; Kahle, Jörg; Orlowski, Aleksander; Becker-Peters, Karin; Stichel, Diana; Schulze, Jörg; Braner, Markus; Tampé, Robert; Schwabe, Dirk; Königs, Christoph

    2016-07-01

    Following replacement therapy with coagulation factor VIII (FVIII), up to 30 % of haemophilia A patients develop FVIII-specific inhibitory antibodies (FVIII inhibitors). Immune tolerance induction (ITI) is not always successful, resulting in a need for alternative treatments for FVIII inhibitor-positive patients. As tolerance induction in the course of ITI appears to involve the formation of anti-idiotypes specific for anti-FVIII antibodies, such anti-idiotypes might be used to restore haemostasis in haemophilia A patients with FVIII inhibitors. We isolated anti-idiotypic antibody fragments (scFvs) binding to murine FVIII inhibitors 2-76 and 2-77 from phage-displayed libraries. FVIII inhibitor/anti-idiotype interactions were very specific as no cross-reactivity with other FVIII inhibitors or isotype controls was observed. ScFvs blocked binding of FVIII inhibitors to FVIII and neutralised their cognate inhibitors in vitro and a monoclonal mouse model. In addition, scFv JkH5 specific for FVIII inhibitor 2-76 stained 2-76-producing hybridoma cells. JkH5 residues R52 and Y226, located in complementary determining regions, were identified as crucial for the JkH5/2-76 interaction using JkH5 alanine mutants. SPR spectroscopy revealed that JkH5 interacts with FVIII inhibitor 2-76 with nanomolar affinity. Thus, FVIII inhibitor-specific, high-affinity anti-idiotypes can be isolated from phage-displayed libraries and neutralise their respective inhibitors. Furthermore, we show that anti-idiotypic scFvs might be utilised to specifically target inhibitor-specific B cells. Hence, a pool of anti-idiotypes could enable the reestablishment of haemostasis in the presence of FVIII inhibitors in patients or even allow the depletion of inhibitors by targeting inhibitor-specific B cell populations. PMID:27009573

  15. Comparison of immunization strategies in geographical networks

    NASA Astrophysics Data System (ADS)

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

    2009-10-01

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

  16. Network representations of immune system complexity

    PubMed Central

    Subramanian, Naeha; Torabi-Parizi, Parizad; Gottschalk, Rachel A.; Germain, Ronald N.; Dutta, Bhaskar

    2015-01-01

    The mammalian immune system is a dynamic multi-scale system composed of a hierarchically organized set of molecular, cellular and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single cell responses to increasingly complex networks of in vivo cellular interaction, positioning and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather non-linear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multi-scale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating ‘omics’ and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks. PMID:25625853

  17. Network representations of immune system complexity.

    PubMed

    Subramanian, Naeha; Torabi-Parizi, Parizad; Gottschalk, Rachel A; Germain, Ronald N; Dutta, Bhaskar

    2015-01-01

    The mammalian immune system is a dynamic multiscale system composed of a hierarchically organized set of molecular, cellular, and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single-cell responses to increasingly complex networks of in vivo cellular interaction, positioning, and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather nonlinear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multiscale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels, while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating 'omics' and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular- and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks. PMID:25625853

  18. Antibodies elicited by pneumococcal antigens bear an anti-DNA--associated idiotype.

    PubMed Central

    Grayzel, A; Solomon, A; Aranow, C; Diamond, B

    1991-01-01

    There is evidence in both murine and human lupus that the production of anti-DNA antibodies may be triggered by environmental antigens. To explore this further, we studied the serum of 10 nonautoimmune individuals immunized with a polyvalent pneumococcal polysaccharide vaccine. All 10 patients showed a rise in the titer of antipneumococcal antibodies bearing an anti-DNA-associated idiotype. The antipneumococcal response was specific as no idiotypic antitetanus antibodies were detected. Furthermore, no anti-DNA antibodies were present in postvaccination sera. The molecular analysis of antipneumococcal and anti-DNA antibodies bearing a common idiotype will help elucidate how foreign antigen might lead to the production of anti-DNA antibodies in susceptible individuals. PMID:1999497

  19. Handwritten digits recognition based on immune network

    NASA Astrophysics Data System (ADS)

    Li, Yangyang; Wu, Yunhui; Jiao, Lc; Wu, Jianshe

    2011-11-01

    With the development of society, handwritten digits recognition technique has been widely applied to production and daily life. It is a very difficult task to solve these problems in the field of pattern recognition. In this paper, a new method is presented for handwritten digit recognition. The digit samples firstly are processed and features extraction. Based on these features, a novel immune network classification algorithm is designed and implemented to the handwritten digits recognition. The proposed algorithm is developed by Jerne's immune network model for feature selection and KNN method for classification. Its characteristic is the novel network with parallel commutating and learning. The performance of the proposed method is experimented to the handwritten number datasets MNIST and compared with some other recognition algorithms-KNN, ANN and SVM algorithm. The result shows that the novel classification algorithm based on immune network gives promising performance and stable behavior for handwritten digits recognition.

  20. Disialoganglioside GD2 anti-idiotypic monoclonal antibodies.

    PubMed

    Cheung, N K; Canete, A; Cheung, I Y; Ye, J N; Liu, C

    1993-05-28

    Disialoganglioside GD2 is widely expressed among neuroblastomas, melanomas, small-cell lung carcinoma, sarcomas and brain tumors. Immunity directed against this antigen may have anti-tumor utility. Since GD2 is poorly immunogenic, anti-idiotypic antibodies may serve as alternative tumor vaccines. Monoclonal antibody 3F8, a murine IgG3 specific for GD2, has shown excellent tumor-targeting ability in vitro and in vivo. LOU/CN rats were immunized with 3F8 and their spleens were used in somatic-cell hybridization, using SP2/0, P3 and Y3 as fusion partners. Six anti-idiotypic (anti-id) MAbs (C2D8, Idio-2, AIG4, C2H7, C4E4, A2A6) were selected based on their reactivity with 3F8 and non-reactivity with murine IgG3 myelomas. Specificity of each anti-id was demonstrated by using various ELISA: (i) lack of direct binding to solid phase myelomas and serum proteins; (ii) inability of other myelomas to inhibit anti-id binding to 3F8; (iii) absence of cross-reactivity of other myelomas to solid-phase anti-id; (iv) lack of inhibition by anti-id of binding of other ganglioside antibodies to their antigens. Antigen specificity was further examined by inhibition of binding of 3F8 to GD2 on immuno-thin-layer chromatography, and by inhibition of 3F8 immunostaining of neuroblastoma cell lines. These 6 antibodies were demonstrated to be distinct, in view of their cross-reactivity, fusion partners and relative strength of binding to 3F8. Anti-GD2 antibodies were induced after immunization with these anti-id antibodies in C57Bl/6 mice. These rat anti-3F8-idiotypic antibodies with exquisite specificity for anti-GD2 antibodies may be useful in vaccine construction.

  1. Enhancing robustness and immunization in geographical networks

    SciTech Connect

    Huang Liang; Yang Kongqing; Yang Lei

    2007-03-15

    We find that different geographical structures of networks lead to varied percolation thresholds, although these networks may have similar abstract topological structures. Thus, strategies for enhancing robustness and immunization of a geographical network are proposed. Using the generating function formalism, we obtain an explicit form of the percolation threshold q{sub c} for networks containing arbitrary order cycles. For three-cycles, the dependence of q{sub c} on the clustering coefficients is ascertained. The analysis substantiates the validity of the strategies with analytical evidence.

  2. Vaccines for lymphomas: idiotype vaccines and beyond.

    PubMed

    Houot, Roch; Levy, Ronald

    2009-05-01

    Therapeutic vaccines for lymphomas have been developed to induce active and long-lasting immune responses against lymphoma capable of eradicating the tumor. Most of these vaccines use the tumor B cell idiotype (the unique variable region of the surface immunoglobulin) as a tumor-specific antigen. The first human clinical trial for lymphoma vaccine was initiated 20 years ago. Along with several other phase I/II trials, it showed encouraging results which supported the initiation of three phase III trials. The results of these trials have recently been released (although not published yet) which failed to demonstrate a prolongation in progression-free survival following chemotherapy. Despite this disappointing result, a number of observations have accumulated over the years that suggest some clinical efficacy of lymphoma vaccines. Several strategies are being developed to improve these results that include optimization of antigen delivery and presentation as well as enhancement of anti-tumor T cell function. This review describes the clinical development of lymphoma vaccines and delineates advances, problems and prospects towards integration of this strategy in the therapeutic armamentarium for lymphoma. PMID:18951668

  3. Production of anti-idiotype antibodies for deoxynivalenol and their evaluation with three immunoassay platforms.

    PubMed

    Maragos, C M

    2014-05-01

    Immunoassays for deoxynivalenol (DON) that involve binding to DON-specific antibodies have been widely developed. In such assays, the responses of samples are generally compared with calibration curves generated by using DON in competition with labeled reagents such as enzymatic or fluorescent conjugates of the toxin. However, materials that mimic the toxin can also be used, provided that they compete effectively with the labeled reagents for the DON-specific antibodies. Examples include certain types of anti-idiotype antibodies, obtained by the immunization of animals with toxin-specific antibodies. In the present work, anti-idiotype antibodies were developed which mimicked DON in the ability to bind to a DON-specific monoclonal antibody (Mab). Fab fragments of the Mab (Ab1) were used to immunize rabbits. Sera were screened by competitive direct enzyme linked immunosorbent assay (CD-ELISA) for the presence of anti-idiotype antibodies (Ab2). In order to determine the most effective screening format and also the potential efficacy in various forms of biosensors, the sera were further evaluated in biolayer interferometry (BLI) and fluorescence polarization immunoassay (FPIA) formats. All three formats were used to demonstrate the presence of anti-idiotypes capable of binding to the paratope of the DON antibody (subtypes Ab2β or Ab2γ). Such materials have the potential to replace DON as calibrants in immunoassays for this toxin.

  4. Idiotypic manipulation in mice: BALB/c mice can express the crossreactive idiotype of A/J mice.

    PubMed Central

    Moser, M; Leo, O; Hiernaux, J; Urbain, J

    1983-01-01

    The response of A/J mice to arsonate-coupled keyhole limpet hemocyanin is characterized by a crossreactive idiotype (CRIA). CRIA+ antibodies are restricted to the Igh-Ic haplotype and are never expressed in BALB/c mice after immunization with antigen. Studies at the DNA level suggest that the gene encoding the CRIA heavy chain in A/J mice is probably absent in the genome of BALB/c mice. Despite this, using the immunization cascade tool, we have been able to induce the expression of CRIA+ antibodies in BALB/c mice. These studies led to an apparent paradox, whose understanding will provide new insights into the regulatory mechanisms of the immune system. We suggest that clones secreting CRIA-like Igs in BALB/c mice are "somatic variants" that could arise from gene conversion events. PMID:6576348

  5. Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype

    SciTech Connect

    Mendlovic, S.; Brocke, S.; Meshorer, A.; Mozes, E. ); Shoenfeld, Y.; Bakimer, R. ); Ben-Bassat, M. )

    1988-04-01

    Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. The authors report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens (Sm, SS-A (Ro), and SS-B (La)), and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.

  6. Characterization of anti-anti-idiotypic antibodies that bind antigen and an anti-idiotype

    PubMed Central

    Goldbaum, Fernando A.; Velikovsky, C. Alejandro; Dall’Acqua, William; Fossati, Carlos A.; Fields, Barry A.; Braden, Bradford C.; Poljak, Roberto J.; Mariuzza, Roy A.

    1997-01-01

    Two mouse monoclonal anti-anti-idiotopic antibodies (anti-anti-Id, Ab3), AF14 and AF52, were prepared by immunizing BALB/c mice with rabbit polyclonal anti-idiotypic antibodies (anti-Id, Ab2) raised against antibody D1.3 (Ab1) specific for the antigen hen egg lysozyme. AF14 and AF52 react with an “internal image” monoclonal mouse anti-Id antibody E5.2 (Ab2), previously raised against D1.3, with affinity constants (1.0 × 109 M−1 and 2.4 × 107 M−1, respectively) usually observed in secondary responses against protein antigens. They also react with the antigen but with lower affinity (1.8 × 106 M−1 and 3.8 × 106 M−1). This pattern of affinities for the anti-Id and for the antigen also was displayed by the sera of the immunized mice. The amino acid sequences of AF14 and AF52 are very close to that of D1.3. In particular, the amino acid side chains that contribute to contacts with both antigen and anti-Id are largely conserved in AF14 and AF52 compared with D1.3. Therapeutic immunizations against different pathogenic antigens using anti-Id antibodies have been proposed. Our experiments show that a response to an anti-Id immunogen elicits anti-anti-Id antibodies that are optimized for binding the anti-Id antibodies rather than the antigen. PMID:9238040

  7. Down-regulation of collagen arthritis after in vivo treatment with a syngeneic monoclonal anti-idiotypic antibody to a cross-reactive idiotope on collagen II auto-antibodies.

    PubMed Central

    Nordling, C; Holmdahl, R; Klareskog, L

    1991-01-01

    Monoclonal anti-idiotypic antibodies previously shown to react with a cross-reactive idiotope of anti-collagen II auto-antibodies were used for in vivo treatment of DBA/1 mice receiving immunization with arthritogenic native rat collagen type II. Injection of 100 micrograms of the anti-idiotypic antibody 3 weeks before the collagen immunization resulted in a significant suppression of collagen arthritis, compared with mice treated with a monoclonal control antibody. The treatment with anti-idiotypic antibody 3 weeks before collagen immunization could also cause a marked down-regulation of the total serum levels of anti-collagen II antibodies. When the anti-idiotypic antibodies were administered near the time for induction of arthritis (2 days after collagen immunization) a significant effect was seen on the collagen arthritis, but not on the levels of anti-collagen antibody. As collagen-induced arthritis is a disease where both T- and B-cell mediated immunity are believed to play critical roles, the present effects of the in vivo anti-idiotype treatment on arthritis development could provide an interesting system for the study of idiotype regulation on both B- and T-cell arthritis-associated autoimmunity. PMID:2037311

  8. An improved acquaintance immunization strategy for complex network.

    PubMed

    Chen, Li; Wang, Dongyi

    2015-11-21

    The acquaintance immunization strategy is a common strategy to suppress epidemic on complex network which achieves a seemingly perfect balance between cost and effectiveness compared with other canonical immunization strategies. However, the acquaintance immunization strategy fails to take the time-varying factor and local information of nodes into consideration, which limits its effectiveness in some specific network topology. Our improved immunization strategy is based on a new mathematical model Network Structure Index (NSI), which digs deep to measure the connection property and surrounding influence of a node's neighbor nodes to better determine the importance of nodes during immunization. Both mathematical derivation and the simulation program tested on various network topology support our idea that this improved acquaintance immunization strategy protects more nodes from infection and immunizes important nodes more efficiently than the original strategies. As to say, our strategy has more adaptability and achieves a more reasonable balanced point between cost and effectiveness.

  9. An improved acquaintance immunization strategy for complex network.

    PubMed

    Chen, Li; Wang, Dongyi

    2015-11-21

    The acquaintance immunization strategy is a common strategy to suppress epidemic on complex network which achieves a seemingly perfect balance between cost and effectiveness compared with other canonical immunization strategies. However, the acquaintance immunization strategy fails to take the time-varying factor and local information of nodes into consideration, which limits its effectiveness in some specific network topology. Our improved immunization strategy is based on a new mathematical model Network Structure Index (NSI), which digs deep to measure the connection property and surrounding influence of a node's neighbor nodes to better determine the importance of nodes during immunization. Both mathematical derivation and the simulation program tested on various network topology support our idea that this improved acquaintance immunization strategy protects more nodes from infection and immunizes important nodes more efficiently than the original strategies. As to say, our strategy has more adaptability and achieves a more reasonable balanced point between cost and effectiveness. PMID:26300068

  10. Cellular and humoral immune response to N-Glycolyl-GM3 elicited by prolonged immunotherapy with an anti-idiotypic vaccine in high-risk and metastatic breast cancer patients.

    PubMed

    Guthmann, Marcelo D; Castro, Mónica A; Cinat, Gabriela; Venier, Cecilia; Koliren, Leonardo; Bitton, Roberto J; Vázquez, Ana María; Fainboim, Leonardo

    2006-01-01

    In this study, the immunogenicity and toxicity profile of 1E10, an anti-idiotypic vaccine mimicking the N-glycolyl-GM3 ganglioside, was investigated with an extended vaccination protocol. The year-long vaccination scheme consisted of 6 biweekly intradermal injections (induction phase), followed by 10 monthly boosters (maintenance). Nineteen patients with high-risk (stage III) or metastatic breast cancer were vaccinated with different dose levels of 1E10 (0.5, 1, and 2 mg). The humoral and cellular responses to 1E10 and the targeted ganglioside were assessed at baseline and throughout the treatment. Local skin reactions represented the most common adverse event (National Cancer Institute Toxicity Criteria (NCIC) grades I and II), followed by mild flu-like symptoms lasting for 1 to 2 days. Two patients were removed from the study because of vaccine-related hypersensitivity reactions. A third patient was removed from the study after a transient loss of consciousness with uncertain relation to the vaccine. All patients showed a strong antibody response to the targeted ganglioside. In addition, ganglioside-specific T-cell responses were recorded in 5 of 13 evaluable patients. Vaccination with 1E10 was immunogenic and relatively well tolerated. Because similar results were observed with the 3 tested dose levels, the 0.5-mg dose level was selected for future trials. PMID:16531822

  11. Generation of anti-idiotype antibodies for application in clinical immunotherapy laboratory analyses.

    PubMed

    Liu, Zhanqi; Panousis, Con; Smyth, Fiona E; Murphy, Roger; Wirth, Veronika; Cartwright, Glenn; Johns, Terrance G; Scott, Andrew M

    2003-08-01

    The chimeric monoclonal antibody ch806 specifically targets the tumor-associated mutant epidermal growth factor receptor (de 2-7EGFR or EGFRVIII) and is currently under investigation for its potential use in cancer therapy. The humanised monoclonal antibody hu3S193 specifically targets the Lewis Y epithelial antigen and is currently in Phase I clinical trials in patients with advanced breast, colon, and ovarian carcinomas. To assist the clinical evaluation of ch806 and hu3S193, laboratory assays are required to monitor their serum pharmacokinetics and quantitate any immune responses to the antibodies. Mice immunized with ch806 or hu3S193 were used to generate hybridomas producing antibodies with specific binding to ch806 or hu3S193 and competitive for antigen binding. These anti-idiotype antibodies (designated Ludwig Melbourne Hybridomas, LMH) were investigated as reagents suitable for use as positive controls for HAHA or HACA analyses and for measuring hu3S193 or ch806 in human serum. Anti-idiotypes with the ability to concurrently bind two target antibody molecules were identified, which enabled the development of highly reproducible, sensitive, specific ELISA assays for determining serum concentrations of hu3S193 and ch806 with a 3 ng/mL limit of quantitation using LMH-3 and LMH-12, respectively. BIAcore analyses determined high apparent binding affinity for both idiotypes: LMH-3 binding immobilized hu3S193, Ka = 4.76 x 10(8) M(-1); LMH-12 binding immobilised ch806, Ka = 1.74 x 10(9) M(-1). Establishment of HAHA or HACA analysis of sera samples using BIAcore was possible using LMH-3 and LMH-12 as positive controls for quantitation of immune responses to hu3S193 or ch806 in patient sera. These anti-idiotypes could also be used to study the penetrance and binding of ch806 or hu3S193 to tumor cells through immunohistochemical analysis of tumor biopsies. The generation of anti-idiotype antibodies capable of concurrently binding a target antibody on each variable

  12. Induction of IgG antibodies against GD3 ganglioside in rabbits by an anti-idiotypic monoclonal antibody.

    PubMed Central

    Chapman, P B; Houghton, A N

    1991-01-01

    Anti-idiotypic MAb were raised in syngeneic mice against a mouse MAb recognizing GD3 ganglioside (MAb R24). Two anti-idiotypic MAb, designated BEC2 and BEC3, recognized distinct determinants on MAb R24 that mapped near or within the GD3-binding site. New Zealand white rabbits, which express GD3 on normal tissues, were immunized with either BEC2, BEC3, or control MAb FLOPC-21. All rabbits developed high and equivalent titers of antibodies against mouse immunoglobulins. Immunization with BEC2 and BEC3 induced rabbit antibodies expressing R24 idiotype as demonstrated by their ability to inhibit BEC2 binding to R24. Antibodies (IgG and IgM) reacting with GD3 developed in five of eight rabbits immunized with BEC2 but not in rabbits immunized with BEC3 or with control MAb. Serum antibodies against GD3 did not cross-react with other gangliosides. These results show that MAb BEC2 can mimic GD3 ganglioside and can induce antibodies against GD3 ganglioside despite expression of GD3 on normal rabbit tissue. Images PMID:2056117

  13. The Reticular Cell Network: A Robust Backbone for Immune Responses

    PubMed Central

    Textor, Johannes; Mandl, Judith N.; de Boer, Rob J.

    2016-01-01

    Lymph nodes are meeting points for circulating immune cells. A network of reticular cells that ensheathe a mesh of collagen fibers crisscrosses the tissue in each lymph node. This reticular cell network distributes key molecules and provides a structure for immune cells to move around on. During infections, the network can suffer damage. A new study has now investigated the network’s structure in detail, using methods from graph theory. The study showed that the network is remarkably robust to damage: it can still support immune responses even when half of the reticular cells are destroyed. This is a further important example of how network connectivity achieves tolerance to failure, a property shared with other important biological and nonbiological networks. PMID:27727272

  14. Anti-idiotype antibody vaccine therapy for cancer.

    PubMed

    Bhattacharya-Chatterjee, Malaya; Chatterjee, Sunil K; Foon, Kenneth A

    2002-12-01

    The use of anti-idiotype (Id) antibodies as vaccines to stimulate antitumour immunity is one of several promising immunologic approaches to the therapy of cancer. Extensive studies in animal tumour models have demonstrated the efficacy of anti-Id vaccines in preventing tumour growth and curing mice with established tumours. A number of monoclonal anti-Id antibodies that mimic distinct human tumour-associated antigens (TAAs) have been developed and tested in the clinic, and demonstrate encouraging results. In general, the antigen mimicry by anti-Id antibodies has reflected structural homology in the majority of the cases, and amino acid sequence homology in a few of them. The greatest challenge of immunotherapy by means of anti-Id vaccines is to identify the optimal anti-Id antibody that will function as a true surrogate antigen for a TAA system, and ideally will generate both humoral and cellular immune responses. Although several clinical studies have shown enhanced survival of patients receiving anti-Id vaccines, the efficacy of these vaccines will depend on the results of several randomised Phase III clinical trials that are currently planned or ongoing. PMID:12517266

  15. The immune network in thyroid cancer.

    PubMed

    Galdiero, Maria Rosaria; Varricchi, Gilda; Marone, Gianni

    2016-06-01

    The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression. PMID:27471646

  16. Epidemic spreading and immunization in node-activity networks

    NASA Astrophysics Data System (ADS)

    Wu, Qingchu; Chen, Shufang

    2015-09-01

    In this paper, we study the epidemic spreading in node-activity networks, where an individual participates in social networks with a certain rate h. There are two cases for h: the state-independent case and the state-dependent case. We investigate the epidemic threshold as a function of h compared to the static network. Our results suggest the epidemic threshold cannot be exactly predicted by using the analysis approach in the static network. In addition, we further propose a local information-based immunization protocol on node-activity networks. Simulation analysis shows that the immunization can not only eliminate the infectious disease, but also change the epidemic threshold via increasing the immunization parameter.

  17. Differential protein network analysis of the immune cell lineage.

    PubMed

    Clancy, Trevor; Hovig, Eivind

    2014-01-01

    Recently, the Immunological Genome Project (ImmGen) completed the first phase of the goal to understand the molecular circuitry underlying the immune cell lineage in mice. That milestone resulted in the creation of the most comprehensive collection of gene expression profiles in the immune cell lineage in any model organism of human disease. There is now a requisite to examine this resource using bioinformatics integration with other molecular information, with the aim of gaining deeper insights into the underlying processes that characterize this immune cell lineage. We present here a bioinformatics approach to study differential protein interaction mechanisms across the entire immune cell lineage, achieved using affinity propagation applied to a protein interaction network similarity matrix. We demonstrate that the integration of protein interaction networks with the most comprehensive database of gene expression profiles of the immune cells can be used to generate hypotheses into the underlying mechanisms governing the differentiation and the differential functional activity across the immune cell lineage. This approach may not only serve as a hypothesis engine to derive understanding of differentiation and mechanisms across the immune cell lineage, but also help identify possible immune lineage specific and common lineage mechanism in the cells protein networks. PMID:25309909

  18. Detection of auto-anti-idiotypic antibodies to Lol p I (rye I) IgE antibodies in human sera by the use of murine idiotypes: levels in atopic and non-atopic subjects and effects of immunotherapy.

    PubMed

    Hébert, J; Bernier, D; Mourad, W

    1990-06-01

    Anti-idiotypic antibodies (anti-Id Abs) are involved in the regulation of a number of immune responses including the IgE antibody production. In atopic patients, the increased synthesis of IgE antibodies could be related to a defective production of regulatory anti-Id Abs. In the present study, we first developed a sensitive assay for measuring the levels of anti-Id Abs directed against antibodies specific for Lol p I, the major allergenic determinant of Lolium perenne (rye grass). In this assay, we used previously described murine monoclonal anti-Lol p I antibodies that were shown to share epitopic specificities with human anti-Lol p I IgE and IgG antibodies, thus short-cutting the need for purification of F(ab')2 fragments of human IgG Abs and insuring optimal specificity and sensitivity. Levels of anti-Id Abs against two anti-Lol p I monoclonal antibodies (290A-167, 348A-6) were higher in normal volunteers than in untreated atopic patients. Specific immunotherapy increased the levels of anti-Id Abs to those of normal volunteers. These observations suggest a role for the Id-anti-Id network in the regulation of IgE antibody production.

  19. Extracellular idiotypic immunoglobulin arising from human leukemic B lymphocytes

    PubMed Central

    1980-01-01

    The peripheral blood lymphocytes of nine out of nine patients with typical surface Ig-positive chronic lymphocytic leukemia but no paraprotein visible on serum electrophoresis have been shown by radioimmunoassay to export small amounts of pentameric IgM during culture (in the range of 2.4-7.2 ng/10(7) cells per h); three out of nine also exported monomeric IgD (0.7-1.4 ng/10(7) cells per h). Immunoglobulin turned over on the cell surface did not appear to contribute to material in the culture fluid, except possibly as vesicle- bound Ig. In three cases, which included two of the IgD producers, anti- idiotypic antibody raised against the cell surface Fab mu was used to demonstrate the idiotypic nature of the exported Ig. Anti-idiotypic antibody was also used to measure levels of idiotypic Ig in the sera of these three patients as a proportion of the total Ig. Total serum IgM was depressed in all three patients, and the idiotypic IgM represented 43%, 65%, and 96% of the IgM. The findings suggest that in typical chronic lymphocytic leukemia involving B lymphocytes, the export of a small amount of idiotypic Ig by the neoplastic cells in a common or even usual occurrence. PMID:6969771

  20. Antifungal innate immunity: recognition and inflammatory networks.

    PubMed

    Becker, Katharina L; Ifrim, Daniela C; Quintin, Jessica; Netea, Mihai G; van de Veerdonk, Frank L

    2015-03-01

    A large variety of fungi are present in the environment, among which a proportion colonizes the human body, usually without causing any harm. However, depending on the host immune status, commensals can become opportunistic pathogens that induce diseases ranging from superficial non-harmful infection to life-threatening systemic disease. The interplay between the host and the fungal commensal flora is being orchestrated by an efficient recognition of the microorganisms, which in turn ensures a proper balance between tolerance of the normal fungal flora and induction of immune defense mechanisms when invasion occurs. Pattern recognition receptors (PRRs) play a significant role in maintaining this balance due to their capacity to sense fungi and induce host responses such as the induction of proinflammatory cytokines involved in the activation of innate and adaptive immune responses. In the present review, we will discuss the most recent findings regarding the recognition of Candida albicans and Aspergillus fumigatus and the different types of immune cells that play a role in antifungal host defense. PMID:25527294

  1. A biologically inspired immunization strategy for network epidemiology.

    PubMed

    Liu, Yang; Deng, Yong; Jusup, Marko; Wang, Zhen

    2016-07-01

    Well-known immunization strategies, based on degree centrality, betweenness centrality, or closeness centrality, either neglect the structural significance of a node or require global information about the network. We propose a biologically inspired immunization strategy that circumvents both of these problems by considering the number of links of a focal node and the way the neighbors are connected among themselves. The strategy thus measures the dependence of the neighbors on the focal node, identifying the ability of this node to spread the disease. Nodes with the highest ability in the network are the first to be immunized. To test the performance of our method, we conduct numerical simulations on several computer-generated and empirical networks, using the susceptible-infected-recovered (SIR) model. The results show that the proposed strategy largely outperforms the existing well-known strategies. PMID:27113785

  2. Immunization strategy for epidemic spreading on multilayer networks

    NASA Astrophysics Data System (ADS)

    Buono, C.; Braunstein, L. A.

    2015-01-01

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

  3. A danger-theory-based immune network optimization algorithm.

    PubMed

    Zhang, Ruirui; Li, Tao; Xiao, Xin; Shi, Yuanquan

    2013-01-01

    Existing artificial immune optimization algorithms reflect a number of shortcomings, such as premature convergence and poor local search ability. This paper proposes a danger-theory-based immune network optimization algorithm, named dt-aiNet. The danger theory emphasizes that danger signals generated from changes of environments will guide different levels of immune responses, and the areas around danger signals are called danger zones. By defining the danger zone to calculate danger signals for each antibody, the algorithm adjusts antibodies' concentrations through its own danger signals and then triggers immune responses of self-regulation. So the population diversity can be maintained. Experimental results show that the algorithm has more advantages in the solution quality and diversity of the population. Compared with influential optimization algorithms, CLONALG, opt-aiNet, and dopt-aiNet, the algorithm has smaller error values and higher success rates and can find solutions to meet the accuracies within the specified function evaluation times.

  4. The immune system as a self-centered network of lymphocytes.

    PubMed

    Santori, Fabio R

    2015-08-01

    This essay makes a brief historical and comparative review of selective and network theories of the immune system which is presented as a chemical sensory system with immune and non-immune functions. The ontogeny of immune networks is the result of both positive and negative selection of lymphocytes to self-epitopes that serve as a "template" for the recognition of foreign antigens. The development of immune networks progresses from single individual clones in early ontogeny into complex "information processing networks" in which lymphocytes are linked to inhibitory and stimulatory immune cells. The results of these regulatory interactions modulate immune responses and tolerance.

  5. Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in panic disorder.

    PubMed

    Coplan, J D; Tamir, H; Calaprice, D; DeJesus, M; de la Nuez, M; Pine, D; Papp, L A; Klein, D F; Gorman, J M

    1999-04-01

    The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations within brain stress systems that secondarily influence the immune system have been documented. A recent report indicated elevations of serotonin (5-HT) and ganglioside antibodies in patients with primary fibromyalgia, a condition with documented associations with panic disorder. In line with our interest in dysregulated 5-HT systems in panic disorder (PD), we wished to assess if antibodies directed at the 5-HT system were elevated in patients with PD in comparison to healthy volunteers. Sixty-three patients with panic disorder and 26 healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti-5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors). To include all subjects in one experiment, three different batches were run during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a significant group effect [patients > controls (p = .007)] and batch effect but no interaction. The mean effect size for the three batches was .76. Following Z-score transformation of each separate batch and then combining all scores, patients demonstrated significantly elevated levels of plasma serotonin anti-idiotypic antibodies. Neither sex nor age as covariates affected the significance of the results. There was a strong correlation between anti-serotonin antibody and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies: there was a significant diagnosis effect [patients > controls (p = .037)]. Mean effect size for the three batches was .52. Upon Z-score transformation, there was a diagnosis effect with antibody elevations in patients. Covaried for sex and age, the result falls below significance to trend levels. The data raise the possibility that psychoimmune dysfunction, specifically related to the 5-HT system, may be present in PD. Potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of

  6. Anti-idiotypic antibodies induce neutralizing antibodies to bovine herpesvirus 1.

    PubMed Central

    Srikumaran, S; Onisk, D V; Borca, M V; Nataraj, C; Zamb, T J

    1990-01-01

    A neutralizing murine monoclonal antibody (mAb) of the IgG2a isotype (MM-113), specific for bovine herpesvirus 1 (BHV-1) glycoprotein gIV, was used to develop anti-idiotypic antibodies (anti-Id) in a calf. The bovine anti-Id were isolated from the serum of the immunized calf by affinity chromatography on an MM-113-Sepharose column, followed by repeated adsorption on a murine IgG2a column. The anti-Id thus obtained specifically reacted with MM-113, but not with isotype-matched controls. They also inhibited the binding of MM-113 to BHV-1 in a concentration-dependent manner. Mice immunized with the anti-Id produced neutralizing antibodies to BHV-1. The anti-Id bound to cells permissive to BHV-1 in a cell-binding radioimmunoassay (RIA). PMID:2165998

  7. Immune allied genetic algorithm for Bayesian network structure learning

    NASA Astrophysics Data System (ADS)

    Song, Qin; Lin, Feng; Sun, Wei; Chang, KC

    2012-06-01

    Bayesian network (BN) structure learning is a NP-hard problem. In this paper, we present an improved approach to enhance efficiency of BN structure learning. To avoid premature convergence in traditional single-group genetic algorithm (GA), we propose an immune allied genetic algorithm (IAGA) in which the multiple-population and allied strategy are introduced. Moreover, in the algorithm, we apply prior knowledge by injecting immune operator to individuals which can effectively prevent degeneration. To illustrate the effectiveness of the proposed technique, we present some experimental results.

  8. Complement and platelets: Mutual interference in the immune network.

    PubMed

    Speth, Cornelia; Rambach, Günter; Würzner, Reinhard; Lass-Flörl, Cornelia; Kozarcanin, Huda; Hamad, Osama A; Nilsson, Bo; Ekdahl, Kristina N

    2015-09-01

    In recent years, the view of platelets has changed from mere elements of hemostasis to immunological multitaskers. They are connected in manifold ways to other cellular and humoral components of the immune network, one of which is the complement system, a potent player in soluble innate immunity. Our article reviews the crucial and complex interplay between platelets and complement, focusing on mutual regulation of these two interaction partners by their respective molecular mechanisms. Furthermore, the putative relevance of these processes to infectious diseases, inflammatory conditions, and autoimmune disorders, as well as the treatment of patients with biomaterials is highlighted.

  9. The immune system as a self-centered network of lymphocytes

    PubMed Central

    Santori, Fabio R.

    2015-01-01

    This essay makes a brief historical and comparative review of selective and network theories of the immune system which is presented as a chemical sensory system with immune and non-immune functions. The ontogeny of immune networks is the result of both positive and negative selection of lymphocytes to self-epitopes that serve as a “template” for the recognition of foreign antigens. The development of immune networks progresses from single individual clones in early ontogeny into complex “information processing networks” in which lymphocytes are linked to inhibitory and stimulatory immune cells. The results of these regulatory interactions modulate immune responses and tolerance. PMID:26092524

  10. Global efficiency of local immunization on complex networks

    NASA Astrophysics Data System (ADS)

    Hébert-Dufresne, Laurent; Allard, Antoine; Young, Jean-Gabriel; Dubé, Louis J.

    2013-07-01

    Epidemics occur in all shapes and forms: infections propagating in our sparse sexual networks, rumours and diseases spreading through our much denser social interactions, or viruses circulating on the Internet. With the advent of large databases and efficient analysis algorithms, these processes can be better predicted and controlled. In this study, we use different characteristics of network organization to identify the influential spreaders in 17 empirical networks of diverse nature using 2 epidemic models. We find that a judicious choice of local measures, based either on the network's connectivity at a microscopic scale or on its community structure at a mesoscopic scale, compares favorably to global measures, such as betweenness centrality, in terms of efficiency, practicality and robustness. We also develop an analytical framework that highlights a transition in the characteristic scale of different epidemic regimes. This allows to decide which local measure should govern immunization in a given scenario.

  11. Global efficiency of local immunization on complex networks

    PubMed Central

    Hébert-Dufresne, Laurent; Allard, Antoine; Young, Jean-Gabriel; Dubé, Louis J.

    2013-01-01

    Epidemics occur in all shapes and forms: infections propagating in our sparse sexual networks, rumours and diseases spreading through our much denser social interactions, or viruses circulating on the Internet. With the advent of large databases and efficient analysis algorithms, these processes can be better predicted and controlled. In this study, we use different characteristics of network organization to identify the influential spreaders in 17 empirical networks of diverse nature using 2 epidemic models. We find that a judicious choice of local measures, based either on the network's connectivity at a microscopic scale or on its community structure at a mesoscopic scale, compares favorably to global measures, such as betweenness centrality, in terms of efficiency, practicality and robustness. We also develop an analytical framework that highlights a transition in the characteristic scale of different epidemic regimes. This allows to decide which local measure should govern immunization in a given scenario. PMID:23842121

  12. Network immunization under limited budget using graph spectra

    NASA Astrophysics Data System (ADS)

    Zahedi, R.; Khansari, M.

    2016-03-01

    In this paper, we propose a new algorithm that minimizes the worst expected growth of an epidemic by reducing the size of the largest connected component (LCC) of the underlying contact network. The proposed algorithm is applicable to any level of available resources and, despite the greedy approaches of most immunization strategies, selects nodes simultaneously. In each iteration, the proposed method partitions the LCC into two groups. These are the best candidates for communities in that component, and the available resources are sufficient to separate them. Using Laplacian spectral partitioning, the proposed method performs community detection inference with a time complexity that rivals that of the best previous methods. Experiments show that our method outperforms targeted immunization approaches in both real and synthetic networks.

  13. Epidemic spreading and immunization strategy in multiplex networks

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  14. Preclinical evaluation in nonhuman primates of murine monoclonal anti-idiotype antibody that mimics the disialoganglioside GD2.

    PubMed

    Sen, G; Chakraborty, M; Foon, K A; Reisfeld, R A; Bhattacharya-Chatterjee, M

    1997-11-01

    The antiganglioside GD2 monoclonal antibody 14G2a (Ab1) served as an immunogen to generate the anti-idiotype (anti-Id) 1A7 (IgG1,kappa), which mimics GD2 both antigenically and biologically. Anti-Id 1A7 induced anti-GD2 antibodies in mice and rabbits. In this preclinical study, a pair of cynomolgus monkeys, immunized with 1A7 that had been mixed with QS-21 adjuvant, produced anti-anti-Id antibodies (Ab3), which reacted with the GD2-positive melanoma cell line M21/P6 cells but not with GD2-negative LS174-T cells. The Ab3 shared Ids with mAb 14G2a (Ab1), as demonstrated by their ability to inhibit binding of 1A7 to this Ab1. The Ab3 bound specifically to purified GD2 antigen and competed with the Ab1 14G2a in binding to a GD2-positive melanoma cell line or to purified GD2, suggesting that Ab1 and Ab3 may bind to the same epitope and may behave as an Ab1-like antibody (Ab1'). The isotype of the GD2-specific antibodies was mostly IgG in nature. The specificity of the antibodies for GD2 was further confirmed by dot blot analysis. These antisera also specifically lysed GD2-positive target cells in an antibody-dependent cellular cytotoxicity assay. The induction of anti-GD2 responses in monkeys did not cause any apparent side effects, despite the fact that GD2 antigen is expressed by many normal tissues of these animals. Taken together, these results suggest that anti-Id 1A7 can induce GD2-specific antibodies in nonhuman primates and can thus serve as a potential network antigen for triggering active anti-GD2 antibodies in patients with GD2-positive neuroectodermal tumors. PMID:9815586

  15. Structural Basis for the Recognition in an Idiotype-Anti-Idiotype Antibody Complex Related to Celiac Disease

    PubMed Central

    Vangone, Anna; Abdel-Azeim, Safwat; Caputo, Ivana; Sblattero, Daniele; Di Niro, Roberto; Cavallo, Luigi; Oliva, Romina

    2014-01-01

    Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2. PMID:25076134

  16. Sweet immunity in the plant circadian regulatory network.

    PubMed

    Bolouri Moghaddam, Mohammad Reza; Van den Ende, Wim

    2013-04-01

    All organisms have an internal timing mechanism, termed the circadian clock, to anticipate the light/dark cycle. The clock, with an oscillating rhythm that approximates 24h, is a rather robust system persisting to a great extent in continuous light and dark. It is widely accepted that plant growth and development are regulated by the clock, hormones, and sugar signals. On the one hand, sugar signalling can affect circadian rhythms by altering the expression pattern of clock-regulated genes. More in particular, the clock seems to be particularly sensitive to sucrose-mediated signalling which is also associated with immunity and abiotic stress responses. Also, hormonal interaction with the clock can contribute to appropriate plant immune responses. Recent data show a prominent role for the clock in growth and stress responses. On the other hand, the clock seems to be essential in controlling the gene expression and activity of an array of carbohydrate-metabolizing enzymes, suggesting a complex reciprocal relationship between the clock and metabolic signalling processes. Therefore, the clock fulfils a crucial role at the heart of cellular networks. The players involved in the complex plant circadian network and their possible contribution to the novel 'sweet immunity' concept are discussed.

  17. Responsive immunization and intervention for infectious diseases in social networks

    NASA Astrophysics Data System (ADS)

    Wu, Qingchu; Zhang, Haifeng; Zeng, Guanghong

    2014-06-01

    By using the microscopic Markov-chain approximation approach, we investigate the epidemic spreading and the responsive immunization in social networks. It is assumed that individual vaccination behavior depends on the local information of an epidemic. Our results suggest that the responsive immunization has negligible impact on the epidemic threshold and the critical value of initial epidemic outbreak, but it can effectively inhibit the outbreak of epidemic. We also analyze the influence of the intervention on the disease dynamics, where the vaccination is available only to those individuals whose number of neighbors is greater than a certain value. Simulation analysis implies that the intervention strategy can effectively reduce the vaccine use under the epidemic control.

  18. Immunization and epidemic threshold of an SIS model in complex networks

    NASA Astrophysics Data System (ADS)

    Wu, Qingchu; Fu, Xinchu

    2016-02-01

    We propose an improved mean-field model to investigate immunization strategies of an SIS model in complex networks. Unlike the traditional mean-field approach, the improved model utilizes the degree information of before and after the immunization. The epidemic threshold of degree-correlated networks can be obtained by linear stability analysis. For degree-uncorrelated networks, the model is reduced to the SIS epidemic model in networks after removing the immunized nodes. Compared to the previous results of random and targeted immunization schemes on degree-uncorrelated networks, we find that the infectious disease has a lower epidemic threshold.

  19. SUPPRESSION OF IDIOTYPIC SPECIFICITIES IN ADULT MICE BY ADMINISTRATION OF ANTIIDIOTYPIC ANTIBODY

    PubMed Central

    Hart, David A.; Wang, Ai-Lan; Pawlak, Laura L.; Nisonoff, Alfred

    1972-01-01

    It has previously been shown that there are extensive idiotypic cross-reactions among antiphenylarsonate antibodies of A/J mice. The present work indicates that administration, into normal, adult A/J mice, of rabbit antiidiotypic antibody directed to A/J antiphenylarsonate antibody suppresses almost completely the subsequent production of antibody of the corresponding idiotype. No effect was noted on the formation of antibodies to the protein carrier or of antiphenylarsonate antibody of a different idiotype. The data are consistent with central suppression of production of the idiotypic antibody mediated through interaction with immunoglobulin receptors on lymphocytes. PMID:4623607

  20. Towards an integrated network of coral immune mechanisms.

    PubMed

    Palmer, C V; Traylor-Knowles, N

    2012-10-22

    Reef-building corals form bio-diverse marine ecosystems of high societal and economic value, but are in significant decline globally due, in part, to rapid climatic changes. As immunity is a predictor of coral disease and thermal stress susceptibility, a comprehensive understanding of this new field will likely provide a mechanistic explanation for ecological-scale trends in reef declines. Recently, several strides within coral immunology document defence mechanisms that are consistent with those of both invertebrates and vertebrates, and which span the recognition, signalling and effector response phases of innate immunity. However, many of these studies remain discrete and unincorporated into the wider fields of invertebrate immunology or coral biology. To encourage the rapid development of coral immunology, we comprehensively synthesize the current understanding of the field in the context of general invertebrate immunology, and highlight fundamental gaps in our knowledge. We propose a framework for future research that we hope will stimulate directional studies in this emerging field and lead to the elucidation of an integrated network of coral immune mechanisms. Once established, we are optimistic that coral immunology can be effectively applied to pertinent ecological questions, improve current prediction tools and aid conservation efforts.

  1. Molecular networks involved in the immune control of BK polyomavirus.

    PubMed

    Girmanova, Eva; Brabcova, Irena; Klema, Jiri; Hribova, Petra; Wohlfartova, Mariana; Skibova, Jelena; Viklicky, Ondrej

    2012-01-01

    BK polyomavirus infection is the important cause of virus-related nephropathy following kidney transplantation. BK virus reactivates in 30%-80% of kidney transplant recipients resulting in BK virus-related nephropathy in 1%-10% of cases. Currently, the molecular processes associated with asymptomatic infections in transplant patients infected with BK virus remain unclear. In this study we evaluate intrarenal molecular processes during different stages of BKV infection. The gene expression profiles of 90 target genes known to be associated with immune response were evaluated in kidney graft biopsy material using TaqMan low density array. Three patient groups were examined: control patients with no evidence of BK virus reactivation (n = 11), infected asymptomatic patients (n = 9), and patients with BK virus nephropathy (n = 10). Analysis of biopsies from asymptomatic viruria patients resulted in the identification of 5 differentially expressed genes (CD3E, CD68, CCR2, ICAM-1, and SKI) (P < 0.05), and functional analysis showed a significantly heightened presence of costimulatory signals (e.g., CD40/CD40L; P < 0.05). Gene ontology analysis revealed several biological networks associated with BKV immune control in comparison to the control group. This study demonstrated that asymptomatic BK viruria is associated with a different intrarenal regulation of several genes implicating in antiviral immune response.

  2. Towards an integrated network of coral immune mechanisms.

    PubMed

    Palmer, C V; Traylor-Knowles, N

    2012-10-22

    Reef-building corals form bio-diverse marine ecosystems of high societal and economic value, but are in significant decline globally due, in part, to rapid climatic changes. As immunity is a predictor of coral disease and thermal stress susceptibility, a comprehensive understanding of this new field will likely provide a mechanistic explanation for ecological-scale trends in reef declines. Recently, several strides within coral immunology document defence mechanisms that are consistent with those of both invertebrates and vertebrates, and which span the recognition, signalling and effector response phases of innate immunity. However, many of these studies remain discrete and unincorporated into the wider fields of invertebrate immunology or coral biology. To encourage the rapid development of coral immunology, we comprehensively synthesize the current understanding of the field in the context of general invertebrate immunology, and highlight fundamental gaps in our knowledge. We propose a framework for future research that we hope will stimulate directional studies in this emerging field and lead to the elucidation of an integrated network of coral immune mechanisms. Once established, we are optimistic that coral immunology can be effectively applied to pertinent ecological questions, improve current prediction tools and aid conservation efforts. PMID:22896649

  3. Anti-idiotypic antibodies function as a surrogate surface epitope of Brugia malayi infective larvae.

    PubMed

    Carlow, C K; Busto, P; Storey, N; Philipp, M

    1990-07-01

    Anti-idiotypic (AB2) antibodies were generated in rabbits following immunization with a murine IgM monoclonal antibody (AB1) recognizing a surface determinant of Brugia malayi infective stage larvae. AB2 specifically inhibited the binding of AB1 to B. malayi larvae. Furthermore, AB2 had the ability to mimic the original antigen since mice immunized with AB2 possessed serum antibodies (AB3) specific for the B. malayi surface determinant. The presence of anti-surface antibodies (AB3 and AB1) induced either by AB2 immunization or by administration of AB1, did not alter the outcome of an intraperitoneal infection of B. malayi larvae in BABL/c mice when compared to untreated animals. AB3 antibodies like AB1, were IgM, thus indicating an isotype restricted response to the B. malayi epitope. There were no detectable cell mediated responses to the surface determinant in mice immunized with AB2, assessed by lymphocyte blastogenesis or IL3 production in vitro in response to the idiotope as presented by living larvae. The lack of cellular responses and/or the previously demonstrated rapid shedding of the epitope may explain the inability of AB1 or AB2 to protect mice against larval challenge in this study.

  4. Immune networks: multi-tasking capabilities at medium load

    NASA Astrophysics Data System (ADS)

    Agliari, E.; Annibale, A.; Barra, A.; Coolen, A. C. C.; Tantari, D.

    2013-08-01

    Associative network models featuring multi-tasking properties have been introduced recently and studied in the low-load regime, where the number P of simultaneously retrievable patterns scales with the number N of nodes as P ˜ log N. In addition to their relevance in artificial intelligence, these models are increasingly important in immunology, where stored patterns represent strategies to fight pathogens and nodes represent lymphocyte clones. They allow us to understand the crucial ability of the immune system to respond simultaneously to multiple distinct antigen invasions. Here we develop further the statistical mechanical analysis of such systems, by studying the medium-load regime, P ˜ Nδ with δ ∈ (0, 1]. We derive three main results. First, we reveal the nontrivial architecture of these networks: they exhibit a high degree of modularity and clustering, which is linked to their retrieval abilities. Second, by solving the model we demonstrate for δ < 1 the existence of large regions in the phase diagram where the network can retrieve all stored patterns simultaneously. Finally, in the high-load regime δ = 1 we find that the system behaves as a spin-glass, suggesting that finite-connectivity frameworks are required to achieve effective retrieval.

  5. Anti-bevacizumab idiotype antibody vaccination is effective in inducing vascular endothelial growth factor-binding response, impairing tumor outgrowth.

    PubMed

    Sanches, Jéssica de Souza; de Aguiar, Rodrigo Barbosa; Parise, Carolina Bellini; Suzuki, Juliana Mayumi; Chammas, Roger; de Moraes, Jane Zveiter

    2016-04-01

    Tumors require blood supply and, to overcome this restriction, induce angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in this process, which explains the great number of antiangiogenic therapies targeting VEGF. The research and development of targeted therapy has led to the approval of bevacizumab, a humanized anti-VEGF monoclonal antibody (mAb), in clinical settings. However, side effects have been reported, usually as a consequence of bolus-dose administration of the antibody. This limitation could be circumvented through the use of anti-idiotype (Id) antibodies. In the present study, we evaluated the efficacy of an active VEGF-binding immune response generated by an anti-bevacizumab idiotype mAb, 10.D7. The 10.D7 anti-Id mAb vaccination led to detectable levels of VEGF-binding anti-anti-Id antibodies. In order to examine whether this humoral immune response could have implications for tumor development, 10.D7-immunized mice were challenged with B16-F10 tumor cells. Mice immunized with 10.D7 anti-Id mAb revealed reduced tumor growth when compared to control groups. Histological analyses of tumor sections from 10.D7-immunized mice showed increased necrotic areas, decreased CD31-positive vascular density and reduced CD68-positive cell infiltration. Our results encourage further therapeutic studies, particularly if one considers that the anti-Id therapeutic vaccination maintains stable levels of VEGF-binding antibodies, which might be useful in the control of tumor relapse.

  6. Characterization of a purified nicotinic receptor from rat brain by using idiotypic and anti-idiotypic antibodies

    SciTech Connect

    Abood, L.G.; Langone, J.J.; Bjercke, R.; Lu, X.; Banerjee, S.

    1987-09-01

    The availability of an anti-nicotine monoclonal antibody has made it possible to further establish the nature of the nicotine recognition proteins purified from rat brain by affinity chromatography and to provide a highly sensitive assay for determining (/sup 3/H)nicotine binding to the purified material. An enantiomeric analogue of nicotine. (-)-6-hydroxymethylnicotine, was used to prepare the affinity column. In addition, with the use of an anti-idiotypic monoclonal antibody, it was confirmed that the recognition site for nicotine resides on a protein complex composed of two components with molecular masses of 62 and 57 kDa. It was also demonstrated that the same two proteins could be purified by immunoaffinity chromatography with the use of an anti-idiotypic monoclonal antibody. With the use of the anti-nicotine antibody to measure (/sup 3/H)nicotine binding, the purified material was shown to bind 250 pmol/mg of protein. By utilizing a procedure in which the purified receptor protein was conjugated to membranes by disulfide bonds, a binding activity of 80 pmol/mg was obtained. With the availability of sterospecific monoclonal antibodies to (-)-nicotine as well as monoclonal anti-idiotypic antibodies derived when the anti-nicotine antibodies were used as immunogens, additional procedures became available for the further characterization of the purified nicotine receptor and examining its (-)-(/sup 3/H)nicotine-binding characteristics.

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

    NASA Astrophysics Data System (ADS)

    Bellingeri, Michele; Agliari, Elena; Cassi, Davide

    2015-10-01

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

  8. Reconfiguration of the immune system network during food limitation in the caterpillar Manduca sexta.

    PubMed

    Adamo, Shelley A; Davies, Gillian; Easy, Russell; Kovalko, Ilya; Turnbull, Kurtis F

    2016-03-01

    Dwindling resources might be expected to induce a gradual decline in immune function. However, food limitation has complex and seemingly paradoxical effects on the immune system. Examining these changes from an immune system network perspective may help illuminate the purpose of these fluctuations. We found that food limitation lowered long-term (i.e. lipid) and short-term (i.e. sugars) energy stores in the caterpillar Manduca sexta. Food limitation also: altered immune gene expression, changed the activity of key immune enzymes, depressed the concentration of a major antioxidant (glutathione), reduced resistance to oxidative stress, reduced resistance to bacteria (Gram-positive and -negative bacteria) but appeared to have less effect on resistance to a fungus. These results provide evidence that food limitation led to a restructuring of the immune system network. In severely food-limited caterpillars, some immune functions were enhanced. As resources dwindled within the caterpillar, the immune response shifted its emphasis away from inducible immune defenses (i.e. those responses that are activated during an immune challenge) and increased emphasis on constitutive defenses (i.e. immune components that are produced consistently). We also found changes suggesting that the activation threshold for some immune responses (e.g. phenoloxidase) was lowered. Changes in the configuration of the immune system network will lead to different immunological strengths and vulnerabilities for the organism.

  9. Reconfiguration of the immune system network during food limitation in the caterpillar Manduca sexta.

    PubMed

    Adamo, Shelley A; Davies, Gillian; Easy, Russell; Kovalko, Ilya; Turnbull, Kurtis F

    2016-03-01

    Dwindling resources might be expected to induce a gradual decline in immune function. However, food limitation has complex and seemingly paradoxical effects on the immune system. Examining these changes from an immune system network perspective may help illuminate the purpose of these fluctuations. We found that food limitation lowered long-term (i.e. lipid) and short-term (i.e. sugars) energy stores in the caterpillar Manduca sexta. Food limitation also: altered immune gene expression, changed the activity of key immune enzymes, depressed the concentration of a major antioxidant (glutathione), reduced resistance to oxidative stress, reduced resistance to bacteria (Gram-positive and -negative bacteria) but appeared to have less effect on resistance to a fungus. These results provide evidence that food limitation led to a restructuring of the immune system network. In severely food-limited caterpillars, some immune functions were enhanced. As resources dwindled within the caterpillar, the immune response shifted its emphasis away from inducible immune defenses (i.e. those responses that are activated during an immune challenge) and increased emphasis on constitutive defenses (i.e. immune components that are produced consistently). We also found changes suggesting that the activation threshold for some immune responses (e.g. phenoloxidase) was lowered. Changes in the configuration of the immune system network will lead to different immunological strengths and vulnerabilities for the organism. PMID:26747906

  10. Influence of dynamic immunization on epidemic spreading in networks

    NASA Astrophysics Data System (ADS)

    Wu, Qingchu; Fu, Xinchu; Jin, Zhen; Small, Michael

    2015-02-01

    We introduce a new dynamic immunization method based on the static immunization algorithm and study the relationship between dynamic and static immunization. By nodes to be immunized according to static immunization strategies, we build a connection between dynamic and static immunization. Using theoretical arguments and computational simulation we show that dynamic immunization (from a finite vaccine reservoir) is not sufficient to prevent epidemic outbreak, nor does it significantly change the asymptotic prevalence. Nonetheless, we do find that less total vaccine is required to implement this strategy. To help understand this better, we examine the extent and distribution of dynamic immunization required to achieve this reduced vaccine demand. Our results suggest that it is not necessary to increase the immunization rate when the infection rate is relatively small.

  11. Sensitive detection of idiotypic platelet-reactive alloantibodies by an electrical protein chip.

    PubMed

    Quiel, Annett; Jürgen, Britta; Greinacher, Andreas; Lassen, Susan; Wörl, Ralf; Witt, Sabine; Schweder, Thomas

    2012-01-01

    To prevent and treat immune-mediated platelet disorders (e.g. neonatal allo-immune thrombocytopenia and platelet transfusion refractoriness) the causative idiotypic platelet-reactive antibodies have to be detected with high sensitivity and specificity. The "Monoclonal Antibody Immobilization Platelet Assay" (MAIPA) is the diagnostic gold standard for immunotyping sera with respect to alloantibodies against human platelet antigens (HPA). However, it is labor-intensive and time-consuming. In this work, an automated protein chip assay (enzyme-linked sandwich immunoassay) based on interdigitated gold microelectrodes in combination with an electrical read-out system was developed and optimized. For this purpose, specific capture antibodies were immobilized on the gold electrodes. The binding of the target is detected via an enzyme-labeled detection antibody by a redox-recycling process that corresponds to the amount of bound target molecule. With this electrical chip assay it is possible to detect antibodies against HPA-1a, HPA-5b and HLA with high sensitivity and specificity in less than half the duration of the MAIPA protocol with similar intra- and interassay variance. PMID:22572157

  12. Sensitive detection of idiotypic platelet-reactive alloantibodies by an electrical protein chip.

    PubMed

    Quiel, Annett; Jürgen, Britta; Greinacher, Andreas; Lassen, Susan; Wörl, Ralf; Witt, Sabine; Schweder, Thomas

    2012-01-01

    To prevent and treat immune-mediated platelet disorders (e.g. neonatal allo-immune thrombocytopenia and platelet transfusion refractoriness) the causative idiotypic platelet-reactive antibodies have to be detected with high sensitivity and specificity. The "Monoclonal Antibody Immobilization Platelet Assay" (MAIPA) is the diagnostic gold standard for immunotyping sera with respect to alloantibodies against human platelet antigens (HPA). However, it is labor-intensive and time-consuming. In this work, an automated protein chip assay (enzyme-linked sandwich immunoassay) based on interdigitated gold microelectrodes in combination with an electrical read-out system was developed and optimized. For this purpose, specific capture antibodies were immobilized on the gold electrodes. The binding of the target is detected via an enzyme-labeled detection antibody by a redox-recycling process that corresponds to the amount of bound target molecule. With this electrical chip assay it is possible to detect antibodies against HPA-1a, HPA-5b and HLA with high sensitivity and specificity in less than half the duration of the MAIPA protocol with similar intra- and interassay variance.

  13. Functional idiotypic mimicry of an adhesion- and differentiation-promoting site on acetylcholinesterase.

    PubMed

    Johnson, Glynis; Moore, Samuel W

    2004-04-01

    Acetylcholinesterase mediates cell adhesion and neurite outgrowth through a site associated with the peripheral anionic site (PAS). Monoclonal antibodies raised to this site block cell adhesion. We have raised anti-idiotypic antibodies to one of these antibodies. The anti-idiotypic antibodies recognized the immunogenic antibody and non-specific mouse IgG, but not acetylcholinesterase. Five antibodies (out of 143 clones, an incidence of 3.5%) were able to promote neurite outgrowth in human neuroblastoma cells in vitro in a similar manner to acetylcholinesterase itself, suggesting that these antibodies carry an internal image of the neuritogenic site. Two of the antibodies were significantly more effective (P < 0.01) than acetylcholinesterase in this regard. The antibodies also bound specifically to mouse laminin-1 and human collagen IV, as does acetylcholinesterase. This binding was displaced by unlabelled antibody, as well as by acetylcholinesterase itself, indicating competition with acetylcholinesterase. We have also investigated the development of anti-anti-idiotypic antibodies in mice in vivo, and have observed that four of these (out of 318 clones, an incidence of 1.26%) mimic the idiotypic antibody and abrogate adhesion in neuroblastoma cells. We have thus demonstrated functional mimicry of the neuritogenic site on acetylcholinesterase in anti-idiotypic antibodies, enhancement of this activity in one antibody, and mimicry of the idiotypic antibody site in anti-anti-idiotypic antibodies. Implications of these findings for differentiation-promoting cancer therapy are discussed.

  14. Formation and Stability of a Memory State in the Immune Network

    NASA Astrophysics Data System (ADS)

    Sonoda, Takashi

    1992-04-01

    The immune system is investigated as a complex adaptive network. A nonlinear dynamical model is proposed to study roles of lymphocyte and antibody in the regulation of the immune response. Three kinds of lymphocytes; B cell, TH cell, and TS cell, interact and compose a functional unit. Furthermore this unit interacts with other units through antibodies. These two types of interactions cooperatively work and regulate the immune response. The model can explain how the memory state is formed and stabilized in the immune network. Behaviors of the model are verified by the computer simulations.

  15. Yeast killer toxin-like candidacidal Ab6 antibodies elicited through the manipulation of the idiotypic cascade.

    PubMed

    Polonelli, Luciano; Beninati, Concetta; Teti, Giuseppe; Felici, Franco; Ciociola, Tecla; Giovati, Laura; Sperindè, Martina; Lo Passo, Carla; Pernice, Ida; Domina, Maria; Arigò, Milena; Papasergi, Salvatore; Mancuso, Giuseppe; Conti, Stefania; Magliani, Walter

    2014-01-01

    A mouse anti-anti-anti-idiotypic (Id) IgM monoclonal antibody (mAb K20, Ab4), functionally mimicking a Wyckerhamomyces anomalus (Pichia anomala) killer toxin (KT) characterized by fungicidal activity against yeasts presenting specific cell wall receptors (KTR) mainly constituted by β-1,3-glucan, was produced from animals presenting anti-KT Abs (Ab3) following immunization with a rat IgM anti-Id KT-like mAb (mAb K10, Ab2). MAb K10 was produced by immunization with a KT-neutralizing mAb (mAb KT4, Ab1) bearing the internal image of KTR. MAb K20, likewise mAb K10, proved to be fungicidal in vitro against KT-sensitive Candida albicans cells, an activity neutralized by mAb KT4, and was capable of binding to β-1,3-glucan. MAb K20 and mAb K10 competed with each other and with KT for binding to C. albicans KTR. MAb K20 was used to identify peptide mimics of KTR by the selection of phage clones from random peptide phage display libraries. Using this strategy, four peptides (TK 1-4) were selected and used as immunogen in mice in the form of either keyhole limpet hemocyanin (KLH) conjugates or peptide-encoding minigenes. Peptide and DNA immunization could induce serum Abs characterized by candidacidal activity, which was inhibited by laminarin, a soluble β-1,3-glucan, but not by pustulan, a β-1,6-glucan. These findings show that the idiotypic cascade can not only overcome the barrier of animal species but also the nature of immunogens and the type of technology adopted. PMID:25162681

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  17. Demonstration of anti-idiotypic antibodies directed against IgM rheumatoid factor in the serum of rheumatoid arthritis patients.

    PubMed Central

    Hancock, W K; Barnett, E V

    1989-01-01

    We have identified the presence of anti-idiotypic activity against IgMRF in the sera of RA patients. Only patients seropositive for IgMRF had significant levels of anti-idiotypic activity, while seronegative patients and normal volunteers did not. When this anti-idiotypic activity was affinity-purified from a single RA patient, two separate binding activities were identified. IgG antibodies were pepsin-digested to F(ab')2 fragments before affinity-purification to remove the Fc portion capable of binding to IgMRF. Anti-idiotypic F(ab')2 fragments of IgG were eluted from an IgMRF-Sepharose 4B column. These F(ab')2 bound preferentially to IgMRF bearing an idiotype recognized by the anti-idiotypic murine monoclonal 17.109. A second anti-idiotypic F(ab')2 was affinity purified using rabbit anti-human Fc antibody bound to Sepharose 4B. These eluted antibodies behaved as the internal image of IgG, binding five out of seven IgMRF's tested. The binding of both anti-idiotypic F(ab')2 was inhibited with human IgG. The presence of both IgMRF and anti-idiotypic antibodies directed against it in the sera of RA patients suggests that anti-idiotypic antibodies alone are not capable of inhibiting the production of rheumatoid factor. PMID:2702773

  18. Further studies on the problem of immune network modelling.

    PubMed

    Faro, J; Carneiro, J; Velasco, S

    1997-02-21

    In a previous work we have analysed a family of antibody and B-cell network models (basic AB models) of the immune system. This analysis focused principally on the physiological interpretation of their parameters. Our approach consisted in building a detailed and general mathematical model (referred to as the GIB model) and then simplifying it formally to a version (named the RIB model) that belongs to the family of AB models, but which is more general than the basic AB models. From that study it was clear that some of the assumptions necessary to simplify the GIB model into the RIB one, as well as to recover the basic AB models from the RIB one, are quite unrealistic from a physiological point of view. All this raised the issue of the reliability, or even the heuristic value, of theoretical studies based on current network models for experimental immunologists. One approach to clarify this issue is to ask whether the unrealism of the assumptions implicit in the RIB and AB models entails qualitatively different behaviours between them compared to the GIB one. We initiate here such a work by performing a comparative study of a two-clone system of the AB and RIB models, and a variant of the GIB model in which the different molecular compartments were merged into a single one (labelled IGB model). Because all those models rely critically on certain B-cell activation functions, which constitute the core of an implicit model of individual B-cell reactivity or "local rules", we focused the present numerical study, to a great extent, on two parameters determining those activation functions (Hill coefficient and thresholds). Our results indicate that: (1) the RIB and IGB models display in general a much larger diversity of steady states than the AB models; (2) only under a very restricted parameter regime did all studied models behave similarly; (3) the parameter regime under which the AB and IGB models, but not the RIB one, behave similarly is still rather restricted

  19. Clonal deletion of specific thymocytes by an immunoglobulin idiotype.

    PubMed Central

    Bogen, B; Dembic, Z; Weiss, S

    1993-01-01

    We have investigated whether immunoglobulin can induce clonal deletion of thymocytes by employing two strains of transgenic mice. One strain is transgenic for an alpha/beta T cell receptor (TCR) which recognizes a processed idiotypic peptide of the lambda 2(315) light chain variable region, bound to the I-Ed class II major histocompatibility complex molecule. The other mouse strain is transgenic for the lambda 2(315) gene. Double transgenic offspring from a TCR-transgenic female mated with a lambda 2(315) transgenic male exhibit a pronounced clonal deletion of CD4+CD8+ thymocytes. Analysis of neonates from the reciprocal (lambda 2(315)-transgenic female x TCR-transgenic male) cross suggests that the deletion in double transgenic offspring most likely is caused by lambda 2(315) produced within the thymus rather than by maternally derived IgG, lambda 2(315). Nevertheless, IgG, lambda 2(315) can cause deletion of CD4+CD8+ thymocytes when injected in large amounts intraperitoneally into either adult or neonatal TCR-transgenic mice. Deletion is evident 48 and 72 h after injection, but by day 7 the thymus has already regained its normal appearance. A serum concentration of several hundred microgram/ml is required for deletion to be observed. Therefore, the heterogeneous idiotypes of serum Ig are probably each of too low concentration to cause thymocyte deletion in normal animals. Images PMID:8428591

  20. Neuroendocrine and immune network re-modeling in chronic fatigue syndrome: an exploratory analysis.

    PubMed

    Fuite, Jim; Vernon, Suzanne D; Broderick, Gordon

    2008-12-01

    This work investigates the significance of changes in association patterns linking indicators of neuroendocrine and immune activity in patients with chronic fatigue syndrome (CFS). Gene sets preferentially expressed in specific immune cell isolates were integrated with neuroendocrine data from a large population-based study. Co-expression patterns linking immune cell activity with hypothalamic-pituitary-adrenal (HPA), thyroidal (HPT) and gonadal (HPG) axis status were computed using mutual information criteria. Networks in control and CFS subjects were compared globally in terms of a weighted graph edit distance. Local re-modeling of node connectivity was quantified by node degree and eigenvector centrality measures. Results indicate statistically significant differences between CFS and control networks determined mainly by re-modeling around pituitary and thyroid nodes as well as an emergent immune sub-network. Findings align with known mechanisms of chronic inflammation and support possible immune-mediated loss of thyroid function in CFS exacerbated by blunted HPA axis responsiveness.

  1. Idiotypic mimicry and the assembly of a supramolecular structure: an anti-idiotypic antibody that mimics taxol in its tubulin-microtubule interactions.

    PubMed Central

    Leu, J G; Chen, B X; Diamanduros, A W; Erlanger, B F

    1994-01-01

    Taxol, originally extracted from the bark of the western yew, Taxus brevifolia, is reportedly the first of a new class of anti-cancer agents. It acts by promoting and irreversibly stabilizing microtubule assembly, thus interfering with the dynamic processes required for cell viability and multiplication. With the aim of using immunological techniques to study the mechanism of action of taxol, a monoclonal anti-idiotypic antibody that mimics taxol was prepared, using an auto-anti-idiotypic strategy. It and its Fab fragment inhibited the binding of [3H]taxol to microtubules. Moreover, like taxol, both promoted the assembly of tubulin into microtubules. These findings provide an example of an anti-idiotypic antibody capable of assembling an organized supramolecular structure from soluble cellular components. In addition, it further establishes the ability of anti-idiotypic antibodies to be functional mimics of ligand molecules bearing no structural similarity to immunoglobulins. The variable regions of the antibody have been sequenced. With the exception of the complementarity-determining region 3, the sequence of the heavy chain variable region is strikingly similar to that of an anti-idiotypic antibody raised to anti-insulin. The finding that a polypeptide can mimic taxol raises the possibility that taxol acts as a peptidomimetic compound that interferes with the function of an endogenous polypeptide. Images PMID:7840821

  2. Anti-idiotypic nanobody as citrinin mimotope from a naive alpaca heavy chain single domain antibody library.

    PubMed

    Xu, Yang; Xiong, Liang; Li, Yanping; Xiong, Yonghua; Tu, Zhui; Fu, Jinheng; Chen, Bo

    2015-07-01

    Compared with peptide-based mimotope, anti-idiotypic antibodies (AIds) are considered as promising biosynthetic surrogate antigen because these antibodies display stable protein conformation. Nevertheless, conventional AIds are generated by immunizing animals with heterologous idiotypic antibody in vivo; isolated AIds commonly exhibit a higher affinity to primary antibodies than target analytes because AIds undergo an affinity-matured process during immune responses, resulting in low sensitivity in competitive immunoassay. In the present study, an anti-citrinin monoclonal antibody (anti-CIT McAb) was designed as primary antibody; one β-type AI alpaca heavy chain single domain antibody (β-AI VHH) was selected as a citrinin (CIT) surrogate from a naive phage-displayed VHH library. The affinity constant (K D) of obtained β-AI VHH to anti-CIT McAb (160 nM) is 2.35 times lower than that of CIT and ovalbumin conjugates (CIT-OVA) to anti-CIT McAb (68 nM). The developed VHH-based enzyme-linked immunosorbent assay (V-ELISA) can be used to perform dynamic linear detection of CIT in 10% (v/v) methanol/PBS from 5.0 to 300.0 ng/mL, with a median inhibitory concentration (IC50) of 44.6 ng/mL (n = 3); this result was twice as good as that of indirect competitive ELISA (ic-ELISA, IC50 = 96.2 ng/mL) with CIT-OVA as a coating antigen. Moreover, the precision of V-ELISA was evaluated by analyzing average recoveries and coefficient of variations of CIT-spiked cereal sample; the reliability of V-ELISA was also validated with a conventional ic-ELISA. In summary, the proposed strategy has a great potential for panning other β-AI VHH toward small organic molecules from a naive VHH library.

  3. Revealing Shared and Distinct Gene Network Organization in Arabidopsis Immune Responses by Integrative Analysis1

    PubMed Central

    Dong, Xiaobao; Jiang, Zhenhong; Peng, You-Liang; Zhang, Ziding

    2015-01-01

    Pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) are two main plant immune responses to counter pathogen invasion. Genome-wide gene network organizing principles leading to quantitative differences between PTI and ETI have remained elusive. We combined an advanced machine learning method and modular network analysis to systematically characterize the organizing principles of Arabidopsis (Arabidopsis thaliana) PTI and ETI at three network resolutions. At the single network node/edge level, we ranked genes and gene interactions based on their ability to distinguish immune response from normal growth and successfully identified many immune-related genes associated with PTI and ETI. Topological analysis revealed that the top-ranked gene interactions tend to link network modules. At the subnetwork level, we identified a subnetwork shared by PTI and ETI encompassing 1,159 genes and 1,289 interactions. This subnetwork is enriched in interactions linking network modules and is also a hotspot of attack by pathogen effectors. The subnetwork likely represents a core component in the coordination of multiple biological processes to favor defense over development. Finally, we constructed modular network models for PTI and ETI to explain the quantitative differences in the global network architecture. Our results indicate that the defense modules in ETI are organized into relatively independent structures, explaining the robustness of ETI to genetic mutations and effector attacks. Taken together, the multiscale comparisons of PTI and ETI provide a systems biology perspective on plant immunity and emphasize coordination among network modules to establish a robust immune response. PMID:25614062

  4. Neonatal Idiotypic Exposure Alters Subsequent Cytokine, Pathology, and Survival Patterns in Experimental Schistosoma mansoni Infections

    PubMed Central

    Angela Montesano, M.; Colley, Daniel G.; Eloi-Santos, Silvana; Freeman, George L.; Secor, W. Evan

    1999-01-01

    Exposure to maternal idiotypes (Ids) or antigens might predispose a child to develop an immunoregulated, asymptomatic clinical presentation of schistosomiasis. We have used an experimental murine system to address the role of Ids in this immunoregulation. Sera from mice with 8-wk Schistosoma mansoni infection, chronic (20-wk infection) moderate splenomegaly syndrome (MSS), or chronic hypersplenomegaly syndrome (HSS) were passed over an S. mansoni soluble egg antigen (SEA) immunoaffinity column to prepare Ids (8WkId, MSS Id, HSS Id). Newborn mice were injected with 8WkId, MSS Id, HSS Id, or normal mouse immunoglobulin (NoMoIgG) and infected with S. mansoni 8 wk later. Mice exposed to 8WkId or MSS Id as newborns had prolonged survival and decreased morbidity compared with mice that received HSS Id or NoMoIgG. When stimulated with SEA, 8WkId, or MSS Id, spleen cells from mice neonatally injected with 8WkId or MSS Id produced more interferon γ than spleen cells from mice neonatally injected with HSS Id or NoMoIgG. Furthermore, neonatal exposure to 8WkId or MSS Id, but not NoMoIgG or HSS Id, led to significantly smaller granuloma size and lower hepatic fibrosis levels in infected mice. Together, these results indicate that perinatal exposure to appropriate anti-SEA Ids induces long-term effects on survival, pathology, and immune response patterns in mice subsequently infected with S. mansoni. PMID:9989978

  5. Induction of IgG antibodies by an anti-idiotype antibody mimicking disialoganglioside GD2.

    PubMed

    Sen, G; Chakraborty, M; Foon, K A; Reisfeld, R A; Bhattacharya-Chatterjee, M B

    1998-01-01

    The anti-idiotype (Id) monoclonal antibody (mAb) 1A7 immunoglobulin G1 (IgG1, kappa), raised in syngeneic mice against the murine anti-ganglioside GD2 mAb 14G2a mimics a carbohydrate epitope on GD2 and serves as a surrogate protein antigen for this disialoganglioside. Immunization of allogeneic C57BL/6 mice and rabbits with 1A7 induced anti-GD2 antibodies of IgG isotype that recognize purified GD2 by enzyme-linked immunosorbent assay (ELISA) and GD2-positive human melanoma cells (M21/P6) by fluorescence-activated cell sorter (FACS) analysis. The specificity of the antisera for GD2 was further confirmed by dot-blot analysis. These antisera also specifically lyse GD2-positive M21/P6 target cells in an antibody-dependent cellular cytotoxicity assay. Taken together, these results suggest that the anti-Id 1A7 can induce GD2-specific IgG antibodies that can recognize cell surface-associated as well as soluble disialoganglioside GD2. PMID:9456440

  6. Cytotoxic effect of anti-idiotype antibody-chlorambucil conjugates against human lymphoblastoid cells.

    PubMed

    Tung, E; Goust, J M; Chen, W Y; Kang, S S; Wang, I Y; Wang, A C

    1983-09-01

    The secreted IgMs of two human lymphoblastoid cell lines, RPMI-6410 and RPMI-8392, were purified. Antisera against these two IgMs were raised in rabbits and made idiotypically specific to the respective antigens through various absorption procedures. By immunofluorescence and radioimmunoassay techniques, the purified anti-idiotype antibodies were found to react also with the membrane Igs of the respective cell lines, but not with those of other cell lines. The purified anti-idiotype antibodies were then coupled with Chlorambucil to form antibody-drug conjugates, whose effectiveness in the in-vitro killing of target cells was evaluated by a chromium-release cytotoxicity assay. The results showed that these anti-idiotype antibody-Chlorambucil conjugates were specifically cytotoxic to lymphoblastoid cells that bore membrane Igs carrying the respective idiotypic determinant(s). Furthermore, the conjugates were far more effective in causing cytolysis to the target cells than either Chlorambucil or the anti-idiotype antibodies alone. PMID:6350169

  7. Cytotoxic effect of anti-idiotype antibody-chlorambucil conjugates against human lymphoblastoid cells.

    PubMed Central

    Tung, E; Goust, J M; Chen, W Y; Kang, S S; Wang, I Y; Wang, A C

    1983-01-01

    The secreted IgMs of two human lymphoblastoid cell lines, RPMI-6410 and RPMI-8392, were purified. Antisera against these two IgMs were raised in rabbits and made idiotypically specific to the respective antigens through various absorption procedures. By immunofluorescence and radioimmunoassay techniques, the purified anti-idiotype antibodies were found to react also with the membrane Igs of the respective cell lines, but not with those of other cell lines. The purified anti-idiotype antibodies were then coupled with Chlorambucil to form antibody-drug conjugates, whose effectiveness in the in-vitro killing of target cells was evaluated by a chromium-release cytotoxicity assay. The results showed that these anti-idiotype antibody-Chlorambucil conjugates were specifically cytotoxic to lymphoblastoid cells that bore membrane Igs carrying the respective idiotypic determinant(s). Furthermore, the conjugates were far more effective in causing cytolysis to the target cells than either Chlorambucil or the anti-idiotype antibodies alone. PMID:6350169

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

    PubMed

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Zu, Yun-Xiao; Zhou, Jie

    2012-01-01

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

  10. Security framework for networked storage system based on artificial immune system

    NASA Astrophysics Data System (ADS)

    Huang, Jianzhong; Xie, Changsheng; Zhang, Chengfeng; Zhan, Ling

    2007-11-01

    This paper proposed a theoretical framework for the networked storage system addressing the storage security. The immune system is an adaptive learning system, which can recognize, classify and eliminate 'non-self' such as foreign pathogens. Thus, we introduced the artificial immune technique to the storage security research, and proposed a full theoretical framework for storage security system. Under this framework, it is possible to carry out the quantitative evaluation for the storage security system using modeling language of artificial immune system (AIS), and the evaluation can offer security consideration for the deployment of networked storage system. Meanwhile, it is potential to obtain the active defense technique suitable for networked storage system via exploring the principle of AIS and achieve a highly secure storage system with immune characteristic.

  11. Propagation and immunization of infection on general networks with both homogeneous and heterogeneous components

    NASA Astrophysics Data System (ADS)

    Liu, Zonghua; Lai, Ying-Cheng; Ye, Nong

    2003-03-01

    We consider the entire spectrum of architectures of general networks, ranging from being heterogeneous (scale-free) to homogeneous (random), and investigate the infection dynamics by using a three-state epidemiological model that does not involve the mechanism of self-recovery. This model is relevant to realistic situations such as the propagation of a flu virus or information over a social network. Our heuristic analysis and computations indicate that (1) regardless of the network architecture, there exists a substantial fraction of nodes that can never be infected and (2) heterogeneous networks are relatively more robust against spreads of infection as compared with homogeneous networks. We have also considered the problem of immunization for preventing wide spread of infection, with the result that targeted immunization is effective for heterogeneous networks.

  12. Development of non-toxic (anti-idiotypic) mucosal vaccines to block the absorption of the chemical carcinogen 2-acetylaminofluorene (AAF)

    SciTech Connect

    Silbart, L.K.; Keren, D.F.; McDonald, R.A.; Goslinoski, L.; Brownlee, B.E.; Lash, C.; Smart, J.B. )

    1991-03-15

    One difficulty in developing mucosal vaccines to block carcinogen absorption has been the necessity of using carcinogen, or closely related structural analogs, coupled to carrier proteins in the vaccine preparation. The authors have developed anti-idiotypic (anti-Id) antibodies capable of mimicking the carcinogenic epitope. Anti-AAF antibodies (Ab{sub 1}) were prepared from three different sources. Groups of four female BALB/c mice were immunized intramuscularly with 50 ug of either the rabbit polyclonal IgG anti-AAF, or the most anti-AAF monoclonal IgG{sub 1}-KLH conjugate in a 50:50 emulsion of complete Freund's adjuvant; booster doses were given four weeks later. A third group of two mice was immunized with approximately 1 ug of affinity-purified rat IgG anti-AAF, and boosted four weeks later, then one year later. Retro-orbital blood samples were collected and assayed for anti-Id activity by ELISA. Although all three groups produced anti-idiotypic antibodies, the strongest response was observed in mice receiving the affinity-purified polyclonal rat IgG anti-AAF. Once anti-Id producing hybridoma clones have been isolated, the anti-Id antibodies will replace the carcinogen in vaccine preparations designed to elicit anti-carcinogen antibodies.

  13. Enhanced antigen-antibody binding affinity mediated by an anti-idiotypic antibody

    SciTech Connect

    Sawutz, D.G.; Koury, R.; Homcy, C.J.

    1987-08-25

    The authors previously described the production of four monoclonal antibodies to the ..beta..-adrenergic receptor antagonist alprenolol. One of these antibodies, 5B7 (IgG/sub 2a/, kappa), was used to raise anti-idiotypic antisera in rabbits. In contrast to the expected results, one of the anti-idiotypic antisera (R9) promotes (/sup 125/I)iodocyanopinodolol (ICYP) binding to antibody 5B7. In the presence of R9, the dissociation constant decreases 100-fold from 20 to 0.3 nM. This increase in binding affinity of antibody 5B7 for ICYP is not observed in the presence of preimmune, rabbit anti-mouse or anti-idiotypic antisera generated to a monoclonal antibody of a different specificity. Furthermore, R9 in the absence of 5B7 does not bind ICYP. The F(ab) fragments of 5B7 and T9 behaved in a similar manner, and the soluble complex responsible for the high-affinity interaction with ICYP can be identified by gel filtration chromatography. The elution position of the complex is consistent with a 5B7 F(ab)-R9 F(ab) dimer, indicating that polyvalency is not responsible for the enhanced ligand binding. Kinetic analysis of ICYP-5B7 binding revealed that the rate of ICYP dissociation from 5B7 in the presence of R9 is approximately 100 times slower than in the absence of R9, consistent with the 100-fold change in binding affinity of 5B7 for ICYP. The available data best fit a model in which an anti-idiotypic antibody binds at or near the binding site of the idiotype participating in the formation of a hybrid ligand binding site. This would allow increased contact of the ligand with the idiotype-anti-idiotype complex and result in an enhanced affinity of the ligand interaction.

  14. Immunization

    MedlinePlus

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

  15. Immunizations

    MedlinePlus

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

  16. Antibodies to Trypanosoma cruzi express idiotypic patterns that can differentiate between patients with asymptomatic or severe Chagas' disease.

    PubMed

    Reis, D D; Gazzinelli, R T; Gazzinelli, G; Colley, D G

    1993-02-15

    Immunization of rabbits with pools of immunoaffinity-purified anti-Trypanosoma cruzi epimastigote antibodies derived from patients with different clinical forms of Chagas' disease induces antiidiotypic sera that can distinguish between anti-epimastigote antibodies from patients with asymptomatic (indeterminate (IND)) or severe (cardiac (CARD)) Chagas' disease. These idiotypically different anti-EPI antibodies from patients with the different clinical forms do not differ in their anti-epimastigote activities or isotypes. Analysis of immunoaffinity purified antibodies from individual chagasic patients by specific competitive ELISA generally confirms that Id-specific rabbit antisera can differentiate the clinical forms of the source of the antibodies. Based on these data, immunoaffinity-purified antibodies from patients share many Id with those from IND patients, although antibodies from IND patients express much lower levels of the distinctive Id characteristic of CARD patients. Reduction and alkylation of antibodies from IND patients reduces somewhat, but does not abolish, the ability of their Id to be recognized idiotypically, and to effectively inhibit in competitive ELISA. In contrast, reduction and alkylation of antibodies from CARD patients almost completely eliminates the ability of their predominant Id to be either recognized by, or inhibit, the appropriate systems. These data imply that the expression of the major Id that define CARD patients by these serologic anti-Id systems is largely dependent on the tertiary conformation of the Ig molecule. This agrees with our earlier studies on the respective differential abilities of CARD vs IND Id to stimulate anti-Id T cells by direct stimulation vs processing and presentation mechanisms.

  17. The simple neuroendocrine-immune regulatory network in oyster Crassostrea gigas mediates complex functions

    NASA Astrophysics Data System (ADS)

    Liu, Zhaoqun; Wang, Lingling; Zhou, Zhi; Sun, Ying; Wang, Mengqiang; Wang, Hao; Hou, Zhanhui; Gao, Dahai; Gao, Qiang; Song, Linsheng

    2016-05-01

    The neuroendocrine-immune (NEI) regulatory network is a complex system, which plays an indispensable role in the immunity of the host. In the present study, the bioinformatical analysis of the transcriptomic data from oyster Crassostrea gigas and further biological validation revealed that oyster TNF (CgTNF-1 CGI_10018786) could activate the transcription factors NF-κB and HSF (heat shock transcription factor) through MAPK signaling pathway, and then regulate apoptosis, redox reaction, neuro-regulation and protein folding in oyster haemocytes. The activated immune cells then released neurotransmitters including acetylcholine, norepinephrine and [Met5]-enkephalin to regulate the immune response by arising the expression of three TNF (CGI_10005109, CGI_10005110 and CGI_10006440) and translocating two NF-κB (Cgp65, CGI_10018142 and CgRel, CGI_10021567) between the cytoplasm and nuclei of haemocytes. Neurotransmitters exhibited the immunomodulation effects by influencing apoptosis and phagocytosis of oyster haemocytes. Acetylcholine and norepinephrine could down-regulate the immune response, while [Met5]-enkephalin up-regulate the immune response. These results suggested that the simple neuroendocrine-immune regulatory network in oyster might be activated by oyster TNF and then regulate the immune response by virtue of neurotransmitters, cytokines and transcription factors.

  18. The simple neuroendocrine-immune regulatory network in oyster Crassostrea gigas mediates complex functions

    PubMed Central

    Liu, Zhaoqun; Wang, Lingling; Zhou, Zhi; Sun, Ying; Wang, Mengqiang; Wang, Hao; Hou, Zhanhui; Gao, Dahai; Gao, Qiang; Song, Linsheng

    2016-01-01

    The neuroendocrine-immune (NEI) regulatory network is a complex system, which plays an indispensable role in the immunity of the host. In the present study, the bioinformatical analysis of the transcriptomic data from oyster Crassostrea gigas and further biological validation revealed that oyster TNF (CgTNF-1 CGI_10018786) could activate the transcription factors NF-κB and HSF (heat shock transcription factor) through MAPK signaling pathway, and then regulate apoptosis, redox reaction, neuro-regulation and protein folding in oyster haemocytes. The activated immune cells then released neurotransmitters including acetylcholine, norepinephrine and [Met5]-enkephalin to regulate the immune response by arising the expression of three TNF (CGI_10005109, CGI_10005110 and CGI_10006440) and translocating two NF-κB (Cgp65, CGI_10018142 and CgRel, CGI_10021567) between the cytoplasm and nuclei of haemocytes. Neurotransmitters exhibited the immunomodulation effects by influencing apoptosis and phagocytosis of oyster haemocytes. Acetylcholine and norepinephrine could down-regulate the immune response, while [Met5]-enkephalin up-regulate the immune response. These results suggested that the simple neuroendocrine-immune regulatory network in oyster might be activated by oyster TNF and then regulate the immune response by virtue of neurotransmitters, cytokines and transcription factors. PMID:27193598

  19. Reverse engineering biological networks :applications in immune responses to bio-toxins.

    SciTech Connect

    Martino, Anthony A.; Sinclair, Michael B.; Davidson, George S.; Haaland, David Michael; Timlin, Jerilyn Ann; Thomas, Edward Victor; Slepoy, Alexander; Zhang, Zhaoduo; May, Elebeoba Eni; Martin, Shawn Bryan; Faulon, Jean-Loup Michel

    2005-12-01

    Our aim is to determine the network of events, or the regulatory network, that defines an immune response to a bio-toxin. As a model system, we are studying T cell regulatory network triggered through tyrosine kinase receptor activation using a combination of pathway stimulation and time-series microarray experiments. Our approach is composed of five steps (1) microarray experiments and data error analysis, (2) data clustering, (3) data smoothing and discretization, (4) network reverse engineering, and (5) network dynamics analysis and fingerprint identification. The technological outcome of this study is a suite of experimental protocols and computational tools that reverse engineer regulatory networks provided gene expression data. The practical biological outcome of this work is an immune response fingerprint in terms of gene expression levels. Inferring regulatory networks from microarray data is a new field of investigation that is no more than five years old. To the best of our knowledge, this work is the first attempt that integrates experiments, error analyses, data clustering, inference, and network analysis to solve a practical problem. Our systematic approach of counting, enumeration, and sampling networks matching experimental data is new to the field of network reverse engineering. The resulting mathematical analyses and computational tools lead to new results on their own and should be useful to others who analyze and infer networks.

  20. Idiotypes of pre-existing human anti-carcinoma anti-T and anti-Tn antibodies.

    PubMed

    Zanetti, M; Lenert, G; Springer, G F

    1993-02-01

    All humans normally possess antibodies, predominantly IgM, that react specifically with the Thomsen-Friedenreich (T) and the Tn antigens which are present in immunoreactive form on > 85% of all human carcinomas, but not in healthy and otherwise diseased tissues. We report here a serological study of idiotype expression and antigen reactivity of the anti-T and anti-Tn antibodies. Idiotypy was analyzed with rabbit antibodies raised against, and made specific for, affinity-purified polyclonal anti-T and anti-Tn antibodies from blood group A1B healthy adult donors. Anti-T and anti-Tn antibodies cross-reacted idiotypically in spite of their distinct epitope specificities. By adsorbing anti-T antibodies on insolubilized synthetic T carbohydrate we could firmly link idiotype expression with antigen reactivity. The relation of idiotype expression to the antigen-binding site of plant seed lectins was also studied; one originated from Arachis hypogaea [peanut agglutinin (PNA)], the other from Artocarpus integrifolia (Jacalin). PNA inhibited only anti-T antibodies. Jacalin inhibited both anti-T and anti-Tn antibodies in a dose-dependent manner. Neither idiotypic nor anti-idiotypic antibodies diminished the binding of lectins to T and Tn epitopes. The shared idiotypes on natural anti-T and anti-Tn antibodies permit consideration of application of their anti-idiotypes in treatment and/or prevention of human carcinoma.

  1. MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma

    NASA Astrophysics Data System (ADS)

    Huang, Chen-Tsung; Oyang, Yen-Jen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2014-09-01

    Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with low death rate but increased incidence and recurrence in recent years. MicroRNAs (miRNAs) are small non-coding RNAs with diverse regulatory capacities in eukaryotes and have been frequently implied in human cancer. Despite current progress, however, a panoramic overview concerning miRNA regulatory networks in PTC is still lacking. Here, we analyzed the expression datasets of PTC from The Cancer Genome Atlas (TCGA) Data Portal and demonstrate for the first time that immune responses are significantly enriched and under specific regulation in the direct miRNA-target network among distinctive PTC variants to different extents. Additionally, considering the unconventional properties of miRNAs, we explore the protein-coding competing endogenous RNA (ceRNA) and the modulatory networks in PTC and unexpectedly disclose concerted regulation of immune responses from these networks. Interestingly, miRNAs from these conventional and unconventional networks share general similarities and differences but tend to be disparate as regulatory activities increase, coordinately tuning the immune responses that in part account for PTC tumor biology. Together, our systematic results uncover the intensive regulation of immune responses underlain by miRNA-mediated networks in PTC, opening up new avenues in the management of thyroid cancer.

  2. A cascade reaction network mimicking the basic functional steps of acquired immune response

    PubMed Central

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

    2015-01-01

    Biological systems use complex ‘information processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS which we call Adaptive Immune Response Simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system which responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner which is superficially similar to the most basic responses of the vertebrate acquired immune system, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices. PMID:26391084

  3. [Effect of forest therapy on the human psycho-neuro-endocrino-immune network].

    PubMed

    Li, Qing; Kawada, Tomoyuki

    2011-09-01

    Traditional thinking considered the nervous system, endocrine system and immune system to be independent of each other. However, it is now widely accepted that these systems interact through the psycho-neuro-endocrino-immune network. The nervous system affects the endocrine and immune systems by releasing neurotransmitters through the hypothalamus in the hypothalamic-pituitary portal circulation. The endocrine system affects the nervous and immune systems by secreting hormones and the immune system feeds back to the nervous and endocrine systems via cytokines. Forest therapy reduces sympathetic nervous activity, increases parasympathetic nervous activity, and regulates the balance of autonomic nerves. As a result, forest therapy decreases blood pressure and heart rate and has a relaxing effect. Forest therapy affects psychological responses via the brain and nervous system thereby decreasing the scores for anxiety, depression, anger, fatigue, and confusion, and increasing the score for vigor in the POMS test. Forest therapy acts on the endocrine system to reduce stress hormone levels such as urinary adrenaline, urinary noradrenaline, salivary cortisol, and blood cortisol levels and shows a relaxing effect. Forest therapy also acts directly and indirectly on the immune system to promote NK activity by increasing the number of NK cells and intracellular levels of anticancer proteins such as perforin, granulysin and granzymes. Taken together, forest therapy brings various effects on human health via the psycho-neuro-endocrino-immune network. PMID:21996762

  4. Prokaryotic ancestry of eukaryotic protein networks mediating innate immunity and apoptosis.

    PubMed

    Dunin-Horkawicz, Stanislaw; Kopec, Klaus O; Lupas, Andrei N

    2014-04-01

    Protein domains characteristic of eukaryotic innate immunity and apoptosis have many prokaryotic counterparts of unknown function. By reconstructing interactomes computationally, we found that bacterial proteins containing these domains are part of a network that also includes other domains not hitherto associated with immunity. This network is connected to the network of prokaryotic signal transduction proteins, such as histidine kinases and chemoreceptors. The network varies considerably in domain composition and degree of paralogy, even between strains of the same species, and its repetitive domains are often amplified recently, with individual repeats sharing up to 100% sequence identity. Both phenomena are evidence of considerable evolutionary pressure and thus compatible with a role in the "arms race" between host and pathogen. In order to investigate the relationship of this network to its eukaryotic counterparts, we performed a cluster analysis of organisms based on a census of its constituent domains across all fully sequenced genomes. We obtained a large central cluster of mainly unicellular organisms, from which multicellular organisms radiate out in two main directions. One is taken by multicellular bacteria, primarily cyanobacteria and actinomycetes, and plants form an extension of this direction, connected via the basal, unicellular cyanobacteria. The second main direction is taken by animals and fungi, which form separate branches with a common root in the α-proteobacteria of the central cluster. This analysis supports the notion that the innate immunity networks of eukaryotes originated from their endosymbionts and that increases in the complexity of these networks accompanied the emergence of multicellularity.

  5. Increasing Influenza and Pneumococcal Immunization Rates in a Nursing Home Network

    PubMed Central

    Nace, David A.; Perera, Subashan; Handler, Steven M.; Muder, Robert; Hoffman, Erika L.

    2016-01-01

    Introduction and Rationale Influenza and pneumonia remain serious health concerns for long-term care (LTC) residents. Vaccination of LTC residents and health care workers are reasonable preventive strategies, although most facilities fall short of Healthy People 2010 goals. Improving immunization rates across multiple LTC facilities remains an elusive challenge. This quality improvement study sought to improve immunization rates across 6 LTC facilities and identify persistent barriers to better performance. Methods In 2002, 6 facilities associated with the University of Pittsburgh Institute on Aging established a quality improvement network addressing immunization rates. The facilities were provided with a written educational toolkit and shared information through an e-mail distribution list. To help determine optimal program structure in future years, 3 of the facilities participated in a single half-day collaborative training session. Change in immunization rates from baseline to year 2 were compared between those participating in the collaborative training and those not participating. Barriers to improved performance were sought from all groups through focus group analysis. Results Facilities participating in the single collaborative training program improved immunization rates modestly, whereas facilities not participating in the collaborative training saw decreases in immunization rates. Staff turnover was cited as a significant barrier to improved performance. Discussion It may be possible to improve immunization rates in LTC facilities, at least modestly, using a collaborative training process. Staff turnover may be an important barrier to improved LTC immunization rates. PMID:21450182

  6. Trail networks formed by populations of immune cells

    NASA Astrophysics Data System (ADS)

    Yang, Taeseok Daniel; Kwon, Tae Goo; Park, Jin-sung; Lee, Kyoung J.

    2014-02-01

    Populations of biological cells that communicate with each other can organize themselves to generate large-scale patterns. Examples can be found in diverse systems, ranging from developing embryos, cardiac tissues, chemotaxing ameba and swirling bacteria. The similarity, often shared by the patterns, suggests the existence of some general governing principle. On the other hand, rich diversity and system-specific properties are exhibited, depending on the type of involved cells and the nature of their interactions. The study on the similarity and the diversity constitutes a rapidly growing field of research. Here, we introduce a new class of self-organized patterns of cell populations that we term as ‘cellular trail networks’. They were observed with populations of rat microglia, the immune cells of the brain and the experimental evidence suggested that haptotaxis is the key element responsible for them. The essential features of the observed patterns are well captured by the mathematical model cells that actively crawl and interact with each other through a decomposing but non-diffusing chemical attractant laid down by the cells. Our finding suggests an unusual mechanism of socially cooperative long-range signaling for the crawling immune cells.

  7. Canadian paediatricians’ approaches to managing patients with adverse events following immunization: The role of the Special Immunization Clinic network

    PubMed Central

    Top, Karina A; Zafack, Joseline; De Serres, Gaston; Halperin, Scott A

    2014-01-01

    BACKGROUND: When moderate or severe adverse events occur after vaccination, physicians and patients may have concerns about future immunizations. Similar concerns arise in patients with underlying conditions whose risk for adverse events may differ from the general population. The Special Immunization Clinic (SIC) network was established in 2013 at 13 sites in Canada to provide expertise in the clinical evaluation and vaccination of these patients. OBJECTIVES: To assess referral patterns for patients with vaccine adverse events or potential vaccine contraindications among paediatricians and to assess the anticipated utilization of an SIC. METHODS: A 12-item questionnaire was distributed to paediatricians and subspecialists participating in the Canadian Paediatric Surveillance Program through monthly e-mail and mail contacts. RESULTS: The response rate was 24% (586 of 2490). Fifty-three percent of respondents practiced general paediatrics exclusively and 52% reported that they administer vaccines. In the previous 12 months, 26% of respondents had encountered children with challenging adverse events or potential vaccine contraindications in their practice and 29% had received referrals for such patients, including 27% of subspecialists. Overall, 69% of respondents indicated that they would be likely or very likely to refer patients to an SIC, and 34% indicated that they would have referred at least one patient to an SIC in the previous 12 months. CONCLUSIONS: Patients who experience challenging adverse events following immunization or potential vaccine contraindications are encountered by paediatricians and subspecialists in all practice settings. The SIC network will be able to respond to a clinical need and support paediatricians in managing these patients. PMID:25332661

  8. Independently Evolved Virulence Effectors Converge onto Hubs in a Plant Immune System Network

    PubMed Central

    Mukhtar, M. Shahid; Carvunis, Anne-Ruxandra; Dreze, Matija; Epple, Petra; Steinbrenner, Jens; Moore, Jonathan; Tasan, Murat; Galli, Mary; Hao, Tong; Nishimura, Marc T.; Pevzner, Samuel J.; Donovan, Susan E.; Ghamsari, Lila; Santhanam, Balaji; Romero, Viviana; Poulin, Matthew M.; Gebreab, Fana; Gutierrez, Bryan J.; Tam, Stanley; Monachello, Dario; Boxem, Mike; Harbort, Christopher J.; McDonald, Nathan; Gai, Lantian; Chen, Huaming; He, Yijian; Vandenhaute, Jean; Roth, Frederick P.; Hill, David E.; Ecker, Joseph R.; Vidal, Marc; Beynon, Jim; Braun, Pascal; Dangl, Jeffery L.

    2011-01-01

    Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they interact physically with host proteins to modulate defense. We generated a plant-pathogen immune system protein interaction network using effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of Arabidopsis immune system proteins and ~8,000 other Arabidopsis proteins. We noted convergence of effectors onto highly interconnected host proteins, and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life cycle strategies. PMID:21798943

  9. A statistical mechanics approach to autopoietic immune networks

    NASA Astrophysics Data System (ADS)

    Barra, Adriano; Agliari, Elena

    2010-07-01

    In this work we aim to bridge theoretical immunology and disordered statistical mechanics. We introduce a model for the behavior of B-cells which naturally merges the clonal selection theory and the autopoietic network theory as a whole. From the analysis of its features we recover several basic phenomena such as low-dose tolerance, dynamical memory of antigens and self/non-self discrimination.

  10. Thymus-independent type 2 antigen induces a long-term IgG-related network memory.

    PubMed

    Lange, Hans; Zemlin, Michael; Tanasa, Radu Iulian; Trad, Ahmad; Weiss, Thomas; Menning, Hauke; Lemke, Hilmar

    2008-05-01

    Thymus-independent type 2 (TI-2) antigens occasionally induce long-lasting IgM memory, but do not prime for typical secondary IgG responses. However, contrary to current understanding, we detected several TI-2-induced long-term memory effects in subsequent thymus-dependent (TD) responses to the hapten 2-phenyloxazolone coupled to a protein carrier. The early primary TD response, even 3 months after TI-2 immunization, included non-mutated IgM as well as IgG antibodies exhibiting higher affinities than the Ox1 idiotype which dominates and has highest affinity in sole TD responses. The secondary exclusive IgG response 8 weeks later contained major hitherto non-observed clones. Somatic hypermutation on the normally dominant V(H)Ox1 gene was largely silenced while the associated VkappaOx1 exhibited the classical affinity-enhancing mutations, thus suggesting a separate regulation of this process for V(H) and V(L) genes. Mutations accumulated in genes which normally are rarely or non-expressed or non-mutating. First evidence is presented that receptor revision by V(H) replacement may occur during immune maturation in genetically non-engineered wildtype mice. We conclude that the TI-2 antigen-induced altered selection of TD Ag-inducible clones and its severe gene-specific influence on further somatic mutations and affinity maturation represents a network memory, which we hypothesize to be mediated by anti-idiotypic regulatory T cells.

  11. Identifying causal networks linking cancer processes and anti-tumor immunity using Bayesian network inference and metagene constructs.

    PubMed

    Kaiser, Jacob L; Bland, Cassidy L; Klinke, David J

    2016-03-01

    Cancer arises from a deregulation of both intracellular and intercellular networks that maintain system homeostasis. Identifying the architecture of these networks and how they are changed in cancer is a pre-requisite for designing drugs to restore homeostasis. Since intercellular networks only appear in intact systems, it is difficult to identify how these networks become altered in human cancer using many of the common experimental models. To overcome this, we used the diversity in normal and malignant human tissue samples from the Cancer Genome Atlas (TCGA) database of human breast cancer to identify the topology associated with intercellular networks in vivo. To improve the underlying biological signals, we constructed Bayesian networks using metagene constructs, which represented groups of genes that are concomitantly associated with different immune and cancer states. We also used bootstrap resampling to establish the significance associated with the inferred networks. In short, we found opposing relationships between cell proliferation and epithelial-to-mesenchymal transformation (EMT) with regards to macrophage polarization. These results were consistent across multiple carcinomas in that proliferation was associated with a type 1 cell-mediated anti-tumor immune response and EMT was associated with a pro-tumor anti-inflammatory response. To address the identifiability of these networks from other datasets, we could identify the relationship between EMT and macrophage polarization with fewer samples when the Bayesian network was generated from malignant samples alone. However, the relationship between proliferation and macrophage polarization was identified with fewer samples when the samples were taken from a combination of the normal and malignant samples. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:470-479, 2016.

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  13. Creating a two-layered augmented artificial immune system for application to computer network intrusion detection

    NASA Astrophysics Data System (ADS)

    Judge, Matthew G.; Lamont, Gary B.

    2009-05-01

    Computer network security has become a very serious concern of commercial, industrial, and military organizations due to the increasing number of network threats such as outsider intrusions and insider covert activities. An important security element of course is network intrusion detection which is a difficult real world problem that has been addressed through many different solution attempts. Using an artificial immune system has been shown to be one of the most promising results. By enhancing jREMISA, a multi-objective evolutionary algorithm inspired artificial immune system, with a secondary defense layer; we produce improved accuracy of intrusion classification and a flexibility in responsiveness. This responsiveness can be leveraged to provide a much more powerful and accurate system, through the use of increased processing time and dedicated hardware which has the flexibility of being located out of band.

  14. Local immunization program for susceptible-infected-recovered network epidemic model

    NASA Astrophysics Data System (ADS)

    Wu, Qingchu; Lou, Yijun

    2016-02-01

    The immunization strategies through contact tracing on the susceptible-infected-recovered framework in social networks are modelled to evaluate the cost-effectiveness of information-based vaccination programs with particular focus on the scenario where individuals belonging to a specific set can get vaccinated due to the vaccine shortages and other economic or humanity constraints. By using the block heterogeneous mean-field approach, a series of discrete-time dynamical models is formulated and the condition for epidemic outbreaks can be established which is shown to be not only dependent on the network structure but also closely related to the immunization control parameters. Results show that increasing the immunization strength can effectively raise the epidemic threshold, which is different from the predictions obtained through the susceptible-infected-susceptible network framework, where epidemic threshold is independent of the vaccination strength. Furthermore, a significant decrease of vaccine use to control the infectious disease is observed for the local vaccination strategy, which shows the promising applications of the local immunization programs to disease control while calls for accurate local information during the process of disease outbreak.

  15. Using an agent-based model to analyze the dynamic communication network of the immune response

    PubMed Central

    2011-01-01

    Background The immune system behaves like a complex, dynamic network with interacting elements including leukocytes, cytokines, and chemokines. While the immune system is broadly distributed, leukocytes must communicate effectively to respond to a pathological challenge. The Basic Immune Simulator 2010 contains agents representing leukocytes and tissue cells, signals representing cytokines, chemokines, and pathogens, and virtual spaces representing organ tissue, lymphoid tissue, and blood. Agents interact dynamically in the compartments in response to infection of the virtual tissue. Agent behavior is imposed by logical rules derived from the scientific literature. The model captured the agent-to-agent contact history, and from this the network topology and the interactions resulting in successful versus failed viral clearance were identified. This model served to integrate existing knowledge and allowed us to examine the immune response from a novel perspective directed at exploiting complex dynamics, ultimately for the design of therapeutic interventions. Results Analyzing the evolution of agent-agent interactions at incremental time points from identical initial conditions revealed novel features of immune communication associated with successful and failed outcomes. There were fewer contacts between agents for simulations ending in viral elimination (win) versus persistent infection (loss), due to the removal of infected agents. However, early cellular interactions preceded successful clearance of infection. Specifically, more Dendritic Agent interactions with TCell and BCell Agents, and more BCell Agent interactions with TCell Agents early in the simulation were associated with the immune win outcome. The Dendritic Agents greatly influenced the outcome, confirming them as hub agents of the immune network. In addition, unexpectedly high frequencies of Dendritic Agent-self interactions occurred in the lymphoid compartment late in the loss outcomes. Conclusions

  16. Development of an ELISA using anti-idiotypic antibody for diagnosis of opisthorchiasis.

    PubMed

    Bulashev, Aitbay K; Borovikov, Sergey N; Serikova, Shynar S; Suranshiev, Zhanbolat A; Kiyan, Vladimir S; Eskendirova, Saule Z

    2016-01-01

    Monoclonal antibody specific for an epitope of cretory-secretory antigen protein of Opisthorchis felineus (Rivolta, 1884) (Trematoda: Opisthorchiidae) with a molecular weight of 28 kDa was used in a sandwich enzyme-linked immunosorbent assay (ELISA) for immobilisation of liver fluke specific antigen to the solid phase. Examination of human sera by this ELISA compared with commercial assays demonstrated that the monoclonal antibody epitope is located within this significant parasite protein. Anti-idiotypic antibody specific for the paratope of this monoclonal antibody was obtained by a hybridoma technique. Mimicking an epitope of excretory-secretory antigen of O. felineus, it had the capacity to bind specific antibody and elicit an antibody response. The value of anti-idiotypic antibody as a substitute for the liver fluke antigen was tested by ELISA using serum samples of infected dogs. Anti-idiotypic antibody proved to be of value in both an indirect-ELISA and a competitive-ELISA for diagnosis of opisthorchiasis. Mature trematodes were isolated from all infected animals. The faecal egg counts were negative in dogs with a relatively small number of parasites, despite finding antibodies in serum by ELISA. Substitution of parasite antigen with anti-idiotype avoids the use of experimental animals and also reduces time-consuming steps of antigen preparation. PMID:27507639

  17. Influence of helper T cells on the expression of a murine intrastrain crossreactive idiotype.

    PubMed Central

    Hathcock, K S; Gurish, M F; Nisonoff, A; Conger, J D; Hodes, R J

    1986-01-01

    The requirement for idiotype-specific helper T (Th) cells in the generation of a major intrastrain crossreactive idiotype was investigated. This idiotype, designated CRIA, is associated with a large proportion of anti-p-azobenzenearsonate (anti-Ar) antibodies in A/J mice. Secondary in vitro responses were studied. Using carrier-primed heterogeneous Th-cell populations, it was found that CRIA expression is determined by the mouse strain that provides the responding B cells and is independent of the strain of the Th cells functioning in vitro. Thus, A/J or A.BY (Ighe) B-plus-accessory-cell populations, primed in vivo to keyhole limpet hemocyanin-Ar (KLH-Ar), generated CRIA-dominant responses in vitro in the presence of KLH-Ar regardless of whether the KLH-primed Th cells were derived from CRIA+ strains (A/J or A.BY, Ighe) or CRIA- strains (B10.A or C57BL/10, Ighb). Further, when major histocompatibility complex-restricted, KLH-specific Th-cell clones were used, the CRIA dominance of the Ar-specific responses was again determined by the strain providing B plus accessory cells. Similar levels of expression of CRIA in Ar-specific antibodies were generated in the presence of heterogeneous or cloned Th cells. The results suggest that there is no absolute requirement for idiotype-specific Th cells in generating an Ar-specific secondary antibody response in vitro. PMID:2934739

  18. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

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

  19. Enhancement of Antibody Response by Mouse Dendritic Cells Pulsed with Tobacco Mosaic Virus or with Rabbit Antiidiotypic Antibodies Raised against a Private Rabbit Idiotype

    NASA Astrophysics Data System (ADS)

    Francotte, M.; Urbain, J.

    1985-12-01

    The role of splenic lymphoid dendritic cells (DC) and macrophages (Mφ ) from mice in induction of immune responses in vivo has been investigated. Varying numbers of purified DC and Mφ pulsed in vitro with tobacco mosaic virus (TMV) or with rabbit antiidiotypic antibodies (Ab2) directed against a private rabbit anti-TMV idiotype were injected back into syngeneic mice. In both systems, DC appeared to strongly enhance the primary and secondary responses to the virus. Optimal responses were obtained with 5 × 104 purified DC carrying TMV or rabbit Ab2. In contrast, Mφ were less efficient by a factor of at least 100. These results show the potency of lymphoid DC as inducing cells in T-dependent antibody responses in vivo.

  20. Analysis and optimization of cross-immunity epidemic model on complex networks

    NASA Astrophysics Data System (ADS)

    Chen, Chao; Zhang, Hao; Wu, Yin-Hua; Feng, Wei-Qiang; Zhang, Jian

    2015-09-01

    There are various infectious diseases in real world, and these diseases often spread on a network of population and compete for the limited hosts. Cross-immunity is an important disease competing pattern, which has attracted the attention of many researchers. In this paper, we discovered an important conclusion for two cross-immunity epidemics on a network. When the infectious ability of the second epidemic takes a fixed value, the infectious ability of the first epidemic has an optimal value which minimizes the sum of the infection sizes of the two epidemics. We also proposed a simple mathematical analysis method for the infection size of the second epidemic using the cavity method. The proposed method and conclusion are verified by simulation results. Minor inaccuracies of the existing mathematical methods for the infection size of the second epidemic are also found and discussed in experiments, which have not been noticed in existing research.

  1. A radial basis function neural network based on artificial immune systems for remote sensing image classification

    NASA Astrophysics Data System (ADS)

    Yan, Qin; Zhong, Yanfei

    2008-12-01

    The radial basis function (RBF) neural network is a powerful method for remote sensing image classification. It has a simple architecture and the learning algorithm corresponds to the solution of a linear regression problem, resulting in a fast training process. The main drawback of this strategy is the requirement of an efficient algorithm to determine the number, position, and dispersion of the RBF. Traditional methods to determine the centers are: randomly choose input vectors from the training data set; vectors obtained from unsupervised clustering algorithms, such as k-means, applied to the input data. These conduce that traditional RBF neural network is sensitive to the center initialization. In this paper, the artificial immune network (aiNet) model, a new computational intelligence based on artificial immune networks (AIN), is applied to obtain appropriate centers for remote sensing image classification. In the aiNet-RBF algorihtm, each input pattern corresonds to an antigenic stimulus, while each RBF candidate center is considered to be an element, or cell, of the immune network model. The steps are as follows: A set of candidate centers is initialized at random, where the initial number of candidates and their positions is not crucial to the performance. Then, the clonal selection principle will control which candidates will be selected and how they will be upadated. Note that the clonal selection principle will be responsible for how the centers will represent the training data set. Finally, the immune network will identify and eliminate or suppress self-recognizing individuals to control the number of candidate centers. After the above learning phase, the aiNet network centers represent internal images of the inuput patterns presented to it. The algorithm output is taken to be the matrix of memory cells' coordinates that represent the final centers to be adopted by the RBF network. The stopping criterion of the proposed algorithm is given by a pre

  2. Uncovering the liver's role in immunity through RNA co-expression networks.

    PubMed

    Harrall, Kylie K; Kechris, Katerina J; Tabakoff, Boris; Hoffman, Paula L; Hines, Lisa M; Tsukamoto, Hidekazu; Pravenec, Michal; Printz, Morton; Saba, Laura M

    2016-10-01

    Gene co-expression analysis has proven to be a powerful tool for ascertaining the organization of gene products into networks that are important for organ function. An organ, such as the liver, engages in a multitude of functions important for the survival of humans, rats, and other animals; these liver functions include energy metabolism, metabolism of xenobiotics, immune system function, and hormonal homeostasis. With the availability of organ-specific transcriptomes, we can now examine the role of RNA transcripts (both protein-coding and non-coding) in these functions. A systems genetic approach for identifying and characterizing liver gene networks within a recombinant inbred panel of rats was used to identify genetically regulated transcriptional networks (modules). For these modules, biological consensus was found between functional enrichment analysis and publicly available phenotypic quantitative trait loci (QTL). In particular, the biological function of two liver modules could be linked to immune response. The eigengene QTLs for these co-expression modules were located at genomic regions coincident with highly significant phenotypic QTLs; these phenotypes were related to rheumatoid arthritis, food preference, and basal corticosterone levels in rats. Our analysis illustrates that genetically and biologically driven RNA-based networks, such as the ones identified as part of this research, provide insight into the genetic influences on organ functions. These networks can pinpoint phenotypes that manifest through the interaction of many organs/tissues and can identify unannotated or under-annotated RNA transcripts that play a role in these phenotypes. PMID:27401171

  3. Uncovering the liver's role in immunity through RNA co-expression networks.

    PubMed

    Harrall, Kylie K; Kechris, Katerina J; Tabakoff, Boris; Hoffman, Paula L; Hines, Lisa M; Tsukamoto, Hidekazu; Pravenec, Michal; Printz, Morton; Saba, Laura M

    2016-10-01

    Gene co-expression analysis has proven to be a powerful tool for ascertaining the organization of gene products into networks that are important for organ function. An organ, such as the liver, engages in a multitude of functions important for the survival of humans, rats, and other animals; these liver functions include energy metabolism, metabolism of xenobiotics, immune system function, and hormonal homeostasis. With the availability of organ-specific transcriptomes, we can now examine the role of RNA transcripts (both protein-coding and non-coding) in these functions. A systems genetic approach for identifying and characterizing liver gene networks within a recombinant inbred panel of rats was used to identify genetically regulated transcriptional networks (modules). For these modules, biological consensus was found between functional enrichment analysis and publicly available phenotypic quantitative trait loci (QTL). In particular, the biological function of two liver modules could be linked to immune response. The eigengene QTLs for these co-expression modules were located at genomic regions coincident with highly significant phenotypic QTLs; these phenotypes were related to rheumatoid arthritis, food preference, and basal corticosterone levels in rats. Our analysis illustrates that genetically and biologically driven RNA-based networks, such as the ones identified as part of this research, provide insight into the genetic influences on organ functions. These networks can pinpoint phenotypes that manifest through the interaction of many organs/tissues and can identify unannotated or under-annotated RNA transcripts that play a role in these phenotypes.

  4. An artificial immune system approach with secondary response for misbehavior detection in mobile ad hoc networks.

    PubMed

    Sarafijanović, Slavisa; Le Boudec, Jean-Yves

    2005-09-01

    In mobile ad hoc networks, nodes act both as terminals and information relays, and they participate in a common routing protocol, such as dynamic source routing (DSR). The network is vulnerable to routing misbehavior, due to faulty or malicious nodes. Misbehavior detection systems aim at removing this vulnerability. In this paper, we investigate the use of an artificial immune system (AIS) to detect node misbehavior in a mobile ad hoc network using DSR. The system is inspired by the natural immune system (IS) of vertebrates. Our goal is to build a system that, like its natural counterpart, automatically learns, and detects new misbehavior. We describe our solution for the classification task of the AIS; it employs negative selection and clonal selection, the algorithms for learning and adaptation used by the natural IS. We define how we map the natural IS concepts such as self, antigen, and antibody to a mobile ad hoc network and give the resulting algorithm for classifying nodes as misbehaving. We implemented the system in the network simulator Glomosim; we present detection results and discuss how the system parameters affect the performance of primary and secondary response. Further steps will extend the design by using an analogy to the innate system, danger signal, and memory cells.

  5. Network Topologies and Dynamics Leading to Endotoxin Tolerance and Priming in Innate Immune Cells

    NASA Astrophysics Data System (ADS)

    Fu, Yan; Glaros, Trevor; Zhu, Meng; Wang, Ping; Wu, Zhanghan; Tyson, John; Li, Liwu; Xing, Jianhua

    2012-01-01

    The innate immune system, acting as the first line of host defense, senses and adapts to foreign challenges through complex intracellular and intercellular signaling networks. Endotoxin tolerance and priming elicited by macrophages are classic examples of the complex adaptation of innate immune cells. Upon repetitive exposures to different doses of bacterial endotoxin (lipopolysaccharide) or other stimulants, macrophages show either suppressed or augmented inflammatory responses compared to a single exposure to the stimulant. Endotoxin tolerance and priming are critically involved in both immune homeostasis and the pathogenesis of diverse inflammatory diseases. However, the underlying molecular mechanisms are not well understood. By means of a computational search through the parameter space of a coarse-grained three-node network with a two-stage Metropolis sampling approach, we enumerated all the network topologies that can generate priming or tolerance. We discovered three major mechanisms for priming (pathway synergy, suppressor deactivation, activator induction) and one for tolerance (inhibitor persistence). These results not only explain existing experimental observations, but also reveal intriguing test scenarios for future experimental studies to clarify mechanisms of endotoxin priming and tolerance.

  6. Potentially Pathogenic Immune Cells and Networks in Apparently Healthy Lacrimal Glands

    PubMed Central

    Mircheff, Austin K.; Wang, Yanru; Ding, Chuanqing; Warren, Dwight W.; Schechter, Joel E.

    2014-01-01

    Lacrimal glands of people over 40 years old frequently contain lymphocytic infiltrates. Relationships between histopathological presentation and physiological dysfunction are not straightforward. Data from rabbit studies have suggested that at least two immune cell networks form in healthy lacrimal glands, one responding to environmental dryness, the other to high temperatures. New findings indicate that mRNAs for several chemokines and cytokines are expressed primarily in epithelial cells; certain others are expressed in both epithelial cells and immune cells. Transcript abundances vary substantially across glands from animals that have experienced the same conditions, allowing for correlation analyses, which detect clusters that map to various cell types and to networks of coordinately functioning cells. A core network—expressing mRNAs including IL-1α, IL-6, IL-17A, and IL-10—expands adaptively with exposure to dryness, suppressing IFN-γ, but potentially causing physiological dysfunction. High temperature elicits concurrent increases of mRNAs for prolactin (PRL), CCL21, and IL-18. PRL is associated with crosstalk to IFN-γ, BAFF, and IL-4. The core network reacts to the resulting PRL-BAFF-IL-4 network, creating a profile reminiscent of Sjögren’s disease. In a warmer, moderately dry setting, PRL-associated increases of IFN-γ are associated with suppression of IL-10 and augmentations of IL-1α and IL-17, creating a profile reminiscent of severe chronic inflammation. PMID:25557346

  7. Network-Based Comparative Analysis of Arabidopsis Immune Responses to Golovinomyces orontii and Botrytis cinerea Infections

    PubMed Central

    Jiang, Zhenhong; Dong, Xiaobao; Zhang, Ziding

    2016-01-01

    A comprehensive exploration of common and specific plant responses to biotrophs and necrotrophs is necessary for a better understanding of plant immunity. Here, we compared the Arabidopsis defense responses evoked by the biotrophic fungus Golovinomyces orontii and the necrotrophic fungus Botrytis cinerea through integrative network analysis. Two time-course transcriptional datasets were integrated with an Arabidopsis protein-protein interaction (PPI) network to construct a G. orontii conditional PPI sub-network (gCPIN) and a B. cinerea conditional PPI sub-network (bCPIN). We found that hubs in gCPIN and bCPIN played important roles in disease resistance. Hubs in bCPIN evolved faster than hubs in gCPIN, indicating the different selection pressures imposed on plants by different pathogens. By analyzing the common network from gCPIN and bCPIN, we identified two network components in which the genes were heavily involved in defense and development, respectively. The co-expression relationships between interacting proteins connecting the two components were different under G. orontii and B. cinerea infection conditions. Closer inspection revealed that auxin-related genes were overrepresented in the interactions connecting these two components, suggesting a critical role of auxin signaling in regulating the different co-expression relationships. Our work may provide new insights into plant defense responses against pathogens with different lifestyles. PMID:26750561

  8. Construction and comparison of gene co-expression networks shows complex plant immune responses

    PubMed Central

    López, Camilo; López-Kleine, Liliana

    2014-01-01

    Gene co-expression networks (GCNs) are graphic representations that depict the coordinated transcription of genes in response to certain stimuli. GCNs provide functional annotations of genes whose function is unknown and are further used in studies of translational functional genomics among species. In this work, a methodology for the reconstruction and comparison of GCNs is presented. This approach was applied using gene expression data that were obtained from immunity experiments in Arabidopsis thaliana, rice, soybean, tomato and cassava. After the evaluation of diverse similarity metrics for the GCN reconstruction, we recommended the mutual information coefficient measurement and a clustering coefficient-based method for similarity threshold selection. To compare GCNs, we proposed a multivariate approach based on the Principal Component Analysis (PCA). Branches of plant immunity that were exemplified by each experiment were analyzed in conjunction with the PCA results, suggesting both the robustness and the dynamic nature of the cellular responses. The dynamic of molecular plant responses produced networks with different characteristics that are differentiable using our methodology. The comparison of GCNs from plant pathosystems, showed that in response to similar pathogens plants could activate conserved signaling pathways. The results confirmed that the closeness of GCNs projected on the principal component space is an indicative of similarity among GCNs. This also can be used to understand global patterns of events triggered during plant immune responses. PMID:25320678

  9. Monocytes and Macrophages Regulate Immunity through Dynamic Networks of Survival and Cell Death

    PubMed Central

    Parihar, Arti; Eubank, Timothy D.; Doseff, Andrea I.

    2010-01-01

    Monocytes and macrophages are central cells of the innate immune system, responsible for defending against diverse pathogens. While they originate from a common myeloid precursor and share functions in innate immunity, each has a very distinct life span finely tuned by the apoptotic caspases. Normally, circulating monocytes are short-lived and undergo spontaneous apoptosis on a daily basis. Macrophages, however, have a longer life span. In chronic inflammatory diseases and, as recently recognized, in the tumor microenvironment, the inhibition of the apoptotic program promotes monocyte survival contributing to the accumulation of macrophages and the persistence of an inflammatory milieu. A complex network of differentiation factors and inflammatory stimuli determine monocyte/macrophage life span by blocking the apoptotic pathway and activating a myriad of survival pathways. Our understanding of apoptosis has flourished over the last decade, and its relevance in the regulation of the immune system is now indisputable. Nevertheless, how the complicated networks of survival and apoptotic regulators are integrated to determine cellular life span remains elusive. This review summarizes the contribution of the caspases and their regulators in monocyte/macrophage cell fate and discusses how these molecules orchestrate the initiation, maintenance, and resolution of inflammation. More provocatively, we discuss possible strategies to control inflammation by manipulating leukocyte life span. PMID:20375558

  10. Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials.

    PubMed

    Kohrt, Holbrook E; Tumeh, Paul C; Benson, Don; Bhardwaj, Nina; Brody, Joshua; Formenti, Silvia; Fox, Bernard A; Galon, Jerome; June, Carl H; Kalos, Michael; Kirsch, Ilan; Kleen, Thomas; Kroemer, Guido; Lanier, Lewis; Levy, Ron; Lyerly, H Kim; Maecker, Holden; Marabelle, Aurelien; Melenhorst, Jos; Miller, Jeffrey; Melero, Ignacio; Odunsi, Kunle; Palucka, Karolina; Peoples, George; Ribas, Antoni; Robins, Harlan; Robinson, William; Serafini, Tito; Sondel, Paul; Vivier, Eric; Weber, Jeff; Wolchok, Jedd; Zitvogel, Laurence; Disis, Mary L; Cheever, Martin A

    2016-01-01

    The efficacy of PD-1/PD-L1 targeted therapies in addition to anti-CTLA-4 solidifies immunotherapy as a modality to add to the anticancer arsenal. Despite raising the bar of clinical efficacy, immunologically targeted agents raise new challenges to conventional drug development paradigms by highlighting the limited relevance of assessing standard pharmacokinetics (PK) and pharmacodynamics (PD). Specifically, systemic and intratumoral immune effects have not consistently correlated with standard relationships between systemic dose, toxicity, and efficacy for cytotoxic therapies. Hence, PK and PD paradigms remain inadequate to guide the selection of doses and schedules, both starting and recommended Phase 2 for immunotherapies. The promise of harnessing the immune response against cancer must also be considered in light of unique and potentially serious toxicities. Refining immune endpoints to better inform clinical trial design represents a high priority challenge. The Cancer Immunotherapy Trials Network investigators review the immunodynamic effects of specific classes of immunotherapeutic agents to focus immune assessment modalities and sites, both systemic and importantly intratumoral, which are critical to the success of the rapidly growing field of immuno-oncology.

  11. Identification of a human neonatal immune-metabolic network associated with bacterial infection.

    PubMed

    Smith, Claire L; Dickinson, Paul; Forster, Thorsten; Craigon, Marie; Ross, Alan; Khondoker, Mizanur R; France, Rebecca; Ivens, Alasdair; Lynn, David J; Orme, Judith; Jackson, Allan; Lacaze, Paul; Flanagan, Katie L; Stenson, Benjamin J; Ghazal, Peter

    2014-01-01

    Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis. PMID:25120092

  12. Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials.

    PubMed

    Kohrt, Holbrook E; Tumeh, Paul C; Benson, Don; Bhardwaj, Nina; Brody, Joshua; Formenti, Silvia; Fox, Bernard A; Galon, Jerome; June, Carl H; Kalos, Michael; Kirsch, Ilan; Kleen, Thomas; Kroemer, Guido; Lanier, Lewis; Levy, Ron; Lyerly, H Kim; Maecker, Holden; Marabelle, Aurelien; Melenhorst, Jos; Miller, Jeffrey; Melero, Ignacio; Odunsi, Kunle; Palucka, Karolina; Peoples, George; Ribas, Antoni; Robins, Harlan; Robinson, William; Serafini, Tito; Sondel, Paul; Vivier, Eric; Weber, Jeff; Wolchok, Jedd; Zitvogel, Laurence; Disis, Mary L; Cheever, Martin A

    2016-01-01

    The efficacy of PD-1/PD-L1 targeted therapies in addition to anti-CTLA-4 solidifies immunotherapy as a modality to add to the anticancer arsenal. Despite raising the bar of clinical efficacy, immunologically targeted agents raise new challenges to conventional drug development paradigms by highlighting the limited relevance of assessing standard pharmacokinetics (PK) and pharmacodynamics (PD). Specifically, systemic and intratumoral immune effects have not consistently correlated with standard relationships between systemic dose, toxicity, and efficacy for cytotoxic therapies. Hence, PK and PD paradigms remain inadequate to guide the selection of doses and schedules, both starting and recommended Phase 2 for immunotherapies. The promise of harnessing the immune response against cancer must also be considered in light of unique and potentially serious toxicities. Refining immune endpoints to better inform clinical trial design represents a high priority challenge. The Cancer Immunotherapy Trials Network investigators review the immunodynamic effects of specific classes of immunotherapeutic agents to focus immune assessment modalities and sites, both systemic and importantly intratumoral, which are critical to the success of the rapidly growing field of immuno-oncology. PMID:26981245

  13. Identification of a human neonatal immune-metabolic network associated with bacterial infection.

    PubMed

    Smith, Claire L; Dickinson, Paul; Forster, Thorsten; Craigon, Marie; Ross, Alan; Khondoker, Mizanur R; France, Rebecca; Ivens, Alasdair; Lynn, David J; Orme, Judith; Jackson, Allan; Lacaze, Paul; Flanagan, Katie L; Stenson, Benjamin J; Ghazal, Peter

    2014-08-14

    Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis.

  14. Identification of a human neonatal immune-metabolic network associated with bacterial infection

    PubMed Central

    Smith, Claire L.; Dickinson, Paul; Forster, Thorsten; Craigon, Marie; Ross, Alan; Khondoker, Mizanur R.; France, Rebecca; Ivens, Alasdair; Lynn, David J.; Orme, Judith; Jackson, Allan; Lacaze, Paul; Flanagan, Katie L.; Stenson, Benjamin J.; Ghazal, Peter

    2014-01-01

    Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis. PMID:25120092

  15. A Stochastic Model for CD4+ T Cell Proliferation and Dissemination Network in Primary Immune Response

    PubMed Central

    Boianelli, Alessandro; Pettini, Elena; Prota, Gennaro; Medaglini, Donata; Vicino, Antonio

    2015-01-01

    The study of the initial phase of the adaptive immune response after first antigen encounter provides essential information on the magnitude and quality of the immune response. This phase is characterized by proliferation and dissemination of T cells in the lymphoid organs. Modeling and identifying the key features of this phenomenon may provide a useful tool for the analysis and prediction of the effects of immunization. This knowledge can be effectively exploited in vaccinology, where it is of interest to evaluate and compare the responses to different vaccine formulations. The objective of this paper is to construct a stochastic model based on branching process theory, for the dissemination network of antigen-specific CD4+ T cells. The devised model is validated on in vivo animal experimental data. The model presented has been applied to the vaccine immunization context making references to simple proliferation laws that take into account division, death and quiescence, but it can also be applied to any context where it is of interest to study the dynamic evolution of a population. PMID:26301680

  16. Shared idiotypes and restricted immunoglobulin variable region heavy chain genes characterize murine autoantibodies of various specificities.

    PubMed Central

    Monestier, M; Manheimer-Lory, A; Bellon, B; Painter, C; Dang, H; Talal, N; Zanetti, M; Schwartz, R; Pisetsky, D; Kuppers, R

    1986-01-01

    The study of the Ig variable region heavy chain (VH) genes used to encode antibodies specific for self-epitopes from murine hybridomas showed that three VH families are primarily utilized: VH J558, the largest family, and VH QPC52 and VH 7183, the families most proximal to the Ig joining region heavy chain genes. These monoclonal autoantibodies express cross-reactive idiotopes shared by rheumatoid factors and antibodies specific for Sm. The expression of these idiotypes is independent of major histocompatibility complex and Ig constant region heavy chain haplotypes, self-antigen specificity, and even the VH gene family utilized. Though the experiments described here are limited to murine autoantibodies, similarities exist between murine and human autoimmune diseases. Studies that aim to investigate the relationship between VH gene expression and the presence of cross-reactive idiotypes among human autoantibodies should enable us to better understand the mechanisms of autoimmunity and self-tolerance. Images PMID:2427543

  17. Chemokines and Heart Disease: A Network Connecting Cardiovascular Biology to Immune and Autonomic Nervous Systems

    PubMed Central

    Dusi, Veronica; Ghidoni, Alice; Ravera, Alice; De Ferrari, Gaetano M.; Calvillo, Laura

    2016-01-01

    Among the chemokines discovered to date, nineteen are presently considered to be relevant in heart disease and are involved in all stages of cardiovascular response to injury. Chemokines are interesting as biomarkers to predict risk of cardiovascular events in apparently healthy people and as possible therapeutic targets. Moreover, they could have a role as mediators of crosstalk between immune and cardiovascular system, since they seem to act as a “working-network” in deep linkage with the autonomic nervous system. In this paper we will describe the single chemokines more involved in heart diseases; then we will present a comprehensive perspective of them as a complex network connecting the cardiovascular system to both the immune and the autonomic nervous systems. Finally, some recent evidences indicating chemokines as a possible new tool to predict cardiovascular risk will be described. PMID:27242392

  18. Suppression of the benzylpenicilloyl- (BPO) specific IgE formation with isologous anti-idiotypic antibodies in BALB/c mice.

    PubMed

    Blaser, K; Nakagawa, T; de Weck, A L

    1980-07-01

    In vivo effects of actively produced or passively administered isologous anti-idiotypic antisera (aId) on the benzylpenicilloyl- (BPO) specific IgE and IgG formation in BALB/c mice have been studied. Isologous anti-BPO aId were raised in BALB/c mice by immunization with purified anti-BPO antibodies isolated from ascites induced with BPO-bovine gamma-globulin in the same mouse strain. Mice producing isologous anti-BPO aId exhibited long-term suppression of BPO-specific IgE and IgG antibody responses induced by BPO-ovalbumin (BPO-OVA) in aluminum hydroxide. Simultaneously, they produced increased amounts of anti-BPO aId after each challenge with the BPO-OVA antigens. Passive administration of isologous anti-BPO aId into syngeneic mice previously sensitized with BPO-OVA caused depression of BPO-specific IgE antibody levels for 2 to 3 weeks. When anti-BPO IgE had again reached its previous level, passively administered aId had decreased to the level of untreated mice. Passive administration of anti-BPO aId also depressed the primary anti-BPO IgE formation for 2 to 3 weeks. In all these experiments the IgE antibody formation against the carrier proteins used for BPO-antigens was not affected. These results show that IgE and IgG antibodies share major idiotypic determinants and that IgE production is accessible to regulation by aId.

  19. Monoclonal yeast killer toxin-like candidacidal anti-idiotypic antibodies.

    PubMed Central

    Polonelli, L; Séguy, N; Conti, S; Gerloni, M; Bertolotti, D; Cantelli, C; Magliani, W; Cailliez, J C

    1997-01-01

    Rat monoclonal yeast killer toxin (KT)-like immunoglobulin M (IgM) anti-idiotypic antibodies (KT-IdAbs) were produced by idiotypic vaccination with a mouse monoclonal antibody (MAb; MAb KT4) that neutralized a Pichia anomala KT characterized by a wide spectrum of antimicrobial activity. The characteristics of the KT-IdAbs were demonstrated by their capacity to compete with the KT to the idiotype of MAb KT4 and to interact with putative KT cell wall receptors (KTRs) of sensitive Candida albicans cells. The internal-image properties of KT-IdAbs were proven by their killer activity against KT-sensitive yeasts. This lethal effect was abolished by prior adsorption of KT-IdAbs with MAb KT4. These findings stressed the potential importance of antibody-mediated immunoprotection against candidiasis and suggested a feasible experimental approach for producing antimicrobial receptor antibodies without purifying the receptor. KT-IdAbs might represent the basis for producing engineered derivatives with a high potential for effective therapeutic antifungal activity. PMID:9067647

  20. Anti-idiotypic antibody: A new strategy for the development of a growth hormone receptor antagonist.

    PubMed

    Lan, Hainan; Zheng, Xin; Khan, Muhammad Akram; Li, Steven

    2015-11-01

    In general, traditional growth hormone receptor antagonist can be divided into two major classes: growth hormone (GH) analogues and anti-growth hormone receptor (GHR) antibodies. Herein, we tried to explore a new class of growth hormone receptor (GHR) antagonist that may have potential advantages over the traditional antagonists. For this, we developed a monoclonal anti-idiotypic antibody growth hormone, termed CG-86. A series of experiments were conducted to characterize and evaluate this antibody, and the results from a competitive receptor-binding assay, Enzyme Linked Immunosorbent Assays (ELISA) and epitope mapping demonstrate that CG-86 behaved as a typical Ab2β. Next, we examined its antagonistic activity using in vitro cell models, and the results showed that CG-86 could effectively inhibit growth hormone receptor-mediated signalling and effectively inhibit growth hormone-induced Ba/F3-GHR638 proliferation. In summary, these studies show that an anti-idiotypic antibody (CG-86) has promise as a novel growth hormone receptor antagonist. Furthermore, the current findings also suggest that anti-idiotypic antibody may represent a novel strategy to produce a new class of growth hormone receptor antagonist, and this strategy may be applied with other cytokines or growth factors.

  1. Approaching mathematical model of the immune network based DNA Strand Displacement system.

    PubMed

    Mardian, Rizki; Sekiyama, Kosuke; Fukuda, Toshio

    2013-12-01

    One biggest obstacle in molecular programming is that there is still no direct method to compile any existed mathematical model into biochemical reaction in order to solve a computational problem. In this paper, the implementation of DNA Strand Displacement system based on nature-inspired computation is observed. By using the Immune Network Theory and Chemical Reaction Network, the compilation of DNA-based operation is defined and the formulation of its mathematical model is derived. Furthermore, the implementation on this system is compared with the conventional implementation by using silicon-based programming. From the obtained results, we can see a positive correlation between both. One possible application from this DNA-based model is for a decision making scheme of intelligent computer or molecular robot.

  2. Immune response to racotumomab in a child with relapsed neuroblastoma.

    PubMed

    Sampor, C; Guthmann, M D; Scursoni, A; Cacciavillano, W; Torbidoni, A; Galluzzo, L; Camarero, S; Lopez, J; de Dávila, M T G; Fainboim, L; Chantada, G L

    2012-01-01

    Immunotherapy targeting ganglioside antigens is a powerful tool for the treatment of high risk neuroblastoma. However, only treatment with anti-GD2 antibodies has been used in clinical practice and other options may be pursued. We report the use of racotumomab, an anti-idiotype vaccine against N-glycolyl neuraminic acid (NeuGc)- containing gangliosides, eliciting an immune response in a child with relapsed neuroblastoma expressing the NeuGcGM3 ganglioside.

  3. A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1

    PubMed Central

    Wilkinson, R W; Ross, E L; Lee-MacAry, A E; Laylor, R; Burchell, J; Taylor-Papadimitriou, J; Snary, D

    2000-01-01

    MUC1 is a membrane bound, polymorphic epithelial mucin expressed at the luminal surface of glandular epithelium. It is highly expressed in an underglycosylated form on carcinomas and metastatic lesions and is, therefore, a potential target for immunotherapy of cancer. The monoclonal antibody HMFG1 binds the linear core protein sequence, PDTR, contained within the immunodominant domain of the tandem repeat of MUC1. The efficacy of murine and humanized HMFG1 (Ab1) used as an anti-idiotypic vaccine was examined in mice transgenic for human MUC1 (MUC1.Tg) challenged with murine epithelial tumour cells transfected with human MUC1. Humoral idiotypic cascade through Ab2 and Ab3 antibodies was observed in MUC1.Tg mice following multiple antibody inoculations in the presence of adjuvant. Impaired tumour growth at day 35 and highest Ab3 levels were found in mice that had received mHMFG1 with RAS adjuvant. However, comparison of Ab3 levels in individual mice with tumour size in all treatment groups did not show a correlation between smaller tumours and increased levels of anti-idiotype antibody. This suggests that the anti-tumour effects of anti-idiotype vaccination are not solely related to the induction of idiotypic antibody cascades and probably involve other mechanisms. © 2000 Cancer Research Campaign PMID:11027434

  4. Vaccinomics, adversomics, and the immune response network theory: Individualized vaccinology in the 21st century

    PubMed Central

    Poland, Gregory A.; Kennedy, Richard B.; McKinney, Brett A.; Ovsyannikova, Inna G.; Lambert, Nathaniel D.; Jacobson, Robert M.; Oberg, Ann L.

    2013-01-01

    Vaccines, like drugs and medical procedures, are increasingly amenable to individualization or personalization, often based on novel data resulting from high throughput “omics” technologies. As a result of these technologies, 21st century vaccinology will increasingly see the abandonment of a “one size fits all” approach to vaccine dosing and delivery, as well as the abandonment of the empiric “isolate–inactivate–inject” paradigm for vaccine development. In this review, we discuss the immune response network theory and its application to the new field of vaccinomics and adversomics, and illustrate how vaccinomics can lead to new vaccine candidates, new understandings of how vaccines stimulate immune responses, new biomarkers for vaccine response, and facilitate the understanding of what genetic and other factors might be responsible for rare side effects due to vaccines. Perhaps most exciting will be the ability, at a systems biology level, to integrate increasingly complex high throughput data into descriptive and predictive equations for immune responses to vaccines. Herein, we discuss the above with a view toward the future of vaccinology. PMID:23755893

  5. Securing mobile ad hoc networks using danger theory-based artificial immune algorithm.

    PubMed

    Abdelhaq, Maha; Alsaqour, Raed; Abdelhaq, Shawkat

    2015-01-01

    A mobile ad hoc network (MANET) is a set of mobile, decentralized, and self-organizing nodes that are used in special cases, such as in the military. MANET properties render the environment of this network vulnerable to different types of attacks, including black hole, wormhole and flooding-based attacks. Flooding-based attacks are one of the most dangerous attacks that aim to consume all network resources and thus paralyze the functionality of the whole network. Therefore, the objective of this paper is to investigate the capability of a danger theory-based artificial immune algorithm called the mobile dendritic cell algorithm (MDCA) to detect flooding-based attacks in MANETs. The MDCA applies the dendritic cell algorithm (DCA) to secure the MANET with additional improvements. The MDCA is tested and validated using Qualnet v7.1 simulation tool. This work also introduces a new simulation module for a flooding attack called the resource consumption attack (RCA) using Qualnet v7.1. The results highlight the high efficiency of the MDCA in detecting RCAs in MANETs. PMID:25946001

  6. Securing Mobile Ad Hoc Networks Using Danger Theory-Based Artificial Immune Algorithm

    PubMed Central

    2015-01-01

    A mobile ad hoc network (MANET) is a set of mobile, decentralized, and self-organizing nodes that are used in special cases, such as in the military. MANET properties render the environment of this network vulnerable to different types of attacks, including black hole, wormhole and flooding-based attacks. Flooding-based attacks are one of the most dangerous attacks that aim to consume all network resources and thus paralyze the functionality of the whole network. Therefore, the objective of this paper is to investigate the capability of a danger theory-based artificial immune algorithm called the mobile dendritic cell algorithm (MDCA) to detect flooding-based attacks in MANETs. The MDCA applies the dendritic cell algorithm (DCA) to secure the MANET with additional improvements. The MDCA is tested and validated using Qualnet v7.1 simulation tool. This work also introduces a new simulation module for a flooding attack called the resource consumption attack (RCA) using Qualnet v7.1. The results highlight the high efficiency of the MDCA in detecting RCAs in MANETs. PMID:25946001

  7. Securing mobile ad hoc networks using danger theory-based artificial immune algorithm.

    PubMed

    Abdelhaq, Maha; Alsaqour, Raed; Abdelhaq, Shawkat

    2015-01-01

    A mobile ad hoc network (MANET) is a set of mobile, decentralized, and self-organizing nodes that are used in special cases, such as in the military. MANET properties render the environment of this network vulnerable to different types of attacks, including black hole, wormhole and flooding-based attacks. Flooding-based attacks are one of the most dangerous attacks that aim to consume all network resources and thus paralyze the functionality of the whole network. Therefore, the objective of this paper is to investigate the capability of a danger theory-based artificial immune algorithm called the mobile dendritic cell algorithm (MDCA) to detect flooding-based attacks in MANETs. The MDCA applies the dendritic cell algorithm (DCA) to secure the MANET with additional improvements. The MDCA is tested and validated using Qualnet v7.1 simulation tool. This work also introduces a new simulation module for a flooding attack called the resource consumption attack (RCA) using Qualnet v7.1. The results highlight the high efficiency of the MDCA in detecting RCAs in MANETs.

  8. Learning Effective Connectivity Network Structure from fMRI Data Based on Artificial Immune Algorithm.

    PubMed

    Ji, Junzhong; Liu, Jinduo; Liang, Peipeng; Zhang, Aidong

    2016-01-01

    Many approaches have been designed to extract brain effective connectivity from functional magnetic resonance imaging (fMRI) data. However, few of them can effectively identify the connectivity network structure due to different defects. In this paper, a new algorithm is developed to infer the effective connectivity between different brain regions by combining artificial immune algorithm (AIA) with the Bayes net method, named as AIAEC. In the proposed algorithm, a brain effective connectivity network is mapped onto an antibody, and four immune operators are employed to perform the optimization process of antibodies, including clonal selection operator, crossover operator, mutation operator and suppression operator, and finally gets an antibody with the highest K2 score as the solution. AIAEC is then tested on Smith's simulated datasets, and the effect of the different factors on AIAEC is evaluated, including the node number, session length, as well as the other potential confounding factors of the blood oxygen level dependent (BOLD) signal. It was revealed that, as contrast to other existing methods, AIAEC got the best performance on the majority of the datasets. It was also found that AIAEC could attain a relative better solution under the influence of many factors, although AIAEC was differently affected by the aforementioned factors. AIAEC is thus demonstrated to be an effective method for detecting the brain effective connectivity. PMID:27045295

  9. Learning Effective Connectivity Network Structure from fMRI Data Based on Artificial Immune Algorithm

    PubMed Central

    Ji, Junzhong; Liu, Jinduo; Liang, Peipeng; Zhang, Aidong

    2016-01-01

    Many approaches have been designed to extract brain effective connectivity from functional magnetic resonance imaging (fMRI) data. However, few of them can effectively identify the connectivity network structure due to different defects. In this paper, a new algorithm is developed to infer the effective connectivity between different brain regions by combining artificial immune algorithm (AIA) with the Bayes net method, named as AIAEC. In the proposed algorithm, a brain effective connectivity network is mapped onto an antibody, and four immune operators are employed to perform the optimization process of antibodies, including clonal selection operator, crossover operator, mutation operator and suppression operator, and finally gets an antibody with the highest K2 score as the solution. AIAEC is then tested on Smith’s simulated datasets, and the effect of the different factors on AIAEC is evaluated, including the node number, session length, as well as the other potential confounding factors of the blood oxygen level dependent (BOLD) signal. It was revealed that, as contrast to other existing methods, AIAEC got the best performance on the majority of the datasets. It was also found that AIAEC could attain a relative better solution under the influence of many factors, although AIAEC was differently affected by the aforementioned factors. AIAEC is thus demonstrated to be an effective method for detecting the brain effective connectivity. PMID:27045295

  10. Network Intrusion Detection Based on a General Regression Neural Network Optimized by an Improved Artificial Immune Algorithm

    PubMed Central

    Wu, Jianfa; Peng, Dahao; Li, Zhuping; Zhao, Li; Ling, Huanzhang

    2015-01-01

    To effectively and accurately detect and classify network intrusion data, this paper introduces a general regression neural network (GRNN) based on the artificial immune algorithm with elitist strategies (AIAE). The elitist archive and elitist crossover were combined with the artificial immune algorithm (AIA) to produce the AIAE-GRNN algorithm, with the aim of improving its adaptivity and accuracy. In this paper, the mean square errors (MSEs) were considered the affinity function. The AIAE was used to optimize the smooth factors of the GRNN; then, the optimal smooth factor was solved and substituted into the trained GRNN. Thus, the intrusive data were classified. The paper selected a GRNN that was separately optimized using a genetic algorithm (GA), particle swarm optimization (PSO), and fuzzy C-mean clustering (FCM) to enable a comparison of these approaches. As shown in the results, the AIAE-GRNN achieves a higher classification accuracy than PSO-GRNN, but the running time of AIAE-GRNN is long, which was proved first. FCM and GA-GRNN were eliminated because of their deficiencies in terms of accuracy and convergence. To improve the running speed, the paper adopted principal component analysis (PCA) to reduce the dimensions of the intrusive data. With the reduction in dimensionality, the PCA-AIAE-GRNN decreases in accuracy less and has better convergence than the PCA-PSO-GRNN, and the running speed of the PCA-AIAE-GRNN was relatively improved. The experimental results show that the AIAE-GRNN has a higher robustness and accuracy than the other algorithms considered and can thus be used to classify the intrusive data. PMID:25807466

  11. Integrated Systems View on Networking by Hormones in Arabidopsis Immunity Reveals Multiple Crosstalk for Cytokinin[W

    PubMed Central

    Naseem, Muhammad; Philippi, Nicole; Hussain, Anwar; Wangorsch, Gaby; Ahmed, Nazeer; Dandekar, Thomas

    2012-01-01

    Phytohormones signal and combine to maintain the physiological equilibrium in the plant. Pathogens enhance host susceptibility by modulating the hormonal balance of the plant cell. Unlike other plant hormones, the detailed role of cytokinin in plant immunity remains to be fully elucidated. Here, extensive data mining, including of pathogenicity factors, host regulatory proteins, enzymes of hormone biosynthesis, and signaling components, established an integrated signaling network of 105 nodes and 163 edges. Dynamic modeling and system analysis identified multiple cytokinin-mediated regulatory interactions in plant disease networks. This includes specific synergism between cytokinin and salicylic acid pathways and previously undiscovered aspects of antagonism between cytokinin and auxin in plant immunity. Predicted interactions and hormonal effects on plant immunity are confirmed in subsequent experiments with Pseudomonas syringae pv tomato DC3000 and Arabidopsis thaliana. Our dynamic simulation is instrumental in predicting system effects of individual components in complex hormone disease networks and synergism or antagonism between pathways. PMID:22643121

  12. Generation and Characterization of a Human/Mouse Chimeric GD2-Mimicking Anti-Idiotype Antibody Ganglidiximab for Active Immunotherapy against Neuroblastoma

    PubMed Central

    Eger, Christin; Siebert, Nikolai; Seidel, Diana; Zumpe, Maxi; Jüttner, Madlen; Brandt, Sven; Müller, Hans-Peter; Lode, Holger N.

    2016-01-01

    Vaccination with proteins mimicking GD2 that is highly expressed on neuroblastoma (NB) cells is a promising strategy in treatment of NB, a pediatric malignancy with poor prognosis. We previously showed efficacy of ganglidiomab in vivo, a murine anti-idiotype (anti-Id) IgG1. In order to tailor immune responses to variable regions, we generated a new human/mouse chimeric anti-Id antibody (Ab) ganglidiximab by replacing murine constant fragments with corresponding human IgG1 regions. DNA sequences encoding for variable regions of heavy (VH) and light chains (VL) were synthesized by RT-PCR from total RNA of ganglidiomab-producing hybridoma cells and further ligated into mammalian expression plasmids with coding sequences for constant regions of human IgG1 heavy and light chains, respectively. We established a stable production cell line using Chinese hamster ovarian (CHO) cells co-transfected with two expression plasmids driving the expression of either ganglidiximab heavy or light chain. After purification from supernatants, anti-idiotypic characteristics of ganglidiximab were demonstrated. Binding of ganglidiximab to anti-GD2 Abs of the 14.18 family as well as to NK-92tr cells expressing a GD2-specific chimeric antigen receptor (scFv(ch14.18)-zeta) was shown using standard ELISA and flow cytometry analysis, respectively. Ganglidiximab binding affinities to anti-GD2 Abs were further determined by surface plasmon resonance technique. Moreover, binding of anti-GD2 Abs to the nominal antigen GD2 as well as GD2-specific Ab-mediated cytotoxicity (ADCC, CDC) was competitively inhibited by ganglidiximab. Finally, ganglidiximab was successfully used as a protein vaccine in vivo to induce a GD2-specific humoral immune response. In summary, we report generation and characterization of a new human/mouse chimeric anti-Id Ab ganglidiximab for active immunotherapy against NB. This Ab may be useful to tailor immune responses to the paratope regions mimicking GD2 overexpressed in NB

  13. Generation and Characterization of a Human/Mouse Chimeric GD2-Mimicking Anti-Idiotype Antibody Ganglidiximab for Active Immunotherapy against Neuroblastoma.

    PubMed

    Eger, Christin; Siebert, Nikolai; Seidel, Diana; Zumpe, Maxi; Jüttner, Madlen; Brandt, Sven; Müller, Hans-Peter; Lode, Holger N

    2016-01-01

    Vaccination with proteins mimicking GD2 that is highly expressed on neuroblastoma (NB) cells is a promising strategy in treatment of NB, a pediatric malignancy with poor prognosis. We previously showed efficacy of ganglidiomab in vivo, a murine anti-idiotype (anti-Id) IgG1. In order to tailor immune responses to variable regions, we generated a new human/mouse chimeric anti-Id antibody (Ab) ganglidiximab by replacing murine constant fragments with corresponding human IgG1 regions. DNA sequences encoding for variable regions of heavy (VH) and light chains (VL) were synthesized by RT-PCR from total RNA of ganglidiomab-producing hybridoma cells and further ligated into mammalian expression plasmids with coding sequences for constant regions of human IgG1 heavy and light chains, respectively. We established a stable production cell line using Chinese hamster ovarian (CHO) cells co-transfected with two expression plasmids driving the expression of either ganglidiximab heavy or light chain. After purification from supernatants, anti-idiotypic characteristics of ganglidiximab were demonstrated. Binding of ganglidiximab to anti-GD2 Abs of the 14.18 family as well as to NK-92tr cells expressing a GD2-specific chimeric antigen receptor (scFv(ch14.18)-zeta) was shown using standard ELISA and flow cytometry analysis, respectively. Ganglidiximab binding affinities to anti-GD2 Abs were further determined by surface plasmon resonance technique. Moreover, binding of anti-GD2 Abs to the nominal antigen GD2 as well as GD2-specific Ab-mediated cytotoxicity (ADCC, CDC) was competitively inhibited by ganglidiximab. Finally, ganglidiximab was successfully used as a protein vaccine in vivo to induce a GD2-specific humoral immune response. In summary, we report generation and characterization of a new human/mouse chimeric anti-Id Ab ganglidiximab for active immunotherapy against NB. This Ab may be useful to tailor immune responses to the paratope regions mimicking GD2 overexpressed in NB.

  14. Spectral characteristics of fluorescence and circular dichroism of aflatoxin B1 reaction with its anti-idiotypic antibody

    NASA Astrophysics Data System (ADS)

    Liu, Aiping; Yang, Hongxiu; Wang, Xiaohong; Chen, Fusheng

    2012-11-01

    Aflatoxin B1 (AFB1) is a toxic secondary metabolite and sensitive methods for its analysis have been developed. In our lab, a number of works have been carried out, including exploitation of detection methods and production of anti-idiotypic antibody (Ab2) against Fab fragment of anti-AFB1 antibody (Ab1). In this paper, Ab2 was generated upon the immunization of mice with F(ab')2 fragment, which was specific to AFB1 and obtained by pepsin digestion of Ab1. The characteristics of Ab2 was primarily investigated by indirect competitive enzyme-linked immunosorbent assay (icELISA), which indicated that Ab2, might bear an internal image of antigen AFB1 and was able to combine to F(ab')2 in competition with AFB1, and the concentration of Ab2 to cause 50% inhibition of binding (IC50) was 131.8 μg/mL. In addition, fluorescence and circular dichroism studies were designed to explore the mutual relationship among AFB1, F(ab')2 and Ab2. The fluorescence spectroscopy implied that both AFB1 and Ab2 act as a quencher upon F(ab')2, and the Ab2 could compete with AFB1 when both of Ab2 and AFB1 reacted with F(ab')2. The circular dichroism (CD) spectrum suggested that both the binding of Ab2 and AFB1 on F(ab')2 brought secondary conformation change of F(ab')2, especially in the changes of α helix and β sheet. The research performed would provide unique insight into the comprehension of interaction among AFB1, F(ab')2 and Ab2 as well as offer structural information for substitution researches of toxic antigen like AFB1.

  15. QML-AiNet: An immune network approach to learning qualitative differential equation models

    PubMed Central

    Pang, Wei; Coghill, George M.

    2015-01-01

    In this paper, we explore the application of Opt-AiNet, an immune network approach for search and optimisation problems, to learning qualitative models in the form of qualitative differential equations. The Opt-AiNet algorithm is adapted to qualitative model learning problems, resulting in the proposed system QML-AiNet. The potential of QML-AiNet to address the scalability and multimodal search space issues of qualitative model learning has been investigated. More importantly, to further improve the efficiency of QML-AiNet, we also modify the mutation operator according to the features of discrete qualitative model space. Experimental results show that the performance of QML-AiNet is comparable to QML-CLONALG, a QML system using the clonal selection algorithm (CLONALG). More importantly, QML-AiNet with the modified mutation operator can significantly improve the scalability of QML and is much more efficient than QML-CLONALG. PMID:25648212

  16. Immune Markers and Differential Signaling Networks in Ulcerative Colitis and Crohn’s Disease

    PubMed Central

    Christophi, George P.; Rong, Rong; Holtzapple, Philip G.; Massa, Paul T.; Landas, Steve K.

    2012-01-01

    Background & Aims Cytokine signaling pathways play a central role in the pathogenesis of inflammatory bowel disease (IBD). Ulcerative colitis (UC) and Crohn’s disease (CD) have unique as well as overlapping phenotypes, susceptibility genes, and gene expression profiles. This study aimed to delineate patterns within cytokine signaling pathways in colonic mucosa of UC and CD patients, explore molecular diagnostic markers, and identify novel immune-mediators in IBD pathogenesis. Methods We quantified 70 selected immune genes that are important in IBD signaling from formalin-fixed, paraffin-embedded (FFPE) colon biopsy samples from normal control subjects and UC and CD patients having either severe colitis or quiescent disease (n=98 subjects). We utilized and validated a new modified real-time RT-PCR technique for gene quantification. Results Expression levels of signaling molecules including IL-6/10/12/13/17/23/33, STAT1/3/6, T-bet, GATA3, FOXp3, SOCS1/3, and downstream inflammatory mediators such as chemokines CCL-2/11/17/20, oxidative stress inducers, proteases, and mucosal genes were differentially regulated between UC and CD and between active and quiescent disease. We also document the possible role of novel genes in IBD, including SHP-1, IRF-1,TARC, Eotaxin, NOX2, Arginase I, and ADAM 8. Conclusions This comprehensive approach to quantifying gene expression provides insights into the pathogenesis of IBD by elucidating distinct immune signaling networks in CD and UC. Furthermore, this is the first study demonstrating that gene expression profiling in FFPE colon biopsies might be a practical and effective tool in the diagnosis and prognosis of IBD and may help identify molecular markers that can predict and monitor response to individualized therapeutic treatments. PMID:22467146

  17. Idiotypes of murine monoclonal antibodies to clotting factor VIII:C

    SciTech Connect

    Pechet, L.; Tiarks, C.Y.; Ghalili, K.; Humphreys, R.E.

    1986-03-05

    The authors goal is to study idiotypic immunoregulation of inhibitors to clotting factor VIII:C. To this end, they used monoclonal antibodies (MoAbs) against VIII:C: Synbiotics, C7F7, and C5, directed against epitopes on the C terminal fragment of VIII:C; C2, C6, C8 directed against epitopes on the N terminal fragment of VIII:C; C10, directed against a non-functional epitope; IB3, Chemicon and Hybritech, to undetermined epitopes. Anti-idiotypic antibodies against C7F7, C8, Synbiotics and Hybritech were produced in rabbits. Competitive radioimmunoassays (RIA) tested cross-reactivity between each immunogen and the other MoAbs. Synbiotics cross-reacted with Chemicon and IB3, indicating they were directed against the same epitope on the C terminal fragment of VIII:C. They did not cross-react with Hybritech, C7F7, C2, C5, C6, C8, or C10. C7F7 showed no cross-reactivities. C8 cross-reacted with C6 but not with C2, C5, C10, C7F7, Synbiotics, or Hybritech. Hybritech did not did not cross-react with any of the other MoAbs. In conclusion, with four anti-idiotypic antibodies and ten MoAbs to VIII:C, they defined at least five functional epitopes and one non-functional epitope on the factor VIII:C molecule to which inhibitors may develop: C2, C6-C8 (N terminal), C7F7, C5, Synbiotics (C terminal), Hybritech (undetermined epitope) and C10 (non-functional).

  18. Positive network assortativity of influenza vaccination at a high school: implications for outbreak risk and herd immunity.

    PubMed

    Barclay, Victoria C; Smieszek, Timo; He, Jianping; Cao, Guohong; Rainey, Jeanette J; Gao, Hongjiang; Uzicanin, Amra; Salathé, Marcel

    2014-01-01

    Schools are known to play a significant role in the spread of influenza. High vaccination coverage can reduce infectious disease spread within schools and the wider community through vaccine-induced immunity in vaccinated individuals and through the indirect effects afforded by herd immunity. In general, herd immunity is greatest when vaccination coverage is highest, but clusters of unvaccinated individuals can reduce herd immunity. Here, we empirically assess the extent of such clustering by measuring whether vaccinated individuals are randomly distributed or demonstrate positive assortativity across a United States high school contact network. Using computational models based on these empirical measurements, we further assess the impact of assortativity on influenza disease dynamics. We found that the contact network was positively assortative with respect to influenza vaccination: unvaccinated individuals tended to be in contact more often with other unvaccinated individuals than with vaccinated individuals, and these effects were most pronounced when we analyzed contact data collected over multiple days. Of note, unvaccinated males contributed substantially more than unvaccinated females towards the measured positive vaccination assortativity. Influenza simulation models using a positively assortative network resulted in larger average outbreak size, and outbreaks were more likely, compared to an otherwise identical network where vaccinated individuals were not clustered. These findings highlight the importance of understanding and addressing heterogeneities in seasonal influenza vaccine uptake for prevention of large, protracted school-based outbreaks of influenza, in addition to continued efforts to increase overall vaccine coverage.

  19. Isolation from individual A/J mice of anti-rho-azophenylarsonate antibodies bearing a cross-reactive idiotype

    PubMed Central

    1975-01-01

    Immuization of A/J mice with a KLH-p-azophenylarsonate conjugate induces the formation of antihapten antibodies, some of which share idiotypic specificity common to all recipients. The subpopulation carrying the idiotype generally comprises 20-70% of the total antibody content. Large quantities of antihapten antibody (occasionally over 100 mg) were obtained from individual mice through the induction of an ascites fluid. This facilitated isolation of antibodies with the cross- reactive idiotype by isoelectric focusing. Most of this subpopulation has pI values between 6.65 and 6.95 and essentially all is of the IgG1 subclass. Two peaks, near pI 6.7 and 6.9, were frequently observed. Upon refocusing, the protein artifact of the procedure, but indicates microheterogeneity. The antibodies in the two peaks were found to be idiotypically identical by measurements of cross-inhibition. Preliminary studies have indicated that it is feasible to initiate investigations of primary structure with antibodies from individual inbred mice. PMID:46907

  20. Involvement of Immune Cell Network in Aortic Valve Stenosis: Communication between Valvular Interstitial Cells and Immune Cells

    PubMed Central

    Lee, Seung Hyun

    2016-01-01

    Aortic valve stenosis is a heart disease prevalent in the elderly characterized by valvular calcification, fibrosis, and inflammation, but its exact pathogenesis remains unclear. Previously, aortic valve stenosis was thought to be caused by chronic passive and degenerative changes associated with aging. However, recent studies have demonstrated that atherosclerotic processes and inflammation can induce valvular calcification and bone deposition, leading to valvular stenosis. In particular, the most abundant cell type in cardiac valves, valvular interstitial cells, can differentiate into myofibroblasts and osteoblast-like cells, leading to valvular calcification and stenosis. Differentiation of valvular interstitial cells can be trigged by inflammatory stimuli from several immune cell types, including macrophages, dendritic cells, T cells, B cells, and mast cells. This review indicates that crosstalk between immune cells and valvular interstitial cells plays an important role in the development of aortic valve stenosis. PMID:26937229

  1. Gene networks specific for innate immunity define post-traumatic stress disorder.

    PubMed

    Breen, M S; Maihofer, A X; Glatt, S J; Tylee, D S; Chandler, S D; Tsuang, M T; Risbrough, V B; Baker, D G; O'Connor, D T; Nievergelt, C M; Woelk, C H

    2015-12-01

    The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD.

  2. An artificial immune system for securing mobile ad hoc networks against intrusion attacks

    NASA Astrophysics Data System (ADS)

    Hortos, William S.

    2003-08-01

    To mitigate the problem of intrusion attacks by malicious nodes in mobile ad hoc networks (MANETs), security attributes and quantifiable trust levels, unique to the MANET's transient, self-organizing topology, augment or replace traditional protocol metrics of throughput, packet delay and hop-count in the ad hoc route discovery procedures. The new features are unique to the candidate security protocol, which views security as a quality metric to improve the relevance of the routes discovered by established reactive ad hoc routing protocols. Attributes of a secure route are identified in order to define the appropriate metrics to quantify the "level of security" associated with the protocol messaging and the detection of malicious activities by some intrusive nodes. A state vector of features and metrics based on the published Secure Routing Protocol (SRP) for MANETs is constructed to encode network security characteristics. This route discovery protocol mitigates the detrimental effects of various malicious behaviors to provide trustworthy connectivity information. The protocol ensures that fabricated, compromised, or replayed route replies would either be rejected or never reach the querying source node. In this paper, the pattern of values, taken by the state vector of the SRP features in the route request, discovery and reply operations, are analyzed to detect evidence of intrusion attacks by malicious nodes that could lead to denial of service and network shutdown. The pattern analysis applies a technique based on negative selection found in natural immune systems that can detect extraneous patterns in the (nonself) space that is the complement of vector values associated with correct route discovery and route maintenance. The immune system is well-suited to the distributed nature of the MANET. It does not rely on a central controller, but instead uses a distributed detection and response mechanism in order to respond to foreign invaders, mirroring the

  3. Construction and characterization of DNA vaccines encoding the single-chain variable fragment of the anti-idiotype antibody 1A7 mimicking the tumor-associated antigen disialoganglioside GD2.

    PubMed

    Zeytin, H E; Tripathi, P K; Bhattacharya-Chatterjee, M; Foon, K A; Chatterjee, S K

    2000-11-01

    Anti-idiotype antibody, 1A7, functionally mimics the tumor-associated antigen disialoganglioside GD2, which is overexpressed on the surface of a number of neuroectodermal tumors such as melanoma, neuroblastoma, soft tissue sarcoma, and small cell carcinoma of the lung. Immunization of mice with 1A7 generated the production of anti-GD2 antibodies. In a phase I clinical trial, immunization of patients with 1A7, mixed with the adjuvant QS21, demonstrated that 1A7 could act as a surrogate antigen for GD2 and induce strong humoral immune responses in advanced stage melanoma patients. DNA vaccines have recently been shown to invoke humoral as well as cellular responses in injected hosts against the transgene product. To evaluate the efficiency of DNA vaccines encoding anti-idiotype antibodies, we constructed expression plasmids encoding the variable heavy (VH) and variable light (VL) chains of 1A7. The plasmids were made in two configurations, expressing either the VH (pc1A7VHLnVL) or the VL (pc1A7VLLnVH) chain of 1A7 at the amino terminus, linked together by a 15-amino acid linker (Ln). In vitro transcription/translation assays and transfection of CHO-K1 cells with the plasmids demonstrated that a approximately 30-kDa protein was expressed by both configurations of the single-chain variable fragment. This protein can be specifically precipitated by monoclonal anti-GD2 antibody, 14G2a. Following intramuscular injection in mice, the plasmids were detectable in the injected tissues for at least 3 months and the injected plasmids actively transcribed the single-chain variable fragment 1A7 gene at the injected site. A single, intramuscular immunization of a group of C57BL/6 mice with pc1A7VLLnVH in phosphate-buffered saline induced humoral immune responses against 1A7 as well as GD2, the nominal antigen. Multiple immunizations, however, were required to elicit stronger immune responses. PMID:11129285

  4. A murine monoclonal anti-idiotypic antibody detects a common idiotope on human, mouse and rabbit antibodies to allergen Lol p IV.

    PubMed

    Zhou, E M; Dzuba-Fischer, J M; Rector, E S; Sehon, A H; Kisil, F T

    1991-09-01

    A syngeneic mouse monoclonal anti-idiotypic antibody (anti-Id), designated as B1/1, was generated against a monoclonal antibody (MoAb 91) specific for Ryegrass pollen allergen Lol p IV. This anti-Id recognized an idiotope (Id) that was also present on other monoclonal antibodies with the same specificity as MoAb 91. Observations that (i) the anti-Id inhibited the binding of MoAb 91 to Lol p IV and (ii) the Id-anti-Id interaction could be inhibited by Lol p IV indicated that the Id was located within or near the antigen combining site. These properties served to characterize B1/1 as an internal image anti-Id. Evidence that an immune response in different species to Lol p IV elicits the formation of antibodies which express a common Id was provided by the observations that (i) the Id-anti-Id interactions could be inhibited by mouse, human and rabbit antisera to Lol p IV and (ii) the binding of these antisera to Lol p IV could be inhibited by the anti-Id. Interestingly, the internal image anti-Id B1/1 also recognized an Id on a monoclonal antibody which was directed to an epitope of Lol p IV, different from that recognized by MoAb 91.

  5. RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways

    PubMed Central

    Jiang, Lulu; Hindmarch, Charles C. T.; Rogers, Mark; Campbell, Colin; Waterfall, Christy; Coghill, Jane; Mathieson, Peter W.; Welsh, Gavin I.

    2016-01-01

    Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or ‘podocytes’, the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes. PMID:27774996

  6. A cross-reacting human idiotype (B17) associated with antibodies to N-acetyl-D-glucosamine. Specificity, immunoglobulin class association, and distribution in the population.

    PubMed

    Emmrich, F; Greger, B; Eichmann, K

    1983-04-01

    This report describes the study of the expression of an idiotype in the human population which is associated with antibodies to N-acetyl-D-glucosamine (GlcNAc) present in most human sera presumably due to streptococcal infections. The idiotype is identified with antisera and monoclonal antibodies prepared against the IgM (kappa) antibody secreted by the Epstein-Barr virus-transformed human B cell line B17. At least 90% of 207 individuals tested had immunoglobulin with B17 idiotypic determinants in their sera, as demonstrated with conventional and one monoclonal anti-idiotypic antibody. Another monoclonal anti-idiotypic antibody reacted with antibodies in only a few of the sera. No correlation was found between the level of expression of different idiotopes in individual human sera, suggesting molecular heterogeneity of the B17-positive antibody population. B17-positive immunoglobulins are to a large extent specific for GlcNAc but represent only a minor population of all GlcNAc-specific antibodies in human sera. B17 determinants are on IgM (kappa) in all human sera and on IgG and IgA in some. In addition, some lambda-bearing Ig was found to react with anti-B17 antisera, suggesting the detection of VH-associated idiotypic determinants in this experimental system.

  7. Infection propagator approach to compute epidemic thresholds on temporal networks: impact of immunity and of limited temporal resolution

    NASA Astrophysics Data System (ADS)

    Valdano, Eugenio; Poletto, Chiara; Colizza, Vittoria

    2015-12-01

    The epidemic threshold of a spreading process indicates the condition for the occurrence of the wide spreading regime, thus representing a predictor of the network vulnerability to the epidemic. Such threshold depends on the natural history of the disease and on the pattern of contacts of the network with its time variation. Based on the theoretical framework introduced in [E. Valdano, L. Ferreri, C. Poletto, V. Colizza, Phys. Rev. X 5, 21005 (2015)] for a susceptible-infectious-susceptible model, we formulate here an infection propagator approach to compute the epidemic threshold accounting for more realistic effects regarding a varying force of infection per contact, the presence of immunity, and a limited time resolution of the temporal network. We apply the approach to two temporal network models and an empirical dataset of school contacts. We find that permanent or temporary immunity do not affect the estimation of the epidemic threshold through the infection propagator approach. Comparisons with numerical results show the good agreement of the analytical predictions. Aggregating the temporal network rapidly deteriorates the predictions, except for slow diseases once the heterogeneity of the links is preserved. Weight-topology correlations are found to be the critical factor to be preserved to improve accuracy in the prediction.

  8. Association of the Idiotype:Antiidiotype Antibody Ratio With the Efficacy of Intravenous Immunoglobulin Treatment for the Prevention of Recurrent Autoimmune-Associated Congenital Heart Block

    PubMed Central

    Routsias, John G.; Kyriakidis, Nikolaos C.; Friedman, Deborah M.; Llanos, Carolina; Clancy, Robert; Moutsopoulos, Haralampos M.; Buyon, Jill; Tzioufas, Athanasios G.

    2013-01-01

    Objective Congenital heart block (CHB), a manifestation of neonatal lupus, is associated with maternal anti-Ro/SSA and anti-La/SSB autoantibodies and recurs in ~18% of subsequent pregnancies. This study was undertaken to investigate the effect of the idiotype: antiidiotype (Id:anti-Id) antibody ratio in the ability of intravenous immunoglobulin (IVIG) administered during subsequent pregnancies to prevent CHB. Methods We studied 16 anti-Ro/SSA and anti-La/ SSB–positive pregnant women from the Preventive IVIG Therapy for Congenital Heart Block study who had previously given birth to a child with neonatal lupus. In 3 of the mothers, the study pregnancy resulted in the birth of a child with neonatal lupus (2 with CHB and 1 with rash). Sequential serum samples were obtained from all mothers immediately before the administration of IVIG during pregnancy and were evaluated for antibodies against the major B cell epitope 349–364aa of La/SSB (idiotype) and its antiidiotypic antibodies. Results Following IVIG treatment, serum titers of anti-La(349–364) (Id antibodies) decreased in 80% of the mothers, and in 60% an increase in anti-Id antibodies against anti-La(349–364) was observed. The Id: anti-Id ratio was significantly higher in mothers whose offspring developed neonatal lupus compared to mothers who gave birth to a healthy child (P < 0.0001). Removal of anti-Id antibodies substantially increased the reactivity against La(349–364) in sera from 5 of 7 mothers tested. All IVIG preparations were examined for Id and anti-Id antibody activity. IVIG from batches administered to mothers who gave birth to a healthy child had an Id:anti-Id activity ratio of <1, in contrast to that given to mothers who gave birth to a child with neonatal lupus. Addition of the IVIG preparations to the maternal sera further enhanced antiidiotypic activity (by up to 4.7-fold) in 11 of 13 patients studied. Conclusion This is the first study in humans to demonstrate that IVIG influences the

  9. Seronegative rheumatoid arthritis, rheumatoid factor cross reactive idiotype expression, and hidden rheumatoid factors.

    PubMed

    Bonagura, V R; Wedgwood, J F; Agostino, N; Hatam, L; Mendez, L; Jaffe, I; Pernis, B

    1989-06-01

    The major rheumatoid factor cross reactive idiotype (RCRI), defined by prototypic monoclonal rheumatoid factors (RFs), is expressed as a dominant idiotype by pokeweed mitogen induced plasma cells obtained from seropositive (RF+) patients with rheumatoid arthritis (RA). Some patients who meet clinical diagnostic criteria for RA set by the American Rheumatism Association fail to express RFs at any time during their clinical course. To determine if seronegative (RF-) patients with RA, so designated by the latex fixation, Rose-Waaler classic binding assays, or a RF enzyme linked immunosorbent assay (ELISA), express the RCRI in the absence of detectable RFs we examined pokeweed mitogen plasma cells from these patients by indirect immunofluorescence. In addition, we used an inhibition ELISA to detect RCRI bearing molecules in the sera of RF- patients with RA. Five of 10 RF- patients with RA had a high prevalence of RCRI+ plasma cells (16-49% of total pokeweed mitogen plasma cells in culture). Six of 20 RF- patients with RA had high serum concentrations of molecules marked by the RCRI, equivalent to 21-110 micrograms/ml of RCRI+ reference monoclonal IgM RF. Four of five patients who expressed the RCRI in high prevalence in pokeweed mitogen plasma cells, also demonstrated high concentrations of RCRI in their sera detected by inhibition ELISA. There was significant concordance of RCRI expression determined by the two different assays. Four RF- patients with RA who expressed RCRI in their whole sera had hidden RFs detected in their 19S and, in one case, 7S serum fraction. Detection of RF related molecules in whole sera by the expression of RCRI in RF- patients with RA identifies a subgroup of RF- patients with RA who possess hidden RFs. Some RF- patients with RA can express the major RCRI in pokeweed mitogen plasma cells and in their sera and therefore are related to patients with prototypic Waldenstrom's macroglobulinaemia, who produce RCRI+ 19S IgM monoclonal RFs.

  10. Anti-receptor antibodies designed to elicit "internal image"-bearing anti-idiotypes: a possible AIDS vaccine.

    PubMed

    Ludwig, D S; Schoolnik, G K

    1987-07-01

    Two obstacles hinder the development of an AIDS vaccine: (1) the AIDS virus exhibits extensive amino acid heterogeneity between isolates and (2) antibodies elicited by virus during the course of natural infection are often non-neutralizing. A vaccine designed to induce anti-idiotypic antibodies against the virus' receptor on T-cells, T4, should, in principle, overcome these obstacles. Such antibody could contain an "internal image" of T4 and bind the receptor binding domain of the virus. Since this domain is both critical to function and, therefore, poorly susceptible to antigenic variation, anti-receptor anti-idiotypic antibodies may demonstrate broad, strain-independent crossreactivity and block viral adherence.

  11. Anti-idiotypic Fab Fragments Image a Conserved N-terminal Epitope Patch of Grass Pollen Allergen Phl p 1.

    PubMed

    Lukschal, Anna; Fuhrmann, Jan; Sobanov, Juryj; Neumann, Dirk; Wallmann, Julia; Knittelfelder, Regina; Hemmer, Wolfgang; Scheiner, Otto; Vogel, Monique; Stadler, Beda M; Jensen-Jarolim, Erika; Szalai, Krisztina

    2011-05-23

    BACKGROUND AND AIMS: Naturally occurring anti-idiotypic antibodies structurally mimic the original antibody epitope. Anti-idiotypes, therefore, are interesting tools for the portrayal of conformational B-cell epitopes of allergens. In this study we used this strategy particularly for major timothy grass pollen (Phleum pratense) allergen Phl p 1. METHODS AND RESULTS: We used a combinatorial phage display library constructed from the peripheral IgG repertoire of a grass pollen allergic patient which was supposed to contain anti-idiotypic Fab specificities. Using purified anti-Phl p 1 IgG for biopanning, several Fab displaying phage clones could be isolated. 100 amplified colonies were screened for their binding capacity to anti-Phl p 1-specific antibodies, finally resulting in four distinct Fab clones according to sequence analysis. Interestingly, heavy chains of all clones derived from the same germ line sequence and showed high homology in their CDRs. Projecting their sequence information on the surface of the natural allergen Phl p 1 (PDB ID: 1N10) indicated matches on the N-terminal domain of the homo-dimeric allergen, including the bridging region between the two monomers. The resulting epitope patches were formed by spatially distant sections of the primary allergen sequence. CONCLUSION: In this study we report that anti-idiotypic specificities towards anti-Phl p 1 IgG, selected from a Fab library of a grass pollen allergic patient, mimic a conformational epitope patch being distinct from a previously reported IgE epitope area. PMID:22318973

  12. Anti-idiotypic VHH phage display-mediated immuno-PCR for ultrasensitive determination of mycotoxin zearalenone in cereals.

    PubMed

    Wang, Xianxian; He, Qinghua; Xu, Yang; Liu, Xing; Shu, Mei; Tu, Zhui; Li, Yanping; Wang, Wei; Cao, Dongmei

    2016-01-15

    Immunoassay is frequently used to analyze mycotoxin contamination. However, the introduction of mycotoxins or their conjugates in conventional immunoassay threatens the safety of individuals and the environment. The variable domain of heavy-chain antibodies (VHHs) can be used as alternative compounds to produce anti-idiotypic antibodies, which work as non-toxic surrogate reagents in immunoassay. In this work, anti-zearalenone (ZEN) monoclonal antibody (mAb) was used as the target for biopanning anti-idiotypic VHH from a naïve alpaca VHH phage display library. After four panning cycles, one anti-idiotypic VHH phage clone (Z1) was isolated and the Z1 based phage ELISA for ZEN showed a half inhibitory concentration (IC50) of 0.25±0.02ng/mL, a linear range of 0.11-0.55ng/mL, and a limit of detection (LOD) of 0.08ng/mL. Furthermore, the phage particles of Z1 were also applied to immuno-polymerase chain reaction (PD-IPCR), which supplied both the detection antigens and deoxyribonucleic acid (DNA) templates. Compared with that of phage ELISA, the LOD of Z1 based PD-IPCR was 12-fold improved, with a detection limit of 6.5pg/mL and a linear range of 0.01-100ng/mL. The proposed method was then validated with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results showed the reliability of PD-IPCR for the determination of ZEN in cereal samples. The use of anti-idiotypic VHH phage as non-toxic surrogate and signal-amplification function of PCR make it a promising method for actual ZEN analysis in cereals. PMID:26592626

  13. Preferential expression of the systemic lupus erythematosus-associated idiotype 8.12 in sera containing monoclonal immunoglobulins.

    PubMed

    Livneh, A; Preud'Homme, J L; Solomon, A; Diamond, B

    1987-12-01

    The 8.12 idiotype defines a population of anti-DNA antibodies present in the serum of patients with systemic lupus erythematosus. As part of our studies to elucidate the genetic origin and structural features of anti-DNA antibodies, we examined monoclonal immunoglobulin (Ig)-containing sera from 706 patients for expression of the 8.12 idiotype. We found 41 such sera to have significant 8.12 reactivity (greater than 4 SD above the mean of normal controls) and demonstrated that in 24 of these sera (8 IgM, 14 IgG, and 2 IgA) this reactivity could be localized to the monoclonal protein. In addition, 12 of the 8.12-reactive monoclonal Ig (11 IgG and 1 IgA) bind dsDNA. In the other 17 sera, the 8.12 reactivity could be attributed to polyclonal antibody. These findings provide further evidence that the serum monoclonal Ig frequently express the antigenic and idiotypic reactivities of autoantibodies. Furthermore, these data support the contention that anti-DNA specificity may result from somatic diversification of germ-line Ig gene sequences. PMID:3119715

  14. Neuro-Endocrine Networks Controlling Immune System in Health and Disease

    PubMed Central

    Procaccini, Claudio; Pucino, Valentina; De Rosa, Veronica; Marone, Gianni; Matarese, Giuseppe

    2014-01-01

    The nervous and immune systems have long been considered as compartments that perform separate and different functions. However, recent clinical, epidemiological, and experimental data have suggested that the pathogenesis of several immune-mediated disorders, such as multiple sclerosis (MS), might involve factors, hormones, and neural mediators that link the immune and nervous system. These molecules are members of the same superfamily, which allow the mutual and bi-directional neural–immune interaction. More recently, the discovery of leptin, one of the most abundant adipocyte-derived hormones that control food intake and metabolism, has suggested that nutritional/metabolic status, acting at central level, can control immune self-tolerance, since it promotes experimental autoimmune encephalomyelitis, an animal model of MS. Here, we summarize the most recent advances and the key players linking the central nervous system, immune tolerance, and the metabolic status. Understanding this coordinated interaction may pave the way for novel therapeutic approaches to increase host defense and suppress immune-mediated disorders. PMID:24778633

  15. V(H)3 antibody response to immunization with pneumococcal polysaccharide vaccine in middle-aged and elderly persons.

    PubMed

    Serpa, Jose A; Valayam, Josemon; Musher, Daniel M; Rossen, Roger D; Pirofski, Liise-anne; Rodriguez-Barradas, Maria C

    2011-03-01

    Pneumococcal disease continues to cause substantial morbidity and mortality among the elderly. Older adults may have high levels of anticapsular antibody after vaccination, but their antibodies show decreased functional activity. In addition, the protective effect of the pneumococcal polysaccharide vaccine (PPV) seems to cease as early as 3 to 5 years postvaccination. Recently, it was suggested that PPV elicits human antibodies that use predominantly V(H)3 gene segments and induce a repertoire shift with increased V(H)3 expression in peripheral B cells. Here we compared V(H)3-idiotypic antibody responses in middle-aged and elderly subjects receiving PPV as initial immunization or revaccination. We studied pre- and postvaccination sera from 36 (18 vaccine-naïve and 18 previously immunized subjects) middle-aged and 40 (22 vaccine-naïve and 18 previously immunized subjects) elderly adults who received 23-valent PPV. Concentrations of IgGs to four individual serotypes (6B, 14, 19F, and 23F) and of V(H)3-idiotypic antibodies (detected by the monoclonal antibody D12) to the whole pneumococcal vaccine were determined by enzyme-linked immunosorbent assay (ELISA). PPV elicited significant IgG and V(H)3-idiotypic antibody responses in middle-aged and elderly subjects, regardless of whether they were vaccine naïve or undergoing revaccination. Age did not influence the magnitude of the antibody responses, as evidenced by similar postvaccination IgG and V(H)3 antibody levels in both groups, even after stratifying by prior vaccine status. Furthermore, we found similar proportions (around 50%) of elderly and middle-aged subjects experiencing 2-fold increases in V(H)3 antibody titers after vaccination. Age or repeated immunization does not appear to affect the V(H)3-idiotypic immunogenicity of PPV among middle-aged and elderly adults.

  16. Analysis and simulation of the dynamic spectrum allocation based on parallel immune optimization in cognitive wireless networks.

    PubMed

    Huixin, Wu; Duo, Mo; He, Li

    2014-01-01

    Spectrum allocation is one of the key issues to improve spectrum efficiency and has become the hot topic in the research of cognitive wireless network. This paper discusses the real-time feature and efficiency of dynamic spectrum allocation and presents a new spectrum allocation algorithm based on the master-slave parallel immune optimization model. The algorithm designs a new encoding scheme for the antibody based on the demand for convergence rate and population diversity. For improving the calculating efficiency, the antibody affinity in the population is calculated in multiple computing nodes at the same time. Simulation results show that the algorithm reduces the total spectrum allocation time and can achieve higher network profits. Compared with traditional serial algorithms, the algorithm proposed in this paper has better speedup ratio and parallel efficiency.

  17. Analysis and Simulation of the Dynamic Spectrum Allocation Based on Parallel Immune Optimization in Cognitive Wireless Networks

    PubMed Central

    Huixin, Wu; Duo, Mo; He, Li

    2014-01-01

    Spectrum allocation is one of the key issues to improve spectrum efficiency and has become the hot topic in the research of cognitive wireless network. This paper discusses the real-time feature and efficiency of dynamic spectrum allocation and presents a new spectrum allocation algorithm based on the master-slave parallel immune optimization model. The algorithm designs a new encoding scheme for the antibody based on the demand for convergence rate and population diversity. For improving the calculating efficiency, the antibody affinity in the population is calculated in multiple computing nodes at the same time. Simulation results show that the algorithm reduces the total spectrum allocation time and can achieve higher network profits. Compared with traditional serial algorithms, the algorithm proposed in this paper has better speedup ratio and parallel efficiency. PMID:25254255

  18. CD40L induces functional tunneling nanotube networks exclusively in dendritic cells programmed by mediators of type-1 immunity

    PubMed Central

    Zaccard, Colleen R.; Watkins, Simon C.; Kalinski, Pawel; Fecek, Ronald J.; Yates, Aarika L.; Salter, Russell D.; Ayyavoo, Velpandi; Rinaldo, Charles R.; Mailliard, Robbie B.

    2014-01-01

    The ability of dendritic cells (DC) to mediate CD4+ T cell help for cellular immunity is guided by instructive signals received during DC maturation, and the resulting pattern of DC responsiveness to the Th signal, CD40L. Furthermore, the professional transfer of antigenic information from migratory DC to lymph node-residing DC is critical for the effective induction of cellular immune responses. Here we report that, in addition to their enhanced IL-12p70 producing capacity, human DC matured in the presence of inflammatory mediators of type-1 immunity (DC1) are uniquely programmed to form networks of tunneling nanotube-like structures in response to CD40L-expressing Th cells or recombinant CD40L. This immunologic process of DC ‘reticulation’ facilitates intercellular trafficking of endosome-associated vesicles and Ag, but also pathogens such HIV-1, and is regulated by the opposing roles of IFN-γ and IL-4. The initiation of DC reticulation represents a novel helper function of CD40L and a superior mechanism of intercellular communication possessed by DC1, as well as a target for exploitation by pathogens to enhance direct cell-to-cell spread. PMID:25548234

  19. Network Signatures of IgG Immune Repertoires in Hepatitis B Associated Chronic Infection and Vaccination Responses

    PubMed Central

    Chang, Ya-Hui; Kuan, Hui-Chung; Hsieh, T. C.; Ma, K. H.; Yang, Chung-Hsiang; Hsu, Wei-Bin; Tsai, Shih-Feng; Chao, Anne; Liu, Hong-Hsing

    2016-01-01

    The repertoire of IgG antibody responses to infection and vaccination varies depending on the characteristics of the immunogen and the ability of the host to mount a protective immune response. Chronic hepatitis B virus (HBV) infections are marked by persistent infection and immune tolerance to vaccination. This disease offers a unique opportunity to discover key repertoire signatures during infection and in response to vaccination. Complementarity determining region 3 of an antibody heavy chain (CDR-H3) has a major impact on the antigenic specificity of an antibody. We used next-generation sequencing to characterize the CDR-H3 sequences in paired siblings of 4 families in which only one member of each pair had chronic HBV infection. Blood samples were obtained before and 2 weeks after HBV vaccination. The analysis revealed a huge network of sequence-related CDR-H3 clones found almost exclusively among carriers. In contrast, vaccination induced significant increases of CDR-H3 cluster diversities among siblings without hepatitis B. Several vaccination-associated clone clusters were identified. Similar findings of vaccination-associated clone networks were observed in healthy adults receiving HBV boosters. These strategies can be used to identify signatures of other infectious diseases and accelerate discoveries of antibody sequences with important biomedical implications. PMID:27222149

  20. CD28 Aptamers as Powerful Immune Response Modulators

    PubMed Central

    Pastor, Fernando; Soldevilla, Mario M; Villanueva, Helena; Kolonias, Despina; Inoges, Susana; de Cerio, Ascensión L; Kandzia, Romy; Klimyuk, Victor; Gleba, Yuri; Gilboa, Eli; Bendandi, Maurizio

    2013-01-01

    CD28 is one of the main costimulatory receptors responsible for the proper activation of T lymphocytes. We have isolated two aptamers that bind to the CD28 receptor. As a monomer, one of them interfered with the binding of CD28 to its ligand (B7), precluding the costimulatory signal, whereas the other one was inactive. However, dimerization of any of the anti-CD28 aptamers was sufficient to provide an artificial costimulatory signal. No antibody has featured a dual function (i.e., the ability to work as agonist and antagonist) to date. Two different agonistic structures were engineered for each anti-CD28 aptamer. One showed remarkably improved costimulatory properties, surpassing the agonistic effect of an anti-CD28 antibody. Moreover, we showed in vivo that the CD28 agonistic aptamer is capable of enhancing the cellular immune response against a lymphoma idiotype and of prolonging survival of mice which receive the aptamer together with an idiotype vaccine. The CD28 aptamers described in this work could be used to modulate the immune response either blocking the interaction with B7 or enhancing vaccine-induced immune responses in cancer immunotherapy. PMID:23756353

  1. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system

    PubMed Central

    2010-01-01

    Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information. PMID:20701759

  2. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system.

    PubMed

    Tieri, Paolo; Grignolio, Andrea; Zaikin, Alexey; Mishto, Michele; Remondini, Daniel; Castellani, Gastone C; Franceschi, Claudio

    2010-01-01

    Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information.

  3. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system.

    PubMed

    Tieri, Paolo; Grignolio, Andrea; Zaikin, Alexey; Mishto, Michele; Remondini, Daniel; Castellani, Gastone C; Franceschi, Claudio

    2010-01-01

    Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information. PMID:20701759

  4. Immune System and Disorders

    MedlinePlus

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

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

    PubMed

    Chen, Tinggui; Xiao, Renbin

    2014-01-01

    Artificial bee colony (ABC) algorithm, inspired by the intelligent foraging behavior of honey bees, was proposed by Karaboga. It has been shown to be superior to some conventional intelligent algorithms such as genetic algorithm (GA), artificial colony optimization (ACO), and particle swarm optimization (PSO). However, the ABC still has some limitations. For example, ABC can easily get trapped in the local optimum when handing in functions that have a narrow curving valley, a high eccentric ellipse, or complex multimodal functions. As a result, we proposed an enhanced ABC algorithm called EABC by introducing self-adaptive searching strategy and artificial immune network operators to improve the exploitation and exploration. The simulation results tested on a suite of unimodal or multimodal benchmark functions illustrate that the EABC algorithm outperforms ACO, PSO, and the basic ABC in most of the experiments. PMID:24772023

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

    PubMed Central

    Chen, Tinggui; Xiao, Renbin

    2014-01-01

    Artificial bee colony (ABC) algorithm, inspired by the intelligent foraging behavior of honey bees, was proposed by Karaboga. It has been shown to be superior to some conventional intelligent algorithms such as genetic algorithm (GA), artificial colony optimization (ACO), and particle swarm optimization (PSO). However, the ABC still has some limitations. For example, ABC can easily get trapped in the local optimum when handing in functions that have a narrow curving valley, a high eccentric ellipse, or complex multimodal functions. As a result, we proposed an enhanced ABC algorithm called EABC by introducing self-adaptive searching strategy and artificial immune network operators to improve the exploitation and exploration. The simulation results tested on a suite of unimodal or multimodal benchmark functions illustrate that the EABC algorithm outperforms ACO, PSO, and the basic ABC in most of the experiments. PMID:24772023

  7. The endocrine-immune network during taeniosis by Taenia solium: The role of the pituitary gland.

    PubMed

    Quintanar-Stephano, Andrés; Hernández-Cervantes, Rosalía; Moreno-Mendoza, Norma; Escobedo, Galileo; Carrero, Julio Cesar; Nava-Castro, Karen E; Morales-Montor, Jorge

    2015-12-01

    It is well known that sex hormones play an important role during Taenia solium infection; however, to our knowledge no studies exist concerning the immune response following complete or lobe-specific removal of the pituitary gland during T. solium infection. Thus, the aim of this work was to analyze in hamsters, the effects of lack of pituitary hormones on the duodenal immune response, and their impact on T. solium establishment and development. Thus, in order to achieve this goal, we perform anterior pituitary lobectomy (AL, n = 9), neurointermediate pituitary lobectomy (NIL, n = 9) and total hypophysectomy (HYPOX, n = 8), and related to the gut establishment and growth of T. solium, hematoxylin-eosin staining of duodenal tissue and immunofluorescence of duodenal cytokine expression and compared these results to the control intact (n = 8) and control infected group (n = 8). Our results indicate that 15 days post-infection, HYPOX reduces the number and size of intestinally recovered T. solium adults. Using semiquantitative immunofluorescent laser confocal microscopy, we observed that the mean intensity of duodenal IFN-γ and IL-12 Th1 cytokines was mildly expressed in the infected controls, in contrast with the high level of expression of these cytokines in the NIL infected hamsters. Likewise, the duodenum of HYPOX animals showed an increase in the expression of Th2 cytokines IL-5 and IL-6, when compared to control hamsters. Histological analysis of duodenal mucosa from HYPOX hamsters revealed an exacerbated inflammatory infiltrate located along the lamina propria and related to the presence of the parasite. We conclude that lobe-specific pituitary hormones affect differentially the T. solium development and the gut immune response. PMID:26481692

  8. The endocrine-immune network during taeniosis by Taenia solium: The role of the pituitary gland.

    PubMed

    Quintanar-Stephano, Andrés; Hernández-Cervantes, Rosalía; Moreno-Mendoza, Norma; Escobedo, Galileo; Carrero, Julio Cesar; Nava-Castro, Karen E; Morales-Montor, Jorge

    2015-12-01

    It is well known that sex hormones play an important role during Taenia solium infection; however, to our knowledge no studies exist concerning the immune response following complete or lobe-specific removal of the pituitary gland during T. solium infection. Thus, the aim of this work was to analyze in hamsters, the effects of lack of pituitary hormones on the duodenal immune response, and their impact on T. solium establishment and development. Thus, in order to achieve this goal, we perform anterior pituitary lobectomy (AL, n = 9), neurointermediate pituitary lobectomy (NIL, n = 9) and total hypophysectomy (HYPOX, n = 8), and related to the gut establishment and growth of T. solium, hematoxylin-eosin staining of duodenal tissue and immunofluorescence of duodenal cytokine expression and compared these results to the control intact (n = 8) and control infected group (n = 8). Our results indicate that 15 days post-infection, HYPOX reduces the number and size of intestinally recovered T. solium adults. Using semiquantitative immunofluorescent laser confocal microscopy, we observed that the mean intensity of duodenal IFN-γ and IL-12 Th1 cytokines was mildly expressed in the infected controls, in contrast with the high level of expression of these cytokines in the NIL infected hamsters. Likewise, the duodenum of HYPOX animals showed an increase in the expression of Th2 cytokines IL-5 and IL-6, when compared to control hamsters. Histological analysis of duodenal mucosa from HYPOX hamsters revealed an exacerbated inflammatory infiltrate located along the lamina propria and related to the presence of the parasite. We conclude that lobe-specific pituitary hormones affect differentially the T. solium development and the gut immune response.

  9. Production of an anti-idiotypic antibody single chain variable fragment vaccine against Edwardsiella tarda.

    PubMed

    Qin, Hong; Jin, Xiaohang; Huang, Weiquan; Liu, Yulin

    2010-02-01

    Edwardsiella tarda is the pathogen responsible for edwardsiellosis, a serious infectious disease of freshwater and marine fish species, and currently recognized to be the species pathogenic for human. An anti-idiotypic monoclonal antibody (mAb), 1E11, has been developed. It mimics the protective epitope of E. tarda and can prevent fish from infection of E. tarda. In this study, the correct variable heavy (VH) and variable light (VL) genes were obtained from 1E11 by using bioinformatics methods, and a 15 amino acid (Gly4Ser)3 linker was used to hold the two V domains together for the construction of VL-linker-VH form of single chain variable fragment (scFv) gene. Then, the scFv was subcloned into the vector pET-28a, expressed in the Escherichia coli BL21 cells, and identified by SDS-PAGE and western blotting. Red drum (Sciaenops ocellatus L.) weighing about 50 g was subjected to challenge with different E. tarda strains after 4 weeks followed by vaccination, the mortality rates and relative percentage survival were recorded and calculated, and the survival rate of fish in the scFv subgroups was obviously higher than that of control subgroups (P<0.01). Enzyme-linked immunosorbent assay results show that after 4 weeks of post-vaccination, the level of specific antibody in fish sera of scFv groups was significantly higher than control groups. This study indicates that the recombinant antibody scFv was successfully developed, and it may serve as an effective vaccine candidate against E. tarda. PMID:20119624

  10. Unmasking the anti-La/SSB response in sera from patients with Sjogren's syndrome by specific blocking of anti-idiotypic antibodies to La/SSB antigenic determinants.

    PubMed Central

    Routsias, John G.; Touloupi, Evgenia; Dotsika, Eleni; Moulia, Avrilia; Tsikaris, Vassilios; Sakarellos, Constantinos; Sakarellos-Daitsiotis, Maria; Moutsopoulos, Haralampos M.; Tzioufas, Athanasios G.

    2002-01-01

    BACKGROUND: Autoantigen La/SSB is molecular target of humoral autoimmunity in patients with primary Sjogren's Syndrome (pSS) and systemic lupus erythematosus (SLE). In this study, we investigated the existence and possible influence of anti-idiotypic response to anti-La/SSB antibodies. MATERIALS AND METHODS: Synthetic peptide analogs (pep) of the major antigenic determinants of La/SSB (289-308 aa and 349-364 aa) were prepared. Based on "molecular recognition" theory, complementary peptides (cpep), derived by anti-parallel readings of the noncoding strand of La/SSB DNA encoding for its antigenic determinants, were constructed. Sera from 150 patients with anti-La/SSB antibodies, 30 patients without anti-La/SSB antibodies, and 42 normal individuals were tested against all four peptides. F(ab')(2) fragments from anti-peptide IgG were prepared and F(ab')(2) - IgG interactions were evaluated using a specific anti-idiotypic ELISA. RESULTS: All four peptides were recognized by anti-La positive sera (83% and 51% for pep and cpep 349-364 and 51% and 28% for pep and cpep289-308, respectively). Anti-cpep F(ab')(2 )bound to a common idiotype (Id) located within or spatially close to the antigen combining site of anti La/SSB (anti-pep) antibodies. Homologous and cross-inhibition experiments further confirmed this relation. The anti-idiotypic antibodies inhibited the anti-La/SSB antibody binding to recombinant La/SSB by 91%. To overcome the anti-idiotypic interference in anti-La/SSB detection, a specific assay was developed. Sera were heated for dissociation of Id-anti-Id complexes, anti-Id antibodies blocked with cpep, and anti-La/SSB reactivity was recovered. Application of this method to anti-Ro positive-anti-La/SSB "negative" sera showed that all anti-Ro/SSA positive autoimmune sera also possess anti-La/SSB antibodies. This reaction was not observed in 14 anti-Ro negative- anti-Sm/RNP positive sera from patients with SLE. CONCLUSIONS: Autoimmune sera from patients with p

  11. Transcriptional networks associated with the immune system are disrupted by organochlorine pesticides in largemouth bass (Micropterus salmoides) ovary.

    PubMed

    Martyniuk, Christopher J; Doperalski, Nicholas J; Feswick, April; Prucha, Melinda S; Kroll, Kevin J; Barber, David S; Denslow, Nancy D

    2016-08-01

    were altered by p, p' DDE, MXC, and flutamide. Interestingly, immune-related gene networks were suppressed by all three chemicals. The data suggest that p, p' DDE and flutamide affected more genes in common with each other than either chemical with MXC, consistent with studies suggesting that p, p' DDE is a more potent anti-androgen than MXC. These data demonstrate that reproductive health was not affected by these specific dietary treatments, but rather the immune system, which may be a significant target of organochlorine pesticides. The interaction between the reproductive and immune systems should be considered in future studies on these legacy and persistent pesticides.

  12. Transcriptional networks associated with the immune system are disrupted by organochlorine pesticides in largemouth bass (Micropterus salmoides) ovary.

    PubMed

    Martyniuk, Christopher J; Doperalski, Nicholas J; Feswick, April; Prucha, Melinda S; Kroll, Kevin J; Barber, David S; Denslow, Nancy D

    2016-08-01

    were altered by p, p' DDE, MXC, and flutamide. Interestingly, immune-related gene networks were suppressed by all three chemicals. The data suggest that p, p' DDE and flutamide affected more genes in common with each other than either chemical with MXC, consistent with studies suggesting that p, p' DDE is a more potent anti-androgen than MXC. These data demonstrate that reproductive health was not affected by these specific dietary treatments, but rather the immune system, which may be a significant target of organochlorine pesticides. The interaction between the reproductive and immune systems should be considered in future studies on these legacy and persistent pesticides. PMID:27391359

  13. The Molecular Engineering of an Anti-Idiotypic Antibody for Pharmacokinetic Analysis of a Fully Human Anti-Infective.

    PubMed

    Lim, She Yah; Chan, Conrad E Z; Lisowska, Malgorzata M; Hanson, Brendon J; MacAry, Paul A

    2015-01-01

    Anti-idiotype monoclonal antibodies represent a class of reagents that are potentially optimal for analyzing the pharmacokinetics of fully human, anti-infective antibodies that have been developed as therapeutic candidates. This is particularly important where direct pathogen binding assays are complicated by requirements for biosafety level III or IV for pathogen handling. In this study, we describe the development of a recombinant, anti-idiotype monoclonal antibody termed E1 for the detection of a fully human, serotype-specific, therapeutic antibody candidate for the BSLIII pathogen Dengue virus termed 14c10 hG1. E1 was generated by naïve human Fab phage library panning technology and subsequently engineered as a monoclonal antibody. We show that E1 is highly specific for the fully-folded form of 14c10 hG1 and can be employed for the detection of this antibody in healthy human subjects' serum by enzyme linked immunosorbent assay. In addition, we show that E1 is capable of blocking the binding of 14c10 hG1 to dengue virus serotype 1. Finally, we show that E1 can detect 14c10 hG1 in mouse serum after the administration of the therapeutic antibody in vivo. E1 represents an important new form of ancillary reagent that can be utilized in the clinical development of a therapeutic human antibody candidate. PMID:26700297

  14. A genome-wide CRISPR screen in primary immune cells to dissect regulatory networks

    PubMed Central

    Parnas, Oren; Jovanovic, Marko; Eisenhaure, Thomas M.; Herbst, Rebecca H.; Dixit, Atray; Ye, Chun Jimmie; Przybylski, Dariusz; Platt, Randall J.; Tirosh, Itay; Sanjana, Neville E.; Shalem, Ophir; Satija, Rahul; Raychowdhury, Raktima; Mertins, Philipp; Carr, Steven A.; Zhang, Feng; Hacohen, Nir; Regev, Aviv

    2015-01-01

    Finding the components of cellular circuits and determining their functions systematically remains a major challenge in mammalian cells. Here, we introduced genome-wide pooled CRISPR-Cas9 libraries into dendritic cells (DCs) to identify genes that control the induction of tumor necrosis factor (Tnf) by bacterial lipopolysaccharide (LPS), a key process in the host response to pathogens, mediated by the Tlr4 pathway. We found many of the known regulators of Tlr4 signaling, as well as dozens of previously unknown candidates that we validated. By measuring protein markers and mRNA profiles in DCs that are deficient in the known or candidate genes, we classified the genes into three functional modules with distinct effects on the canonical responses to LPS, and highlighted functions for the PAF complex and oligosaccharyltransferase (OST) complex. Our findings uncover new facets of innate immune circuits in primary cells, and provide a genetic approach for dissection of mammalian cell circuits. PMID:26189680

  15. Functional mapping of the anti-idiotypic antibody anti-TS1 scFv using site-directed mutagenesis and kinetic analysis

    PubMed Central

    Erlandsson, Ann; Holm, Patrik; Jafari, Rozbeh; Stigbrand, Torgny

    2010-01-01

    Recombinant antibodies may be engineered to obtain improved functional properties. Functional mapping of the residues in the binding surfaces is of importance for predicting alterations needed to yield the desired properties. In this investigation, 17 single mutation mutant single-chain variable fragments (scFvs) of the anti-idiotypic antibody anti-TS1 were generated in order to functionally map amino acid residues important for the interaction with its idiotype TS1. Residues in anti-TS1 determined to be very important for the interaction were identified, Y32L, K50L, K33H and Y52H, and they were distributed adjacent to a centrally located hydrophobic area and contributed extensively to the interaction energy (≥2.5 kcal/mol) in the interaction. Quantitative ELISA assays, BIAcore technologies and three-dimensional surface analysis by modeling were employed to visualize the consequences of the mutations. The expression levels varied between 2–1,800 nM as determined by ELISA. All the 17 scFvs displayed higher dissociation rates (60–1,300 times) and all but two of them also displayed faster association rates (1.3–56 times). The decrease in affinity was determined to be 1.6–12,200 times. Two of the mutants displayed almost identical affinity with the wild-type anti-TS1, but with a change in both association and dissociation rates. The present investigation demonstrates that it is possible to generate a large panorama of anti-idiotypic antibodies and single out a few that might be of potential use for future clearing and pre-targeting purposes of idiotypic-anti-idiotypic interactions. PMID:21124071

  16. A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses

    PubMed Central

    Köberlin, Marielle S.; Snijder, Berend; Heinz, Leonhard X.; Baumann, Christoph L.; Fauster, Astrid; Vladimer, Gregory I.; Gavin, Anne-Claude; Superti-Furga, Giulio

    2015-01-01

    Summary Lipid composition affects the biophysical properties of membranes that provide a platform for receptor-mediated cellular signaling. To study the regulatory role of membrane lipid composition, we combined genetic perturbations of sphingolipid metabolism with the quantification of diverse steps in Toll-like receptor (TLR) signaling and mass spectrometry-based lipidomics. Membrane lipid composition was broadly affected by these perturbations, revealing a circular network of coregulated sphingolipids and glycerophospholipids. This evolutionarily conserved network architecture simultaneously reflected membrane lipid metabolism, subcellular localization, and adaptation mechanisms. Integration of the diverse TLR-induced inflammatory phenotypes with changes in lipid abundance assigned distinct functional roles to individual lipid species organized across the network. This functional annotation accurately predicted the inflammatory response of cells derived from patients suffering from lipid storage disorders, based solely on their altered membrane lipid composition. The analytical strategy described here empowers the understanding of higher-level organization of membrane lipid function in diverse biological systems. PMID:26095250

  17. Dendritic type, accessory cells within the mammalian thymic microenvironment. Antigen presentation in the dendritic neuro-endocrine-immune cellular network.

    PubMed

    Bodey, B; Bodey, B; Kaiser, H E

    1997-01-01

    During mammalian ontogenesis, the thymic "pure" endodermal epithelial anlage develops and differentiates into a complex cellular microenvironment. Beginning the 7-8th week of intrauterine development, thymic epithelial cells chemotactically regulate (induce) numerous waves of migration of stem cells into the thymus, including the CD34+, yolk sac-derived, committed hematopoietic stem cells. In vitro experiments have established that CD34+ CD38dim human thymocytes differentiate into T lymphocytes when co-cultured with mouse fetal thymic organs. Hematopoietic stem cells for myeloid and thymic stromal dendritic cells (DCs) are present within the minute population of CD34+ progenitors within the mammalian thymus. The common myeloid, DC, natural killer (NK) and T lymphocyte progenitors have also been identified within the CD34+ stem cell population in the human thymus. Interactions between the endocrine and immune systems have been reported in various regions of the mammalian body including the anterior pituitary (AP), the skin, and the central (thymus) and peripheral lymphatic system. The network of bone marrow derived DCs is a part of the reticuloendothelial system (RES) and DCs represent the cellular mediators of these regulatory endocrine-immune interactions. Folliculo-stellate cells (FSC) in the AP, Langerhans cells (LCs) in the skin and lymphatic system, "veiled" cells, lympho-dendritic and interdigitating cells (IDCs) in a number of tissues comprising the lymphatic system are the cell types of the DC meshwork of "professional" antigen presenting cells (APCs). Most of these cells express the immunocytochemical markers S-100, CD1. CD45, CD54, F418, MHC class I and II antigens, Fc and complement receptors. FSCs are non-hormone secreting cells which communicate directly with hormone producing cells, a form of neuro-endocrine-immune regulation. As a result, an attenuation of secretory responses follows stimulation of these cells. FSCs are also the cells in the AP

  18. Head and Neck Cancer Stem Cells: From Identification to Tumor Immune Network.

    PubMed

    Dionne, L K; Driver, E R; Wang, X J

    2015-11-01

    Head and neck squamous cell carcinoma (HNSCC) is the most common form of head and neck cancer. Annually, more than half a million individuals are diagnosed with this devastating disease, with increasing incidence in Europe and Southeast Asia. The diagnosis of HNSCC often occurs in late stages of the disease and is characterized by manifestation of a high-grade primary tumor and/or lymph node metastasis, precluding timely management of this deadly cancer. Recently, HNSCC cancer stem cells have emerged as an important factor for cancer initiation and maintenance of tumor bulk. Like normal stem cells, cancer stem cells can undergo self-renewal and differentiation. This unique trait allows for maintenance of the cancer stem cell pool and facilitates differentiation into heterogeneous neoplastic progeny when necessary. Recent studies have suggested coexistence of different cancer stem cell populations within a tumor mass, where the tumor initiation and metastasis properties of these cancer stem cells can be uncoupled. Cancer stem cells also possess resistant phenotypes that evade standard chemotherapy and radiotherapy, resulting in tumor relapse. Therefore, understanding distinctive pathways relating to cancer stem cells will provide insight into early diagnosis and treatment of HNSCC. In this review, we highlight current advances in identifying cancer stem cells, detail the interactions of these cells with the immune system within the tumor niche, and discuss the potential use of immunotherapy in managing HNSCC.

  19. Immune response

    MedlinePlus

    Innate immunity; Humoral immunity; Cellular immunity; Immunity; Inflammatory response; Acquired (adaptive) immunity ... and usually does not react against them. INNATE IMMUNITY Innate, or nonspecific, immunity is the defense system ...

  20. High contaminant loads in Lake Apopka's riparian wetland disrupt gene networks involved in reproduction and immune function in largemouth bass.

    PubMed

    Martyniuk, Christopher J; Doperalski, Nicholas J; Prucha, Melinda S; Zhang, Ji-Liang; Kroll, Kevin J; Conrow, Roxanne; Barber, David S; Denslow, Nancy D

    2016-09-01

    Lake Apopka (FL, USA) has elevated levels of some organochlorine pesticides in its sediments and a portion of its watershed has been designated a US Environmental Protection Agency Superfund site. This study assessed reproductive endpoints in Florida largemouth bass (LMB) (Micropterus salmoides floridanus) after placement into experimental ponds adjacent to Lake Apopka. LMB collected from a clean reference site (DeLeon Springs) were stocked at two periods of time into ponds constructed in former farm fields on the north shore of the lake. LMB were stocked during early and late oogenesis to determine if there were different effects of contamination on LMB that may be attributed to their reproductive stage. LMB inhabiting the ponds for ~4months had anywhere from 2 to 800 times higher contaminant load for a number of organochlorine pesticides (e.g. p, p'-DDE, methoxychlor) compared to control animals. Gonadosomatic index and plasma vitellogenin were not different between reproductively-stage matched LMB collected at reference sites compared to those inhabiting the ponds. However, plasma 17β-estradiol was lower in LMB inhabiting the Apopka ponds compared to ovary stage-matched LMB from the St. Johns River, a site used as a reference site. Sub-network enrichment analysis revealed that genes related to reproduction (granulosa function, oocyte development), endocrine function (steroid metabolism, hormone biosynthesis), and immune function (T cell suppression, leukocyte accumulation) were differentially expressed in the ovaries of LMB placed into the ponds. These data suggest that (1) LMB inhabiting the Apopka ponds showed disrupted reproduction and immune responses and that (2) gene expression profiles provided site-specific information by discriminating LMB from different macro-habitats. PMID:27397556

  1. High contaminant loads in Lake Apopka's riparian wetland disrupt gene networks involved in reproduction and immune function in largemouth bass.

    PubMed

    Martyniuk, Christopher J; Doperalski, Nicholas J; Prucha, Melinda S; Zhang, Ji-Liang; Kroll, Kevin J; Conrow, Roxanne; Barber, David S; Denslow, Nancy D

    2016-09-01

    Lake Apopka (FL, USA) has elevated levels of some organochlorine pesticides in its sediments and a portion of its watershed has been designated a US Environmental Protection Agency Superfund site. This study assessed reproductive endpoints in Florida largemouth bass (LMB) (Micropterus salmoides floridanus) after placement into experimental ponds adjacent to Lake Apopka. LMB collected from a clean reference site (DeLeon Springs) were stocked at two periods of time into ponds constructed in former farm fields on the north shore of the lake. LMB were stocked during early and late oogenesis to determine if there were different effects of contamination on LMB that may be attributed to their reproductive stage. LMB inhabiting the ponds for ~4months had anywhere from 2 to 800 times higher contaminant load for a number of organochlorine pesticides (e.g. p, p'-DDE, methoxychlor) compared to control animals. Gonadosomatic index and plasma vitellogenin were not different between reproductively-stage matched LMB collected at reference sites compared to those inhabiting the ponds. However, plasma 17β-estradiol was lower in LMB inhabiting the Apopka ponds compared to ovary stage-matched LMB from the St. Johns River, a site used as a reference site. Sub-network enrichment analysis revealed that genes related to reproduction (granulosa function, oocyte development), endocrine function (steroid metabolism, hormone biosynthesis), and immune function (T cell suppression, leukocyte accumulation) were differentially expressed in the ovaries of LMB placed into the ponds. These data suggest that (1) LMB inhabiting the Apopka ponds showed disrupted reproduction and immune responses and that (2) gene expression profiles provided site-specific information by discriminating LMB from different macro-habitats.

  2. Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling

    PubMed Central

    Burroughs, A. Maxwell; Zhang, Dapeng; Schäffer, Daniel E.; Iyer, Lakshminarayan M.; Aravind, L.

    2015-01-01

    Cyclic di- and linear oligo-nucleotide signals activate defenses against invasive nucleic acids in animal immunity; however, their evolutionary antecedents are poorly understood. Using comparative genomics, sequence and structure analysis, we uncovered a vast network of systems defined by conserved prokaryotic gene-neighborhoods, which encode enzymes generating such nucleotides or alternatively processing them to yield potential signaling molecules. The nucleotide-generating enzymes include several clades of the DNA-polymerase β-like superfamily (including Vibrio cholerae DncV), a minimal version of the CRISPR polymerase and DisA-like cyclic-di-AMP synthetases. Nucleotide-binding/processing domains include TIR domains and members of a superfamily prototyped by Smf/DprA proteins and base (cytokinin)-releasing LOG enzymes. They are combined in conserved gene-neighborhoods with genes for a plethora of protein superfamilies, which we predict to function as nucleotide-sensors and effectors targeting nucleic acids, proteins or membranes (pore-forming agents). These systems are sometimes combined with other biological conflict-systems such as restriction-modification and CRISPR/Cas. Interestingly, several are coupled in mutually exclusive neighborhoods with either a prokaryotic ubiquitin-system or a HORMA domain-PCH2-like AAA+ ATPase dyad. The latter are potential precursors of equivalent proteins in eukaryotic chromosome dynamics. Further, components from these nucleotide-centric systems have been utilized in several other systems including a novel diversity-generating system with a reverse transcriptase. We also found the Smf/DprA/LOG domain from these systems to be recruited as a predicted nucleotide-binding domain in eukaryotic TRPM channels. These findings point to evolutionary and mechanistic links, which bring together CRISPR/Cas, animal interferon-induced immunity, and several other systems that combine nucleic-acid-sensing and nucleotide-dependent signaling

  3. Bisphenol A Disrupts HNF4α-Regulated Gene Networks Linking to Prostate Preneoplasia and Immune Disruption in Noble Rats.

    PubMed

    Lam, Hung-Ming; Ho, Shuk-Mei; Chen, Jing; Medvedovic, Mario; Tam, Neville Ngai Chung

    2016-01-01

    Exposure of humans to bisphenol A (BPA) is widespread and continuous. The effects of protracted exposure to BPA on the adult prostate have not been studied. We subjected Noble rats to 32 weeks of BPA (low or high dose) or 17β-estradiol (E2) in conjunction with T replenishment. T treatment alone or untreated groups were used as controls. Circulating T levels were maintained within the physiological range in all treatment groups, whereas the levels of free BPA were elevated in the groups treated with T+low BPA (1.06 ± 0.05 ng/mL, P < .05) and T+high BPA (10.37 ± 0.43 ng/mL, P < .01) when compared with those in both controls (0.1 ± 0.05 ng/mL). Prostatic hyperplasia, low-grade prostatic intraepithelial neoplasia (PIN), and marked infiltration of CD4+ and CD8+ T cells into the PIN epithelium (P < .05) were observed in the lateral prostates (LPs) of T+low/high BPA-treated rats. In contrast, only hyperplasia and high-grade PIN, but no aberrant immune responses, were found in the T+E2-treated LPs. Genome-wide transcriptome analysis in LPs identified differential changes between T+BPA vs T+E2 treatment. Expression of multiple genes in the regulatory network controlled by hepatocyte nuclear factor 4α was perturbed by the T+BPA but not by the T+E2 exposure. Collectively these findings suggest that the adult rat prostate, under a physiologically relevant T environment, is susceptible to BPA-induced transcriptomic reprogramming, immune disruption, and aberrant growth dysregulation in a manner distinct from those caused by E2. They are more relevant to our recent report of higher urinary levels BPA found in patients with prostate cancer than those with benign disease. PMID:26496021

  4. Community Immunity (Herd Immunity)

    MedlinePlus

    ... Content Marketing Share this: Main Content Area ​Community Immunity ("Herd" Immunity) Vaccines can prevent outbreaks of disease and save ... disease is contained. This is known as "community immunity." In the illustration below, the top box depicts ...

  5. Immunostimulatory Oligodeoxynucleotides Containing the CpG Motif are Effective as Immune Adjuvants in Tumor Antigen Immunization

    NASA Astrophysics Data System (ADS)

    Weiner, George J.; Liu, Hsin-Ming; Wooldridge, James E.; Dahle, Christopher E.; Krieg, Arthur M.

    1997-09-01

    Recent advances in our understanding of the immune response are allowing for the logical design of new approaches to cancer immunization. One area of interest is the development of new immune adjuvants. Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can induce production of a wide variety of cytokines and activate B cells, monocytes, dendritic cells, and NK cells. Using the 38C13 B cell lymphoma model, we assessed whether CpG ODN can function as immune adjuvants in tumor antigen immunization. The idiotype served as the tumor antigen. Select CpG ODN were as effective as complete Freund's adjuvant at inducing an antigen-specific antibody response but were associated with less toxicity. These CpG ODN induced a higher titer of antigen-specific IgG2a than did complete Freund's adjuvant, suggesting an enhanced TH1 response. Mice immunized with CpG ODN as an adjuvant were protected from tumor challenge to a degree similar to that seen in mice immunized with complete Freund's adjuvant. We conclude that CpG ODN are effective as immune adjuvants and are attractive as part of a tumor immunization strategy.

  6. Improving immunization strategies

    NASA Astrophysics Data System (ADS)

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

    2007-04-01

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

  7. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure.

    PubMed

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-01-01

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions. PMID:27185415

  8. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

    PubMed Central

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-01-01

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions. PMID:27185415

  9. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-05-01

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

  10. Single-cell network profiling of peripheral blood mononuclear cells from healthy donors reveals age- and race-associated differences in immune signaling pathway activation.

    PubMed

    Longo, Diane M; Louie, Brent; Putta, Santosh; Evensen, Erik; Ptacek, Jason; Cordeiro, James; Wang, Ena; Pos, Zoltan; Hawtin, Rachael E; Marincola, Francesco M; Cesano, Alessandra

    2012-02-15

    A greater understanding of the function of the human immune system at the single-cell level in healthy individuals is critical for discerning aberrant cellular behavior that occurs in settings such as autoimmunity, immunosenescence, and cancer. To achieve this goal, a systems-level approach capable of capturing the response of the interdependent immune cell types to external stimuli is required. In this study, an extensive characterization of signaling responses in multiple immune cell subpopulations within PBMCs from a cohort of 60 healthy donors was performed using single-cell network profiling (SCNP). SCNP is a multiparametric flow cytometry-based approach that enables the simultaneous measurement of basal and evoked signaling in multiple cell subsets within heterogeneous populations. In addition to establishing the interindividual degree of variation within a broad panel of immune signaling responses, the possible association of any observed variation with demographic variables including age and race was investigated. Using half of the donors as a training set, multiple age- and race-associated variations in signaling responses in discrete cell subsets were identified, and several were subsequently confirmed in the remaining samples (test set). Such associations may provide insight into age-related immune alterations associated with high infection rates and diminished protection following vaccination and into the basis for ethnic differences in autoimmune disease incidence and treatment response. SCNP allowed for the generation of a functional map of healthy immune cell signaling responses that can provide clinically relevant information regarding both the mechanisms underlying immune pathological conditions and the selection and effect of therapeutics.

  11. Anti-NeuGcGM3 antibodies, actively elicited by idiotypic vaccination in nonsmall cell lung cancer patients, induce tumor cell death by an oncosis-like mechanism.

    PubMed

    Hernández, Ana María; Rodríguez, Nely; González, Jorge E; Reyes, Emma; Rondón, Teresa; Griñán, Tania; Macías, Amparo; Alfonso, Sailyn; Vázquez, Ana María; Pérez, Rolando

    2011-03-15

    1E10 is a murine anti-idiotypic mAb specific for an idiotypic mAb that reacts with NeuGc-containing gangliosides, sulfatides, and Ags expressed in some human tumors. In melanoma, breast, and lung cancer patients, this anti-idiotypic Ab was able to induce a specific Ab response against N-glycosylated gangliosides, attractive targets for cancer immunotherapy as these glycolipids are not naturally expressed in humans. A clinical study with nonsmall cell lung cancer patients showed encouraging clinical benefits. Immunological studies performed in 20 of these patients suggested a correlation between the induction of Abs against NeuGcGM3 and longer survival times. The induced anti-NeuGcGM3 Abs recognized and directly killed tumor cells expressing the Ag, by a mechanism independent of complement activation. In the present work, we show that this cytotoxicity differs from apoptosis because it is temperature independent, no chromatin condensation or caspase 3 induction are detected, and the DNA fragmentation induced has a different pattern than the one characteristic for apoptosis. It is a very quick process and involves cytosqeleton reorganization. The Abs induce cellular swelling and the formation of big membrane lesions that allow the leakage of cytoplasm and the loss of the cell membrane integrity. All of these characteristics resemble a process of oncotic necrosis. To our knowledge, this is the first report of the active induction in cancer patients of NeuGcGM3-specific Abs able to induce complement independent oncotic necrosis to tumor cells. These results contribute to reinforcing the therapeutic potential of anti-idiotypic vaccines and the importance of NeuGcGM3 ganglioside as antitumor target. PMID:21300821

  12. Staphylococcus aureus infection induces protein A–mediated immune evasion in humans

    PubMed Central

    Pauli, Noel T.; Kim, Hwan Keun; Falugi, Fabiana; Huang, Min; Dulac, John; Henry Dunand, Carole; Zheng, Nai-Ying; Kaur, Kaval; Andrews, Sarah F.; Huang, Yunping; DeDent, Andrea; Frank, Karen M.; Charnot-Katsikas, Angella; Schneewind, Olaf

    2014-01-01

    Staphylococcus aureus bacterial infection commonly results in chronic or recurrent disease, suggesting that humoral memory responses are hampered. Understanding how S. aureus subverts the immune response is critical for the rescue of host natural humoral immunity and vaccine development. S. aureus expresses the virulence factor Protein A (SpA) on all clinical isolates, and SpA has been shown in mice to expand and ablate variable heavy 3 (VH3) idiotype B cells. The effects of SpA during natural infection, however, have not been addressed. Acutely activated B cells, or plasmablasts (PBs), were analyzed to dissect the ongoing immune response to infection through the production of monoclonal antibodies (mAbs). The B cells that were activated by infection had a highly limited response. When screened against multiple S. aureus antigens, only high-affinity binding to SpA was observed. Consistently, PBs underwent affinity maturation, but their B cell receptors demonstrated significant bias toward the VH3 idiotype. These data suggest that the superantigenic activity of SpA leads to immunodominance, limiting host responses to other S. aureus virulence factors that would be necessary for protection and memory formation. PMID:25348152

  13. Complete amino acid sequence of the variable domains of two human IgM anti-gamma globulins (Lay/Pom) with shared idiotypic specificities.

    PubMed

    Capra, J D; Klapper, D G

    1976-01-01

    On the basis of extensive shared idiotypic specificities, two human IgM anti-gamma-globulins (Lay/Pom) were selected for complete amino acid sequence analysis of their variable domains. Previous studies on the variable regions of the heavy chains of these proteins had shown but eight amino acid differences, only one of which was within a complementarity-determining hypervariable region. The complete amino acid sequence of the variable regions of the light chains of these two proteins is the subject of this report. Protein Lay is a typical VchiI protein with only five 'framework' differences when compared with protein Roy. Protein Pom is best classified as a VchiII, but in the 'framework' there are 16 differences between it and protein Ti. Although there are extensive differences in the first hypervariable region, the second and third light-chain hypervariable regions have an identical sequence. The finding of two identical light-chain and two identical heavy-chain hypervariable regions in these two proteins, which were selected on the basis of their combining specificities and their idiotypic cross-reactions, strongly implicates hypervariable regions in the constitution of the idiotypic determinants and the antibody combining site. Additionally, the finding of identical hypervariable regions in light chains of different V-region subgroups fulfills a prediction of the gene-interaction concept of antibody variability. PMID:824717

  14. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response

    PubMed Central

    1996-01-01

    To investigate the role of TNF alpha in the development of in vivo immune response we have generated TNF alpha-deficient mice by gene targeting. Homozygous mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and show no apparent phenotypic abnormalities, indicating that TNF alpha is not required for normal mouse development. In the absence of TNF alpha mice readily succumb to L. monocytogenes infections and show reduced contact hypersensitivity responses. Furthermore, TNF alpha knockout mice are resistant to the systemic toxicity of LPS upon D-galactosamine sensitization, yet they remain sensitive to high doses of LPS alone. Most interestingly, TNF alpha knockout mice completely lack splenic primary B cell follicles and cannot form organized follicular dendritic cell (FDC) networks and germinal centers. However, despite the absence of B cell follicles, Ig class-switching can still occur, yet deregulated humoral immune responses against either thymus-dependent (TD) or thymus-independent (TI) antigens are observed. Complementation of TNF alpha functioning by the expression of either human or murine TNF alpha transgenes is sufficient to reconstitute these defects, establishing a physiological role for TNF alpha in regulating the development and organization of splenic follicular architecture and in the maturation of the humoral immune response. PMID:8879212

  15. Expression in systemic lupus erythematosus of an idiotype common to DNA-binding and nonbinding monoclonal antibodies produced by normal human lymphoid cells.

    PubMed Central

    Cairns, E; Massicotte, H; Bell, D A

    1989-01-01

    Rabbit antiserum raised against a normal-derived monoclonal anti-DNA antibody KIM 4.6.3 (IgM lambda) was used for idiotype analyses. This anti-serum (anti-4.6.3 ID) was rendered specific for KIM 4.6.3 idiotype (4.6.3 ID) by absorption with normal human IgM and IgG. The specificity of anti-4.6.3 was shown by its ability to bind to KIM 4.6.3 antibody but not to normal human IgM and IgG, by inhibition of anti-4.6.3 ID reactivity with KIM 4.6.3 antibody by the homologous monoclonal antibody and by the ability of anti-4.6.3 ID to inhibit the binding of single stranded DNA with KIM 4.6.3 antibody. The 4.6.3 ID was found to be commonly expressed since it was detected among 33% (10/30) DNA and 32% (23/72) non-DNA-reactive monoclonal antibodies that were obtained from five different unrelated normal individuals. The binding to ssDNA of the majority of idiotype positive anti-DNA antibodies however was not blocked by anti-4.6.3 ID suggesting that among these other monoclonal antibodies its expression is outside of the antigen binding site. The 4.6.3 ID, which was present among some normal-derived monoclonal IgM molecules was also found at a high frequency (90%) in the sera of patients with systemic lupus erythematosus (SLE) but only at a low frequency (24%) and concentration in normal sera. The level of 4.6.3 ID in SLE did not correlate with serum IgM and IgG nor with anti-DNA antibody concentrations. Idiotypic relatedness between SLE serum antibodies and monoclonal anti-DNA antibodies of normals implies the existence of a cross-reactive idiotype family and implies that a conserved common gene or closely related genes exist in the germ line encoding these 4.6.3 ID positive antibodies some of which are not exclusively associated with nucleic acid reactivity. The expression of these germ line genes in vivo thus distinguishes SLE from normals. PMID:2493481

  16. The Integration of Epistasis Network and Functional Interactions in a GWAS Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine

    PubMed Central

    McKinney, Brett A.; Lareau, Caleb; Oberg, Ann L.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Poland, Gregory A.

    2016-01-01

    Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP) tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a smallpox vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA), which has been implicated in a previous epistasis network analysis of smallpox vaccine. PMID:27513748

  17. The Integration of Epistasis Network and Functional Interactions in a GWAS Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine.

    PubMed

    McKinney, Brett A; Lareau, Caleb; Oberg, Ann L; Kennedy, Richard B; Ovsyannikova, Inna G; Poland, Gregory A

    2016-01-01

    Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP) tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a smallpox vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA), which has been implicated in a previous epistasis network analysis of smallpox vaccine. PMID:27513748

  18. Generation of a human anti-idiotypic antibody that mimics the GD2 antigen.

    PubMed

    Saleh, M N; Stapleton, J D; Khazaeli, M B; LoBuglio, A F

    1993-09-15

    In a phase 1 trial, patients with metastatic melanoma received the anti-GD2 murine mAb 14G2a. All patients developed human anti-14G2a antibodies including anti-Id antibodies. Peripheral blood MNCs from one such patient were fused with the murine myeloma cell line Ag8. Four human anti-14G2a secreting hybridomas were generated and the mAb product of one of the hybridomas was characterized. The human mAb 4B5 (hu-IgG, lambda) binds to the variable region of murine 14G2a (anti-Id). The 4B5 binds to the antigen-combining site of 14G2a and inhibits its binding to GD2 expressing Mel-21 cells. Rabbits were immunized with the human anti-Id 4B5. Sera from the immunized rabbits demonstrated anti-4B5 antibodies and anti-Mel-21 and anti-GD2 reactivity. Furthermore, rabbit sera competitively inhibited binding of 14G2a to Mel-21 cells. Rabbits immunized with 4B5 developed a DTH response when challenged with 4B5 antibody and Mel-21 cells. These studies demonstrate that the human anti-Id 4B5 mimics the GD2 antigen and is capable of eliciting both a humoral and cellular anti-GD2 immune response. This antibody could be potentially used as a human anti-Id vaccine in patients with malignant melanoma. PMID:8376782

  19. Characterization of anti-idiotypic antibodies and their use as probes for determination of shared idiotopes expressed on murine and human IgE anti-rye I antibodies.

    PubMed Central

    Mourad, W; Pelletier, G; Hébert, J

    1988-01-01

    This study describes the production and characterization of rabbit anti-idiotypic antibodies (anti-ID Abs) against three idiotypes of three mAbs with different specificities. The anti-ID Abs were rendered idiotype specific by appropriate adsorption. Binding of labelled mAb to homologous anti-ID Ab bound to a polystyrene matrix was completely inhibited when the same mAb was added. In contrast, addition of other mAbs sharing the same isotype and the same light chain but with different specificity did not affect the binding reaction. Each anti-ID Ab inhibited completely and selectively the reaction between the allergen and the homologous mAb idiotype. Labelled rye I binding to a given polystyrene-bound mAb idiotype was completely blocked if the relevant anti-ID Ab was used as an inhibitor. Murine polyclonal anti-rye I antisera inhibited the reaction between all three mAbs and the antigens, as well as the reaction between all three mAb idiotypes and their homologous anti-ID Abs. On another hand, goat polyclonal anti-rye I antisera only inhibited the reaction between the mAbs and the antigens. These results suggest that the anti-ID Abs produced are directed against idiotopes located within the paratopes and such idiotopes are shared by murine monoclonal and polyclonal Abs. Human rye I-specific IgE and murine anti-rye I mAbs could share common idiotopes, since human IgE binding to the antigen was inhibited by the anti-ID Abs. These observations imply structural similarity in the V gene coding for the variable region of the antibody of two different species. PMID:3258278

  20. Development of a Novel, Anti-idiotypic Monoclonal Anti-prolactin Antibody That Mimics the Physiological Functions of Prolactin

    PubMed Central

    Wang, Meng; Zhang, Dian-Cai; Wang, Shen-Tian; Li, Ming-Long

    2016-01-01

    In this work, we prepared a panel of monoclonal anti-idiotypic antibodies to ovine prolactin (oPRL) by the hybridoma technique. Among these antibodies, one anti-idotypic antibody (designated B7) was chosen for further characterization by a series of experiments. We first demonstrated that B7 behaved as a typical Ab2β based on a series of enzyme-linked immunosorbent assays. Subsequently, the results of a competitive receptor-binding assay confirmed that B7 could specifically bind to the prolactin receptor (PRLR) expressed on target cells. Finally, we examined its biological activities in CHO-PRLR and Nb2 cells and observed that B7 could activate Janus kinase 2-signal transducer and activator of transcription signalling in CHO-PRLR and Nb2 cells and induce BaF3 proliferation. The present study suggests that i) B7 can serve as a PRLR agonist or PRL mimic and has potential applications in regulating mammary gland development, milk production and maintenance of lactation in domestic animals and ii) B7 may be a biological reagent that can be used to explore the mechanism of PRLR-mediated intracellular signalling. PMID:26949959

  1. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

    PubMed Central

    Soriano, Jorge L.; Batista, Noyde; Santiesteban, Eduardo; Lima, Mayté; González, Joaquín; García, Robin; Zarza, Yohanka; López, María V.; Rodríguez, Myriam; Loys, Jorge L.; Montejo, Narciso; Aguirre, Frank; Macías, Amparo; Vázquez, Ana M.

    2011-01-01

    The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index ≥60%, were treated with metronomic chemotherapy (50 mg of cyclophospamide orally daily and 2.5 mg of methotrexate orally bi-daily), in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum), followed by reimmunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD) was 18,43 months (12,20–24,10 months), being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration. PMID:22295231

  2. Immune System

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  3. Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling

    PubMed Central

    Pan, Zhichao; Yu, Haishan; Liao, Jie-Lou

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future. PMID:27669518

  4. Quantitative Trait Locus Based Virulence Determinant Mapping of the HSV-1 Genome in Murine Ocular Infection: Genes Involved in Viral Regulatory and Innate Immune Networks Contribute to Virulence

    PubMed Central

    Larsen, Inna; Craven, Mark; Brandt, Curtis R.

    2016-01-01

    Herpes simplex virus type 1 causes mucocutaneous lesions, and is the leading cause of infectious blindness in the United States. Animal studies have shown that the severity of HSV-1 ocular disease is influenced by three main factors; innate immunity, host immune response and viral strain. We previously showed that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) resulted in recombinants that exhibit a range of disease phenotypes from severe to avirulent, suggesting epistatic interactions were involved. The goal of this study was to develop a quantitative trait locus (QTL) analysis of HSV-1 ocular virulence determinants and to identify virulence associated SNPs. Blepharitis and stromal keratitis quantitative scores were characterized for 40 OD4:CJ994 recombinants. Viral titers in the eye were also measured. Virulence quantitative trait locus mapping (vQTLmap) was performed using the Lasso, Random Forest, and Ridge regression methods to identify significant phenotypically meaningful regions for each ocular disease parameter. The most predictive Ridge regression model identified several phenotypically meaningful SNPs for blepharitis and stromal keratitis. Notably, phenotypically meaningful nonsynonymous variations were detected in the UL24, UL29 (ICP8), UL41 (VHS), UL53 (gK), UL54 (ICP27), UL56, ICP4, US1 (ICP22), US3 and gG genes. Network analysis revealed that many of these variations were in HSV-1 regulatory networks and viral genes that affect innate immunity. Several genes previously implicated in virulence were identified, validating this approach, while other genes were novel. Several novel polymorphisms were also identified in these genes. This approach provides a framework that will be useful for identifying virulence genes in other pathogenic viruses, as well as epistatic effects that affect HSV-1 ocular virulence. PMID:26962864

  5. Quantitative Trait Locus Based Virulence Determinant Mapping of the HSV-1 Genome in Murine Ocular Infection: Genes Involved in Viral Regulatory and Innate Immune Networks Contribute to Virulence.

    PubMed

    Kolb, Aaron W; Lee, Kyubin; Larsen, Inna; Craven, Mark; Brandt, Curtis R

    2016-03-01

    Herpes simplex virus type 1 causes mucocutaneous lesions, and is the leading cause of infectious blindness in the United States. Animal studies have shown that the severity of HSV-1 ocular disease is influenced by three main factors; innate immunity, host immune response and viral strain. We previously showed that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) resulted in recombinants that exhibit a range of disease phenotypes from severe to avirulent, suggesting epistatic interactions were involved. The goal of this study was to develop a quantitative trait locus (QTL) analysis of HSV-1 ocular virulence determinants and to identify virulence associated SNPs. Blepharitis and stromal keratitis quantitative scores were characterized for 40 OD4:CJ994 recombinants. Viral titers in the eye were also measured. Virulence quantitative trait locus mapping (vQTLmap) was performed using the Lasso, Random Forest, and Ridge regression methods to identify significant phenotypically meaningful regions for each ocular disease parameter. The most predictive Ridge regression model identified several phenotypically meaningful SNPs for blepharitis and stromal keratitis. Notably, phenotypically meaningful nonsynonymous variations were detected in the UL24, UL29 (ICP8), UL41 (VHS), UL53 (gK), UL54 (ICP27), UL56, ICP4, US1 (ICP22), US3 and gG genes. Network analysis revealed that many of these variations were in HSV-1 regulatory networks and viral genes that affect innate immunity. Several genes previously implicated in virulence were identified, validating this approach, while other genes were novel. Several novel polymorphisms were also identified in these genes. This approach provides a framework that will be useful for identifying virulence genes in other pathogenic viruses, as well as epistatic effects that affect HSV-1 ocular virulence. PMID:26962864

  6. CD4+ T cell–dependent and –independent cytokine-chemokine network changes in the immune responses of HIV-infected individuals

    PubMed Central

    Arnold, Kelly B.; Szeto, Gregory L.; Alter, Galit; Irvine, Darrell J.; Lauffenburger, Douglas A.

    2015-01-01

    A vital defect in the immune systems of HIV-infected individuals is the loss of CD4+ T cells, resulting in impaired immune responses. We hypothesized that there were CD4+ T cell–dependent and –independent alterations in the immune responses of HIV-1+ individuals. To test this, we analyzed the secretion of cytokines and chemokines from stimulated peripheral blood mononuclear cell (PBMC) populations from HIV+ donors, healthy donors, and healthy donors with CD4+ T cells experimentally depleted. Multivariate analyses of 16 cytokines and chemokines at 6 and 72 hours after three stimuli (antibody-coated beads to stimulate T cells and R848 or LPS to stimulate innate immune cells) enabled integrative analysis of secreted profiles. Two major effects in HIV+ PBMCs were not reproduced upon depleting CD4+ T cell in healthy PBMCs: (i) HIV+ PBMCs maintained T cell–associated secreted profiles after T cell stimulation; (ii) HIV+ PBMCs showed impaired IFN-γ secretion early after innate stimulation. These changes arose from hyperactive T cells and debilitated natural killer (NK) cell, respectively. Modeling and experiments showed that early IFN-γ secretion predicted later differences in secreted profiles in vitro. This effect was recapitulated in healthy PBMCs by blocking the interferon-γ (IFN-γ) receptor. Thus, we identified a critical deficiency in NK cell responses of HIV-infected individuals, independent of CD4+ T cell depletion, which directs secreted profiles. Our findings illustrate a broad approach for identifying key disease-associated nodes in a multicellular, multivariate signaling network. PMID:26486173

  7. CD5-positive B-cell malignancies frequently express cross-reactive idiotypes associated with IgM autoantibodies.

    PubMed Central

    Kipps, T. J.; Robbins, B. A.; Tefferi, A.; Meisenholder, G.; Banks, P. M.; Carson, D. A.

    1990-01-01

    Using monoclonal antibodies (MAb) specific for cross-reactive idiotypes (CRIs) associated with human monoclonal IgM autoantibodies, we examined 57 biopsy specimens that previously had been noted to have immunohistologic features of CD5-positive B-cell small lymphocytic (SL) non-Hodgkin's lymphoma (NHL). Twenty-five lymphoma specimens were noted to be from patients with chronic lymphocytic leukemia (CLL). Eight of thirty-four (24%) immunoglobulin (Ig) kappa light-chain expressing lymphomas reacted with 17.109, a MAb specific for a major CRI encoded by a conserved Ig kappa variable region gene (Vk gene) of the VkIIIb sub-subgroup. All 17.109-reactive tissues and two 17.109-negative specimens were recognized by another MAb specific for VkIIIb framework determinant(s). Seven of all fifty-six (13%) Ig-expressing tumors bound G6, a MAb specific for an autoantibody heavy-chain-associated CRI that is encoded by a conserved antibody heavy chain variable region gene(s) (VHgene) of the VH1 subgroup. All seven G6-positive lymphomas and two G6-negative tumors reacted with Cc1, another MAb specific for a rheumatoid factor heavy-chain-associated CRI. A third autoantibody-heavy-chain-associated CRI, termed Lc1, was expressed by seven (13%) other lymphomas. Finally, a fourth MAb specific for RF heavy-chain-associated CRI, named B6, detected two additional tumors. The expression frequencies of autoantibody-associated CRIs among SL NHL patients without peripheral lymphocytosis did not differ from those noted among patients with CLL but were significantly higher than those observed among patients with NHL of follicular center-cell origin. These data imply that the malignant B cells of patients with either CD5-positive B-cell SL NHL or CLL express a restricted set of Ig V genes that have not substantially diversified from the germline DNA. Images Figure 1 PMID:1691593

  8. Poor ex vivo induction of T-cell responses to idiotype or tumor cell lysate-pulsed autologous dendritic cells in advanced pre-treated multiple myeloma.

    PubMed

    Garderet, Laurent; Mazurier, Christelle; Pellat-Deceunynck, Catherine; Karim, Abdul; Baudin, Bruno; Funck-Brentano, Christian; Bouchet, Sandrine; Geffroy, Alexandrine; Bataille, Régis; Gorin, Norbert-Claude; Lopez, Manuel

    2006-07-01

    This study evaluated the feasibility of using dendritic cells (DCs) to generate, ex vivo, anti-tumor cytotoxic T lymphocytes (CTL) in patients with stage III multiple myeloma (MM). Nucleated cells from eight patients who had received chemotherapy (three of whom had undergone autologous hemopoeitic stem cell transplantation) were collected by apheresis. Their monocytes were enriched using counter-current centrifugation, differentiated into DCs which were further co-cultured with autologous CD8 lymphocytes to induce CTL. The DCs were pulsed either with the idiotypic paraprotein (regarded as a tumor-specific antigen) or with autologous MM cell lysate before co-culture. Specific T-cell responses were measured in IFNgamma enzyme-linked immunospot and chromium release assays of autologous plasmocyte targets. A slight increase in IFNgamma secretion by T-cells was observed for two patients (DCs pulsed with idiotypic paraprotein for one, MM cell lysate for the other). No or weak specific lysis of plasmocyte targets was observed in the chromium release assays. In conclusion, the T-cell response to pulsed DCs was very weak or absent. There are clinical and technical reasons that could explain, in part, this lack of response.

  9. Immune response to phosphorylcholine. VIII. The response CBA/N mice to PC-LPS.

    PubMed

    Köhler, H; Smyk, S; Fung, J

    1981-05-01

    CBA/N mice and F1 crosses of CBA/N X BALB/c with the CBA/N phenotype respond to immunization with PC-LPS with a PC-specific and an anti-bridge antibody production. The PC-specific response in defective CBA/N and NBF1 is devoid of the IgG3 subclass and is not T15 idiotype dominant, whereas normal BALB/c and nondefective NBF1 mice express the T15 dominantly in their anti-PC-LPS response. By the criteria of responsiveness to PC-LPS only and the absence of dominant T15 expression, the precursors in defective NBF1 mice for TI-1 antigen PC-LPS can be characterized as being immature B cells similar to those found in neonatal livers of normal BALB/c or in spleens of chronically idiotype suppressed BALB/c mice. This analogy suggests that the developmental defect in CBA/N mice becomes active during the maturation process before selection for clonal dominance occurs and specialization of precursors for the preferred expression of the IgG3 subclass is completed. Alterations in the T cell compartment may contribute to the immature nature of B cells in the sex-linked immunodeficiency of CBA/N mice.

  10. Immune response

    MedlinePlus

    ... cells. T cells are responsible for cell-mediated immunity. This type of immunity becomes deficient in persons with HIV, the virus ... blood. B lymphocytes provide the body with humoral immunity as they circulate in the fluids in search ...

  11. Immune Restoration

    MedlinePlus

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

  12. Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy

    PubMed Central

    Inkeles, Megan S.; Teles, Rosane M.B.; Pouldar, Delila; Andrade, Priscila R.; Madigan, Cressida A.; Ambrose, Mike; Sarno, Euzenir N.; Rea, Thomas H.; Ochoa, Maria T.; Iruela-Arispe, M. Luisa; Swindell, William R.; Ottenhoff, Tom H.M.; Geluk, Annemieke; Bloom, Barry R.

    2016-01-01

    Transcriptome profiles derived from the site of human disease have led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum, which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene coexpression modules by cell-type deconvolution. In lesions from tuberculoid leprosy patients, those with the self-limited form of the disease, dendritic cells were linked with MMP12 as part of a tissue remodeling network that contributes to granuloma formation. In lesions from lepromatous leprosy patients, those with disseminated disease, macrophages were linked with a gene network that programs phagocytosis. In erythema nodosum leprosum, neutrophil and endothelial cell gene networks were identified as part of the vasculitis that results in tissue injury. The present integrated computational approach provides a systems approach toward identifying cell-defined functional networks that contribute to host defense and immunopathology at the site of human infectious disease. PMID:27699251

  13. Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy

    PubMed Central

    Inkeles, Megan S.; Teles, Rosane M.B.; Pouldar, Delila; Andrade, Priscila R.; Madigan, Cressida A.; Ambrose, Mike; Sarno, Euzenir N.; Rea, Thomas H.; Ochoa, Maria T.; Iruela-Arispe, M. Luisa; Swindell, William R.; Ottenhoff, Tom H.M.; Geluk, Annemieke; Bloom, Barry R.

    2016-01-01

    Transcriptome profiles derived from the site of human disease have led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum, which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene coexpression modules by cell-type deconvolution. In lesions from tuberculoid leprosy patients, those with the self-limited form of the disease, dendritic cells were linked with MMP12 as part of a tissue remodeling network that contributes to granuloma formation. In lesions from lepromatous leprosy patients, those with disseminated disease, macrophages were linked with a gene network that programs phagocytosis. In erythema nodosum leprosum, neutrophil and endothelial cell gene networks were identified as part of the vasculitis that results in tissue injury. The present integrated computational approach provides a systems approach toward identifying cell-defined functional networks that contribute to host defense and immunopathology at the site of human infectious disease.

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

    PubMed

    Park, Yong-Soon; Ryu, Choong-Min

    2015-01-01

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

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

    PubMed Central

    Park, Yong-Soon; Ryu, Choong-Min

    2015-01-01

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

  16. 1H NMR-Based Profiling Reveals Differential Immune-Metabolic Networks during Influenza Virus Infection in Obese Mice

    PubMed Central

    Milner, J. Justin; Wang, Jue; Sheridan, Patricia A.; Ebbels, Tim; Beck, Melinda A.; Saric, Jasmina

    2014-01-01

    Obese individuals are at greater risk for death from influenza virus infection. Paralleling human evidence, obese mice are also more susceptible to influenza infection mortality. However, the underlying mechanisms driving greater influenza severity in the obese remain unclear. Metabolic profiling has been utilized in infectious disease models to enhance prognostic or diagnostic methods, and to gain insight into disease pathogenesis by providing a more global picture of dynamic infection responses. Herein, metabolic profiling was used to develop a deeper understanding of the complex processes contributing to impaired influenza protection in obese mice and to facilitate generation of new explanatory hypotheses. Diet-induced obese and lean mice were infected with influenza A/Puerto Rico/8/34. 1H nuclear magnetic resonance-based metabolic profiling of urine, feces, lung, liver, mesenteric white adipose tissue, bronchoalveolar lavage fluid and serum revealed distinct metabolic signatures in infected obese mice, including perturbations in nucleotide, vitamin, ketone body, amino acid, carbohydrate, choline and lipid metabolic pathways. Further, metabolic data was integrated with immune analyses to obtain a more comprehensive understanding of potential immune-metabolic interactions. Of interest, uncovered metabolic signatures in urine and feces allowed for discrimination of infection status in both lean and obese mice at an early influenza time point, which holds prognostic and diagnostic implications for this methodology. These results confirm that obesity causes distinct metabolic perturbations during influenza infection and provide a basis for generation of new hypotheses and use of this methodology in detection of putative biomarkers and metabolic patterns to predict influenza infection outcome. PMID:24844920

  17. Reflex control of immunity

    PubMed Central

    Tracey, Kevin J.

    2015-01-01

    Inflammation can cause damage and even death. What controls this primitive and potentially lethal innate immune response to injury and infection? Molecular and neurophysiological studies during the past decade have revealed a pivotal answer: immunity is coordinated by neural circuits that operate reflexively The afferent arc of the reflex consists of nerves that sense injury and infection. This activates efferent neural circuits, including the cholinergic anti-inflammatory pathway that modulate immune responses and the progression of inflammatory diseases. It might be possible to develop therapeutics that target neural networks for the treatment of inflammatory disorders. PMID:19461672

  18. Prognosis of hormone-dependent breast cancers: implications of the presence of dysfunctional transcriptional networks activated by insulin via the immune transcription factor T-bet.

    PubMed

    McCune, Kasi; Bhat-Nakshatri, Poornima; Thorat, Mangesh A; Nephew, Kenneth P; Badve, Sunil; Nakshatri, Harikrishna

    2010-01-15

    Estrogen receptor alpha (ERalpha)-positive breast cancers that co-express transcription factors GATA-3 and FOXA1 have a favorable prognosis. These transcription factors form an autoregulatory hormonal network that influences estrogen responsiveness and sensitivity to hormonal therapy. Disruption of this network may be a mechanism whereby ERalpha-positive breast cancers become resistant to therapy. The transcription factor T-bet is a negative regulator of GATA-3 in the immune system. In this study, we report that insulin increases the expression of T-bet in breast cancer cells, which correlates with reduced expression of GATA-3, FOXA1, and the ERalpha:FOXA1:GATA-3 target gene GREB-1. The effects of insulin on GATA-3 and FOXA1 could be recapitulated through overexpression of T-bet in MCF-7 cells (MCF-7-T-bet). Chromatin immunoprecipitation assays revealed reduced ERalpha binding to GREB-1 enhancer regions in MCF-7-T-bet cells and in insulin-treated MCF-7 cells. MCF-7-T-bet cells were resistant to tamoxifen in the presence of insulin and displayed prolonged extracellular signal-regulated kinase and AKT activation in response to epidermal growth factor treatment. ERalpha-positive cells with intrinsic tamoxifen resistance as well as MCF-7 cells with acquired tamoxifen and fulvestrant resistance expressed elevated levels of T-bet and/or reduced levels of FOXA1 and GATA-3. Analysis of publicly available databases revealed ERalpha-positive/T-bet-positive breast cancers expressing lower levels of FOXA1 (P = 0.0137) and GATA-3 (P = 0.0063) compared with ERalpha-positive/T-bet-negative breast cancers. Thus, T-bet expression in primary tumors and circulating insulin levels may serve as surrogate biomarkers to identify ERalpha-positive breast cancers with a dysfunctional hormonal network, enhanced growth factor signaling, and resistance to hormonal therapy.

  19. Integrated Immune

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  20. Mediation of cytotoxic functions by classes and subclasses of sheep antibody reactive with cell surface immunoglobulin idiotypic and constant region determinants.

    PubMed Central

    Stevenson, F K; Elliott, E V

    1978-01-01

    Sheep antibodies, reactive with either the idiotypic or constant region antigenic determinants of the immunoglobulin light chain on guinea-pig L2C leukaemic cells, were separated into IgM and into the two subclasses of IgG, IgG1 and IgG2. Antibody of both IgG subclasses inhibited the migration of L2C cells along plastic surfaces; IgM was only weakly inhibitory. Antibody of class IgM and of subclass IgG1 mediated complement cytotoxicity against the L2C cells whereas only that of subclass IgG2 mediated K-cell cytotoxicity; the effector arms were rabbit complement and sheep peripheral leucocytes, respectively. PMID:75184

  1. Biological synthesis of a protein analogue of acetylcholinesterase: Monoclonal anti-idiotype antibody analogue of the esteratic site. Annual report, 15 May 1983-14 May 1984

    SciTech Connect

    August, J.T.

    1984-07-10

    The goal of this research during the first year of the contract was to develop a method for the purification of human erythrocyte acetylcholinesterase and to initiate the preparation and analysis of monoclonal antibodies. This was accomplished by the preparation of red blood cell membrane ghosts, enzyme solubilization with a non-ionic detergent, and enzyme purification by monoclonal antibody affinity chromatography. Sixty ml of packed red blood cells yielded a final fraction of 750 micrograms. approximately 20,000-fold purified. The purified fraction contained a single protein of about 75,000 daltons that was labeled with 3H-diisopropylfluorophosphate and gave a single peak during high-performance liquid chromatography on a TSK-SW3000 silica-enzyme for the preparation of monoclonal antibodies. anti-cholinesterase, anti-active site, and anti-idiotype monoclonal antibodies have been developed.

  2. Immunisation of guinea-pigs with circulating immune complexes from patients with rheumatoid arthritis.

    PubMed

    Hack, C E; Lim, H G; Aalberse, R C

    1984-10-01

    Sixteen guinea-pigs were immunised with immune complexes isolated from serum of nine patients with rheumatoid arthritis. The resulting antisera were analysed by radioimmunoassays. All guinea-pig sera were extensively absorbed with normal human serum. After this absorption eight guinea-pig sera contained antibodies specific for immune complexes isolated from the sera of three patients. One of these antisera reacted not only with immune complexes (and serum) from the corresponding patient but also with immune complexes (and sera) from other patients with rheumatoid arthritis. The antigen(s) to which the guinea-pig antibodies were directed sedimented as IgM, and they bound to IgG Sepharose. Therefore the guinea-pig sera were absorbed with IgM-rheumatoid factors isolated from the serum of the corresponding patient. After this absorption, the guinea-pig sera had lost their reactivity with immune complexes. We conclude that these antisera did not detect an exogenous antigen in immune complexes from patients with rheumatoid arthritis. The positive reactions found were due to antibodies specific for (idiotypic?) antigenic determinants on IgM-rheumatoid factors.

  3. Lupus-specific kidney deposits of HSP90 are associated with altered IgG idiotypic interactions of anti-HSP90 autoantibodies

    PubMed Central

    KENDEROV, A; MINKOVA, V; MIHAILOVA, D; GILTIAY, N; KYURKCHIEV, S; KEHAYOV, I; KAZATCHKINE, M; KAVERI, S; PASHOV, A

    2002-01-01

    Previous studies have shown that autoantibodies to heat shock protein 90 (HSP90) are elevated in a significant proportion of patients with systemic lupus erythematosus (SLE) who are more likely to have renal disease and a low C3 level. Using samples from 24 patients, we searched for glomerular deposits of HSP90 in renal biopsy specimens from seven patients with lupus nephritis and 17 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining for HSP90 was observed in six of seven cases of SLE and positive tubular staining in two of seven SLE patients. The staining for HSP90 was granular in nature and was located in subepithelial, subendothelial and mesangial areas. None of the non-SLE renal biopsies revealed positive staining for HSP90 deposition. Further we showed the presence of anti-HSP90 IgG autoantibodies in IgG from sera of patients with SLE as well as in normal human IgG (IVIg). In normal IgG this autoreactivity could be adsorbed almost completely on F(ab′)2 fragments from the same IgG preparation, coupled to Sepharose and could be inhibited by the effluent obtained after subjecting normal IgG to HSP90 affinity column. These findings indicate that anti-HSP90 natural autoantibodies are blocked by idiotypic interactions within the IgG repertoire. Unlike natural autoantibodies, anti-HSP90 IgG from SLE patients’ sera were only moderately adsorbed on F(ab′)2 fragments of normal IgG. These results demonstrate that immunopathogenesis of lupus nephritis is associated with HSP90 (as an autoantigen) and that the pathology is associated with altered idiotypic regulation of the anti-HSP90 IgG autoantibodies. PMID:12100037

  4. Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease.

    PubMed

    Sivendran, Shanthi; Chang, Rui; Pham, Lisa; Phelps, Robert G; Harcharik, Sara T; Hall, Lawrence D; Bernardo, Sebastian G; Moskalenko, Marina M; Sivendran, Meera; Fu, Yichun; de Moll, Ellen H; Pan, Michael; Moon, Jee Young; Arora, Sonali; Cohain, Ariella; DiFeo, Analisa; Ferringer, Tammie C; Tismenetsky, Mikhail; Tsui, Cindy L; Friedlander, Philip A; Parides, Michael K; Banchereau, Jacques; Chaussabel, Damien; Lebwohl, Mark G; Wolchok, Jedd D; Bhardwaj, Nina; Burakoff, Steven J; Oh, William K; Palucka, Karolina; Merad, Miriam; Schadt, Eric E; Saenger, Yvonne M

    2014-08-01

    Patients with resected stage II-III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II-III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data.

  5. Dissection of Immune Gene Networks in Primary Melanoma Tumors Critical for Antitumor Surveillance of Patients with Stage II–III Resectable Disease

    PubMed Central

    Sivendran, Shanthi; Chang, Rui; Pham, Lisa; Phelps, Robert G.; Harcharik, Sara T.; Hall, Lawrence D.; Bernardo, Sebastian G.; Moskalenko, Marina M.; Sivendran, Meera; Fu, Yichun; de Moll, Ellen H.; Pan, Michael; Moon, Jee Young; Arora, Sonali; Cohain, Ariella; DiFeo, Analisa; Ferringer, Tammie C.; Tismenetsky, Mikhail; Tsui, Cindy L.; Friedlander, Philip A.; Parides, Michael K.; Banchereau, Jacques; Chaussabel, Damien; Lebwohl, Mark G.; Wolchok, Jedd D.; Bhardwaj, Nina; Burakoff, Steven J.; Oh, William K.; Palucka, Karolina; Merad, Miriam; Schadt, Eric E.; Saenger, Yvonne M.

    2014-01-01

    Patients with resected stage II–III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II–III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data. PMID:24522433

  6. Immune Deficiency Foundation

    MedlinePlus

    ... for IDF Join our nationwide network of volunteers Resources For Patients & Families Peer Support Speak with someone who understands Locate a Physician ... secure Legacy Giving Establish your personal legacy and support IDF 'Immune Deficiency Foundation Remembers' Plaque Pay tribute to ... Educational Resources Find a wealth of IDF educational publications and ...

  7. Childhood Immunization

    MedlinePlus

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  8. Immunizations - diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  9. Modulation of the murine immune response to human IgG by complexing with monoclonal antibodies. II. Antibody responses to idiotopes of the human IgG paraprotein and of the mouse monoclonal antibodies.

    PubMed

    Ling, N R; Elliott, D; Lowe, J

    1987-09-01

    Anti-idiotope antibodies produced by mice immunized with a human IgG paraprotein complexed with various mouse monoclonal antibodies (McAbs) have been measured. All animals receiving more than one injection of the paraprotein (free or complexed with a mouse McAb) produced antibodies to the idiotypes of the paraprotein. Complexing with a McAb, especially an anti-Fc-gamma McAb, enhanced the response. Antibodies to the idiotopes of mouse McAbs were more difficult to produce and their production was very dependent on the mode and schedule of the immunization. The best antisera were produced by mice receiving a course of injections of pre-formed complexes of the IgG paraprotein and McAbs. Four of five mice produced antibodies to the idiotopes of an anti-light chain McAb (C4) after a course of immunization (one primary plus four boosts) of an IgG-C4 complex. Two of the six mice receiving a similar course of injections of the paraprotein complexed with an anti-gamma McAb (A55) produced high titres of antibodies to A55 idiotypes. Responses were enhanced when complexes were prepared with a pool of McAbs. It is probable that the formation of large multi-cross-linked complexes containing the McAb under study is important in generating the response. Once a response is initiated, very high titres may be achieved.

  10. T Cell Mediated Antibody lnvariance in an Immune Response Against A Bacterial Carbohydrate Antigen Requires CD28/B7–1 Costimulation

    PubMed Central

    Kölsch, Eckehart; Specht, Christoph

    2001-01-01

    The humoral immune response against α(1→3) dextran (Dex) in BALB/c mice is characterized by the formation of predominantly IgM antibodies bearing the J558 idiotype. IgG antibodies do not appear in euthymic mice. In athymic animals however, the response proceeds to a vigorous IgG production. In euthymic mice formation of IgG is suppressed by J558 idiotype- specific regulatory T cells recognizing in association with I-Ed and in cognate T/B interaction the VH CDR3 derived peptide of the J558 idiotpye. Only B-2 lymphocytes produce IgG whereas B-1 cells do not participate in the production of this Ig class. Using a novel synthetic all α(1→3)-D-gluco configurated tetrasaccharide the Dex-specific B cells can for the first time be analyzed in FACS. In experiments using this newly designed low molecular Dex no signs of B cell apoptosis can be found. This demonstrates a true silencing of persisting Bγ memory cells and supports previous by adoptive transfer experiments. In this suppression an involvement of CD28/B7–1 interaction can be demonstrated which is a necessary costimulatory suppression signal in addition to the cognate TCR/peptide-I-Ed interaction between J558 Id-specific T cells and J558 idiotype beating B cells. This results in an activation of 178–4 Ts cells, leading to an overall suppression of the Dex-specific IgG isotype production on the one hand and on the other hand provides a signal for the survival and clonal expansion of J558 Id-positive B cells. PMID:11785674

  11. Insect Immunity to Entomopathogenic Fungi.

    PubMed

    Lu, H-L; St Leger, R J

    2016-01-01

    The study of infection and immunity in insects has achieved considerable prominence with the appreciation that their host defense mechanisms share many fundamental characteristics with the innate immune system of vertebrates. Studies on the highly tractable model organism Drosophila in particular have led to a detailed understanding of conserved innate immunity networks, such as Toll. However, most of these studies have used opportunistic human pathogens and may not have revealed specialized immune strategies that have arisen through evolutionary arms races with natural insect pathogens. Fungi are the commonest natural insect pathogens, and in this review, we focus on studies using Metarhizium and Beauveria spp. that have addressed immune system function and pathogen virulence via behavioral avoidance, the use of physical barriers, and the activation of local and systemic immune responses. In particular, we highlight studies on the evolutionary genetics of insect immunity and discuss insect-pathogen coevolution.

  12. Echinoderm immunity.

    PubMed

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

    2010-01-01

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

  13. Efficient immunization strategies to prevent financial contagion

    PubMed Central

    Kobayashi, Teruyoshi; Hasui, Kohei

    2014-01-01

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

  14. Efficient immunization strategies to prevent financial contagion

    NASA Astrophysics Data System (ADS)

    Kobayashi, Teruyoshi; Hasui, Kohei

    2014-01-01

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

  15. Hypothalamic neurohormones and immune responses

    PubMed Central

    Quintanar, J. Luis; Guzmán-Soto, Irene

    2013-01-01

    The aim of this review is to provide a comprehensive examination of the current literature describing the neural-immune interactions, with emphasis on the most recent findings of the effects of neurohormones on immune system. Particularly, the role of hypothalamic hormones such as Thyrotropin-releasing hormone (TRH), Corticotropin-releasing hormone (CRH) and Gonadotropin-releasing hormone (GnRH). In the past few years, interest has been raised in extrapituitary actions of these neurohormones due to their receptors have been found in many non-pituitary tissues. Also, the receptors are present in immune cells, suggesting an autocrine or paracrine role within the immune system. In general, these neurohormones have been reported to exert immunomodulatory effects on cell proliferation, immune mediators release and cell function. The implications of these findings in understanding the network of hypothalamic neuropeptides and immune system are discussed. PMID:23964208

  16. Networks.

    ERIC Educational Resources Information Center

    Cerf, Vinton G.

    1991-01-01

    The demands placed on the networks transporting the information and knowledge generated by the increased diversity and sophistication of computational machinery are described. What is needed to support this increased flow, the structures already in place, and what must be built are topics of discussion. (KR)

  17. Immune System

    EPA Science Inventory

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

  18. Maternal immunization

    PubMed Central

    Moniz, Michelle H; Beigi, Richard H

    2014-01-01

    Maternal immunization holds tremendous promise to improve maternal and neonatal health for a number of infectious conditions. The unique susceptibilities of pregnant women to infectious conditions, as well as the ability of maternally-derived antibody to offer vital neonatal protection (via placental transfer), together have produced the recent increased attention on maternal immunization. The Advisory Committee on Immunization Practices (ACIP) currently recommends 2 immunizations for all pregnant women lacking contraindication, inactivated Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Given ongoing research the number of vaccines recommended during pregnancy is likely to increase. Thus, achieving high vaccination coverage of pregnant women for all recommended immunizations is a key public health enterprise. This review will focus on the present state of vaccine acceptance in pregnancy, with attention to currently identified barriers and determinants of vaccine acceptance. Additionally, opportunities for improvement will be considered. PMID:25483490

  19. Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy.

    PubMed

    Godar, Marie; Morello, Virginia; Sadi, Ava; Hultberg, Anna; De Jonge, Natalie; Basilico, Cristina; Hanssens, Valérie; Saunders, Michael; Lambrecht, Bart N; El Khattabi, Mohamed; de Haard, Hans; Michieli, Paolo; Blanchetot, Christophe

    2016-08-22

    Bispecific antibodies are of great interest due to their ability to simultaneously bind and engage different antigens or epitopes. Nevertheless, it remains a challenge to assemble, produce and/or purify them. Here we present an innovative dual anti-idiotypic purification process, which provides pure bispecific antibodies with native immunoglobulin format. Using this approach, a biparatopic IgG1 antibody targeting two distinct, HGF-competing, non-overlapping epitopes on the extracellular region of the MET receptor, was purified with camelid single-domain antibody fragments that bind specifically to the correct heavy chain/light chain pairings of each arm. The purity and functionality of the anti-MET biparatopic antibody was then confirmed by mass spectrometry and binding experiments, demonstrating its ability to simultaneously target the two epitopes recognized by the parental monoclonal antibodies. The improved MET-inhibitory activity of the biparatopic antibody compared to the parental monoclonal antibodies, was finally corroborated in cell-based assays and more importantly in a tumor xenograft mouse model. In conclusion, this approach is fast and specific, broadly applicable and results in the isolation of a pure, novel and native-format anti-MET biparatopic antibody that shows superior biological activity over the parental monospecific antibodies both in vitro and in vivo.

  20. Somatic diversification in the heavy chain variable region genes expressed by human autoantibodies bearing a lupus-associated nephritogenic anti-DNA idiotype

    SciTech Connect

    Demaison, C.; Chastagner, P.; Theze, J.; Zouali, M. )

    1994-01-18

    Monoclonal anti-DNA antibodies bearing a lupus nephritis-associated idiotype were derived from five patients with systemic lupus erythematosus (SLE). Genes encoding their heavy (H)-chain variable (V[sub H]) regions were cloned and sequenced. When compared with their closest V[sub h] germ-line gene relatives, these sequences exhibit a number of silent (S) and replacement (R) substitutions. The ratios of R/S mutations were much higher in the complementarity-determining regions (CDRs) of the antibodies than in the framework regions. Molecular amplification of genomic V[sub H] genes and Southern hybridization with somatic CDR2-specific oligonucleotide probes showed that the configuration of the V[sub H] genes corresponding to V[sub H] sequences in the nephritogenic antibodies is not present in the patient's own germ-line DNA, implying that the B-cell clones underwent somatic mutation in vivo. These findings, together with the characteristics of the diversity and junctional gene elements utilized to form the antibody, indicate that these autoantibodies have been driven through somatic selection processes reminiscent of those that govern antibody responses triggered by exogenous stimuli.

  1. Characterization of the group I and group II antibody response against PC-KLH in normal and T15 idiotype-suppressed BALB/c mice.

    PubMed Central

    Bruderer, U; Aebersold, R; Blaser, K; Heusser, C H

    1988-01-01

    The memory response of BALB/c mice to phosphocholine-keyhole limpet haemocyanin (PC-KLH) consists of two antibody populations, designated Group I and Group II, that differ in their fine specificity, as determined by hapten inhibition using phosphocholine (PC) and p-nitrophenylphosphocholine (NPPC). It is known that Group I response is dominated by T15 idiotype-positive antibodies that utilize the VH1 heavy-chain gene in combination with V kappa 22 light-chain gene. In this paper we show that Group II serum antibodies of BALB/c mice are also highly restricted in their heterogeneity, as determined by N-terminal amino acid sequence analysis. Furthermore, we demonstrate that the Group II response is not affected by neonatally induced T15 suppression, whereas the Group I response in these mice consists of T15-negative antibodies. This suggests that the expression of the two antibody populations is regulated independently. Finally, we show that the isotype distributions within a fine specificity are the same in normal and T15-suppressed mice. Interestingly this is true not only for the Group II but also for the Group I antibodies. Because the isolated Group I antibodies from normal mice differ in structure from those of T15-suppressed mice, i.e. different light chains, our data indicate that the isotype distribution of these two populations is associated with their fine specificity in addition to their clonal origin. PMID:3410491

  2. Anti-idiotypic nanobody-alkaline phosphatase fusion proteins: Development of a one-step competitive enzyme immunoassay for fumonisin B1 detection in cereal.

    PubMed

    Shu, Mei; Xu, Yang; Liu, Xing; Li, Yanping; He, Qinghua; Tu, Zhui; Fu, Jinheng; Gee, Shirley J; Hammock, Bruce D

    2016-06-14

    A rapid and sensitive one-step competitive enzyme immunoassay for the detection of FB1 was developed. The anti-idiotypic nanobody-alkaline phosphatase (Ab2β-Nb-AP) was validated by the AP enzyme activity and the properties of bounding to anti-FB1-mAb (3F11) through colorimetric and chemiluminescence analyses. The 50% inhibitory concentration and the detection limit (LOD) of colorimetric enzyme-linked immunosorbent assay (ELISA) for FB1 were 2.69 and 0.35 ng mL(-1), respectively, with a linear range of 0.93-7.73 ng mL(-1). The LOD of the chemiluminescence ELISA (CLIA) was 0.12 ng mL(-1), and the IC50 was 0.89 ± 0.09 ng mL(-1) with a linear range of 0.29-2.68 ng mL(-1). Compared with LC-MS/MS, the results of this assay indicated the reliability of the Ab2β-Nb-AP fusion protein based one-step competitive immunoassay for monitoring FB1 contamination in cereals. The Ab2β-Nb-AP fusion proteins have the potential to replace chemically-coupled probes in competitive enzyme immunoassay systems.

  3. Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy

    PubMed Central

    Godar, Marie; Morello, Virginia; Sadi, Ava; Hultberg, Anna; De Jonge, Natalie; Basilico, Cristina; Hanssens, Valérie; Saunders, Michael; Lambrecht, Bart N.; El Khattabi, Mohamed; de Haard, Hans; Michieli, Paolo; Blanchetot, Christophe

    2016-01-01

    Bispecific antibodies are of great interest due to their ability to simultaneously bind and engage different antigens or epitopes. Nevertheless, it remains a challenge to assemble, produce and/or purify them. Here we present an innovative dual anti-idiotypic purification process, which provides pure bispecific antibodies with native immunoglobulin format. Using this approach, a biparatopic IgG1 antibody targeting two distinct, HGF-competing, non-overlapping epitopes on the extracellular region of the MET receptor, was purified with camelid single-domain antibody fragments that bind specifically to the correct heavy chain/light chain pairings of each arm. The purity and functionality of the anti-MET biparatopic antibody was then confirmed by mass spectrometry and binding experiments, demonstrating its ability to simultaneously target the two epitopes recognized by the parental monoclonal antibodies. The improved MET-inhibitory activity of the biparatopic antibody compared to the parental monoclonal antibodies, was finally corroborated in cell-based assays and more importantly in a tumor xenograft mouse model. In conclusion, this approach is fast and specific, broadly applicable and results in the isolation of a pure, novel and native-format anti-MET biparatopic antibody that shows superior biological activity over the parental monospecific antibodies both in vitro and in vivo. PMID:27546726

  4. A spontaneous hybridoma producing autoanti-idiotypic antibodies that recognize a V kappa-associated idiotope in mercury-induced autoimmunity.

    PubMed

    Guéry, J C; Druet, P

    1990-05-01

    Anti-idiotypic (Id) antibodies have been suggested to play a role in the self regulation process observed in Brown-Norway rats developing mercury-induced autoimmunity. However, the presence of such antibodies has not yet been directly demonstrated. For that purpose, spleen cells from a mercury-injected rat were fused and the resulting hybridomas tested for their anti-Id activity against monoclonal anti-glomerular basement membrane (GBM) antibodies produced in this model. A monoclonal antibody (mAb) was obtained that specifically reacted in an enzyme-linked immunosorbent assay with an anti-GBM mAb and to a much lesser extent with another one produced in the same fusion. In Western blot experiments this autoanti-Id mAb reacted under reducing conditions with the kappa L chains but not with the H chains of the two anti-GBM mAb. It did not react with the kappa L chains of eight other rat mAb. This mAb is therefore an autoanti-Id mAb that recognizes a V kappa-associated Id expressed on two anti-GBM mAb. These results demonstrate that anti-GBM antibodies and their corresponding autoanti-Id antibodies are simultaneously produced during this disease. Whether or not these autoanti-Id antibodies have a regulatory and/or a pathogenic role in this disease remains to be established.

  5. Immunization Coverage

    MedlinePlus

    ... underused vaccines is increasing. Immunization currently averts an estimated 2 to 3 million deaths every year. An ... avoided, however, if global vaccination coverage improves. An estimated 19.4 million infants worldwide are still missing ...

  6. Adolescent immunization.

    PubMed

    Handal, G A

    2000-06-01

    The dramatic improvements achieved in the control of vaccine-preventable diseases in children have only been shared partially by adolescents and young adults, as today several million adolescents are not receiving the full complement of vaccines recommended by the Advisory Committee on Immunization Practices (ACIP). This article discusses the reasons for this problem and the tools to bridge this gap. In particular, medical societies and the Centers for Disease Control and Prevention (CDC) recommend a close assessment of the adolescentís immunization status between 11 and 12 years of age, inclusion of school immunization, and providing missing immunizations at any opportunity. The article also addresses other vaccines recommended for groups of adolescents with special needs, reporting information, and provides an update on the vaccines of the future.

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

    PubMed

    Nellore, Anoma; Fishman, Jay A

    2016-01-01

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

  8. Skin Immunization Obviates Alcohol-Related Immune Dysfunction.

    PubMed

    Brand, Rhonda M; Stottlemyer, John Mark; Cline, Rachel A; Donahue, Cara; Behari, Jaideep; Falo, Louis D

    2015-01-01

    Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD) and liver-sparing Meadows-Cook (MC) diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA) by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM), directly to liver (hydrodynamic), or cutaneously (biolistic, ID). We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg), and myeloid-derived suppressor cell (MDSC) populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH), antigen-specific cytotoxic T lymphocyte (CTL), and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects. PMID:26561838

  9. Antibody responses to allergen Lol pIV are suppressed following adoptive transfer of B lymphocytes from the internal image anti-idiotypic antibody-treated mice.

    PubMed

    Zhou, E M; Kisil, F T

    1995-10-01

    An internal image anti-idiotypic antibody, designated B1/1, was generated against an idiotope (Id91) of the monoclonal antibody (mAb91) specific for Lol pIV. The administration of B1/1 in PBS, at doses ranging from 100 ng to 100 micrograms/mouse, to syngeneic Balb/c mice resulted in the suppression of the formation of anti-Lol pIV antibodies that possessed the Id91. Spleen cells obtained from the mice 2 weeks after the treatment with B1/1 (25 micrograms/mouse) were adoptively transferred intravenously into the syngeneic recipients which were challenged intraperitoneally with Lol pIV in alum 2 hr after the transfer. The recipients were boosted with Lol pIV 14 days later. It was demonstrated that the transfer of splenic B cells (but not of T cells) from B1/1-treated donors induced a significant suppression of not only the level of IgE and IgG antibodies to Lol pIV, but also the level of antibodies possessing the Id91. Treatment of the B cells with mAb91 plus complement abrogated their ability to transfer the suppression. This study indicates that the treatment with the anti-Id B1/1 generated B cells that were characterized, serologically, as possessing the anti-Id-like antibodies on their surface and were responsible for transferring the suppression of the formation of antibodies to allergen Lol pIV and the expression of Id91.

  10. Regulation of levels of serum antibodies to ryegrass pollen allergen Lol pIV by an internal image anti-idiotypic monoclonal antibody.

    PubMed

    Zhou, E M; Kisil, F T

    1995-03-01

    A murine monoclonal anti-idiotypic antibody (anti-Id), designated B1/1, was produced against an idiotope of a murine antibody (mAb91), which recognizes the epitope, site A, of allergen Lol pIV, one of the major groups of allergens in ryegrass (Lolium perenne) pollen. The ability of B1/1 to modulate the antibody responses to Lol pIV was investigated in murine model systems. In the first system, B1/1-keyhole limpet haemocyanin (KLH) conjugate was administered to treat three different strains of mice (C57BL/6, BALB/c and C3H). In the second and third model systems, a solution of B1/1 in phosphate-buffered saline (PBS) was used to treat syngeneic BALB/c mice at various doses and time intervals, respectively. The treatment with either form of B1/1, administered at doses ranging from 100 ng to 100 micrograms mouse, resulted in a reduction of the levels of the antibodies to Lol pIV. In particular, the level of IgE antibodies to Lol pIV was greatly reduced. The administration of a single intravenous (i.v.) injection of a solution of B1/1 8 weeks prior to the challenge with Lol pIV was still effective in reducing the level of antibodies to the allergen. Moreover, the level of antibodies to Lol pIV that expressed the idiotope mAb91 was also markedly decreased. By contrast, it was observed that the level of antibodies to Lol pIV in mice pretreated with B1/1 in PBS at a dose of 10 ng/mouse increased (albeit slightly) compared to that in mice treated with control mAb. These experimental models lend themselves for investigating the mechanism(s) by which an anti-Id modulates antibody responses to a grass pollen allergen.

  11. Real-time immune-inspired optimum state-of-charge trajectory estimation using upcoming route information preview and neural networks for plug-in hybrid electric vehicles fuel economy

    NASA Astrophysics Data System (ADS)

    Mozaffari, Ahmad; Vajedi, Mahyar; Azad, Nasser L.

    2015-06-01

    The main proposition of the current investigation is to develop a computational intelligence-based framework which can be used for the real-time estimation of optimum battery state-of-charge (SOC) trajectory in plug-in hybrid electric vehicles (PHEVs). The estimated SOC trajectory can be then employed for an intelligent power management to significantly improve the fuel economy of the vehicle. The devised intelligent SOC trajectory builder takes advantage of the upcoming route information preview to achieve the lowest possible total cost of electricity and fossil fuel. To reduce the complexity of real-time optimization, the authors propose an immune system-based clustering approach which allows categorizing the route information into a predefined number of segments. The intelligent real-time optimizer is also inspired on the basis of interactions in biological immune systems, and is called artificial immune algorithm (AIA). The objective function of the optimizer is derived from a computationally efficient artificial neural network (ANN) which is trained by a database obtained from a high-fidelity model of the vehicle built in the Autonomie software. The simulation results demonstrate that the integration of immune inspired clustering tool, AIA and ANN, will result in a powerful framework which can generate a near global optimum SOC trajectory for the baseline vehicle, that is, the Toyota Prius PHEV. The outcomes of the current investigation prove that by taking advantage of intelligent approaches, it is possible to design a computationally efficient and powerful SOC trajectory builder for the intelligent power management of PHEVs.

  12. Studies on the origin of the precursor cells in multiple myeloma, Waldenström's macroglobulinaemia and benign monoclonal gammopathy. I. Cytoplasmic isotype and idiotype distribution in peripheral blood and bone marrow.

    PubMed Central

    Van Camp, B; Reynaert, P; Broodtaerts, L

    1981-01-01

    Lymphocytes and plasma cells in the peripheral blood and bone marrow of patients with multiple myeloma, benign monoclonal gammopathy and Waldenström's macroglobulinaemia were investigated for their cytoplasmic immunoglobulin distribution. Anti-idiotypic sera were used as markers for monoclonality. Double-wavelength fluorescence microscopy made it possible simultaneously to use anti-isotype and anti-idiotype sera with different fluorochromes. It was concluded that, in the bone marrow, the monoclonal event starts at the level of a lymphoid cell which has already been committed to its final isotype. The size of the monoclonal expansion in the bone marrow and the cell types involved in the proliferation may determine whether spread occurs. Polyclonal lymphoid cells containing cytoplasmic immunoglobulins were decreased in the peripheral blood and exhibited a reversed kappa/lambda ratio when compared to the immunoglobulin-containing cells in the bone marrow. This finding suggests a light chain-type related depression of polyclonal B cell precursors. PMID:6790210

  13. Adult immunization

    PubMed Central

    Mehta, Bharti; Chawla, Sumit; Kumar Dharma, Vijay; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Vaccination is recommended throughout life to prevent vaccine-preventable diseases and their sequel. The primary focus of vaccination programs has historically been directed to childhood immunizations. For adults, chronic diseases have been the primary focus of preventive and medical health care, though there has been increased emphasis on preventing infectious diseases. Adult vaccination coverage, however, remains low for most of the routinely recommended vaccines. Though adults are less susceptible to fall prey to traditional infectious agents, the probability of exposure to infectious agents has increased manifold owing to globalization and increasing travel opportunities both within and across the countries. Thus, there is an urgent need to address the problem of adult immunization. The adult immunization enterprise is more complex, encompassing a wide variety of vaccines and a very diverse target population. There is no coordinated public health infrastructure to support an adult immunization program as there is for children. Moreover, there is little coordination among adult healthcare providers in terms of vaccine provision. Substantial improvement in adult vaccination is needed to reduce the health consequences of vaccine-preventable diseases among adults. Routine assessment of adult patient vaccination needs, recommendation, and offer of needed vaccines for adults should be incorporated into routine clinical care of adults. PMID:24128707

  14. Plant Immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants are faced with defending themselves against a multitude of pathogens, including bacteria, fungi, viruses, nematodes, etc. Immunity is multi-layered and complex. Plants can induce defenses when they recognize small peptides, proteins or double-stranded RNA associated with pathogens. Recognitio...

  15. Circadian Clocks, Stress, and Immunity

    PubMed Central

    Dumbell, Rebecca; Matveeva, Olga; Oster, Henrik

    2016-01-01

    In mammals, molecular circadian clocks are present in most cells of the body, and this circadian network plays an important role in synchronizing physiological processes and behaviors to the appropriate time of day. The hypothalamic–pituitary–adrenal endocrine axis regulates the response to acute and chronic stress, acting through its final effectors – glucocorticoids – released from the adrenal cortex. Glucocorticoid secretion, characterized by its circadian rhythm, has an important role in synchronizing peripheral clocks and rhythms downstream of the master circadian pacemaker in the suprachiasmatic nucleus. Finally, glucocorticoids are powerfully anti-inflammatory, and recent work has implicated the circadian clock in various aspects and cells of the immune system, suggesting a tight interplay of stress and circadian systems in the regulation of immunity. This mini-review summarizes our current understanding of the role of the circadian clock network in both the HPA axis and the immune system, and discusses their interactions. PMID:27199894

  16. Alzheimer's disease plaques and tangles: cemeteries of a pyrrhic victory of the immune defence network against herpes simplex infection at the expense of complement and inflammation-mediated neuronal destruction.

    PubMed

    Carter, C J

    2011-02-01

    Plaques and tangles are highly and significantly enriched in herpes simplex (HSV-1) binding proteins (by 11 and 15 fold respectively (P<4.47466E-39) and 132/341 (39%) of the known HSV-1 binding partners or associates are present in these structures. The classes involved include the majority (63-100%) of the known HSV-1 host protein carriers and receptors, 85-91% of the viral associated proteins involved in endocytosis, intracellular transport and exocytosis and 71% of the host proteins associated with the HSV-1 virion. The viral associated proteins found in plaques or tangles trace out a complete itinerary of the virus from entry to exocytosis and the virus also binds to plaque or tangle components involved in apoptosis, DNA transcription, translation initiation, protein chaperoning, the ubiquitin/proteasome system and the immune network. Along this route, the virus deletes mitochondrial DNA, as seen in Alzheimer's disease, sequesters the neuroprotective peptide, ADNP, and interferes with key proteins related to amyloid precursor protein processing and signalling as well as beta-amyloid processing, microtubule stability and tau phosphorylation, the core pathologies of Alzheimer's disease. Amyloid-containing plaques or neurofibrillary tangles also contain a large number of complement, acute phase and immune-related proteins, and the presence of these pathogen defence related classes along with HSV-1 binding proteins suggests that amyloid plaques and tangles represent cemeteries for a battle between the virus and the host's defence network. The presence of the complement membrane attack complex in Alzheimer's disease neurones suggests that complement mediated neuronal lysis may be a consequence of this struggle. HSV-1 infection is known to increase beta-amyloid deposition and tau phosphorylation and also results in cortical and hippocampal neuronal loss, cerebral shrinkage and memory deficits in mice. This survey supports the contention that herpes simplex viral

  17. Transmethylation in immunity and autoimmunity

    PubMed Central

    Lawson, Brian R.; Eleftheriadis, Theodoros; Tardif, Virginie; Gonzalez-Quintial, Rosana; Baccala, Roberto; Kono, Dwight H.; Theofilopoulos, Argyrios N.

    2013-01-01

    The activation of immune cells is mediated by a network of signaling proteins that can undergo post-translational modifications critical for their activity. Methylation of nucleic acids or proteins can have major effects on gene expression as well as protein repertoire diversity and function. Emerging data indicate that indeed many immunologic functions, particularly those of T cells, including thymic education, differentiation and effector function are highly dependent on methylation events. The critical role of methylation in immunocyte biology is further documented by evidence that autoimmune phenomena may be curtailed by methylation inhibitors. Additionally, epigenetic alterations imprinted by methylation can also exert effects on normal and abnormal immune responses. Further work in defining methylation effects in the immune system is likely to lead to a more detailed understanding of the immune system and may point to the development of novel therapeutic approaches. PMID:22364920

  18. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  19. Variable region sequences and idiotypic expression of a protective human immunoglobulin M antibody to capsular polysaccharides of Neisseria meningitidis group B and Escherichia coli K1.

    PubMed Central

    Azmi, F H; Lucas, A H; Raff, H V; Granoff, D M

    1994-01-01

    We determined the heavy (H)- and light (L)-chain variable (V) region nucleotide and translated amino acid sequences of the human immunoglobulin M(kappa) monoclonal antibody (MAb) 5E1, which is specific for the polysaccharide capsule of Escherichia coli K1 and Neisseria meningitidis group B (poly[alpha(2-->8)-N-acetylneuraminic acid]) and which is protective in animal models of infection. The 5E1 VH gene is a member of the VHIIIb family and is 97% homologous to the 9.1 germ line gene. The 5E1 VL gene is a member of the kappa I subgroup and is 98% homologous to the germ line gene, 15A, also known as KLO12. The VL and/or VH genes used by 5E1 are highly homologous to the V genes encoding antibodies to the Haemophilus influenzae type b polysaccharide and to antibodies reactive with self-antigens such as erythrocyte "i," DNA, and thyroid peroxidase. We also produced three murine anti-idiotype (Id) MAbs against 5E1. All three anti-Ids recognize a minor subset of antimeningococcal B polysaccharide antibodies present in serum from normal adults. Two of the anti-Ids define distinct Ids associated with antibodies having kappa I-15A V regions. These 15A-associated Ids are expressed by some heterologous human antimeningococcal B polysaccharide MAbs, and they also are independently expressed by two human MAbs that are specific for either the H. influenzae b polysaccharide or the i erythrocyte antigen and that utilize the kappa I-15A V region. Taken together, these data indicate that the 5E1 antibody uses V regions that recur in the human antibody repertoires to this polysaccharide and to structurally dissimilar polysaccharides and autoantigens. Thus, the poor immunogenicity of poly[alpha(2-->8)-N-acetylneuraminic acid] cannot be explained by the unavailability of certain critical VH and VL genes required for generation of antibody response. PMID:8168940

  20. Increased IgA rheumatoid factor and VH1 associated cross reactive idiotype expression in patients with Lyme arthritis and neuroborreliosis

    PubMed Central

    Axford, J.; Rees, D.; Mageed, R.; Wordsworth, P.; Alavi, A.; Steere, A.

    1999-01-01

    OBJECTIVE—To investigate whether autoreactive mechanisms occur in Lyme disease (LD) by determining IgA, IgG and IgM rheumatoid factor (RF) concentrations and RF associated cross reactive idiotype (CRI) expression in the serum of LD patients, with comparison to patients with rheumatoid arthritis (RA).
METHODS—The RF isotype profiles were determined in 59 patients with LD; erythema migrans (EM) (n=19), neuroborreliosis (NB) (n=20) and Lyme arthritis (LA) (n=20). Mouse monoclonal antibodies (mAbs) G6 and G8 (VH1 gene associated), D12 (VH3 gene associated) and C7 (VκIII gene associated) were then used to determine the RF associated CRI expression on IgM antibodies in 16 of these LD patients (eight seropositive for RF); (EM (n=3), NB (n=6), LA (n=7)).
RESULTS—Seven (18%) patients with either NB or LA had increased concentrations of IgA RF compared with none with EM. Significant differences in the number of patients with raised concentrations of IgG RF or IgM RF were not found between the LD patient groups. Five (3NB, 1LA and 1 EM) (31%) and three (2NB and 1LA) (19%) of LD patients had raised concentrations of the CRIs recognised by mAbs G6 and G8, respectively. These CRIs were detected in LD sera both with and without raised concentrations of RF and were not demonstrated on anti-Borrelia burgdorferi antibodies using ELISA. No LD sera tested had raised concentrations of the determinants recognised by mAbs C7 or D12.
CONCLUSION—Significantly raised concentrations of IgA RF and increased use of VH1 germline gene associated CRIs are found on IgM antibodies in the serum of LD patients. These data indicate the recruitment of autoreactive B lymphocytes in some patients with the later stages of LD.

 PMID:10577962

  1. Numerical analysis of a model of ligand-induced B-cell antigen-receptor clustering. Implications for simple models of B-cell activation in an immune network.

    PubMed

    Faro, J; Velasco, S

    1994-03-01

    B-cell activation driven by ligand-induced crosslinking of membrane immunoglobulin (mIg) is one of the most important processes in experimental and theoretical immunology. Although the activation of B cells through mIgs involves a complex series of intracellular processes, in immune network models it is usually assumed that there is a correlation between the degree of mIg crosslinking and the probability of B-cell activation. We explore the implications of this hypothesis by studying a model of ligand-induced B-cell receptor clustering proposed by Bell and further elaborated by Delisi and Perelson (BDP model). In this model, a critical time (tc) is defined at which the probability of infinite size complex formation (i.e., percolation) becomes non-zero. We use this variable, tc, as a means to characterize the degree of mIg crosslinking. To study the dependence of tc with respect to ligand valence, kinetic constants and ligand-receptor affinity x ligand concentration (K x C), we perform a systematic numerical study of the BDP model for parameter ranges including current empirical estimates for the kinetic constants. Concerning tc, we find that, for ranges of immunological interest (namely, those including current estimates of dissociation and receptor crosslinking rate constants), the curves obtained by plotting 1/tc vs. log(K x C) shift sensibly towards higher values of log(K x C), broadening and increasing its maximum amplitude, as the dissociation rate constant increases. As this finding suggests important consequences for immune network models, we further study the BDP model in an extended version for the case of two different ligands interacting simultaneously with a given B cell.3+

  2. Dynamical immunization strategy for seasonal epidemics

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

  3. The B cell repertoire revealed by major histocompatibility complex- specific helper T cells. I. Frequencies of a genetically defined V region marker among mitogen- and T helper cell-reactive B lymphocytes in normal and immunized mice

    PubMed Central

    1984-01-01

    The aim of the present work was to analyze the frequencies of a genetically defined variable (V) region marker in the B cell subset sensitive to T cell help. To this end we used an alloreactive T cell line that has the property of inducing B cells of the appropriate haplotype to exponential growth and polyclonal antibody synthesis. The frequency obtained with this helper line was also directly compared to that obtained with lipopolysaccharide (LPS). We found that in normal BALB/c mice the frequency of M460-positive clonotypes was respectively, 1/100 and 1/1,000 among the T helper- and LPS-sensitive B cell subsets. In mice immunized with antiidiotype coupled to a thymus-dependent antigen, the differences in the numbers of idiotype-positive precursors were even more accentuated, i.e. 1/20 in the B cell subset triggered by T helper cells and 1/800 in those cells responsive to LPS. The frequencies of the M460 determinant in mice immunized with anti- idiotypes coupled to thymus-independent antigens were not significantly different, in either B cell subset, from those obtained with spleen cells of normal nonimmunized animals. Taken as a whole, our results imply that the V gene repertoire revealed by LPS includes precursor distribution, as this distribution occurs during the early stage of B cell development (potential repertoire), while the repertoire revealed by T helper cells includes the V region distribution of those clones that are selected in the periphery of the functional immune system. PMID:6200567

  4. Interactions between the immune and nervous systems in pain

    PubMed Central

    Ren, Ke; Dubner, Ronald

    2010-01-01

    Immune cells and glia interact with neurons to alter pain sensitivity and to mediate the transition from acute to chronic pain. In response to injury, resident immune cells are activated and blood-borne immune cells are recruited to the site of injury. Immune cells not only contribute to immune protection but also initiate the sensitization of peripheral nociceptors. Through the synthesis and release of inflammatory mediators and interactions with neurotransmitters and their receptors, the immune cells, glia and neurons form an integrated network that coordinates immune responses and modulates the excitability of pain pathways. The immune system also reduces sensitization by producing immune-derived analgesic and anti-inflammatory or proresolution agents. A greater understanding of the role of the immune system in pain processing and modulation reveals potential targets for analgesic drug development and new therapeutic opportunities for managing chronic pain. PMID:20948535

  5. Integrated Circuit Immunity

    NASA Technical Reports Server (NTRS)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  6. Peptides mimicking GD2 ganglioside elicit cellular, humoral and tumor-protective immune responses in mice

    PubMed Central

    Wondimu, Assefa; Zhang, Tianqian; Kieber-Emmons, Thomas; Gimotty, Phyllis; Sproesser, Katrin; Somasundaram, Rajasekharan; Ferrone, Soldano; Tsao, Chun-Yen

    2012-01-01

    Introduction Because of its restricted distribution in normal tissues and its high expression on tumors of neuroectodermal origin, GD2 ganglioside is an excellent target for active specific immunotherapy. However, GD2 usually elicits low-titered IgM and no IgG or cellular immune responses, limiting its usefulness as a vaccine for cancer patients. We have previously shown that anti-idiotypic monoclonal antibody mimics of GD2 can induce antigen-specific humoral and cellular immunity in mice, but inhibition of tumor growth by the mimics could not be detected. Methods and results Here, we isolated two peptides from phage display peptide libraries by panning with GD2-specific mAb ME361. The peptides inhibited binding of the mAb to GD2. When coupled to keyhole limpet hemocyanin (KLH) or presented as multiantigenic peptides in QS21 adjuvant, the peptides induced in mice antibodies binding specifically to GD2 and delayed-type hypersensitive lymphocytes reactive specifically with GD2-positive D142.34 mouse melanoma cells. Induction of delayed-type hypersensitivity (DTH) reaction was dependent on CD4-positive lymphocytes. The immunity elicited by the peptides significantly inhibited growth of GD2-positive melanoma cells in mice. Conclusion Our study suggests that immunization with peptides mimicking GD2 ganglioside inhibits tumor growth through antibody and/or CD4-positive T cell-mediated mechanisms. Cytolytic T lymphocytes most likely do not play a role. Our results provide the basis for structural analysis of carbohydrate mimicry by peptides. PMID:18157673

  7. The mechanisms of action of intravenous immunoglobulin and polyclonal anti-d immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know?

    PubMed

    Crow, Andrew R; Lazarus, Alan H

    2008-04-01

    Intravenous immunoglobulin (IVIg) has been used for more than 25 years to treat an ever-increasing number of autoimmune diseases including immune thrombocytopenic purpura. Although the exact mechanism of action of IVIg has remained elusive, many theories have been postulated, including mononuclear phagocytic system blockade/inhibition, autoantibody neutralization by anti-idiotype antibodies, pathogenic autoantibody clearance due to competitive inhibition of the neonatal immunoglobulin Fc receptor, cytokine modulation, complement neutralization, and immune complex formation leading to dendritic cell priming. Polyclonal anti-D immunoglobulin is a polyclonal IVIg product enriched for antibodies directed to the RhD antigen on red blood cells and that has also been successfully used to treat immune thrombocytopenia in RhD(+) patients. The primary theory to explain polyclonal anti-D immunoglobulin function has classically been mononuclear phagocytic system blockade, although modulation of Fcgamma receptor expression and/or immunomodulation may also play a role. Work using a murine model of immune thrombocytopenic purpura to further our understanding of the mechanism of action of these 2 therapeutic agents is a focus of this article.

  8. Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation

    PubMed Central

    Bam, Marpe; Yang, Xiaoming; Zumbrun, Elizabeth E.; Zhong, Yin; Zhou, Juhua; Ginsberg, Jay P.; Leyden, Quinne; Zhang, Jiajia; Nagarkatti, Prakash S.; Nagarkatti, Mitzi

    2016-01-01

    Post-traumatic stress disorder patients experience chronic systemic inflammation. However, the molecular pathways involved and mechanisms regulating the expression of genes involved in inflammatory pathways in PTSD are reported inadequately. Through RNA sequencing and miRNA microarray, we identified 326 genes and 190 miRNAs that were significantly different in their expression levels in the PBMCs of PTSD patients. Expression pairing of the differentially expressed genes and miRNAs indicated an inverse relationship in their expression. Functional analysis of the differentially expressed genes indicated their involvement in the canonical pathways specific to immune system biology. DNA methylation analysis of differentially expressed genes also showed a gradual trend towards differences between control and PTSD patients, again indicating a possible role of this epigenetic mechanism in PTSD inflammation. Overall, combining data from the three techniques provided a holistic view of several pathways in which the differentially expressed genes were impacted through epigenetic mechanisms, in PTSD. Thus, analysis combining data from RNA-Seq, miRNA array and DNA methylation, can provide key evidence about dysregulated pathways and the controlling mechanism in PTSD. Most importantly, the present study provides further evidence that inflammation in PTSD could be epigenetically regulated. PMID:27510991

  9. Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation.

    PubMed

    Bam, Marpe; Yang, Xiaoming; Zumbrun, Elizabeth E; Zhong, Yin; Zhou, Juhua; Ginsberg, Jay P; Leyden, Quinne; Zhang, Jiajia; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2016-01-01

    Post-traumatic stress disorder patients experience chronic systemic inflammation. However, the molecular pathways involved and mechanisms regulating the expression of genes involved in inflammatory pathways in PTSD are reported inadequately. Through RNA sequencing and miRNA microarray, we identified 326 genes and 190 miRNAs that were significantly different in their expression levels in the PBMCs of PTSD patients. Expression pairing of the differentially expressed genes and miRNAs indicated an inverse relationship in their expression. Functional analysis of the differentially expressed genes indicated their involvement in the canonical pathways specific to immune system biology. DNA methylation analysis of differentially expressed genes also showed a gradual trend towards differences between control and PTSD patients, again indicating a possible role of this epigenetic mechanism in PTSD inflammation. Overall, combining data from the three techniques provided a holistic view of several pathways in which the differentially expressed genes were impacted through epigenetic mechanisms, in PTSD. Thus, analysis combining data from RNA-Seq, miRNA array and DNA methylation, can provide key evidence about dysregulated pathways and the controlling mechanism in PTSD. Most importantly, the present study provides further evidence that inflammation in PTSD could be epigenetically regulated. PMID:27510991

  10. Immunity and immunization in elderly.

    PubMed

    Bourée, Patrice

    2003-12-01

    As the average life expectancy increases, retired people want to travel. Five to 8% of travellers in tropical areas are old persons. Immune system suffers of old age as the other organs. The number and the functions of the T-lymphocytes decrease, but the B-lymphocytes are not altered. So, the response to the vaccinations is slower and lower in the elderly. Influenza is a great cause of death rate in old people. The seroconversion, after vaccine, is 50% from 60 to 70 years old, 31% from 70 to 80 years old, and only 11% after 80 years old. But in public health, the vaccination reduced the morbidity by 25%, admission to hospital by 20%, pneumonia by 50%, and mortality by 70%. Antipoliomyelitis vaccine is useful for travellers, as the vaccines against hepatitis and typhoid fever. Pneumococcal vaccine is effective in 60%. Tetanus is fatal in at last 32% of the people above 80 years, therefore this vaccine is very important.

  11. Immune System Involvement

    MedlinePlus

    ... Tips" to find out more! Email * Zipcode The Immune System and Psoriatic Disease What is an autoimmune disease? ... swollen and painful joints and tendons. Treating the immune system The immune system is not only the key ...

  12. Immunization and Pregnancy

    MedlinePlus

    Immunization & Pregnancy Vaccines help keep apregnant woman and her growing family healthy. Vaccine Before pregnancy Hepatitis A ... 232-4636) • English or Spanish National Center for Immunization and Respiratory Diseases Immunization Services Division CS238938B 03/ ...

  13. Childhood Immunization Schedule

    MedlinePlus

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  14. Action on low immunization uptake.

    PubMed

    Azubuike, M C; Ehiri, J E

    1998-01-01

    Despite a number of initiatives and campaigns over the years, immunization coverage in most parts of Nigeria remains low. That low coverage contributes to high morbidity and mortality levels among children. Poor transport, an ineffective cold chain, shortages of trained manpower, and inadequate community support and involvement are some of the factors which explain the underutilization of the immunization service. Aba is a city of approximately 500,000 people in eastern Nigeria in which the majority of inhabitants are traders. Aba's primary health care committee decided that immunization centers should be established in or near main trading areas to accommodate traders who did not want to leave their goods in order to take their children to primary care facilities for immunization. Traders' representatives helped to identify 8 suitable locations for vaccination sites in 3 shopping centers, the local authority provided financial and political support, and the state government gave technical and logistical assistance. The project began in September 1990 and was publicized through the traders' networks, which also helped to mobilize the relevant resources. Since many trading families were reached for the first time at the special centers, immunization coverage improved significantly for the 6 vaccine-preventable childhood diseases. Moreover, the project gave health workers the opportunity to deliver other services and counseling on matters of public health importance.

  15. The Immune System in the Pathogenesis of Ovarian Cancer

    PubMed Central

    Charbonneau, Bridget; Goode, Ellen L.; Kalli, Kimberly R.; Knutson, Keith L.; DeRycke, Melissa S.

    2014-01-01

    Clinical outcomes in ovarian cancer are heterogeneous even when considering common features such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling host characteristic is the immune response to ovarian cancer. While several studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease, recent genetic and protein analyses also suggest a role in disease incidence. Recent studies also show that anti-tumor immunity is often negated by immune suppressive cells present in the tumor microenvironment. These suppressive immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, future research into immunotherapy targeting ovarian cancer will likely become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression or by disrupting critical cytokine networks. PMID:23582060

  16. Target extraction of banded blurred infrared images by immune dynamical algorithm with two-dimensional minimum distance immune field

    NASA Astrophysics Data System (ADS)

    Yu, Xiao; Yuan, Ximei; Dong, Enzeng; Ríha, Kamil

    2016-07-01

    Banded blurred Infrared image segmentation is a challenging topic since banded blurred infrared images are characterized by high noise, low contrast, and weak edges. Based on the interconnected and networked collaborative mechanism between innate immune factors and adaptive immune factors, this paper presents an immune dynamical algorithm with two-dimensional minimum distance immune field to solve this puzzle. Firstly, using the original characteristics as antigen surface molecular patterns, innate immune factors in the first layer of immune dynamical network extract banded blurred regions from the whole banded blurred infrared image region. Secondly, innate immune factors in the second layer of immune dynamical network extract new characteristics to design the complex of major histocompatibility complex (MHC) and antigen peptide. Lastly, adaptive immune factors in the last layer will extract object and background antigens from all the banded blurred image antigens, and design the optimal immune field of every adaptive immune factors. Experimental results on hand trace infrared images verified that the proposed algorithm could efficiently extract targets from images, and produce better extraction accuracy.

  17. Epigenetic dynamics in immunity and autoimmunity.

    PubMed

    Zhao, Ming; Wang, Zijun; Yung, Susan; Lu, Qianjin

    2015-10-01

    A tightly synchronized and spatial-temporal interaction among regulatory proteins within genomic DNA and chromatin is essential for cellular commitment and differentiation. During development and activation of the immune system, a complex regulatory network that involves induction of lineage instructive transcription factors, installation or removal of histone modifications and changes in DNA methylation patterns locally orchestrate the three-dimensional chromatin structure and determine immune cell fate and immune responses. In autoimmune diseases, disease associated epigenetic marks and dynamic changes control the dysregulated immune system, thus determining the disease development and clinical phenotype. In this review, we introduce the dynamic epigenetic regulation of DNA and histones, summarize the epigenetic regulatory mechanisms in the development and differentiation of some important immune cell subsets and provide new insights for the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease. PMID:26026281

  18. Nutritional control of immunity: Balancing the metabolic requirements with an appropriate immune function.

    PubMed

    De Rosa, Veronica; Galgani, Mario; Santopaolo, Marianna; Colamatteo, Alessandra; Laccetti, Roberta; Matarese, Giuseppe

    2015-09-01

    The immune system is a highly integrated network of cells sensitive to a number of environmental factors. Interestingly, recent years have seen a dramatic increase in our understanding of how diet makes a crucial contribution to human health, affecting the immune system, secretion of adipocytokines and metabolic pathways. Recent experimental evidence indicates that diet and its components are able to profoundly influence immune responses, thus affecting the development of inflammatory and autoimmune diseases. This review aims to discuss some of the main topics concerning the impact of nutrients and their relative composition on immune cell development and function that may be particularly important for regulating the balance between inflammatory and tolerogenic processes. We also highlight the effects of diet on commensal bacteria and how changes in the composition of the microbiota alter intestinal and systemic immune homeostasis. Finally, we summarize the effects of dietary compounds on epigenetic mechanisms involved in the regulation of several immune related genes.

  19. Our Immune System

    MedlinePlus

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

  20. Immunization for Women

    MedlinePlus

    ... nfid.org/#sthash.eZ72dCSP.dpuf Diseases & Vaccines Overview Immunization Schedules Talk to you doctor about your immunization ... years Immunization Schedule for Children, 7-18 years Immunization News July 8, 2016 HPV-related cancers on ...

  1. Your Child's Immunizations

    MedlinePlus

    ... Things to Know About Zika & Pregnancy Your Child's Immunizations KidsHealth > For Parents > Your Child's Immunizations Print A A A Text Size What's in ... But in both cases, the protection is temporary. Immunization (vaccination) is a way of creating immunity to ...

  2. Understanding Herd Immunity.

    PubMed

    Metcalf, C J E; Ferrari, M; Graham, A L; Grenfell, B T

    2015-12-01

    Individual immunity is a powerful force affecting host health and pathogen evolution. Importantly, the effects of individual immunity also scale up to affect pathogen transmission dynamics and the success of vaccination campaigns for entire host populations. Population-scale immunity is often termed 'herd immunity'. Here we outline how individual immunity maps to population outcomes and discuss implications for control of infectious diseases. Particular immunological characteristics may be more or less likely to result in a population level signature of herd immunity; we detail this and also discuss other population-level outcomes that might emerge from individual-level immunity.

  3. Integrated Immune Experiment

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2009-01-01

    This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  4. Immune Suppression and Immune Activation in Depression

    PubMed Central

    Blume, Joshua; Douglas, Steven D.; Evans, Dwight L.

    2010-01-01

    Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging preclinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities

  5. Reciprocal Interactions of the Intestinal Microbiota and Immune System

    PubMed Central

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

    2013-01-01

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

  6. Protein trafficking during plant innate immunity.

    PubMed

    Wang, Wen-Ming; Liu, Peng-Qiang; Xu, Yong-Ju; Xiao, Shunyuan

    2016-04-01

    Plants have evolved a sophisticated immune system to fight against pathogenic microbes. Upon detection of pathogen invasion by immune receptors, the immune system is turned on, resulting in production of antimicrobial molecules including pathogenesis-related (PR) proteins. Conceivably, an efficient immune response depends on the capacity of the plant cell's protein/membrane trafficking network to deploy the right defense-associated molecules in the right place at the right time. Recent research in this area shows that while the abundance of cell surface immune receptors is regulated by endocytosis, many intracellular immune receptors, when activated, are partitioned between the cytoplasm and the nucleus for induction of defense genes and activation of programmed cell death, respectively. Vesicle transport is an essential process for secretion of PR proteins to the apoplastic space and targeting of defense-related proteins to the plasma membrane or other endomembrane compartments. In this review, we discuss the various aspects of protein trafficking during plant immunity, with a focus on the immunity proteins on the move and the major components of the trafficking machineries engaged. PMID:26345282

  7. Editorial: Immune monitoring in solid organ transplantation.

    PubMed

    Shipkova, Maria; Wieland, Eberhard

    2016-03-01

    Solid organ transplantation is inevitably associated with the activation of the immune system of the graft recipient. An advanced knowledge of the immunological mechanisms leading to acute and chronic rejection, the advent of powerful immunosuppressive drugs, and refined surgical techniques have made solid organ transplantation a standard therapy to replace irretrievable loss of vital functions. The immune system is a complex network involving immune cells, cytokines, chemokines, antibodies, and the complement system. Monitoring and ideally influencing the allo-response of the organ recipient against the donor antigens may help to personalize the immunosuppressive therapy including the disclosure of those patients who are suitable for weaning or even discontinuation of immunosuppression. Immune monitoring comprises as plethora of candidate biomarkers capable of reflecting the donor specific and non-donor specific net activation state of the immune system in transplant recipients both before and after initiation of the immunosuppressive therapy. This special issue of Clinical Biochemistry on Immune Monitoring addresses the basic effects of immune activation in solid organ transplantation and critically reviews candidate biomarkers for immune monitoring and their analytical as well as clinical performance.

  8. Theoretical aspects of immunity.

    PubMed

    Deem, Michael W; Hejazi, Pooya

    2010-01-01

    The immune system recognizes a myriad of invading pathogens and their toxic products. It does so with a finite repertoire of antibodies and T cell receptors. We here describe theories that quantify the dynamics of the immune system. We describe how the immune system recognizes antigens by searching the large space of receptor molecules. We consider in some detail the theories that quantify the immune response to influenza and dengue fever. We review theoretical descriptions of the complementary evolution of pathogens that occurs in response to immune system pressure. Methods including bioinformatics, molecular simulation, random energy models, and quantum field theory contribute to a theoretical understanding of aspects of immunity.

  9. Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator β-glucan in a two-case ex vivo non-small-cell lung cancer study

    PubMed Central

    Fan, Teresa W.-M.; Warmoes, Marc O.; Sun, Qiushi; Song, Huan; Turchan-Cholewo, Jadwiga; Martin, Jeremiah T.; Mahan, Angela; Higashi, Richard M.; Lane, Andrew N.

    2016-01-01

    Cancer and stromal cell metabolism is important for understanding tumor development, which highly depends on the tumor microenvironment (TME). Cell or animal models cannot recapitulate the human TME. We have developed an ex vivo paired cancerous (CA) and noncancerous (NC) human lung tissue approach to explore cancer and stromal cell metabolism in the native human TME. This approach enabled full control of experimental parameters and acquisition of individual patient's target tissue response to therapeutic agents while eliminating interferences from genetic and physiological variations. In this two-case study of non-small-cell lung cancer, we performed stable isotope-resolved metabolomic (SIRM) experiments on paired CA and NC lung tissues treated with a macrophage activator β-glucan and 13C6-glucose, followed by ion chromatography–Fourier transform mass spectrometry (IC-FTMS) and nuclear magnetic resonance (NMR) analyses of 13C-labeling patterns of metabolites. We demonstrated that CA lung tissue slices were metabolically more active than their NC counterparts, which recapitulated the metabolic reprogramming in CA lung tissues observed in vivo. We showed β-glucan-enhanced glycolysis, Krebs cycle, pentose phosphate pathway, antioxidant production, and itaconate buildup in patient UK021 with chronic obstructive pulmonary disease (COPD) and an abundance of tumor-associated macrophages (TAMs) but not in UK049 with no COPD and much less macrophage infiltration. This metabolic response of UK021 tissues was accompanied by reduced mitotic index, increased necrosis, and enhaced inducible nitric oxide synthase (iNOS) expression. We surmise that the reprogrammed networks could reflect β-glucan M1 polarization of human macrophages. This case study presents a unique opportunity for investigating metabolic responses of human macrophages to immune modulators in their native microenvironment on an individual patient basis. PMID:27551682

  10. Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator β-glucan in a two-case ex vivo non-small-cell lung cancer study.

    PubMed

    Fan, Teresa W-M; Warmoes, Marc O; Sun, Qiushi; Song, Huan; Turchan-Cholewo, Jadwiga; Martin, Jeremiah T; Mahan, Angela; Higashi, Richard M; Lane, Andrew N

    2016-07-01

    Cancer and stromal cell metabolism is important for understanding tumor development, which highly depends on the tumor microenvironment (TME). Cell or animal models cannot recapitulate the human TME. We have developed an ex vivo paired cancerous (CA) and noncancerous (NC) human lung tissue approach to explore cancer and stromal cell metabolism in the native human TME. This approach enabled full control of experimental parameters and acquisition of individual patient's target tissue response to therapeutic agents while eliminating interferences from genetic and physiological variations. In this two-case study of non-small-cell lung cancer, we performed stable isotope-resolved metabolomic (SIRM) experiments on paired CA and NC lung tissues treated with a macrophage activator β-glucan and (13)C6-glucose, followed by ion chromatography-Fourier transform mass spectrometry (IC-FTMS) and nuclear magnetic resonance (NMR) analyses of (13)C-labeling patterns of metabolites. We demonstrated that CA lung tissue slices were metabolically more active than their NC counterparts, which recapitulated the metabolic reprogramming in CA lung tissues observed in vivo. We showed β-glucan-enhanced glycolysis, Krebs cycle, pentose phosphate pathway, antioxidant production, and itaconate buildup in patient UK021 with chronic obstructive pulmonary disease (COPD) and an abundance of tumor-associated macrophages (TAMs) but not in UK049 with no COPD and much less macrophage infiltration. This metabolic response of UK021 tissues was accompanied by reduced mitotic index, increased necrosis, and enhaced inducible nitric oxide synthase (iNOS) expression. We surmise that the reprogrammed networks could reflect β-glucan M1 polarization of human macrophages. This case study presents a unique opportunity for investigating metabolic responses of human macrophages to immune modulators in their native microenvironment on an individual patient basis. PMID:27551682

  11. Imbalanced immune homeostasis in immune thrombocytopenia.

    PubMed

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. PMID:27312156

  12. Imbalanced immune homeostasis in immune thrombocytopenia.

    PubMed

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders.

  13. Immunity by equilibrium.

    PubMed

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  14. Immune Responses in Neonates

    PubMed Central

    Basha, Saleem; Surendran, Naveen; Pichichero, Michael

    2015-01-01

    Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents. PMID:25088080

  15. Immunity to cancer

    SciTech Connect

    Reif, A.E.; Mitchell, M.S.

    1985-01-01

    This book contains five sections, each containing several papers. The section titles are: Identification and Characterization of Tumor Antigens; Immune Responses to Tumor Antigens; Regulation of the Immune Response to Tumor Cells, Immunotherapy and Biomodulators, and Immunotherapy and Immunoprophylaxis.

  16. Noncovalent association of protein and capsular polysaccharide on bacteria-sized latex beads as a model for polysaccharide-specific humoral immunity to intact gram-positive extracellular bacteria.

    PubMed

    Colino, Jesus; Duke, Leah; Snapper, Clifford M

    2013-09-15

    Intact Streptococcus pneumoniae expressing type 14 capsular polysaccharide (PPS14) and type III S. agalactiae containing a PPS14 core capsule identical to PPS14 exhibit noncovalent associations of PPS14 and bacterial protein, in contrast to soluble covalent conjugates of these respective Ags. Both bacteria and conjugates induce murine PPS14-specific IgG responses dependent on CD4⁺ T cells. Further, secondary immunization with conjugate and S. agalactiae, although not S. pneumoniae, results in a boosted response. However, in contrast to conjugate, PPS14-specific IgG responses to bacteria lack affinity maturation use the 44.1-idiotype and are dependent on marginal zone B cells. To better understand the mechanism underlying this dichotomy, we developed a minimal model of intact bacteria in which PPS14 and pneumococcal surface protein A (PspA) were stably attached to 1 μm (bacteria-sized) latex beads, but not directly linked to each other, in contrast to PPS14-PspA conjugate. Beads coated simultaneously with PPS14+[PspA], similar to conjugate, induced in mice boosted PPS14-specific IgG secondary responses, dependent on T cells and ICOS-dependent costimulation, and in which priming could be achieved with PspA alone. In contrast to conjugate, but similar to intact bacteria, the primary PPS14-specific IgG response to beads coated simultaneously with PPS14+[PspA] peaked rapidly, with the secondary response highly enriched for the 44.1-idiotype and lacking affinity maturation. These results demonstrate that noncovalent association in a particle, of polysaccharide and protein, recapitulates essential immunologic characteristics of intact bacteria that are distinct from soluble covalent conjugates of these respective Ags.

  17. Autonomic nervous system and immune system interactions.

    PubMed

    Kenney, M J; Ganta, C K

    2014-07-01

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

  18. The immune system, adaptation, and machine learning

    NASA Astrophysics Data System (ADS)

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

    1986-10-01

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

  19. Immune System Quiz

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A Text Size How much do you know about your immune system? Find out by taking this quiz! View Survey ...

  20. Aging changes in immunity

    MedlinePlus

    ... keeps your immune system strong. DO NOT smoke. Smoking weakens your immune system. Limit your intake of alcohol . Ask your provider how much alcohol is safe for you. Look into safety measures to prevent falls and injuries. A weak immune system can ...

  1. Immune Disorder HSCT Protocol

    ClinicalTrials.gov

    2016-01-09

    Immune Deficiency Disorders:; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorder:; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  2. The Immune System Game

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  3. Targeted Immune Therapy of Ovarian Cancer

    PubMed Central

    Knutson, Keith L.; Karyampudi, Lavakumar; Lamichhane, Purushottam; Preston, Claudia

    2014-01-01

    Clinical outcomes, such as recurrence free survival and overall survival, in ovarian cancer are quite variable, independent of common characteristics such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration and therapeutic targeting into the interaction between the tumor and host. One compelling host characteristic that contributes both to the initiation and progression of ovarian cancer is the immune system. Hundreds of studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease. Recent studies also show that anti-tumor immunity is often negated by immune regulatory cells present in the tumor microenvironment. Regulatory immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological targets that influence ovarian cancer outcome as well as include an update on newer immunotherapeutic strategies. PMID:25544369

  4. Microscale Immune Studies Laboratory.

    SciTech Connect

    Poschet, Jens Fredrich; Carroll-Portillo, Amanda; Wu, Meiye; Manginell, Ronald Paul; Herr, Amy Elizabeth; Martino, Anthony A.; Perroud, Thomas D.; Branda, Catherine; Srivastava, Nimisha; Sinclair, Michael B.; Moorman, Matthew Wallace; Apblett, Christopher Alan; Sale, Kenneth L.; James, Conrad D.; Carles, Elizabeth L.; Lidke, Diane S.; Van Benthem, Mark Hilary; Rebeil, Roberto; Kaiser, Julie; Seaman, William; Rempe, Susan; Brozik, Susan Marie; Jones, Howland D. T.; Gemperline, Paul; Throckmorton, Daniel J.; Misra, Milind; Murton, Jaclyn K.; Carson, Bryan D.; Zhang, Zhaoduo; Plimpton, Steven James; Renzi, Ronald F.; Lane, Todd W.; Ndiaye-Dulac, Elsa; Singh, Anup K.; Haaland, David Michael; Faulon, Jean-Loup Michel; Davis, Ryan W.; Ricken, James Bryce; Branda, Steven S.; Patel, Kamlesh D.; Joo, Jaewook; Kubiak, Glenn D.; Brennan, James S.; Martin, Shawn Bryan; Brasier, Allan

    2009-01-01

    The overarching goal is to develop novel technologies to elucidate molecular mechanisms of the innate immune response in host cells to pathogens such as bacteria and viruses including the mechanisms used by pathogens to subvert/suppress/obfuscate the immune response to cause their harmful effects. Innate immunity is our first line of defense against a pathogenic bacteria or virus. A comprehensive 'system-level' understanding of innate immunity pathways such as toll-like receptor (TLR) pathways is the key to deciphering mechanisms of pathogenesis and can lead to improvements in early diagnosis or developing improved therapeutics. Current methods for studying signaling focus on measurements of a limited number of components in a pathway and hence, fail to provide a systems-level understanding. We have developed a systems biology approach to decipher TLR4 pathways in macrophage cell lines in response to exposure to pathogenic bacteria and their lipopolysaccharide (LPS). Our approach integrates biological reagents, a microfluidic cell handling and analysis platform, high-resolution imaging and computational modeling to provide spatially- and temporally-resolved measurement of TLR-network components. The Integrated microfluidic platform is capable of imaging single cells to obtain dynamic translocation data as well as high-throughput acquisition of quantitative protein expression and phosphorylation information of selected cell populations. The platform consists of multiple modules such as single-cell array, cell sorter, and phosphoflow chip to provide confocal imaging, cell sorting, flow cytomtery and phosphorylation assays. The single-cell array module contains fluidic constrictions designed to trap and hold single host cells. Up to 100 single cells can be trapped and monitored for hours, enabling detailed statistically-significant measurements. The module was used to analyze translocation behavior of transcription factor NF-kB in macrophages upon activation by E

  5. [The ageing immune system].

    PubMed

    Djukic, M; Nau, R; Sieber, C

    2014-10-01

    The aging of the immune system, also called immunosenescence, contributes to the increased morbidity and mortality from infections, autoimmune diseases and cancer as well as to the low efficacy of vaccination in elderly persons. Immunosenescence is characterized by a decrease in cell-mediated immune function and by reduced humoral immune responses caused by age-related changes in the innate immune system and age-dependent defects in T-and B-cell function. This paper gives an overview of the most important modifications in the different compartments of the immune system during the ageing process.

  6. [The ageing immune system].

    PubMed

    Djukic, M; Nau, R; Sieber, C

    2014-10-01

    The aging of the immune system, also called immunosenescence, contributes to the increased morbidity and mortality from infections, autoimmune diseases and cancer as well as to the low efficacy of vaccination in elderly persons. Immunosenescence is characterized by a decrease in cell-mediated immune function and by reduced humoral immune responses caused by age-related changes in the innate immune system and age-dependent defects in T-and B-cell function. This paper gives an overview of the most important modifications in the different compartments of the immune system during the ageing process. PMID:25254392

  7. Immune Inspired Security Approach for Manets: a Case Study

    NASA Astrophysics Data System (ADS)

    Mohamed, Yasir Abdelgadir

    2011-06-01

    This paper extends the work that has earlier been established. Immune inspired approach for securing mobile ad hoc networks is specified there. Although it is clearly indicated there that the research scope is the wireless networks in general and hybrid mobile ad hoc networks in particular, we have seen that specifying the security system in one of the communications applications that need further security approach may help to understand how effectively the system can contribute to this vital and important networks sector. Security in this type of networks is important and controversial as it plays a key role in users' eagerness or reluctance for the services provided by these networks. In this paper, the immune inspired security system is specified to secure web services in converged networks.

  8. Sequential Immune Responses: The Weapons of Immunity

    PubMed Central

    Mills, Charles D.; Ley, Klaus; Buchmann, Kurt; Canton, Johnathan

    2016-01-01

    Sequential immune responses (SIR) is a new model that describes what ‘immunity’ means in higher animals. Existing models, such as self/nonself discrimination or danger, focus on how immune responses are initiated. However, initiation is not protection. SIR describes the actual immune responses that provide protection. SIR resulted from a comprehensive analysis of the evolution of immune systems that revealed that several very different types of host innate responses occur (and at different tempos) which together provide host protection. SIR1 uses rapidly activated enzymes like the NADPH oxidases and is present in all animal cells. SIR2 is mediated by the first ‘immune’ cells: macrophage-like cells. SIR3 evolved in animals like invertebrates and provides enhanced protection through advanced macrophage recognition and killing of pathogens and through other innate immune cells such as neutrophils. Finally, in vertebrates, macrophages developed SIR4: the ability to present antigens to T cells. Though much slower than SIR1–3, adaptive responses provide a unique new protection for higher vertebrates. Importantly, newer SIR responses were added on top of older, evolutionarily conserved functions to provide ‘layers’ of host protection. SIR transcends existing models by elucidating the different weapons of immunity that provide host protection in higher animals. PMID:25871013

  9. The immune effects of neuropeptides.

    PubMed

    Berczi, I; Chalmers, I M; Nagy, E; Warrington, R J

    1996-05-01

    Current evidence indicates that the neuroendocrine system is the highest regulator of immune/inflammatory reactions. Prolactin and growth hormone stimulate the production of leukocytes, including lymphocytes, and maintain immunocompetence. The hypothalamus-pituitary-adrenal axis constitutes the most powerful circuit regulating the immune system. The neuropeptides constituting this axis, namely corticotrophin releasing factor, adrenocorticotrophic hormone, alpha-melanocyte stimulating hormone, and beta-endorphin are powerful immunoregulators, which have a direct regulatory effect on lymphoid cells, regulating immune reactions by the stimulation of immunoregulatory hormones (glucocorticoids) and also by acting on the central nervous system which in turn generates immunoregulatory nerve impulses. Peptidergic nerves are major regulators of the inflammatory response. Substance P and calcitonin gene-related peptide are pro-inflammatory mediators and somatostatin is anti-inflammatory. The neuroendocrine regulation of the inflammatory response is of major significance from the point of view of immune homeostasis. Malfunction of this circuit leads to disease and often is life-threatening. The immune system emits signals towards the neuroendocrine system by cytokine mediators which reach significant blood levels (cytokine-hormones) during systemic immune/inflammatory reactions. Interleukin-1, -6, and TNF-alpha are the major cytokine hormones mediating the acute phase response. These cytokines induce profound neuroendocrine and metabolic changes by interacting with the central nervous system and with many other organs and tissues in the body. Corticotrophin releasing factor functions under these conditions as a major co-ordinator of the response and is responsible for activating the ACTH-adrenal axis for regulating fever and for other CNS effects leading to a sympathetic outflow. Increased ACTH secretion leads to glucocorticoid production. alpha-melanocyte stimulating hormone

  10. Neural circuitry and immunity.

    PubMed

    Pavlov, Valentin A; Tracey, Kevin J

    2015-12-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuro-immune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex, are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases define the emerging field of Bioelectronic Medicine.

  11. Origins of adaptive immunity.

    PubMed

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

    2011-01-01

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

  12. Origins of adaptive immunity.

    PubMed

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

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity. PMID:21395512

  13. Feeding the immune system.

    PubMed

    Calder, Philip C

    2013-08-01

    A well-functioning immune system is key to providing good defence against pathogenic organisms and to providing tolerance to non-threatening organisms, to food components and to self. The immune system works by providing an exclusion barrier, by identifying and eliminating pathogens and by identifying and tolerating non-threatening sources of antigens, and by maintaining a memory of immunological encounters. The immune system is complex involving many different cell types distributed throughout the body and many different chemical mediators some of which are involved directly in defence while others have a regulatory role. Babies are born with an immature immune system that fully develops in the first few years of life. Immune competence can decline with ageing. The sub-optimal immune competence that occurs early and late in life increases susceptibility to infection. Undernutrition decreases immune defences, making an individual more susceptible to infection. However, the immune response to an infection can itself impair nutritional status and alter body composition. Practically all forms of immunity are affected by protein-energy malnutrition, but non-specific defences and cell-mediated immunity are most severely affected. Micronutrient deficiencies impair immune function. Here, vitamins A, D and E, and Zn, Fe and Se are discussed. The gut-associated lymphoid tissue is especially important in health and well-being because of its close proximity to a large and diverse population of organisms in the gastrointestinal tract and its exposure to food constituents. Certain probiotic bacteria which modify the gut microbiota enhance immune function in laboratory animals and may do so in human subjects.

  14. Clinical immunity to malaria.

    PubMed

    Schofield, Louis; Mueller, Ivo

    2006-03-01

    Under appropriate conditions of transmission intensity, functional immunity to malaria appears to be acquired in distinct stages. The first phase reduces the likelihood of severe or fatal disease; the second phase limits the clinical impact of 'mild' malaria; and the third provides partial but incomplete protection against pathogen burden. These findings suggest clinical immunity to mortality and morbidity is acquired earlier, with greater ease, and via distinct mechanisms as compared to anti-parasite immunity, which is more difficult to achieve, takes longer and is only ever partially efficacious. The implications of this view are significant in that current vaccination strategies aim predominantly to achieve anti-parasite immunity, although imparting clinical immunity is the public health objective. Despite enormous relevance for global public health, the mechanisms governing these processes remain obscure. Four candidate mechanisms might mediate clinical immunity, namely immunity to cytoadherence determinants, tolerance to toxins, acquired immunity to toxins, and immunoregulation. This review addresses the targets and determinants of clinical immunity, and considers the implications for vaccine development.

  15. Immunity, ageing and cancer

    PubMed Central

    Derhovanessian, Evelyna; Solana, Rafael; Larbi, Anis; Pawelec, Graham

    2008-01-01

    Compromised immunity contributes to the decreased ability of the elderly to control infectious disease and to their generally poor response to vaccination. It is controversial as to how far this phenomenon contributes to the well-known age-associated increase in the occurrence of many cancers in the elderly. However, should the immune system be important in controlling cancer, for which there is a great deal of evidence, it is logical to propose that dysfunctional immunity in the elderly would contribute to compromised immunosurveillance and increased cancer occurrence. The chronological age at which immunosenescence becomes clinically important is known to be influenced by many factors, including the pathogen load to which individuals are exposed throughout life. It is proposed here that the cancer antigen load may have a similar effect on "immune exhaustion" and that pathogen load and tumor load may act additively to accelerate immunosenescence. Understanding how and why immune responsiveness changes in humans as they age is essential for developing strategies to prevent or restore dysregulated immunity and assure healthy longevity, clearly possible only if cancer is avoided. Here, we provide an overview of the impact of age on human immune competence, emphasizing T-cell-dependent adaptive immunity, which is the most sensitive to ageing. This knowledge will pave the way for rational interventions to maintain or restore appropriate immune function not only in the elderly but also in the cancer patient. PMID:18816370

  16. Innate Immunity in Disease

    PubMed Central

    Elliott, David E.; Siddique, Sana S.; Weinstock, Joel V.

    2014-01-01

    Cells can innately recognize generic products of viruses, bacteria, fungi, or injured tissue by engagement of pattern recognition receptors. Innate immune cells rapidly respond to this engagement in order to control commensals, thwart pathogens and/or prompt repair. Insufficient or excessive activation of the innate immune response results in disease. This review focuses on pattern recognition receptors and cells of the innate immune system important for intestinal function. Our improving knowledge pertaining to this important aspect of our immune response is opening potential important new therapeutic opportunities for the treatment of disease. PMID:24632348

  17. Phosphocholine-binding antibody activities are hierarchically encoded in the sequence of the heavy-chain variable region: dominance of self-association activity in the T15 idiotype.

    PubMed

    Srdiċ-Rajiċ, Tatjana; Kekoviċ, Goran; Davidoviċ, Dragomir M; Metlas, Radmila

    2013-06-01

    A methodology based on the representation of each amino acid of a protein sequence by the electron-ion interaction potential and subsequent analysis by signal processing was used to determine the characteristic or common frequency (in Hz) that reflects the biological activity shared among phosphocholine (PC)-binding antibodies. The common frequency for the variable portion of the heavy chain (VH) of the PC-specific antibodies is found to be at f = 0.37 Hz. The VH sequences of the PC-binding antibodies exhibit three subsites for the PC moiety where hypervariable region 2 (CDR2) plays a role in the interaction with the phosphate group. Mutations in this VH region have an impact on the ability of mutant variants to bind PC and its carrier molecule, as well as on the characteristic frequency shift toward f = 0.12 Hz for mutants failing to bind both hapten and carrier. The VH sequence of mutants that retain the ability to bind PC still shows f = 0.37 Hz, suggesting that this frequency determines PC binding. However, this statement was not confirmed as mutation in another PC subsite impairs PC binding but retains both the phosphate-group recognition and the frequency at f = 0.37 Hz. Herein, this finding is discussed to promote the idea that the VH sequence of the PC-binding antibodies encodes the subsite for phosphate-group binding as a dominant functional activity and that only CDR2 of the T15-idiotype antibodies together with FR3 region form an autonomous self-association function represented by the T15VH50-73 peptide with f = 0.37±0.05 Hz. Thus, these data confirmed that T15VH50-73 peptide might be used in superantibody technology. PMID:23382353

  18. Research progress on the mollusc immunity in China.

    PubMed

    Wang, Lingling; Qiu, Limei; Zhou, Zhi; Song, Linsheng

    2013-01-01

    The economical and phylogenic importance of mollusc has led an increasing number of investigations giving emphasis to immune defense mechanism. This review discusses the advances in immunological study of mollusc in China, with special reference to dominant aquaculture species over the past decades. As an invertebrate group, molluscs lack adaptive immunity and consequently they have evolved sophisticated strategies of innate immunity for defense against pathogens. This review aims to present the various immunologically significant pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), lectins, lipopolysaccharide and β-1, 3-glucan binding protein (LGBP), scavenger receptors (SRs) employed by mollucans. This work also highlights immune proteolytic cascade, TLR signaling pathway and an extensive repertoire of immune effectors including antimicrobial peptide, lysozyme, antioxidant enzyme and heat shock protein. Further, the review presents the preliminary progress made on the catecholaminergic neuroendocrine system in scallop and its immunomodulation function to throw light into neuroendocrine-immune regulatory network in lower invertebrates.

  19. Measuring edge importance to improve immunization performance

    NASA Astrophysics Data System (ADS)

    Huang, He; Yan, Zhijun; Pan, Yaohui

    2014-12-01

    The edge heterogeneity has a remarkable influence on disease spreading, but it has seldom been considered in the disease-controlling policies. Based on the gravity model, we propose the edge importance index to describe the influence of edge heterogeneity on immunization strategies. Then the edge importance and contact weight are combined to calculate the infection rates on the I-S (Infected-Susceptible) edges in the complex network, and the difference of the infection rates on strong and weak ties is analyzed. Simulation results show that edge heterogeneity has a significant influence on the performance of immunization strategies, and better immunization efficiency is derived when the vaccination rate of the nodes in the weak I-S edges is increased.

  20. Extracellular nucleotides as negative modulators of immunity

    PubMed Central

    Di Virgilio, Francesco; Boeynaems, Jean-Marie; Robson, Simon C.

    2014-01-01

    Nucleotides are well known for being the universal currency of intracellular energy transactions, but over the last decade it has become clear that they are also ubiquitous extracellular messenger. In the immune system there is increasing awareness that nucleotides serve multiple roles as stimulants of lymphocyte proliferation, ROS generation, cytokine and chemokine secretion: in one word as pro-inflammatory mediators. However, although often neglected, extracellular nucleotides exert an additional more subtle function as negative modulators of immunity, or as immunedepressants. The more we understand the peculiar biochemical composition of the microenvironment generated at inflammatory sites, the more we appreciate how chronic exposure to low extracellular nucleotide levels affect immunity and inflammation. A deeper understanding of this complex network will no doubt help design more effective therapies for cancer and chronic inflammatory diseases. PMID:19628431

  1. Monoclonal antibody-based therapy of neuroblastoma.

    PubMed

    Cheung, N K; Kushner, B H; Kramer, K

    2001-10-01

    The curative potential of mAbs in the treatment of patients with metastatic neuroblastoma is increasingly evident. The idiotype network appears to represent one component of a complex mechanism for success with mAb-based immunotherapy. Ongoing strategies to modify or reconstruct mAbs, to engage them with cytokines, or to unite them with T cells open new avenues for harnessing the unique forces of the immune system against some of the most deadly pediatric cancers.

  2. Immunizations. Position Statement. Revised

    ERIC Educational Resources Information Center

    Bobo, Nichole; Garrett, Jennifer; Teskey, Carmen; Duncan, Kay; Strasser, Kathy; Burrows-Mezu, Alicia L.

    2015-01-01

    It is the position of the National Association of School Nurses (NASN) that immunizations are essential to primary prevention of disease from infancy through adulthood. Promotion of immunizations by the registered professional school nurse (hereinafter referred to as school nurse) is central to the public health focus of school nursing practice…

  3. Innate immunity and adjuvants

    PubMed Central

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  4. Neuroendocrine-immune interactions.

    PubMed

    Marsh, J A; Scanes, C G

    1994-07-01

    The role of the neuroendocrine system in influencing both immune development and function has become an area of active research within many model systems, including the chicken. It is now clear that the neuroendocrine system can exert immediate feedback regulation on the immune system as well as control specific aspects of immune differentiation and development. The primary lymphoid organs of avian species (i.e., the thymus and the bursa of Fabricius) are also known to function as endocrine organs. These produce hormonal products that influence the development of lymphoid cells and that may feed back on the neuroendocrine system. In conjunction with the endocrine activities of the primary lymphoid organs, immune and accessory cells are known to produce a variety of secreted products or cytokines that have the potential not only for the regulation of immune function but also for mediating neuroendocrine activities. Finally, it has been demonstrated in a variety of species that leukocytes are capable of producing endocrine mediators previously believed to be produced only under the direct control of the hypothalamic-pituitary axis. Thus, there are numerous possibilities for bidirectional interactions between the immune and neuroendocrine systems. This discussion focuses primarily on these interactions with an emphasis on the means by which the hormonal mediators, growth hormone and thyroid hormone, may affect the thymus and the thymic microenvironment. The role of the adrenocorticoids and gonadal steroids in regulating immune function and their involvement in immune feedback circuits are also discussed.

  5. The genetics of immunity.

    PubMed

    Lazzaro, Brian P; Schneider, David S

    2014-06-17

    In this commentary, Brian P. Lazzaro and David S. Schneider examine the topic of the Genetics of Immunity as explored in this month's issues of GENETICS and G3: Genes|Genomes|Genetics. These inaugural articles are part of a joint Genetics of Immunity collection (ongoing) in the GSA journals.

  6. Immunization alters body odor.

    PubMed

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. PMID:24524972

  7. Immunity and Nutrition.

    ERIC Educational Resources Information Center

    Dupin, Henri; Guerin, Nicole

    1990-01-01

    The three articles in this issue of a periodical focussed on various aspects of the life and health of children in the tropics concern: (1) immune defenses; (2) interactions between nutrition disorders and infection; and (3) immunity and vaccination. The science of immunology has progressed rapidly in recent years. A brief review of present…

  8. The Genetics of Immunity

    PubMed Central

    Lazzaro, Brian P.; Schneider, David S.

    2014-01-01

    In this commentary, Brian P. Lazzaro and David S. Schneider examine the topic of the Genetics of Immunity as explored in this month's issues of GENETICS and G3: Genes|Genomes|Genetics. These inaugural articles are part of a joint Genetics of Immunity collection (ongoing) in the GSA journals. PMID:24939182

  9. Chemoimmunotherapy: reengineering tumor immunity.

    PubMed

    Chen, Gang; Emens, Leisha A

    2013-02-01

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

  10. Swine immune system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Probably no area of veterinary medicine has seen a greater explosion in knowledge then the immune system and its implications in disease and vaccination. In this chapter on the Swine Immune System for the 10th Edition of Diseases of Swine we expand on the information provided in past editions by in...

  11. Adaptive immunity to fungi.

    PubMed

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

    2014-11-06

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

  12. Autophagy and Immune Senescence.

    PubMed

    Zhang, Hanlin; Puleston, Daniel J; Simon, Anna Katharina

    2016-08-01

    With extension of the average lifespan, aging has become a heavy burden in society. Immune senescence is a key risk factor for many age-related diseases such as cancer and increased infections in the elderly, and hence has elicited much attention in recent years. As our body's guardian, the immune system maintains systemic health through removal of pathogens and damage. Autophagy is an important cellular 'clearance' process by which a cell internally delivers damaged organelles and macromolecules to lysosomes for degradation. Here, we discuss the most current knowledge of how impaired autophagy can lead to cellular and immune senescence. We also provide an overview, with examples, of the clinical potential of exploiting autophagy to delay immune senescence and/or rejuvenate immunity to treat various age-related diseases.

  13. Autophagy genes in immunity

    PubMed Central

    Virgin, Herbert W; Levine, Beth

    2009-01-01

    In its classical form, autophagy is a pathway by which cytoplasmic constituents, including intracellular pathogens, are sequestered in a double-membrane–bound autophagosome and delivered to the lysosome for degradation. This pathway has been linked to diverse aspects of innate and adaptive immunity, including pathogen resistance, production of type I interferon, antigen presentation, tolerance and lymphocyte development, as well as the negative regulation of cytokine signaling and inflammation. Most of these links have emerged from studies in which genes encoding molecules involved in autophagy are inactivated in immune effector cells. However, it is not yet known whether all of the critical functions of such genes in immunity represent ‘classical autophagy’ or possible as-yet-undefined autophagolysosome-independent functions of these genes. This review summarizes phenotypes that result from the inactivation of autophagy genes in the immune system and discusses the pleiotropic functions of autophagy genes in immunity. PMID:19381141

  14. Behavioral Immunity in Insects

    PubMed Central

    de Roode, Jacobus C.; Lefèvre, Thierry

    2012-01-01

    Parasites can dramatically reduce the fitness of their hosts, and natural selection should favor defense mechanisms that can protect hosts against disease. Much work has focused on understanding genetic and physiological immunity against parasites, but hosts can also use behaviors to avoid infection, reduce parasite growth or alleviate disease symptoms. It is increasingly recognized that such behaviors are common in insects, providing strong protection against parasites and parasitoids. We review the current evidence for behavioral immunity in insects, present a framework for investigating such behavior, and emphasize that behavioral immunity may act through indirect rather than direct fitness benefits. We also discuss the implications for host-parasite co-evolution, local adaptation, and the evolution of non-behavioral physiological immune systems. Finally, we argue that the study of behavioral immunity in insects has much to offer for investigations in vertebrates, in which this topic has traditionally been studied. PMID:26466629

  15. Autophagy and Immune Senescence.

    PubMed

    Zhang, Hanlin; Puleston, Daniel J; Simon, Anna Katharina

    2016-08-01

    With extension of the average lifespan, aging has become a heavy burden in society. Immune senescence is a key risk factor for many age-related diseases such as cancer and increased infections in the elderly, and hence has elicited much attention in recent years. As our body's guardian, the immune system maintains systemic health through removal of pathogens and damage. Autophagy is an important cellular 'clearance' process by which a cell internally delivers damaged organelles and macromolecules to lysosomes for degradation. Here, we discuss the most current knowledge of how impaired autophagy can lead to cellular and immune senescence. We also provide an overview, with examples, of the clinical potential of exploiting autophagy to delay immune senescence and/or rejuvenate immunity to treat various age-related diseases. PMID:27395769

  16. Autopolyreactivity Confers a Holistic Role in the Immune System.

    PubMed

    Avrameas, S

    2016-04-01

    In this review, we summarize and discuss some key findings from the study of naturally occurring autoantibodies. The B-cell compartment of the immune system appears to recognize almost all endogenous and environmental antigens. This ability is accomplished principally through autopolyreactive humoral and cellular immune receptors. This extended autopolyreactivity (1) along immunoglobulin gene recombination contributes to the immune system's ability to recognize a very large number of self and non-self constituents; and (2) generates a vast immune network that creates communication channels between the organism's interior and exterior. Thus, the immune system continuously evolves depending on the internal and external stimuli it encounters. Furthermore, this far-reaching network's existence implies activities resembling those of classical biological factors or activities that modulate the function of other classical biological factors. A few such antibodies have already been found. Another important concept is that natural autoantibodies are highly dependent on the presence or absence of commensal microbes in the organism. These results are in line with past and recent findings showing the fundamental influence of the microbiota on proper immune system development, and necessitate the existence of a host-microbe homeostasis. This homeostasis requires that the participating humoral and cellular receptors are able to recognize self-antigens and commensal microbes without damaging them. Autopolyreactive immune receptors expressing low affinity for both types of antigens fulfil this role. The immune system appears to play a holistic role similar to that of the nervous system.

  17. Recommended Immunizations for Adults 50+

    MedlinePlus

    ... page please turn Javascript on. Health Screenings and Immunizations Recommended Immunizations For Adults 50+ The content in this section ... out more, visit How Vaccines Prevent Disease . Vaccines, Vaccinations, and Immunizations Understanding the difference between vaccines, vaccinations, ...

  18. [Mechanisms of innate immunity].

    PubMed

    Sochocka, Marta; Błach-Olszewska, Zofia

    2005-01-01

    Innate (natural) immunity differs from acquired immunity with respect to the detection systems (receptors and structures detected on pathogens), the cells engaged, and the nature of the mechanisms. Innate immunity is an ancient system, with similar structures in plants, invertebrates, and vertebrates are involved in the development of defense against pathogens. Toll-like receptor (TLR) structures are present in all organisms, and some mechanisms (i.e. complement activation) were also discovered in invertebrates and vertebrates. During infection, innate reactions develop before acquired immune reactions do. Natural immunity involves such reactions as the production of different cytokines, chemokines, and interleukins; the innate, cytokines-dependent nonspecific immunity of leukocytes; HLA-independent pathogen-killing cells, and phagocytosis. Such cytokines as interferons, the TNF family, and interleukines 12 and 18 participate in antiviral, antibacterial, antiprotozoan and anticancer natural immunity. NK cells, cytokines of the TNF family, and the complement system activated by lectins are engaged in the non-specific killing of infected or tumor cells. As over-activation of the innate system can be dangerous, the system must be submitted the strict control. The exact mechanism of this control system is not yet known, but there are several indications of its presence.

  19. Immunity in urogenital protozoa.

    PubMed

    Malla, N; Goyal, K; Dhanda, R S; Yadav, M

    2014-09-01

    Innate and adaptive immunity play a significant role in urogenital infections. Innate immunity is provided by the epithelial cells and mucus lining along with acidic pH, which forms a strong physical barrier against the pathogens in female reproductive tract. Cells of innate immune system, antimicrobial peptides, cytokines, chemokines and adaptive immunity in the reproductive tract are evolved during infection, and a pro-inflammatory response is generated to fight against the invading pathogen Trichomonas vaginalis, a primary urogenital protozoa, the etiological agent of human trichomoniasis, a curable sexually transmitted infection. The involvement of the urogenital tract by other protozoal infections such as P. falciparum, Trypanosoma, Leishmania, Toxoplasma, Entamoeba histolytica and Acanthamoeba infection is rarely reported. Trichomonas induce pro-inflammatory and immunosuppressive responses in infected subjects. Multifactorial pathogenic mechanisms including parasite adherence, cysteine proteases, lipophosphoglycan, free radical, cytokine generation and Toll-like receptors appear to interplay with the induction of local and systemic immune responses that ultimately determine the outcome of the infection. However, the involvement of urogenital pathogen-specific immune mechanisms and effect of normal local resident flora on the outcome (symptomatic vs. asymptomatic) of infection are poorly understood. Moreover, immune interactions in trichomoniasis subjects co-infected with bacterial and viral pathogens need to be elucidated.

  20. Novel Anti-idiotype Antibody Therapy for Lipooligosaccharide-Induced Experimental Autoimmune Neuritis: Use Relevant to Guillain-Barré Syndrome

    PubMed Central

    Usuki, S.; Taguchi, K.; Thompson, S.A.; Chapman, P.B.; Yu, R.K.

    2010-01-01

    Campylobacteriosis is a frequent antecedent event in Guillain-Barré syndrome (GBS), inducing high-titer serum antibodies for ganglioside antigens in the peripheral nervous system (PNS). Molecular mimicry between the lipooligosaccharide (LOS) component of Campylobacter jejuni and human peripheral nerve gangliosides is believed to play an important role in the pathogenesis of GBS. Conventional treatment strategies for patients with GBS include plasmapheresis, intravenous immunoglobulin (IVIG), and immunosuppression, which are invasive or relatively ineffective. In this study, we used our animal model of GBS, in which Lewis rats were immunized with GD3-like LOS isolated from C. jejuni. The animals developed anti-GD3 ganglioside antibodies and manifested neuromuscular dysfunction. To develop novel therapeutic strategies, we treated the animals by intraperitoneal administration of an anti-GD3 antiidiotype monoclonal antibody (BEC2) that specifically interacts with the pathogenic antibody. The treated animals had a remarkable reduction of anti-GD3 antibody titers and improvement of motor nerve functions. The results suggest that ganglioside mimics, such as antiidiotype antibodies, may be powerful reagents for therapeutic intervention in GBS by neutralizing specific pathogenic antiganglioside antibodies. PMID:20077429

  1. Transcription Dynamics in Plant Immunity

    PubMed Central

    Moore, John W.; Loake, Gary J.; Spoel, Steven H.

    2011-01-01

    Plant cells maintain sophisticated gene transcription programs to regulate their development, communication, and response to the environment. Environmental stress cues, such as pathogen encounter, lead to dramatic reprogramming of transcription to favor stress responses over normal cellular functions. Transcription reprogramming is conferred by the concerted action of myriad transcription (co)factors that function directly or indirectly to recruit or release RNA Polymerase II. To establish an effective defense response, cells require transcription (co)factors to deploy their activity rapidly, transiently, spatially, and hierarchically. Recent findings suggest that in plant immunity these requirements are met by posttranslational modifications that accurately regulate transcription (co)factor activity as well as by sequential pulse activation of specific gene transcription programs that provide feedback and feedforward properties to the defense gene network. Here, we integrate these recent findings from plant defense studies into the emerging field of transcription dynamics in eukaryotes. PMID:21841124

  2. Immune System to Brain Signaling: Neuropsychopharmacological Implications

    PubMed Central

    Capuron, Lucile; Miller, Andrew H.

    2011-01-01

    There has been an explosion in our knowledge of the pathways and mechanisms by which the immune system can influence the brain and behavior. In the context of inflammation, pro-inflammatory cytokines can access the central nervous system and interact with a cytokine network in the brain to influence virtually every aspect of brain function relevant to behavior including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits that regulate mood, motor activity, motivation, anxiety and alarm. Behavioral consequences of these effects of the immune system on the brain include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction and sleep impairment; symptoms that overlap with those which characterize neuropsychiatric disorders, especially depression. Pathways that appear to be especially important in immune system effects on the brain include the cytokine signaling molecules, p38 mitogen activated protein kinase and nuclear factor kappa B; indoleamine 2,3 dioxygenase and its down stream metabolites, kynurenine, quinolinic acid and kynurenic acid; the neurotransmitters, serotonin, dopamine and glutamate; and neurocircuits involving the basal ganglia and anterior cingulate cortex. A series of vulnerability factors including aging and obesity as well as chronic stress also appear to interact with immune to brain signaling to exacerbate immunologic contributions to neuropsychiatric disease. The elucidation of the mechanisms by which the immune system influences behavior yields a host of targets for potential therapeutic development as well as informing strategies for the prevention of neuropsychiatric disease in at risk populations. PMID:21334376

  3. Immune dysfunction in acute alcoholic hepatitis

    PubMed Central

    Dhanda, Ashwin D; Collins, Peter L

    2015-01-01

    Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogen-associated molecular particles (PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors (mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this. PMID:26576079

  4. Innate Immune Sensing and Response to Influenza

    PubMed Central

    Pulendran, Bali; Maddur, Mohan S.

    2015-01-01

    Influenza viruses pose a substantial threat to human and animal health worldwide. Recent studies in mouse models have revealed an indispensable role for the innate immune system in defense against influenza virus. Recognition of the virus by innate immune receptors in a multitude of cell types activates intricate signaling networks, functioning to restrict viral replication. Downstream effector mechanisms include activation of innate immune cells and, induction and regulation of adaptive immunity. However, uncontrolled innate responses are associated with exaggerated disease, especially in pandemic influenza virus infection. Despite advances in the understanding of innate response to influenza in the mouse model, there is a large knowledge gap in humans, particularly in immunocom-promised groups such as infants and the elderly. We propose here, the need for further studies in humans to decipher the role of innate immunity to influenza virus, particularly at the site of infection. These studies will complement the existing work in mice and facilitate the quest to design improved vaccines and therapeutic strategies against influenza. PMID:25078919

  5. Global analysis of the immune response

    NASA Astrophysics Data System (ADS)

    Ribeiro, Leonardo C.; Dickman, Ronald; Bernardes, Américo T.

    2008-10-01

    The immune system may be seen as a complex system, characterized using tools developed in the study of such systems, for example, surface roughness and its associated Hurst exponent. We analyze densitometric (Panama blot) profiles of immune reactivity, to classify individuals into groups with similar roughness statistics. We focus on a population of individuals living in a region in which malaria endemic, as well as a control group from a disease-free region. Our analysis groups individuals according to the presence, or absence, of malaria symptoms and number of malaria manifestations. Applied to the Panama blot data, our method proves more effective at discriminating between groups than principal-components analysis or super-paramagnetic clustering. Our findings provide evidence that some phenomena observed in the immune system can be only understood from a global point of view. We observe similar tendencies between experimental immune profiles and those of artificial profiles, obtained from an immune network model. The statistical entropy of the experimental profiles is found to exhibit variations similar to those observed in the Hurst exponent.

  6. Advanced Optical Network

    NASA Astrophysics Data System (ADS)

    Braun, Steve; Michael, Xuejun

    The following article describes an advanced dense wavelength division multiplexing (DWDM) Optical Network developed by L-3 Photonics. The network, configured as an amplified optical bus, carries traffic simultaneously in both directions, using multiple wavelengths. As a result, data distribution is of the form peer-to-multi-peer, it is protocol independent, and it is scalable. The network leverages the rapid growth in commercial optical technologies, including wavelength division multiplexing (WDM), and when applied to military and commercial platforms such as aircraft, ships, unmanned and other vehicles, provides a cost-effective, low-weight, high-speed, and high noise-immune data distribution system.

  7. Non-coding RNAs in epithelial immunity to Cryptosporidium infection

    PubMed Central

    Zhou, Rui; Feng, Yaoyu; Chen, Xian-Ming

    2015-01-01

    SUMMARY Cryptosporidium spp. is a protozoan parasite that infects the gastrointestinal epithelium and causes diarrhoeal disease worldwide. It is one of the most common pathogens responsible for moderate to severe diarrhoea in children younger than 2 years. Because of the ‘minimally invasive’ nature of Cryptosporidium infection, mucosal epithelial cells are critical to the host’s anti-Cryptosporidium immunity. Gastrointestinal epithelial cells not only provide the first and most rapid defence against Cryptosporidium infection, they also mobilize immune effector cells to the infection site to activate adaptive immunity. Recent advances in genomic research have revealed the existence of a large number of non-protein-coding RNA transcripts, so called non-coding RNAs (ncRNAs), in mammalian cells. Some ncRNAs may be key regulators for diverse biological functions, including innate immune responses. Specifically, ncRNAs may modulate epithelial immune responses at every step of the innate immune network following Cryptosporidium infection, including production of antimicrobial molecules, expression of cytokines/chemokines, release of epithelial cell-derived exosomes, and feedback regulation of immune homoeostasis. This review briefly summarizes the current science on ncRNA regulation of innate immunity to Cryptosporidium, with a focus on microRNA-associated epithelial immune responses. PMID:24828969

  8. Systems vaccinology: probing humanity's diverse immune systems with vaccines.

    PubMed

    Pulendran, Bali

    2014-08-26

    Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic changes during the past century have created further diversification with respect to age, nutritional status, and the incidence of associated chronic inflammatory disorders and chronic infections. These shifting demographics pose new challenges for vaccination, as emerging evidence suggests that age, the metabolic state, and chronic infections can exert major influences on the immune system. Thus, a key public health challenge is learning how to reprogram suboptimal immune systems to induce effective vaccine immunity. Recent advances have applied systems biological analysis to define molecular signatures induced early after vaccination that correlate with and predict the later adaptive immune responses in humans. Such "systems vaccinology" approaches offer an integrated picture of the molecular networks driving vaccine immunity, and are beginning to yield novel insights about the immune system. Here we discuss the promise of systems vaccinology in probing humanity's diverse immune systems, and in delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. Such insights will be critical in reengineering suboptimal immune systems in immunocompromised populations. PMID:25136102

  9. Road to fulfilment: taming the immune response to restore vision.

    PubMed

    Dick, Andrew D

    2012-01-01

    While traditionally considered to be an immune privileged site, the eye, and in particular the retina, is nonetheless endowed with immune-competent cells capable of engaging powerful immune regulatory networks. By understanding the mechanisms that promote immune well-being in the eye, we are able to generate therapies which combat undue immune-mediated damage not only by revealing mechanisms that promote tissue damage, but also by an ability to restore tissue immune homeostasis by harnessing intrinsic immune-regulatory mechanisms. The result is to maintain or restore immune health as well as combat tissue damage evoked during, for example, intra-ocular inflammatory disease (uveitis), angiogenesis (age-related macular degeneration) and retinal degenerative disorders. Immune activation and regulation is a balance that is dictated by cognate and soluble factors at both a tissue and cellular level. These continuously respond to and eradicate danger and pathogenic signals whilst maintaining tissue function by controlling, and not exclusively, vascular barriers, complement activation, macrophage activation and keeping in check local T cell proliferation. Loss of the balance between activation and inhibitory signals leads to uncontrolled tissue damage. Understanding the mechanisms has gained potential therapeutic opportunities not only to suppress on-going inflammation, but also to restore homeostasis and prevent recrudescence.

  10. Adaptive immunity to fungi.

    PubMed

    Wüthrich, Marcel; Deepe, George S; Klein, Bruce

    2012-01-01

    Only a handful of the more than 100,000 fungal species on our planet cause disease in humans, yet the number of life-threatening fungal infections in patients has recently skyrocketed as a result of advances in medical care that often suppress immunity intensely. This emerging crisis has created pressing needs to clarify immune defense mechanisms against fungi, with the ultimate goal of therapeutic applications. Herein, we describe recent insights in understanding the mammalian immune defenses deployed against pathogenic fungi. The review focuses on adaptive immune responses to the major medically important fungi and emphasizes how dendritic cells and subsets in various anatomic compartments respond to fungi, recognize their molecular patterns, and signal responses that nurture and shape the differentiation of T cell subsets and B cells. Also emphasized is how the latter deploy effector and regulatory mechanisms that eliminate these nasty invaders while also constraining collateral damage to vital tissue.

  11. Immune System (For Parents)

    MedlinePlus

    ... lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has ... can't be prevented, you can help your child's immune system stay stronger and fight illnesses by ...

  12. Antiviral immunity in amphibians.

    PubMed

    Chen, Guangchun; Robert, Jacques

    2011-11-01

    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.

  13. Immunization Action Coalition

    MedlinePlus

    ... IAC | Contact | A-Z Index | Donate | Shop | SUBSCRIBE Immunization Action Coalition Handouts for Patients & Staff A-Z ... Index Supplies Checklist Administering Vaccines Temperature Logs Adult Vaccination Topics of Interest Documenting Vaccination Translations Parent Handouts ...

  14. Pneumonia - weakened immune system

    MedlinePlus

    If you have a weakened immune system, you may receive daily antibiotics to prevent some types of pneumonia. Ask your provider if you should receive the influenza (flu) and pneumococcal (pneumonia) vaccines. Practice ...

  15. Immunizations for Preterm Babies

    MedlinePlus

    ... Prevention Listen Español Text Size Email Print Share Immunizations For Preterm Babies Page Content Some parents of ... full-term and preterm babies. The hepatitis B vaccine deserves special mention. In most circumstances, the AAP ...

  16. Immunization Against Infectious Disease

    ERIC Educational Resources Information Center

    Mortimer, Edward A., Jr.

    1978-01-01

    The success of present and future immunization programs is endangered by public and physician complacency and by complex legal and ethical problems related to informed consent and responsibility for rare, vaccine-related injury. (BB)

  17. Exercise and immunity

    MedlinePlus

    ... immunity. Heavy, long-term exercise (such as marathon running and intense gym training) could actually cause harm. Studies have shown that people who follow a moderately energetic lifestyle, benefit most from starting (and sticking to) an exercise ...

  18. Mucosal immunization and adjuvants.

    PubMed

    Hasegawa, Hideki; van Reit, Elly; Kida, Hiroshi

    2015-01-01

    The goal of the influenza vaccine is to prevent influenza virus infection and control the yearly seasonal epidemic and pandemic. However, the presently available parenteral influenza vaccine induces only systemic humoral immunity, which does not prevent influenza virus infection on the mucosal surface. Secretary IGA antibodies play an important role in preventing natural infection. Moreover, the IgA antibody response mediates cross-protection against variant viruses in animal models. Thus, a mucosal influenza vaccine that induces mucosal immunity would be a powerful tool to protect individuals from the influenza virus. Although the function of the mucosal immune system, especially in the respiratory tract, is not completely understood, there are several studies underway to develop mucosal influenza vaccines. Here, we will review current knowledge concerning the induction of IgA, the role of B-cell production of influenza virus specific IgA antibodies in anti-influenza immunity, and the role of humoral memory responses induced upon vaccination.

  19. Vaccines (immunizations) - overview

    MedlinePlus

    ... mumps, and rubella (MMR) vaccine and the varicella (chickenpox) vaccine are examples. Killed (inactivated) vaccines are made from ... countries. Some countries require this record. COMMON VACCINES ... DTaP immunization (vaccine) Hepatitis A vaccine Hepatitis B ...

  20. Immune System 101

    MedlinePlus

    ... your healthy cells. How HIV Affects This Complex Process HIV disrupts this process by directly infecting the helper T-cells. Your ... T-cells are destroyed in the HIV replication process. For more information, see NIAID's The Immune System . ...

  1. Vaccines: Engineering immune evasion

    NASA Astrophysics Data System (ADS)

    Mascola, John R.

    2006-05-01

    One obstacle to realizing the promise of viral vectors for vaccine delivery is pre-existing immunity to such vectors. An adroit application of structure-based design points to a way around that problem.

  2. FastStats: Immunization

    MedlinePlus

    ... this? Submit What's this? Submit Button NCHS Home Immunization Recommend on Facebook Tweet Share Compartir Data are ... Percent of children 19-35 months old receiving vaccinations for: Diphtheria, Tetanus, Pertussis (4+ doses DTP, DT, ...

  3. Antiviral Immunity in Amphibians

    PubMed Central

    Chen, Guangchun; Robert, Jacques

    2011-01-01

    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

  4. IMMUNE RESPONSES IN VITRO

    PubMed Central

    Pierce, Carl W.; Solliday, Susan M.; Asofsky, Richard

    1972-01-01

    Suppression of Ig class-specific PFC responses by class-specific antibody to mouse immunoglobulin was studied in cultures of spleen cells from immunized mice. In contrast to cultures from normal mice where anti-µ suppressed responses in all Ig classes, anti-µ had progressively less suppressive effect on γ1 and γ2 responses in cultures from immunized mice with time after immunization. This was most pronounced at 10 days after immunization when anti-µ suppressed γM and γA responses, but had no or slight effect on γ1 or γ2 responses which were still suppressed with anti-γ1 and anti-γ2. These changes in precursor cell susceptibility to anti-µ were antigen specific. PMID:4536707

  5. Immune reaction to propanidid.

    PubMed

    Christmas, D

    1984-05-01

    An adverse reaction to the intravenous anaesthetic agent propanidid is described in which the main features were hypotension, facial erythema, and abdominal pain. Changes in serum complement levels and differential white cell counts indicate that this was an immune reaction mediated by the classical complement pathway. The immune reaction apparently involved antibodies other than those of the IgE (reagin) class, and circumstantial evidence suggests that it was specific to propanidid rather than to the entire formulation or to Cremophor EL.

  6. Primary structure of the variable region of monoclonal antibody 2B10, capable of inducing anti-idiotypic antibodies that recognize the C-terminal region of MSA-1 of Plasmodium falciparum.

    PubMed Central

    Su, S; Yang, S; Ding, R; Davidson, E A

    1996-01-01

    Previously, we reported on the properties of a monoclonal antibody, 2B10, which has the same determinant on the human erythrocyte as MSA-1 of Plasmodium falciparum (FCR3 strain); the binding of both ligands to erythrocyte receptors was totally sialic acid dependent. In this work, rabbit anti-2B10 idiopathic antibodies were generated. The anti-idiotypic antibodies recognized both the erythrocyte binding site of 2B10 and the C-terminal region of MSA-1 (amino acids 1047 to 1640); they were able to inhibit 2B10 and MSA-1 binding to erythrocytes and partially prevent P. falciparum merozoites from invading erythrocytes. The utility of 2B10 in the study of the interaction between MSA-1 and human erythrocytes prompted us to determine the nucleotide and deduced amino acid sequences of its VH and VL regions. The data show that the 2B10 VH region is part of the J558 family and is especially homologous to BALB/c anti-nitrophenyl monoclonal antibody 21.1.43; the VL region belongs to the VK1 subgroup and comes from the same genomic locus as (NZB x W)F1 anti-DNA and C57BL anti-dextran monoclonal antibodies BXW-14 and 42.48.12.2, respectively. Most of the differences among the VH and VL segments are located in CDR1 and -3. The binding site of 2B10 contains both negatively and positively charged amino acid residues. The amino acid sequences of the 2B10 VH region and a region of MSA-1 from the Wellcome strain of P. falciparum (amino acids 1002 to 1115) share 43% similarity, and the amino acid sequences between the 2B10 VL region and another segment of the same MSA-1 (amino acids 1247 to 1394) share 48% similarity. We conclude that the interactions between erythrocyte receptors and their ligands, 2B10 and MSA-1, are related and that the C-terminal region of MSA-1 is the erythrocyte binding domain. PMID:8557359

  7. Military Healthcare Battlefield Immunity.

    PubMed

    Kelly, J C

    2012-12-01

    The combatant soldier on the battlefield remains protected from any claim in negligence by the doctrine of combat immunity for any negligent act or omission they may make when fighting. In other words, the combatant soldier does not owe a fellow soldier a duty of care on the battlefield, as the duty of care is non-justiciable. However, the non-combatant Military Healthcare Professional, although sometimes operating in the same hostile circumstances as the fighting soldier, is unlikely to benefit from combat immunity for any clinical negligence on the battlefield. This is because they continue to owe their patient a duty of care, although this has not been tested in the courts. This paper considers if any military healthcare professional could ever benefit from combat immunity, which is unlikely due to their non-combatant status. Instead, this paper suggests that a modified form of immunity; namely, Military Healthcare Battlefield Immunity could be a new, unique and viable doctrine, however, this could only be granted in rare circumstances and to a much lesser degree than combat immunity.

  8. Immune mediated liver failure

    PubMed Central

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of “immune coagulation”, which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure. PMID:26417328

  9. Mammalian Gut Immunity

    PubMed Central

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  10. Microbial manipulation of receptor crosstalk in innate immunity

    PubMed Central

    Hajishengallis, George; Lambris, John D.

    2011-01-01

    In the arms race of host–microbe coevolution, successful microbial pathogens have evolved ingenious ways in which to evade host immunity. In this Review, we focus on ‘crosstalk manipulation’ — the microbial strategies that instigate, subvert or disrupt the molecular signalling crosstalk between receptors of innate immunity. This proactive interference undermines host defences and contributes to microbial adaptive fitness and persistent infections. Understanding how pathogens exploit host receptor crosstalk mechanisms and infiltrate the host signalling network is essential for developing interventions to redirect the host response to protective immunity. PMID:21350579

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

    PubMed

    Boranić, Milivoj; Sabioncello, Ante; Gabrilovac, Jelka

    2008-01-01

    Innate and acquired immune reactions are controlled by their intrinsic regulatory mechanisms, ie. by an array of cytokines that mediate communication among cells of the immune system itself and with other cells and tissues, e. g. in areas of inflammation. In addition, the immune system is also subjected to systemic regulation by the vegetative and endocrine systems since immune cells express receptors for neurotransmitters and hormones. Neuroendocrine signals may enhance or suppress the immune reaction, accelerate or slow it, but do not affect specificity. Various stressful factors, including the psychosocial ones, affect immunity. In turn, cytokines generated by the immune system influence hormonal secretion and central nervous system, producing specific behavioral changes (the "sickness behavior") accompanying infectious and inflammatory diseases. That includes somnolence, loss of apetite, depression or anxiety and decrease of cognitive abilities, attention and memory. Local immune systems in skin and mucosa are also subjected to systemic neuroendocrine regulation and possess intrinsic neuroregulatory networks as well. These mechanisms render skin and respiratory and digestive tracts responsive to various forms of stress. Examples are neurodermitis, asthma and ulcerative colitis. In children, the immune and the neuroendocrine systems are still developing, particularly in fetal, neonatal and early infant periods, and exposure to stressful experiences at that time may result in late consequences in the form of deficient immunity or greater risks for allergic or autoimmune reactions. Recognition of the participation of neuroendocrine mechanisms in regulation of immunity helps us understand alterations and disturbances of immune reactions under the influence of stressful factors but so far has not produced reliable therapeutic implications. Psychosocial interventions involving the child and its family may be useful. PMID:18592962

  12. Modified cooperative immune algorithm for solving classification problems

    NASA Astrophysics Data System (ADS)

    Wójcik, Waldemar; Lytvynenko, Volodymyr; Smailova, Saule

    2013-01-01

    The way of the decision of a problem of classification by means of immune algorithm which is based on a principle of cooperation of antibodies of a population is offered. The formal description of structure of an antibody and ways of their association within the limits of a population in the computer network functioning as a unit is given. The way of an estimation of antibodies as elements of a network is considered. The basic phases of work of algorithm, such as are considered: growth of a network, a mutation of cells, compression of a network.

  13. Strategies to discover regulatory circuits of the mammalian immune system.

    PubMed

    Amit, Ido; Regev, Aviv; Hacohen, Nir

    2011-12-01

    Recent advances in technologies for genome- and proteome-scale measurements and perturbations promise to accelerate discovery in every aspect of biology and medicine. Although such rapid technological progress provides a tremendous opportunity, it also demands that we learn how to use these tools effectively. One application with great potential to enhance our understanding of biological systems is the unbiased reconstruction of genetic and molecular networks. Cells of the immune system provide a particularly useful model for developing and applying such approaches. Here, we review approaches for the reconstruction of signalling and transcriptional networks, with a focus on applications in the mammalian innate immune system.

  14. Immunizations climb, then falter.

    PubMed

    Kane, H

    1994-01-01

    The extended immunization campaign began in the mid 1980s and contributed to immunization of 4 out of every 5 infants worldwide, or 80% by the end of the 1980s. There was a slight relaxation of effort around 1990 and 1991, and declines occurred in 28 developing countries. In developing countries, 101 countries maintained or increased immunization in 1991. Rates dropped in Brazil and Venezuela and sub-Saharan Africa. Rates remained constant in 1992, except for the declines in women's tetanus immunization. Distribution is 4-5 times a year to 100 million infants. The savings in lives amounted to 3 million 1992, and further extension could have saved another 1.7 million. The cost in low income countries is $6 to $20, with an average of $15. Five visits are required for complete immunization into one dose; costs could then be reduced by 70%. Total annual costs amount to $2.2 to $2.4 billion for the United Nations Expanded Programme on Immunization. This sum amounts to 2% of public health expenditures in developing countries. The benefits are in reduction in health care costs and expanded productive potential of people. The measles vaccine alone reduced the death rate from 2.5 million in 1980 to 900,000 in 1990. Nonfatal measles morbidity was reduced from 75 million to 25 million for the same period. From averted measles incidents, the savings in treatment costs and productive potential are immeasurable. The first smallpox vaccine was developed in 1796 by Edward Jenner, but it took nearly two for final smallpox eradication in 1979 worldwide. Over the past 10 years, polio eradication has cost $1.4 billion, but without polio vaccines, the cost would reach $500 million annually. Refrigeration and transportation to remote areas has made immunization difficult. The development of low-dose vaccines that would maintain potency in tropical temperatures would be a welcome contribution.

  15. Ontogeny of Early Life Immunity

    PubMed Central

    Dowling, David J.; Levy, Ofer

    2014-01-01

    The human immune system is comprised of cellular and molecular components designed to coordinately prevent infection while avoiding potentially harmful inflammation and auto-immunity. Immunity varies with age, reflecting unique age-dependent challenges including fetal gestation, the neonatal phase and infancy. Herein, we review novel mechanistic insights into early life immunity, with emphasis on emerging models of human immune ontogeny, which may inform age-specific translational development of novel anti-infectives, immunomodulators and vaccines. PMID:24880460

  16. Immune memory in invertebrates.

    PubMed

    Milutinović, Barbara; Kurtz, Joachim

    2016-08-01

    Evidence for innate immune memory (or 'priming') in invertebrates has been accumulating over the last years. We here provide an in-depth review of the current state of evidence for immune memory in invertebrates, and in particular take a phylogenetic viewpoint. Invertebrates are a very heterogeneous group of animals and accordingly, evidence for the phenomenon of immune memory as well as the hypothesized molecular underpinnings differ largely for the diverse invertebrate taxa. The majority of research currently focuses on Arthropods, while evidence from many other groups of invertebrates is fragmentary or even lacking. We here concentrate on immune memory that is induced by pathogenic challenges, but also extent our view to a non-pathogenic context, i.e. allograft rejection, which can also show forms of memory and can inform us about general principles of specific self-nonself recognition. We discuss definitions of immune memory and a number of relevant aspects such as the type of antigens used, the route of exposure, and the kinetics of reactions following priming. PMID:27402055

  17. Immunity to Fish Rhabdoviruses

    PubMed Central

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non‑virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals. PMID:22355456

  18. Immunity to fish rhabdoviruses.

    PubMed

    Purcell, Maureen K; Laing, Kerry J; Winton, James R

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non‑virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  19. Immunity to fish rhabdoviruses

    USGS Publications Warehouse

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non-virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  20. Immune memory in invertebrates.

    PubMed

    Milutinović, Barbara; Kurtz, Joachim

    2016-08-01

    Evidence for innate immune memory (or 'priming') in invertebrates has been accumulating over the last years. We here provide an in-depth review of the current state of evidence for immune memory in invertebrates, and in particular take a phylogenetic viewpoint. Invertebrates are a very heterogeneous group of animals and accordingly, evidence for the phenomenon of immune memory as well as the hypothesized molecular underpinnings differ largely for the diverse invertebrate taxa. The majority of research currently focuses on Arthropods, while evidence from many other groups of invertebrates is fragmentary or even lacking. We here concentrate on immune memory that is induced by pathogenic challenges, but also extent our view to a non-pathogenic context, i.e. allograft rejection, which can also show forms of memory and can inform us about general principles of specific self-nonself recognition. We discuss definitions of immune memory and a number of relevant aspects such as the type of antigens used, the route of exposure, and the kinetics of reactions following priming.

  1. Durable and sustained immune tolerance to ERT in Pompe disease with entrenched immune responses

    PubMed Central

    Kazi, Zoheb B.; Prater, Sean N.; Kobori, Joyce A.; Viskochil, David; Bailey, Carrie; Gera, Renuka; Stockton, David W.; McIntosh, Paul; Rosenberg, Amy S.; Kishnani, Priya S.

    2016-01-01

    BACKGROUND Enzyme replacement therapy (ERT) has prolonged survival and improved clinical outcomes in patients with infantile Pompe disease (IPD), a rapidly progressive neuromuscular disorder. Yet marked interindividual variability in response to ERT, primarily attributable to the development of antibodies to ERT, remains an ongoing challenge. Immune tolerance to ongoing ERT has yet to be described in the setting of an entrenched immune response. METHODS Three infantile Pompe patients who developed high and sustained rhGAA IgG antibody titers (HSAT) and received a bortezomib-based immune tolerance induction (ITI) regimen were included in the study and were followed longitudinally to monitor the long-term safety and efficacy. A trial to taper the ITI protocol was attempted to monitor if true immune tolerance was achieved. RESULTS Bortezomib-based ITI protocol was safely tolerated and led to a significant decline in rhGAA antibody titers with concomitant sustained clinical improvement. Two of the 3 IPD patients were successfully weaned off all ITI protocol medications and continue to maintain low/no antibody titers. ITI protocol was significantly tapered in the third IPD patient. B cell recovery was observed in all 3 IPD patients. CONCLUSION This is the first report to our knowledge on successful induction of long-term immune tolerance in patients with IPD and HSAT refractory to agents such as cyclophosphamide, rituximab, and methotrexate, based on an approach using the proteasome inhibitor bortezomib. As immune responses limit the efficacy and cost-effectiveness of therapy for many conditions, proteasome inhibitors may have new therapeutic applications. FUNDING This research was supported by a grant from the Genzyme Corporation, a Sanofi Company (Cambridge, Massachusetts, USA), and in part by the Lysosomal Disease Network, a part of NIH Rare Diseases Clinical Research Network (RDCRN). PMID:27493997

  2. The Gut's Little Brain in Control of Intestinal Immunity

    PubMed Central

    de Jonge, Wouter J.

    2013-01-01

    The gut immune system shares many mediators and receptors with the autonomic nervous system. Good examples thereof are the parasympathetic (vagal) and sympathetic neurotransmitters, for which many immune cell types in a gut context express receptors or enzymes required for their synthesis. For some of these the relevance for immune regulation has been recently defined. Earlier and more recent studies in neuroscience and immunology have indicated the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. Sympathetic immune modulation is well described earlier, and in the last decade the parasympathetic vagal nerve has been put forward as an integral part of an immune regulation network via its release of Ach, a system coined “the cholinergic anti-inflammatory reflex.” A prototypical example is the inflammatory reflex, comprised of an afferent arm that senses inflammation and an efferent arm: the cholinergic anti-inflammatory pathway, that inhibits innate immune responses. In this paper, the current understanding of how innate mucosal immunity can be influenced by the neuronal system is summarized, and cell types and receptors involved in this interaction will be highlighted. Focus will be given on the direct neuronal regulatory mechanisms, as well as current advances regarding the role of microbes in modulating communication in the gut-brain axis. PMID:23691339

  3. Immune therapies for neuroblastoma.

    PubMed

    Navid, Fariba; Armstrong, Michael; Barfield, Raymond C

    2009-05-01

    Neuroblastoma, a solid tumor arising from developing cells of the sympathetic nervous system, is the most common extracranial tumor in children. The prognosis for high-risk neuroblastoma remains poor with conventional treatment, and new approaches are therefore being explored to treat this disease. One such alternative therapy that holds promise is immune therapy. We review here the recent advances in four types of immune therapy-cytokine, vaccine, antibody and cellular therapy-to treat neuroblastoma. We present preclinical research and clinical trials on several promising candidates such as IL-12, dendritic cell vaccines, anti-GD2 antibodies and allogeneic hematopoietic stem cell transplant. An optimal treatment plan for neuroblastoma will most likely involve multimodal approaches and combinations of immune therapies.

  4. Immune cells and angiogenesis.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2009-09-01

    Both innate and adaptive immune cells are involved in the mechanisms of endothelial cell proliferation, migration and activation, through the production and release of a large spectrum of pro-angiogenic mediators. These may create the specific microenvironment that favours an increased rate of tissue vascularization. In this review, we will focus on the immune cell component of the angiogenic process in inflammation and tumour growth. As angiogenesis is the result of a net balance between the activities exerted by positive and negative regulators, we will also provide information on some antiangiogenic properties of immune cells that may be utilized for a potential pharmacological use as antiangiogenic agents in inflammation as well as in cancer.

  5. Immune Therapies for Neuroblastoma

    PubMed Central

    Navid, Fariba; Armstrong, Michael; Barfield, Raymond C.

    2009-01-01

    Neuroblastoma, a solid tumor arising from developing cells of the sympathetic nervous system, is the most common extracranial tumor in children. The prognosis for high-risk neuroblastoma remains poor with conventional treatment, and new approaches are therefore being explored to treat this disease. One such alternative therapy that holds promise is immune therapy. We review here the recent advances in 4 types of immune therapy – cytokine, vaccine, antibody, and cellular therapy – to treat neuroblastoma. We present preclinical research and clinical trials on several promising candidates such as IL-12, dendritic cell vaccines, anti-GD2 antibodies, and allogeneic hematopoietic stem cell transplant. An optimal treatment plan for neuroblastoma will most likely involve multimodal approaches and combinations of immune therapies. PMID:19342881

  6. Vitamin D and immunity

    PubMed Central

    Gorman, Shelley; Geldenhuys, Sian; Hart, Prue H.

    2014-01-01

    Vitamin D deficiency has been linked to an increased risk of a wide range of adverse health outcomes. The active form of vitamin D has an important role in calcium metabolism and in bone mineralisation, but the evidence for other health outcomes is mixed, with the strongest effects seen in the weakest epidemiological study designs. There are plausible pathways whereby vitamin D deficiency can impair immune function, resulting in both overactivity and increased risk of autoimmune disease, as well as immune suppression with poorer resistance to infection. Vitamin D status may influence the bacterial flora that constitute the microbiome and affect immune function through this route. Exposure of the skin to ultraviolet radiation causes the production of a range of chemicals, including vitamin D, and new research is exploring possible vitamin D-independent immunomodulatory pathways. PMID:25580272

  7. Modeling Epidemics Spreading on Social Contact Networks

    PubMed Central

    ZHANG, ZHAOYANG; WANG, HONGGANG; WANG, CHONGGANG; FANG, HUA

    2016-01-01

    Social contact networks and the way people interact with each other are the key factors that impact on epidemics spreading. However, it is challenging to model the behavior of epidemics based on social contact networks due to their high dynamics. Traditional models such as susceptible-infected-recovered (SIR) model ignore the crowding or protection effect and thus has some unrealistic assumption. In this paper, we consider the crowding or protection effect and develop a novel model called improved SIR model. Then, we use both deterministic and stochastic models to characterize the dynamics of epidemics on social contact networks. The results from both simulations and real data set conclude that the epidemics are more likely to outbreak on social contact networks with higher average degree. We also present some potential immunization strategies, such as random set immunization, dominating set immunization, and high degree set immunization to further prove the conclusion.

  8. Inflammatory bowel disease related innate immunity and adaptive immunity

    PubMed Central

    Huang, Yuan; Chen, Zhonge

    2016-01-01

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

  9. Endocrine Factors Modulating Immune Responses in Pregnancy

    PubMed Central

    Schumacher, Anne; Costa, Serban-Dan; Zenclussen, Ana Claudia

    2014-01-01

    How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune–immune interactions as well as immune–endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells (DCs), monocytes, and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells. Furthermore, they are involved in the recruitment of mast cells and Treg cells into the fetal–maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field. PMID:24847324

  10. Immunization in urban areas: issues and strategies.

    PubMed Central

    Atkinson, S. J.; Cheyne, J.

    1994-01-01

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

  11. The effect of combined IL10 siRNA and CpG ODN as pathogen-mimicking microparticles on Th1/Th2 cytokine balance in dendritic cells and protective immunity against B cell lymphoma

    PubMed Central

    Pradhan, Pallab; Qin, Hong; Leleux, Jardin; Gwak, Dongho; Sakamaki, Ippei; Kwak, Larry W.; Roy, Krishnendu

    2014-01-01

    Success of an immunotherapy for cancer often depends on the critical balance of T helper 1 (Th1) and T helper 2 (Th2) responses driven by antigen presenting cells, specifically dendritic cells (DCs). Th1-driven cytotoxic T cell (CTL) responses are key to eliminating tumor cells. It is well established that CpG oligonucleotides (ODN), a widely studied Toll-like receptor 9 (TLR9) agonist, used to enhance Th1 response, also induces high levels of the anti-inflammatory, Th2-promoting cytokine IL10, which could dampen the resulting Th1 response. Biomaterials-based immunomodulatory strategies that can reduce IL10 production while maintaining IL12 levels during CpG delivery could further enhance the Th1/Th2 cytokine balance and improve anti-tumor immune response. Here we report that dual-delivery of IL10-silencing siRNA along with CpG ODN to the same DCs using pathogen-mimicking microparticles (PMPs), significantly enhances their Th1/Th2 cytokine ratio through concurrent inhibition of CpG-induced IL10 production. Co-delivery of poly(I:C), a TLR3 agonist had only minor effects on IL10 levels. Further, simultaneous immunotherapy with CpG ODN and IL10 siRNA enhanced immune protection of an idiotype DNA vaccine in a prophylactic murine model of B cell lymphoma whereas co-delivery of poly(I:C) and CpG did not enhance protection. These results suggest that PMPs can be used to precisely modulate TLR ligand-mediated immune-stimulation in DCs, through co-delivery of cytokine-silencing siRNAs and thereby boost antitumor immunity. PMID:24720881

  12. Quercetin, Inflammation and Immunity

    PubMed Central

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

    2016-01-01

    In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID:26999194

  13. Quercetin, Inflammation and Immunity.

    PubMed

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

    2016-03-01

    In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID:26999194

  14. Mammalian glycosylation in immunity

    PubMed Central

    Marth, Jamey D.; Grewal, Prabhjit K.

    2009-01-01

    Glycosylation produces a diverse and abundant repertoire of glycans, which are collectively known as the glycome. Glycans are one of the four fundamental macromolecular components of all cells, and are highly regulated in the immune system. Their diversity reflects their multiple biological functions that encompass ligands for proteinaceous of receptors known as lectins. Since the discovery that selectins and their glycan ligands are important for the regulation of leukocyte trafficking, it has been shown that additional features of the vertebrate immune system are also controlled by endogenous cellular glycosylation. This Review focuses on the emerging immunological roles of the mammalian glycome. PMID:18846099

  15. Vaccines and Immunization Practice.

    PubMed

    Hogue, Michael D; Meador, Anna E

    2016-03-01

    Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

  16. JASMONATE-TRIGGERED PLANT IMMUNITY

    PubMed Central

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

    2014-01-01

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

  17. CDPKs in immune and stress signaling

    PubMed Central

    Boudsocq, Marie; Sheen, Jen

    2012-01-01

    Ca2+ has long been recognized as a conserved second messenger and principal mediator in plant immune and stress responses. How Ca2+ signals are sensed and relayed into diverse primary and global signaling events is still largely unknown. Comprehensive analyses of the plant-specific multigene family of Ca2+-dependent protein kinases (CDPKs) are unraveling the molecular, cellular and genetic mechanisms of Ca2+ signaling. CDPKs, which exhibit overlapping and distinct expression patterns, sub-cellular localizations, substrate specificities and Ca2+ sensitivities, play versatile roles in the activation and repression of enzymes, channels and transcription factors. Here, we review the recent advances on the multifaceted functions of CDPKs in the complex immune and stress signaling networks, including oxidative burst, stomatal movements, hormonal signaling and gene regulation. PMID:22974587

  18. Platelets as immune cells in infectious diseases.

    PubMed

    Speth, Cornelia; Löffler, Jürgen; Krappmann, Sven; Lass-Flörl, Cornelia; Rambach, Günter

    2013-11-01

    Platelets have been shown to cover a broad range of functions. Besides their role in hemostasis, they have immunological functions and thus participate in the interaction between pathogens and host defense. Platelets have a broad repertoire of receptor molecules that enable them to sense invading pathogens and infection-induced inflammation. Consequently, platelets exert antimicrobial effector mechanisms, but also initiate an intense crosstalk with other arms of the innate and adaptive immunity, including neutrophils, monocytes/macrophages, dendritic cells, B cells and T cells. There is a fragile balance between beneficial antimicrobial effects and detrimental reactions that contribute to the pathogenesis, and many pathogens have developed mechanisms to influence these two outcomes. This review aims to highlight aspects of the interaction strategies between platelets and pathogenic bacteria, viruses, fungi and parasites, in addition to the subsequent networking between platelets and other immune cells, and the relevance of these processes for the pathogenesis of infections.

  19. Photodynamic immune modulation (PIM)

    NASA Astrophysics Data System (ADS)

    North, John R.; Hunt, David W. C.; Simkin, Guillermo O.; Ratkay, Leslie G.; Chan, Agnes H.; Lui, Harvey; Levy, Julia G.

    1999-09-01

    Photodynamic Therapy (PDT) is accepted for treatment of superficial and lumen-occluding tumors in regions accessible to activating light and is now known to be effective in closure of choroidal neovasculature in Age Related Macular Degeneration. PDT utilizes light absorbing drugs (photosensitizers) that generate the localized formation of reactive oxygen species after light exposure. In a number of systems, PDT has immunomodulatory effects; Photodynamic Immune Modulation (PIM). Using low- intensity photodynamic regimens applied over a large body surface area, progression of mouse autoimmune disease could be inhibited. Further, this treatment strongly inhibited the immunologically- medicated contact hypersensitivity response to topically applied chemical haptens. Immune modulation appears to result from selective targeting of activated T lymphocytes and reduction in immunostimulation by antigen presenting cells. Psoriasis, an immune-mediated skin condition, exhibits heightened epidermal cell proliferation, epidermal layer thickening and plaque formation at different body sites. In a recent clinical trial, approximately one-third of patients with psoriasis and arthritis symptoms (psoriatic arthritis) displayed a significant clinical improvement in several psoriasis-related parameters after four weekly whole-body PIM treatments with verteporfin. The safety profile was favorable. The capacity of PIM to influence other human immune disorders including rheumatoid arthritis is under extensive evaluation.

  20. Bed rest and immunity

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, Gerald; Aviles, Hernan; Butel, Janet S.; Shearer, William T.; Niesel, David; Pandya, Utpal; Allen, Christopher; Ochs, Hans D.; Blancher, Antoine; Abbal, Michel

    2007-02-01

    Space flight has been shown to result in altered immune responses. The current study was designed to investigate this possibility by using the bed rest model of some space flight conditions. A large number of women are included as subjects in the study. The hypothesis being tested is: 60 days head-down tilt bed rest of humans will affect the immune system and resistance to infection. Blood, urine and saliva samples will be obtained from bed rest subjects prior to, at intervals during, and after completion of 60 days of head-down tilt bed rest. Leukocyte blastogenesis, cytokine production and virus reactivation will be assessed. The ability of the subjects to respond appropriately to immunization with the neoantigen bacteriophage φX-174 will also be determined. Bed rest is being carried out at MEDES, Toulouse France, and the University of Texas Medical Branch, Galveston, TX. The studies to be carried out in France will also allow assessment of the effects of muscle/bone exercise and nutritional countermeasures on the immune system in addition to the effects of bed rest.

  1. Increasing Immunization Compliance

    ERIC Educational Resources Information Center

    Toole, Kimberly; Perry, Cynthia S.

    2004-01-01

    School nurses often have the responsibility to ensure that students meet all immunization requirements for school entry and school attendance. In large inner-city school districts, many obstacles exist which make this task daunting and often result in lengthy absences and exclusions for students. It is critical that school nurses find creative and…

  2. Maternal immune transfer in mollusc.

    PubMed

    Wang, Lingling; Yue, Feng; Song, Xiaorui; Song, Linsheng

    2015-02-01

    Maternal immunity refers to the immunity transferred from mother to offspring via egg, playing an important role in protecting the offspring at early life stages and contributing a trans-generational effect on offspring's phenotype. Because fertilization is external in most of the molluscs, oocytes and early embryos are directly exposed to pathogens in the seawater, and thus maternal immunity could provide a better protection before full maturation of their immunological systems. Several innate immune factors including pattern recognition receptors (PRRs) like lectins, and immune effectors like lysozyme, lipopolysaccharide binding protein/bacterial permeability-increasing proteins (LBP/BPI) and antioxidant enzymes have been identified as maternally derived immune factors in mollusc eggs. Among these immune factors, some maternally derived lectins and antibacterial factors have been proved to endue mollusc eggs with effective defense ability against pathogen infection, while the roles of other factors still remain untested. The physiological condition of mollusc broodstock has a profound effect on their offspring fitness. Many other factors such as nutrients, pathogens, environment conditions and pollutants could exert considerable influence on the maternal transfer of immunity. The parent molluscs which have encountered an immune stimulation endow their offspring with a trans-generational immune capability to protect them against infections effectively. The knowledge on maternal transfer of immunity and the trans-generational immune effect could provide us with an ideal management strategy of mollusc broodstock to improve the immunity of offspring and to establish a disease-resistant family for a long-term improvement of cultured stocks.

  3. Evolutionary responses of innate Immunity to adaptive immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Innate immunity is present in all metazoans, whereas the evolutionarily more novel adaptive immunity is limited to jawed fishes and their descendants (gnathostomes). We observe that the organisms that possess adaptive immunity lack diversity in their innate pattern recognition receptors (PRRs), rais...

  4. The multitasking organ: recent insights into skin immune function.

    PubMed

    Di Meglio, Paola; Perera, Gayathri K; Nestle, Frank O

    2011-12-23

    The skin provides the first line defense of the human body against injury and infection. By integrating recent findings in cutaneous immunology with fundamental concepts of skin biology, we portray the skin as a multitasking organ ensuring body homeostasis. Crosstalk between the skin and its microbial environment is also highlighted as influencing the response to injury, infection, and autoimmunity. The importance of the skin immune network is emphasized by the identification of several skin-resident cell subsets, each with its unique functions. Lessons learned from targeted therapy in inflammatory skin conditions, such as psoriasis, provide further insights into skin immune function. Finally, we look at the skin as an interacting network of immune signaling pathways exemplified by the development of a disease interactome for psoriasis.

  5. Immune diseases caused by mutations in kinases and components of the ubiquitin system.

    PubMed

    Cohen, Philip

    2014-06-01

    The signaling networks that control the immune system are coordinated by a myriad of interconnecting phosphorylation and ubiquitylation events. This review provides an overview of mutations in human genes encoding these proteins that give rise to immune diseases. Analysis of the biological effects of these mutations has revealed the true physiological roles of particular signaling networks and promises to revolutionize the treatment of these diseases.

  6. Technique Selectively Represses Immune System

    MedlinePlus

    ... Research Matters December 3, 2012 Technique Selectively Represses Immune System Myelin (green) encases and protects nerve fibers (brown). A new technique prevents the immune system from attacking myelin in a mouse model of ...

  7. Multitasking associative networks.

    PubMed

    Agliari, Elena; Barra, Adriano; Galluzzi, Andrea; Guerra, Francesco; Moauro, Francesco

    2012-12-28

    We introduce a bipartite, diluted and frustrated, network as a sparse restricted Boltzmann machine and we show its thermodynamical equivalence to an associative working memory able to retrieve several patterns in parallel without falling into spurious states typical of classical neural networks. We focus on systems processing in parallel a finite (up to logarithmic growth in the volume) amount of patterns, mirroring the low-level storage of standard Amit-Gutfreund-Sompolinsky theory. Results obtained through statistical mechanics, the signal-to-noise technique, and Monte Carlo simulations are overall in perfect agreement and carry interesting biological insights. Indeed, these associative networks pave new perspectives in the understanding of multitasking features expressed by complex systems, e.g., neural and immune networks.

  8. Multitasking Associative Networks

    NASA Astrophysics Data System (ADS)

    Agliari, Elena; Barra, Adriano; Galluzzi, Andrea; Guerra, Francesco; Moauro, Francesco

    2012-12-01

    We introduce a bipartite, diluted and frustrated, network as a sparse restricted Boltzmann machine and we show its thermodynamical equivalence to an associative working memory able to retrieve several patterns in parallel without falling into spurious states typical of classical neural networks. We focus on systems processing in parallel a finite (up to logarithmic growth in the volume) amount of patterns, mirroring the low-level storage of standard Amit-Gutfreund-Sompolinsky theory. Results obtained through statistical mechanics, the signal-to-noise technique, and Monte Carlo simulations are overall in perfect agreement and carry interesting biological insights. Indeed, these associative networks pave new perspectives in the understanding of multitasking features expressed by complex systems, e.g., neural and immune networks.

  9. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis.

    PubMed

    Faleiro, Rebecca J; Kumar, Rajiv; Bunn, Patrick T; Singh, Neetu; Chauhan, Shashi Bhushan; Sheel, Meru; Amante, Fiona H; Montes de Oca, Marcela; Edwards, Chelsea L; Ng, Susanna S; Best, Shannon E; Haque, Ashraful; Beattie, Lynette; Hafner, Louise M; Sacks, David; Nylen, Susanne; Sundar, Shyam; Engwerda, Christian R

    2016-02-01

    Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR) on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL) patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of combining different

  10. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis

    PubMed Central

    Bunn, Patrick T.; Singh, Neetu; Chauhan, Shashi Bhushan; Sheel, Meru; Amante, Fiona H.; Montes de Oca, Marcela; Edwards, Chelsea L.; Ng, Susanna S.; Best, Shannon E.; Haque, Ashraful; Beattie, Lynette; Hafner, Louise M.; Sacks, David; Nylen, Susanne; Sundar, Shyam; Engwerda, Christian R.

    2016-01-01

    Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR) on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL) patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of combining different

  11. Programmed cell death in the plant immune system

    PubMed Central

    Coll, N S; Epple, P; Dangl, J L

    2011-01-01

    Cell death has a central role in innate immune responses in both plants and animals. Besides sharing striking convergences and similarities in the overall evolutionary organization of their innate immune systems, both plants and animals can respond to infection and pathogen recognition with programmed cell death. The fact that plant and animal pathogens have evolved strategies to subvert specific cell death modalities emphasizes the essential role of cell death during immune responses. The hypersensitive response (HR) cell death in plants displays morphological features, molecular architectures and mechanisms reminiscent of different inflammatory cell death types in animals (pyroptosis and necroptosis). In this review, we describe the molecular pathways leading to cell death during innate immune responses. Additionally, we present recently discovered caspase and caspase-like networks regulating cell death that have revealed fascinating analogies between cell death control across both kingdoms. PMID:21475301

  12. Nanoparticle-Based Modulation of the Immune System.

    PubMed

    Fang, Ronnie H; Zhang, Liangfang

    2016-06-01

    The immune system is an incredibly complex biological network that plays a significant role in almost all disease pathogenesis. With an increased understanding of how this vital system operates, there has been a great emphasis on leveraging, manipulating, and/or supplementing endogenous immunity to better prevent or treat different disease states. More recently, the advent of nanotechnology has ushered in a plethora of new nanoparticle-based platforms that can be used to improve existing immunomodulation modalities. As the ability to engineer at the nanoscale becomes increasingly sophisticated, nanoparticles can be finely tuned to effect the desired immune responses, leading to exciting new avenues for addressing pressing issues in public health. In this review, we give an overview of the different areas in which nanoparticle technology has been applied toward modulating the immune system and highlight the recent advances within each.

  13. Immune surveillance of the CNS following infection and injury

    PubMed Central

    Russo, Matthew; McGavern, Dorian B.

    2015-01-01

    The central nervous system (CNS) contains a sophisticated neural network that must be constantly surveyed in order to detect and mitigate a diverse array of challenges. The innate and adaptive immune systems actively participate in this surveillance, which is critical for the maintenance of CNS homeostasis and can facilitate the resolution of infections, degeneration, and tissue damage. Infections and sterile injuries represent two common challenges imposed on the CNS that require a prompt immune response. While the inducers of these two challenges differ in origin, the resultant responses orchestrated by the CNS share some overlapping features. Here, we review how the CNS immunologically discriminates between pathogens and sterile injuries, mobilizes an immune reaction, and, ultimately, regulates local and peripherally-derived immune cells to provide a supportive milieu for tissue repair. PMID:26431941

  14. Clonal Selection Based Artificial Immune System for Generalized Pattern Recognition

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terry

    2011-01-01

    The last two decades has seen a rapid increase in the application of AIS (Artificial Immune Systems) modeled after the human immune system to a wide range of areas including network intrusion detection, job shop scheduling, classification, pattern recognition, and robot control. JPL (Jet Propulsion Laboratory) has developed an integrated pattern recognition/classification system called AISLE (Artificial Immune System for Learning and Exploration) based on biologically inspired models of B-cell dynamics in the immune system. When used for unsupervised or supervised classification, the method scales linearly with the number of dimensions, has performance that is relatively independent of the total size of the dataset, and has been shown to perform as well as traditional clustering methods. When used for pattern recognition, the method efficiently isolates the appropriate matches in the data set. The paper presents the underlying structure of AISLE and the results from a number of experimental studies.

  15. Omental immune aggregates and tumor metastasis within the peritoneal cavity.

    PubMed

    Sorensen, Elizabeth W; Gerber, Scott A; Sedlacek, Abigail L; Rybalko, Viktoriya Y; Chan, Winnie M; Lord, Edith M

    2009-12-01

    The omentum, an important peritoneal tissue, is studded with a high number of immune aggregates, or "milky spots," the number, function, and phenotype of which is largely unknown. We have analyzed the immune composition on the normal omentum and also have shown that both free immune cells and tumor cells in the peritoneal fluid bind preferentially to these immune aggregates. This binding may be mediated by the network of collagen I fibers, which overlay these areas. In addition, we have shown that not only do omental vessels express vascular endothelial growth factor receptor 3 (VEGFR3), a receptor that is only found on angiogenic blood vessels, but that tumor cells co-localize with these vessels, possibly increasing the ability of tumor to induce neovascularization and therefore thrive. PMID:19253004

  16. miRNA-124 in Immune System and Immune Disorders

    PubMed Central

    Qin, Zhen; Wang, Peng-Yuan; Su, Ding-Feng; Liu, Xia

    2016-01-01

    In recent years, miR-124 has emerged as a critical modulator of immunity and inflammation. Here, we summarize studies on the function and mechanism of miR-124 in the immune system and immunity-related diseases. They indicated that miR-124 exerts a crucial role in the development of immune system, regulation of immune responses, and inflammatory disorders. It is evident that miR-124 may serve as an informative diagnostic biomarker and therapeutic target in the future. PMID:27757114

  17. The immune system and its modulation mechanism in scallop.

    PubMed

    Song, Linsheng; Wang, Lingling; Zhang, Huan; Wang, Mengqiang

    2015-09-01

    Scallops are a cosmopolitan family of bivalves, and some of them are highly prized as dominant aquaculture species. In the past decades, there have been increasing studies on the basic biology and immunology of scallops, and this review summarizes the research progresses of immune system and its modulation mechanism in scallop. As invertebrate, scallops lack adaptive immunity and they have evolved an array of sophisticated strategies to recognize and eliminate various invaders by employing a set of molecules and cells. It is evident that basic immune reactions such as immune recognition, signal transduction, and effector synthesis involved in immune response are accomplished in a variety of ways. They rely upon an extensive repertoire of phagocytosis, apoptosis and encapsulation of the circulating hemocytes for eliminating invasive pathogens, as well as the production of immune effectors that are active against a large range of pathogens or sensitive for the environmental stress. Furthermore, the molecular constitutions, metabolic pathways and immunomodulation mechanisms of the primitive catecholaminergic, cholinergic, enkephalinergic system and NO system in scallop are also discussed, which can be taken as an entrance to better understand the origin and evolution of the neuroendocrine-immune regulatory network in lower invertebrates.

  18. Roles of plant hormones and their interplay in rice immunity.

    PubMed

    Yang, Dong-Lei; Yang, Yinong; He, Zuhua

    2013-05-01

    Plant hormones have been extensively studied for their importance in innate immunity particularly in the dicotyledonous model plant Arabidopsis thaliana. However, only in the last decade, plant hormones were demonstrated to play conserved and divergent roles in fine-tuning immune in rice (Oryza sativa L.), a monocotyledonous model crop plant. Emerging evidence showed that salicylic acid (SA) plays a role in rice basal defense but is differentially required by rice pattern recognition receptor (PRR) and resistance (R) protein-mediated immunity, and its function is likely dependent on the signaling pathway rather than the change of endogenous levels. Jasmonate (JA) plays an important role in rice basal defense against bacterial and fungal infection and may be involved in the SA-mediated resistance. Ethylene (ET) can act as a positive or negative modulator of disease resistance, depending on the pathogen type and environmental conditions. Brassinosteroid (BR) signaling and abscisic acid (ABA) either promote or defend against infection of pathogens with distinct infection/colonization strategies. Auxin and gibberellin (GA) are generally thought of as negative regulators of innate immunity in rice. Moreover, GA interacts antagonistically with JA signaling in rice development and immunity through the DELLA protein as a master regulator of the two hormone pathways. In this review, we summarize the roles of plant hormones in rice immunity and discuss their interplay/crosstalk mechanisms and the complex regulatory network of plant hormone pathways in fine-tuning rice immunity and growth.

  19. Modeling Systems-Level Regulation of Host Immune Responses

    PubMed Central

    Thakar, Juilee; Pilione, Mylisa; Kirimanjeswara, Girish; Harvill, Eric T; Albert, Réka

    2007-01-01

    Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or of bacterial factors changes the dynamics of the infection. We synthesize the network of interactions between host immune components and two closely related bacteria in the genus Bordetellae. We incorporate existing experimental information on the timing of immune regulatory events into a discrete dynamic model, and verify the model by comparing the effects of simulated disruptions to the experimental outcome of knockout mutations. Our model indicates that the infection time course of both Bordetellae can be separated into three distinct phases based on the most active immune processes. We compare and discuss the effect of the species-specific virulence factors on disrupting the immune response during their infection of naive, antibody-treated, diseased, or convalescent hosts. Our model offers predictions regarding cytokine regulation, key immune components, and clearance of secondary infections; we experimentally validate two of these predictions. This type of modeling provides new insights into the virulence, pathogenesis, and host adaptation of disease-causing microorganisms and allows systems-level analysis that is not always possible using traditional methods. PMID:17559300

  20. Intravenous Rh immune globulin for treating immune thrombocytopenic purpura.

    PubMed

    Sandler, S G

    2001-11-01

    Intravenous Rh [corrected] immune globulin was licensed by the U. S. Food and Drug administration in 1995 for the treatment of acute and chronic immune thrombocytopenic purpura in children and chronic immune thrombocytopenic purpura in adults. In 1996, the American Society of Hematology published a practice guideline for immune thrombocytopenic purpura, but treatment recommendations of necessity were formulated using only results of early clinical trials with intravenous Rh immune globulin. To date, there are no published results of large-scale clinical trials comparing conventional doses of intravenous immune globulin with the most promising dose range for intravenous Rh immune globulin (50-75 microg/kg). However, clinical experience is accumulating to indicate that intravenous Rh immune globulin is as effective, probably safer, and easier to administer than intravenous immune globulin. Acute intravascular hemolysis after infusions of intravenous Rh immune globulin for immune thrombocytopenic purpura has been reported with an estimated incidence of 1 in 1,115 patients. The risk factors for this adverse event have not been defined.

  1. The optimal dynamic immunization under a controlled heterogeneous node-based SIRS model

    NASA Astrophysics Data System (ADS)

    Yang, Lu-Xing; Draief, Moez; Yang, Xiaofan

    2016-05-01

    Dynamic immunizations, under which the state of the propagation network of electronic viruses can be changed by adjusting the control measures, are regarded as an alternative to static immunizations. This paper addresses the optimal dynamical immunization under the widely accepted SIRS assumption. First, based on a controlled heterogeneous node-based SIRS model, an optimal control problem capturing the optimal dynamical immunization is formulated. Second, the existence of an optimal dynamical immunization scheme is shown, and the corresponding optimality system is derived. Next, some numerical examples are given to show that an optimal immunization strategy can be worked out by numerically solving the optimality system, from which it is found that the network topology has a complex impact on the optimal immunization strategy. Finally, the difference between a payoff and the minimum payoff is estimated in terms of the deviation of the corresponding immunization strategy from the optimal immunization strategy. The proposed optimal immunization scheme is justified, because it can achieve a low level of infections at a low cost.

  2. Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

    PubMed Central

    He, Yukai; Munn, David; Falo, Louis D

    2011-01-01

    Summary Encouraged by remarkable successes in preventing infectious diseases and by the well established potential of immune system for controlling tumor growth, active therapeutic immunization approaches hold great promise for treating malignant tumors. In recent years, engineered recombinant viral vectors have been carefully examined as genetic immunization vehicles and have been demonstrated to induce potent T cell mediated immune responses that can control tumor growth. Very recent efforts suggest that lentivectors possess important advantages over other candidate recombinant viral vectors for genetic immunization. Here we review the development of recombinant lentivectors and the characteristics of T cell immune responses elicited by lentivector immunization, including the mechanism of T cell priming with a focus on the role of skin dendritic cells (DC) and potential applications for tumor immunotherapy. PMID:18377355

  3. Modelling the spread of sexually transmitted diseases on scale-free networks

    NASA Astrophysics Data System (ADS)

    Liu, Mao-Xing; Ruan, Jiong

    2009-06-01

    In this paper a new model for the spread of sexually transmitted diseases (STDs) is presented. The dynamic behaviors of the model on a heterogenous scale-free (SF) network are considered, where the absence of a threshold on the SF network is demonstrated, and the stability of the disease-free equilibrium is obtained. Three immunization strategies, uniform immunization, proportional immunization and targeted immunization, are applied in this model. Analytical and simulated results are given to show that the proportional immunization strategy in the model is effective on SF networks.

  4. Sunitinib Induced Immune Thrombocytopenia.

    PubMed

    Shekarriz, Ramin; Koulaeinejad, Neda; Nosrati, Anahita; Salehifa, Ebrahim

    2015-01-01

    Sunitinib is an oral tyrosine kinase inhibitor which prevents tumor growth and metastatic progression. It was approved for treatment of advanced renal cell cancer, gastrointestinal stromal tumor and advanced pancreatic neuroendocrine tumors. It has several adverse reactions on multi organ systems including hematologic system. Although the neutropenia and thrombocytopenia commonly happens as Grade 3 or 4 abnormalities following bone marrow suppression, in the rare cases, the immune mediated abnormality may drive the sunitinib-induced hematologic disorder. In this report, we present a case of immune-mediated thrombocytopenia induced by sunitinib. One month after first treatment cycle with sunitinib, leucopenia and thrombocytopenia were occurred. The patient had a normal bone marrow aspiration and biopsy, the thrombocytopenia was resistant to platelet transfusion which successfully was treated with prednisolone. PMID:26664400

  5. Sunitinib Induced Immune Thrombocytopenia

    PubMed Central

    Shekarriz, Ramin; Koulaeinejad, Neda; Nosrati, Anahita; Salehifa, Ebrahim

    2015-01-01

    Sunitinib is an oral tyrosine kinase inhibitor which prevents tumor growth and metastatic progression. It was approved for treatment of advanced renal cell cancer, gastrointestinal stromal tumor and advanced pancreatic neuroendocrine tumors. It has several adverse reactions on multi organ systems including hematologic system. Although the neutropenia and thrombocytopenia commonly happens as Grade 3 or 4 abnormalities following bone marrow suppression, in the rare cases, the immune mediated abnormality may drive the sunitinib-induced hematologic disorder. In this report, we present a case of immune-mediated thrombocytopenia induced by sunitinib. One month after first treatment cycle with sunitinib, leucopenia and thrombocytopenia were occurred. The patient had a normal bone marrow aspiration and biopsy, the thrombocytopenia was resistant to platelet transfusion which successfully was treated with prednisolone. PMID:26664400

  6. Immunity to amoeba.

    PubMed

    Nowak, Barbara; Valdenegro-Vega, Victoria; Crosbie, Philip; Bridle, Andrew

    2014-04-01

    Amoebic infections in fish are most likely underestimated and sometimes overlooked due to the challenges associated with their diagnosis. Amoebic diseases reported in fish affect either gills or internal organs or may be systemic. Host response ranges from hyperplastic response in gill infections to inflammation (including granuloma formation) in internal organs. This review focuses on the immune response of Atlantic salmon to Neoparamoeba perurans, the causative agent of Amoebic Gill Disease (AGD).

  7. Auto immune hepatitis.

    PubMed

    van Gerven, Nicole Mf; de Boer, Ynto S; Mulder, Chris Jj; van Nieuwkerk, Carin Mj; Bouma, Gerd

    2016-05-21

    To provide an update of the latest trends in epidemiology, clinical course, diagnostics, complications and treatment of auto immune hepatitis (AIH). A search of the MEDLINE database was performed using the search terms: "auto immune hepatitis", "clinical presentation", "symptoms", "signs", "diagnosis", "auto antibodies", "laboratory values", "serology", "histopathology", "histology", "genetics", "HLA genes", "non-HLA genes", "environment", "epidemiology", "prevalence", "incidence", "demographics", "complications", "HCC", "PBC", "PSC", "corticosteroid", "therapy", "treatment", "alternative treatment". English-language full-text articles and abstracts were considered. Articles included reviews, meta-analysis, prospective retrospective studies. No publication date restrictions were applied. AIH is an immune meditated progressive inflammatory liver disease that predominantly affects middle-aged females but may affect people of all ages. The clinical spectrum of AIH is wide, ranging from absent or mild symptoms to fulminant hepatic failure. The aetiology of AIH is still unknown, but is believed to occur as the consequence of an aberrant immune response towards an un-known trigger in a genetically susceptible host. In the absence of a gold standard, diagnosis is based on the combination of clinical, biochemical and histopathological criteria. Immunosuppressive treatment has been the cornerstone of treatment since the earliest description of the disease in 1950 by Waldenström. Such treatment is often successful at inducing remission and generally leads to normal life expectancy. Nevertheless, there remain significant areas of unmet aetiological a clinical needs including fundamental insight in disease pathogenesis, optimal therapy, duration of treatment and treatment alternatives in those patients unresponsive to standard treatment regimens. PMID:27217697

  8. Auto immune hepatitis

    PubMed Central

    van Gerven, Nicole MF; de Boer, Ynto S; Mulder, Chris JJ; van Nieuwkerk, Carin MJ; Bouma, Gerd

    2016-01-01

    To provide an update of the latest trends in epidemiology, clinical course, diagnostics, complications and treatment of auto immune hepatitis (AIH). A search of the MEDLINE database was performed using the search terms: “auto immune hepatitis”, “clinical presentation”, “symptoms”, “signs”, “diagnosis”, “auto antibodies”, “laboratory values”, “serology”, “histopathology”, “histology”, “genetics”, “HLA genes”, “non-HLA genes”, “environment”, “epidemiology”, “prevalence”, “incidence”, “demographics”, “complications”, “HCC”, “PBC”, “PSC”, “corticosteroid”, “therapy”, “treatment”, “alternative treatment”. English-language full-text articles and abstracts were considered. Articles included reviews, meta-analysis, prospective retrospective studies. No publication date restrictions were applied. AIH is an immune meditated progressive inflammatory liver disease that predominantly affects middle-aged females but may affect people of all ages. The clinical spectrum of AIH is wide, ranging from absent or mild symptoms to fulminant hepatic failure. The aetiology of AIH is still unknown, but is believed to occur as the consequence of an aberrant immune response towards an un-known trigger in a genetically susceptible host. In the absence of a gold standard, diagnosis is based on the combination of clinical, biochemical and histopathological criteria. Immunosuppressive treatment has been the cornerstone of treatment since the earliest description of the disease in 1950 by Waldenström. Such treatment is often successful at inducing remission and generally leads to normal life expectancy. Nevertheless, there remain significant areas of unmet aetiological a clinical needs including fundamental insight in disease pathogenesis, optimal therapy, duration of treatment and treatment alternatives in those patients unresponsive to standard treatment regimens. PMID:27217697

  9. Why parents refuse immunization?

    PubMed

    Kajetanowicz, Andrzej; Kajetanowicz, Aleksandra

    2016-01-01

    Rates of child immunization are falling in many countries, leading to the increase of morbidity and mortality from diseases controlled by vaccinations. The simplified model of the natural history of immunization follows a sequence of fear of the disease before vaccination, followed by acceptance of the vaccination until plateau, where the population forgets the morbidity and mortality of pre-immunization. Historical factors including withdrawals of vaccines, and publications regarding the true or falsified dangers of vaccines still resonate with parents. Building on these historical factors, unscientific sources such as naturopaths, homeopaths, chiropractors, celebrities and lay-people with anecdotal evidence and even scientific sources such as some universities and some medical doctors push their views on anti-vaccination, which proves to make the decision to vaccinate more difficult on parents. The main reason that parents refuse vaccination is a desire to protect their children. These parents believe that vaccination is harmful, or that not vaccinated children are healthier than vaccinated children. Scientific data often will lose with pseudoscientific, false or anecdotal data that have higher sensational and emotional impact on parents. With so many sources giving so many factors which sometimes contradict themselves, it is indeed difficult for a parent to make a clear decision for their child. PMID:27486715

  10. Bateman's principle and immunity.

    PubMed Central

    Rolff, Jens

    2002-01-01

    The immunocompetence handicap hypothesis (ICHH) of Folstad and Karter has inspired a large number of studies that have tried to understand the causal basis of parasite-mediated sexual selection. Even though this hypothesis is based on the double function of testosterone, a hormone restricted to vertebrates, studies of invertebrates have tended to provide central support for specific predictions of the ICHH. I propose an alternative hypothesis that explains many of the findings without relying on testosterone or other biochemical feedback loops. This alternative is based on Bateman's principle, that males gain fitness by increasing their mating success whilst females increase fitness through longevity because their reproductive effort is much higher. Consequently, I predict that females should invest more in immunity than males. The extent of this dimorphism is determined by the mating system and the genetic correlation between males and females in immune traits. In support of my arguments, I mainly use studies on insects that share innate immunity with vertebrates and have the advantage that they are easier to study. PMID:11958720

  11. Immune function in PTSD.

    PubMed

    Altemus, Margaret; Dhabhar, Firdaus S; Yang, Ruirong

    2006-07-01

    Disturbed regulation of both the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenomedullary system in posttraumatic stress disorder (PTSD) suggests that immune function, which is modulated by these systems, may also be dysregulated. Two dermatologic, in vivo measures of immune function, delayed-type hypersensitivity (DTH) and skin barrier function recovery, were examined in female subjects with PTSD and compared to measures in healthy female comparison subjects. In addition, at the time of DTH test placement, circulating numbers of lymphocyte subtypes were assessed. In separate studies, the effects of acute psychological stress on DTH and skin barrier function recovery were examined in healthy volunteer subjects. Both DTH and barrier function recovery were enhanced in women with PTSD. These findings contrast with the effects of acute stress in healthy control subjects, which was associated with suppression of DTH responses and skin barrier function recovery. There was no difference between subjects with PTSD and healthy control subjects in proportions of circulating lymphocyte subsets or in expression of the lymphocyte markers CD62, CD25, and CD45RO/CD45RA. These results suggest that cell-mediated immune function is enhanced in individuals with PTSD, a condition that imposes chronic physiologic and mental stress on sufferers. These findings contrast with suppression of DTH and skin barrier function recovery in healthy volunteers in response to acute psychological stress.

  12. Cystatins in immune system.

    PubMed

    Magister, Spela; Kos, Janko

    2013-01-01

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

  13. RECONSTRUCTING IMMUNE PHYLOGENY: NEW PERSPECTIVES

    PubMed Central

    Litman, Gary W.; Cannon, John P.; Dishaw, Larry J.

    2013-01-01

    Numerous studies of the mammalian immune system have begun to uncover profound interrelationships, as well as fundamental differences, between the adaptive and innate systems of immune recognition. Coincident with these investigations, the increasing experimental accessibility of non-mammalian jawed vertebrates, jawless vertebrates, protochordates and invertebrates has provided intriguing new information regarding the likely patterns of emergence of immune-related molecules during metazoan phylogeny, as well as the evolution of alternative mechanisms for receptor diversification. Such findings blur traditional distinctions between adaptive and innate immunity and emphasize that, throughout evolution, the immune system has used a remarkably extensive variety of solutions to meet fundamentally similar requirements for host protection. PMID:16261174

  14. Immunity to influenza in ferrets

    PubMed Central

    McLaren, C.; Potter, C. W.; Jennings, R.

    1974-01-01

    The degree of immunity due to cross-reactions between antibody to influenza virus A/Hong Kong/1/68 and A/England/42/72 was studied in ferrets. Ferrets were immunized with the viruses by either live infection or by inoculation with inactivated virus vaccines. The vaccines were given with Freund's incomplete adjuvant or were given to ferrets previously infected with influenza virus A/PR/8/34. As a result of these immunizations the animals all produced similar titres of serum HI antibody to the immunizing virus, although the degree of cross-reaction with the other virus strain was variable. After immunization the animals were challenged by infection with an A/Eng/42/72-like virus and their degree of immunity was measured. It was found that the greatest immunity was in ferrets previously infected with the homologous A/Eng/42/72 virus. Animals previously infected with A/HK/68 virus also showed a measurable degree of immunity to A/Eng/42/72 infection, and this was greater than that found in animals given inactivated virus vaccines. The immunity produced by the vaccines was approximately equal, regardless of which vaccine or method of immunization was used. Thus, live infection produced a more effective, broader immunity than did the use of inactivated virus vaccines. PMID:4531448

  15. Who knows more about immunization?

    PubMed Central

    Buxton, Jane A.; McIntyre, Cheryl C.; Tu, Andrew W.; Eadie, Brennan D.; Remple, Valencia P.; Halperin, Beth; Pielak, Karen L.

    2013-01-01

    Abstract Objective To report the findings of a knowledge survey of nurse and physician immunization providers. Design Cross-sectional postal survey assessing demographic characteristics and vaccine knowledge. Setting British Columbia (BC). Participants Nurse and physician immunization providers in BC. Main outcome measures Knowledge of vaccine-preventable diseases, vaccines in general, and vaccine administration and handling practices. Results Survey responses were received from 256 nurses and 292 physicians (response rates of 48.6% and 18.3%, respectively). Most nurses (98.4%) reported receiving immunization training outside of the academic setting compared with 55.6% of physicians. Overall, nurse immunizers scored significantly higher than physician immunizers on all 3 domains of immunization knowledge (83.7% vs 72.8%, respectively; P < .001). Physicians scored highest on the vaccine-preventable disease domain and least well on the general vaccine domain. Nurses with more experience as health care providers scored higher. Physicians scored higher if they were female, served patient populations predominantly younger than 5 years, or received immunization training outside of academic settings. Conclusion In BC, nurse immunizers appear to have higher overall immunization knowledge than physicians and are more likely to receive immunization training when in practice. Physician immunizers might benefit most from further training on vaccines and vaccine administration and handling. PMID:24235210

  16. Sex Hormones and Immune Dimorphism

    PubMed Central

    Bhatia, Aruna; Sekhon, Harmandeep Kaur; Kaur, Gurpreet

    2014-01-01

    The functioning of the immune system of the body is regulated by many factors. The abnormal regulation of the immune system may result in some pathological conditions. Sex hormones of reproductive system are one of the major factors that regulate immune system due to the presence of hormone receptors on immune cells. The interaction of sex hormones and immune cells through the receptors on these cells effect the release of cytokines which determines the proliferation, differentiation, and maturation of different types of immunocytes and as a result the outcome of inflammatory or autoimmune diseases. The different regulations of sex hormones in both sexes result in immune dimorphism. In this review article the mechanism of regulation of immune system in different sexes and its impact are discussed. PMID:25478584

  17. Ocular Immune Privilege and Transplantation.

    PubMed

    Taylor, Andrew W

    2016-01-01

    Allografts are afforded a level of protection from rejection within immune-privileged tissues. Immune-privileged tissues involve mechanisms that suppress inflammation and promote immune tolerance. There are anatomical features, soluble factors, membrane-associated proteins, and alternative antigen-presenting cells (APC) that contribute to allograft survival in the immune-privileged tissue. This review presents the current understanding of how the mechanism of ocular immune privilege promotes tolerogenic activity by APC, and T cells in response to the placement of foreign antigen within the ocular microenvironment. Discussed will be the unique anatomical, cellular, and molecular mechanisms that lessen the chance for graft destroying immune responses within the eye. As more is understood about the molecular mechanisms of ocular immune privilege greater is the potential for using these molecular mechanisms in therapies to prevent allograft rejection.

  18. Comparative immune systems in animals.

    PubMed

    Yuan, Shaochun; Tao, Xin; Huang, Shengfeng; Chen, Shangwu; Xu, Anlong

    2014-02-01

    Animal immune systems can be classified into those of innate immunity and those of adaptive immunity. It is generally thought that the former are universal for all animals and depend on germline-encoded receptors that recognize highly conserved pathogen-associated molecular patterns (PAMPs), whereas the latter are vertebrate specific and are mediated primarily by lymphocytes bearing a unique antigen receptor. However, novel adaptive or adaptive-like immunities have been found in invertebrates and jawless vertebrates, and extraordinarily complex innate immunities, created through huge expansions of many innate gene families, have recently been found in the cephalochordate amphioxus and the echinoderm sea urchin. These studies not only inspire immunologists to seek novel immune mechanisms in invertebrates but also raise questions about the origin and evolution of vertebrate immunities.

  19. An Expanded Lateral Interactive Clonal Selection Algorithm and Its Application

    NASA Astrophysics Data System (ADS)

    Gao, Shangce; Dai, Hongwei; Zhang, Jianchen; Tang, Zheng

    Based on the clonal selection principle proposed by Burnet, in the immune response process there is no crossover of genetic material between members of the repertoire, i. e., there is no knowledge communication during different elite pools in the previous clonal selection models. As a result, the search performance of these models is ineffective. To solve this problem, inspired by the concept of the idiotypic network theory, an expanded lateral interactive clonal selection algorithm (LICS) is put forward. In LICS, an antibody is matured not only through the somatic hypermutation and the receptor editing from the B cell, but also through the stimuli from other antibodies. The stimuli is realized by memorizing some common gene segment on the idiotypes, based on which a lateral interactive receptor editing operator is also introduced. Then, LICS is applied to several benchmark instances of the traveling salesman problem. Simulation results show the efficiency and robustness of LICS when compared to other traditional algorithms.

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

    PubMed

    Martin, Stefan F

    2014-11-01

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